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occuring in up to 42&#46;6&#37; of patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;11</span></a> despite the use of prophylactic heparin treatment since the intensive care unit &#40;ICU&#41; admission&#46; However&#44; limited evidence exists to guide the prophylactic and therapeutic antithrombotic regimens&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Low-molecular-weigth heparin &#40;LMWH&#41; is the preferred heparin because of its safety profile&#44; efficacy&#44; bioavailability and persistent anticoagulant response&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;15</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Throughout the pandemic&#44; guidelines have been constantly updated&#46; Initaliy&#44; prophylactic&#44; intermediate and therapeutic doses&#44; were considered&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10&#44;12&#44;16</span></a> Currently&#44; randomized clinical trials have demonstrated that anticoagulation at therapeutic doses&#44; without evidence of thrombosis&#44; increases bleeding complications and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Likewise&#44; the INSPIRATION clinical trial showed that anticoagulation at intermediate doses did not reduce the incidende of thromboembolic events&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Currently&#44; clinicians are preventing and treating thromboembolic events in patients with severe COVID-19 with prophylactic and therapeutic doses of enoxaparin&#44; as suggested by clinical practice guidelines for venous thromboembolism&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14&#44;19&#8211;21</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; we are concerned about its accuracy&#46; It would likely be more precise to monitor anti-Xa activity with the aim of guiding LMWH prophylaxis and treatment&#46; Critically ill patients may be heparin-resistant<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> and may need higher doses of LMWH to achieve the desired prophylactic and therapeutic anticoagulation effect&#46; Some studies have shown that the mean level of anti-Xa activity in patients with severe COVID-19 is subtherapeutic&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#8211;27</span></a> Until now&#44; because of the safety profile of LMWH&#44; monitoring has only been indicated in special situations&#44; such as those involving obesity&#44; renal injury&#44; pregnancy and elderly individuals&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;15</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Due to the high incidence of thromboembolic events and the likely resistance to heparin in these patients&#44; the aim of this study was to analyse the relationship between anti-Xa activity below range and the diagnosis of new thromboembolic events in patients with severe COVID-19 admitted to the ICU&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">This was an observational prospective longitudinal cohort study&#46; Patients were recruited from the ICU of the Germans Trias i Pujol University Hospital between 18th February and 4th November&#44; 2021 and were followed until discharge from the ICU&#46; The study was started after the approval of the thromboprophylaxis protocol for severe COVID-19 by the hospital thrombosis committee &#40;Germans Trias i Pujol University Hospital&#46; Document Code&#58; CMT-PM-008&#44; revised February 1&#44; 2021&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">The eligibility criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">The inclusion criteria were patients eighteen years or older and admitted to the ICU because of severe COVID-19&#46; The exclusion criteria were active bleeding&#44; a glomerular filtration rate &#40;GFR&#41; less than 15&#160;mL&#47;min per 1&#46;73 m<span class="elsevierStyleSup">2</span> and a platelet count less than 30&#160;&#215;&#160;10&#94;9&#47;L&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Initial dosing of enoxaparin</span><p id="par0035" class="elsevierStylePara elsevierViewall">The initial dose of enoxaparin was based on weight and renal function &#40;Table S1&#44; supplementary material&#41;&#46; Prophylactic enoxaparin was administered at 6 am&#44; and therapeutic enoxaparin was administered at 6 am and 6&#160;pm&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Anti-Xa monitoring</span><p id="par0040" class="elsevierStylePara elsevierViewall">The draw time of the anti-Xa assay is generally 4&#160;h after the dose of enoxaparin so sample extractions were carried out at 10 am&#46; Blood draws were performed on Mondays and Thursdays until patient discharge from the ICU&#46; Anti-Xa monitoring was performed after at least two enoxaparin injections to ensure the achievement of a functional drug steady state&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> The levels of procoagulant &#40;platelets&#44; D-dimer&#44; fibrinogen&#41; and inflammatory biomarkers &#91;C-reactive protein&#44; procalcitonin &#40;PCT&#41;&#44; monocyte distribution width &#40;MDW&#41;&#44; interleukin-6 &#40;IL-6&#41;&#44; ferritin&#44; and lactate dehydrogenase &#40;LDH&#41;&#93; and the glomerular filtration rate &#40;GFR&#41; were determined at the same time as the anti-Xa levels&#46; Data on pharmacotherapy &#40;tocilizumab&#44; dexamethasone&#44; and enoxaparin&#41; and support therapies &#91;invasive mechanical ventilation and extracorporeal membrane oxygenation &#40;ECMO&#41;&#93; were collected on the same day that blood samples were collected for anti-Xa monitoring&#46; The anti-Xa levels were available after four hours of sample collection to adjust the dose of enoxaparin dosing on the same day&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Anti-Xa assay characteristics&#58; Blood samples were collected in 3&#46;8&#37; &#40;0&#46;129&#160;M&#41; sodium citrate &#40;anticoagulant&#41; tubes &#40;BD Vacutainer&#41; and plasma was obtained by 10-minute centrifugation at 3000&#160;rpm&#46; The anti-Xa activity of enoxaparin was measured using a chromogenic assay &#40;Liquid AntiXa&#174;&#44; Instrumentation Laboratory&#44; Bedford&#44; MA&#44; USA&#41; on an automated coagulation analyser &#40;ACL TOP 750&#44; Instrumentation Laboratory&#44; Bedford&#44; MA&#44; USA&#41; and was reported in IU&#47;mL&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The expected anti-Xa prophylactic and therapeutic ranges were 0&#46;2 to 0&#46;4 IU&#47;mL and 0&#46;5&#8211;1 IU&#47;mL&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> Anti-Xa activity was categorized as subprophylactic&#44; prophylactic or supraprophylactic and subtherapeutic&#44; therapeutic and supratherapeutic &#40;Table S2&#44; supplementary material&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Enoxaparin dose adjustment</span><p id="par0055" class="elsevierStylePara elsevierViewall">Enoxaparin dose adjustment was based on anti-Xa activity according to Manresa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and the hospital protocol &#40;Table S3&#44; supplementary material&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Screening for new thromboembolic events</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">US screening for DVT</span><p id="par0060" class="elsevierStylePara elsevierViewall">US screening for DVT was always done upon ICU admission&#59; routinely on Tuesday and Thursday &#40;simultaneously with the determination of anti-Xa activity&#41;&#44; and on Saturday or Sunday&#59; when there were significant differences between D-dimer results and when thrombosis was suspected on physical examination &#40;pain or swelling&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Intensive care physicians performed the screening&#46; These physicians had a long-standing experience in US &#40;more than ten vascular examinations performed per week and more than one year of experience in performing and interpreting US examinations&#41;&#46; Veins were scanned transversally over their entire length&#44; with probe compression applied at 1&#8722;2&#160;cm intervals&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">If needed&#44; augmentation manoeuvers were performed to find spontaneous or reverse-flow intraluminal color filling&#46; The veins scanned in the lower extremities included the common femoral&#44; femoral&#44; popliteal&#44; tibial&#44; peroneal&#44; gastrocnemius&#44; soleal and saphenous veins&#46; The veins scanned in the upper extremities were the radial&#44; ulnar&#44; axillary&#44; basilic and cephalic veins&#46; Additionally&#44; the subclavian&#44; internal&#44; and external jugular veins were scanned&#46; The arteries were scanned in the same way as the veins but only when ischemic complications occurred&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">US studies were performed using a Canon Ultrasound CUS-X100&#160;G &#40;Xario 100&#160;G&#41;&#44; with a linear transducer &#40;4&#46;2&#8722;14&#160;MHz&#41; and a FUJIFILM SonoSite M-Turbo Ultrasound&#44; with a linear transducer &#40;6&#8722;13&#160;MHz&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Transthoracic echocardiography screening for PE</span><p id="par0080" class="elsevierStylePara elsevierViewall">Transthoracic echocardiography was performed upon ICU admission and when PE was clinically suspected &#40;worsening hypoxemia and&#47;or unexpected shock&#41;&#46; Both intensive care physicians trained in Focus Cardiac Ultrasound and cardiologists performed the echocardiograms&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The US studies were performed using a Canon Ultrasound CUS-X100&#160;G &#40;Xario 100&#160;G&#41;&#44; with a sector transducer &#40;1&#46;8&#8211;5&#46;2&#160;MHz&#41; and a FUJIFILM SonoSite M-Turbo Ultrasound&#44; with a sector transducer &#40;1&#8722;5&#160;MHz&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Angio-CT screening for PE</span><p id="par0090" class="elsevierStylePara elsevierViewall">To confirm PE&#44; angio-CT was performed when severe hypoxemia and&#47;or shock could not be explained by other causes&#44; if the patient&#8217;s condition allowed it&#46; The radiology department was far from the ICU&#44; and the transfer required taking the elevator and placing the patient on a transfer stretcher&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Outcomes</span><p id="par0095" class="elsevierStylePara elsevierViewall">The primary aim was to determine the relative risk &#40;RR&#41; of new thromboembolic events in patients with severe COVID-19 with anti-Xa activity below range compared to anti-Xa activity within range&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The secondary outcome was to indentify the independent factors related to thomboembolic events in patients with severe COVID-19&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Institutional review board statement</span><p id="par0105" class="elsevierStylePara elsevierViewall">The study was carried out in accordance with the ethical principles for medical research involving human subjects &#40;revised Declaration of Helsinki&#44; Brazil&#44; 2013&#41;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and the Good Clinical Practice Guidelines of the International Conference of Harmonization &#40;2016&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The data were stored securely&#44; and all procedures related to data management complied with the General Data Protection Regulation&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The clinical research ethics committee of the Germans Trias i Pujol Hospital approved the development of the study &#40;resolution number&#58; PI-22-056&#41; in February 2021&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Sample size</span><p id="par0115" class="elsevierStylePara elsevierViewall">Considering an estimated 42&#46;6&#37; incidence of thromboembolic events in patients with severe COVID-19 patients admitted to the ICU&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and an estimated 10&#37; reduction in the incidence of thromboembolic events with enoxaparin dose adjustment based on anti-Xa activity&#44; two-tailed statistical significance&#44; 5&#37; alpha risk&#44; 85&#37; power&#44; and assuming a 2&#37; of losses&#44; we estimated a sample size of 228 patients &#40;<span class="elsevierStyleItalic">nsize</span> Stata&#174; v&#46;16&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Data collection</span><p id="par0120" class="elsevierStylePara elsevierViewall">Demographics&#44; prognosis &#91;Acute Physiology&#44; Age and Chronic Health Evaluation II &#40;APACHE II&#41;&#93;&#44; body-mass index and comorbidities were collected from the patient&#8217;s clinical health records&#46; The following parameters were prospectively collected&#58; antiplatelet therapy&#44; COVID-19 anti-inflammatory treatment &#40;tocilizumab&#44; dexamethasone&#41;&#44; enoxaparin dosing&#44; anti-Xa activity&#44; need for invasive mechanical ventilation&#44; shock&#44; GFR&#44; new thromboembolic events &#40;DVT&#44; PE and AT&#41;&#44; severe hemorrhage&#44; length of ICU stay and mortality&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Statistical analysis</span><p id="par0125" class="elsevierStylePara elsevierViewall">The statistical analysis of the data was performed in Stata&#174; v&#46;16&#46; The <span class="elsevierStyleItalic">means and medians</span> with their respective 95&#37; confidence intervals &#40;CIs&#41; were calculated for quantitative variables and <span class="elsevierStyleItalic">percentages</span> with their 95&#37; CIs were calculated for qualitative variables&#46; The Kolmogorov-Smirnov test was applied to confirm the normal distribution of the data&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Simple logistic regression</span> was used to determine the bivariate analysis of possible factors associated with the probability of developing new thromboembolic events and to identify potential confounders&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Multivariable logistic regression analysis</span> was used to determine the significant factors associated with new thromboembolic events and to construct a predictive model&#44; illustrated with a receiver operating characteristic &#40;ROC&#41; curve&#46; To perform the <span class="elsevierStyleItalic">multivariable logistic regression analysis</span>&#44; we considered those variables that were significantly associated with new thromboembolic events in the simple logistic regression&#46; Those variables with a large percentage of missing values &#40;&#62;60&#37;&#41; were discarded &#40;Table S4&#44; supplementary material&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The statistical method used to choose the best model was the <span class="elsevierStyleItalic">all-possible-subset method</span> &#40;based on the cut-off point of 0&#46;1&#41; for logistic regression&#44; and the final model chosen was the most parsimonious model with the best Hosmer&#8211;Lemeshow score and best area under the curve&#46; A ROC curve was generated&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Results</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Study population and thromboembolic events</span><p id="par0145" class="elsevierStylePara elsevierViewall">A total of 245 patients were screened between 18th February and 4th November&#44; 2021 and a total of 228 patients were enrolled&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">At the end of the follow-up&#44; 85 &#40;37&#46;2&#37;&#59; 95&#37; CI&#58; 31&#8211;44&#41; thromboembolic events were diagnosed in 75 patients&#44; so 32&#46;9&#37; &#40;95&#37; CI&#58; 26&#46;8&#8211;39&#46;4&#41; of these patients had a thrombosis&#46; Nineteen thromboembolic events &#40;8&#46;3&#37;&#41; were diagnosed pre-ICU in 15 patients &#91;6 &#40;2&#46;6&#37;&#41; with PE&#44; 5 &#40;2&#46;2&#37;&#41; with DVT and 4 &#40;1&#46;8&#37;&#41; with PE plus DVT&#93;&#44; so 6&#46;6&#37; patients were enrolled with a thromboembolic event already diagnosed&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Sixty-six &#40;28&#46;9&#37;&#59; 95&#37; CI&#58; 23&#46;2&#8211;35&#46;3&#41; new thromboembolic events were diagnosed after enrolment in the ICU in 62 patients&#44; so 27&#46;2&#37; &#40;95&#37; CI&#58; 21&#46;5&#8211;33&#46;5&#41; of patients had a new thromboembolic event &#91;13 &#40;5&#46;7&#37;&#41; PE&#44; 40 &#40;17&#46;6&#37;&#41; DVT&#44; 3 &#40;1&#46;3&#37;&#41; PE plus DVT and 6 &#40;2&#46;6&#37;&#41; AT&#93; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Patient baseline characteristics</span><p id="par0160" class="elsevierStylePara elsevierViewall">Overall&#44; 71&#46;2&#37; &#40;95&#37; CI&#44; 65&#46;7&#8722;77&#46;4&#41; were male and the median age was 62 years old &#40;95&#37; CI&#44; 59&#8722;63&#41;&#46; A body-mass index &#62;30&#160;kg&#47;m<span class="elsevierStyleSup">2</span> &#40;obesity&#41; was the most common coexisting condition &#40;51&#46;8&#37;&#59; 95&#37; CI&#44; 45&#46;2&#8722;58&#46;2&#41; followed by hypertension &#40;44&#46;7&#37;&#59; 38&#46;4&#8722;51&#46;3&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">Most patients needed invasive mechanical ventilation &#40;87&#46;7&#37;&#59; 95&#37; CI&#44; 82&#46;8&#8722;91&#46;4&#41; and 8&#46;8&#37; &#40;95&#37; IC&#44; 5&#46;7&#8722;13&#46;2&#41; needed ECMO support&#46; Many patients &#40;70&#46;2&#37;&#59; 95&#37; CI&#44; 63&#46;8&#8722;76&#41; were receiving dexamethasone treatment and 24&#46;1&#37; &#40;95&#37; CI&#44; 19&#8722;30&#46;1&#41; received tocilizumab&#46; All patients were under enoxaparin treatment&#58; 6&#46;6&#37; &#40;95&#37; CI&#44; 4&#8722;10&#46;6&#41; at therapeutic doses&#44; 66&#46;2&#37; &#40;95&#37; CI&#44; 59&#46;9&#8722;72&#46;1&#41; at prophylactic doses because no new thromboembolic event was diagnosed&#44; and 27&#46;2&#37; &#40;21&#46;8&#8722;33&#46;3&#41; at prophylactic doses first and at therapeutic doses when a new thromboembolic event was diagnosed&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Anti-Xa measurements</span><p id="par0170" class="elsevierStylePara elsevierViewall">A total of 896 anti-Xa measurements were performed&#44; and 27&#46;1&#37; &#40;95&#37; CI&#44; 24&#46;3&#8211;30&#46;1&#41; of them were below range&#44; 62&#46;1&#37; &#40;95&#37; CI&#44; 58&#46;8&#8211;65&#46;2&#41; were within range and 10&#46;8&#37; &#40;8&#46;9&#8211;13&#41; were above range&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">When prophylactic enoxaparin was used&#44; 27&#46;8&#37; &#40;95&#37; CI&#44; 26&#46;7&#8211;31&#46;5&#41; were subprophylactic and when therapeutic enoxaparin was used&#44; 25&#46;9&#37; &#40;95&#37; CI&#44; 21&#46;3&#8211;31&#46;1&#41; were subtherapeutic &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">The median number of measurements was 3 per patient&#46; Only four patients had one measurement&#44; and two patients had fifteen measurements&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Many new thromboembolic events were diagnosed at the first &#40;39&#46;4&#37;&#59; 95&#37; CI&#44; 28&#46;5&#8211;51&#46;5&#41;&#44; second &#40;34&#46;8&#37;&#59; 95&#37; CI&#44; 24&#46;5&#8211;46&#46;9&#41; and third &#40;16&#46;7&#37;&#59; 9&#46;6&#8211;27&#46;4&#41; anti-Xa measurements &#40;Table S5&#44; supplementary material&#41;&#46; Most anti-Xa level were within range after the third measurement&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Bivariate analysis</span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Crude relative risk of new thromboembolic events</span><p id="par0190" class="elsevierStylePara elsevierViewall">The incidence of new PE and new DVT when anti-Xa activity was below range was 4&#46;9&#37; &#40;crude RR 8&#46;7&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;005&#41; and 12&#46;4&#37; &#40;crude RR 5&#46;5&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;000&#41;&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0195" class="elsevierStylePara elsevierViewall">The incidence of new AT when therapeutic enoxaparin was used was 3&#46;8&#37; &#40;crude RR 3&#46;5&#59; 95&#37; CI 0&#46;6&#8211;21&#46;5&#59; <span class="elsevierStyleItalic">p&#160;&#61;</span>&#160;0&#46;17&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">Crude relative risk of severe hemorrhage</span><p id="par0200" class="elsevierStylePara elsevierViewall">Only 1 patient suffered a severe hemorrhage when anti-Xa was above range and the patient was under therapeutic anticoagulation&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">Bivariate analysis for risk of new thromboembolic events</span><p id="par0205" class="elsevierStylePara elsevierViewall">New thromboembolic events were related to illness severity &#40;APACHE II&#59; RR&#44; 1&#46;1&#59; 95&#37; CI&#44; 1&#46;01&#8211;1&#46;12&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;03&#41;&#44; ECMO support &#40;RR&#44; 3&#46;06&#59; 95&#37; CI&#44; 1&#46;2&#8211;7&#46;77&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;02&#41;&#44; the ARC &#40;augmented renal clearance&#41; &#40;glomerular filtration rate above 130&#160;ml&#47;minute per 1&#46;73 m<span class="elsevierStyleSup">2</span>&#41; &#40;RR&#44; 3&#59; 95&#37; CI&#44;1&#46;42&#8211;6&#46;29&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;004&#41;&#44; increased D-dimer &#40;RR&#44; 1&#46;0001&#44; 95&#37; CI&#44; 1&#46;00003&#8211;1&#46;0001&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;000&#41;&#44; serum inflammation-related parameters such as C-reactive protein &#40;RR&#44; 1&#46;007&#44; 95&#37; CI&#44; 1&#46;004&#8211;1&#46;009&#59; <span class="elsevierStyleItalic">p&#160;&#61;</span>&#160;0&#46;000&#41; and anti-Xa activity below range &#40;RR&#44; 6&#44; 95&#37; CI&#44; 3&#46;4&#8722;10&#46;7&#59; <span class="elsevierStyleItalic">p&#160;&#61;</span>&#160;0&#46;000&#41; &#40;Table S6&#41;&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Clinical situations that were found to protect against new thromboembolic events included a GFR between 90 and 130&#160;ml&#47;minute&#47; 1&#46;73 m<span class="elsevierStyleSup">2</span> &#40;RR&#44; 0&#46;49&#59; 95&#37; CI&#44; 0&#46;26&#8722;0&#46;94&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;03&#41; compared with a GFR under 90&#160;ml&#47;minute per 1&#46;73 m<span class="elsevierStyleSup">2</span> and tocilizumab treatment &#40;RR 0&#46;51&#59; 95&#37; CI&#44; 0&#46;25&#8722;0&#46;99&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;04&#41; &#40;Table S6&#44; supplementary material&#41;&#46;</p></span></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Multivariable analysis</span><p id="par0215" class="elsevierStylePara elsevierViewall">The variables included to perform the best model for multivariable analysis were APACHE II score&#44; ECMO&#44; ARC&#44; tocilizumab treatment&#44; D-dimer&#44; C-reactive protein&#44; IL-6&#44; LDH and anti-Xa levels below range&#46; After applying the all-possible-subset method for logistic regression&#44; the model included ARC&#44; D-dimer&#44; C-reactive protein and anti-Xa levels below range&#46; <span class="elsevierStyleItalic">Multicollinearity</span> was checked for all those variables and because the variance inflation factors &#40;VIFs&#41; between the ARC and anti-Xa level and between the ARC and C-reactive protein were high &#40;6&#46;2 and 5&#46;4&#44; respectively&#41;&#44; the ARC was discarded from the final model&#46; Therefore&#44; the best final model included anti-Xa below range&#44; D-dimer and C-reactive protein levels&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Multivariable logistic regression analysis revealed that anti-Xa activity below range &#40;RR&#44; 4&#46;2&#59; 95&#37; CI&#44; 2&#46;01&#8722;8&#46;91&#59; <span class="elsevierStyleItalic">p&#160;&#61;</span>&#160;0&#46;000&#41;&#44; C-reactive protein &#40;25&#160;mg&#47;L increase&#93; &#40;RR 1&#46;14&#59; 95&#37; CI&#44; 1&#46;04&#8722;1&#46;24&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;005&#41; and D-dimer &#40;1000&#160;ng&#47;L increase&#41; &#40;RR&#44; 1&#46;06&#59; 95&#37; CI&#44; 1&#46;02&#46;1&#46;09&#59; <span class="elsevierStyleItalic">p&#160;&#61;</span>&#160;0&#46;002&#41; were the independent factors related to new thromboembolic events in patients with severe COVID-19 &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0225" class="elsevierStylePara elsevierViewall">The resulting predictive model forecasted the probability of developing new thromboembolic events with a good ROC curve &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Discussion</span><p id="par0230" class="elsevierStylePara elsevierViewall">Our findings suggested that patients admitted to the ICU because of severe COVID-19 were at high risk of developing thromboembolic events&#44; partly due to inadequate subprophylactic or subtherapeutic anticoagulation treatment&#46; Because the real incidence of thromboembolic events was lower &#40;27&#46;2&#37;&#41; than the expected &#40;42&#46;6&#37;&#41;&#44; the power of the study was better &#40;close to 99&#37;&#41;&#44; so these findings should be considered&#46; This is the largest study relating COVID-19 thrombosis to anti-Xa activity below range&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Taccone et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> suggested that high-dose thromboprophylaxis may decrease the occurrence of pulmonary embolism in ventilated COVID-19 patients&#44; and observed that patients treated with high-dose thromboprophylaxis had significantly greater anti-Xa activity than those treated with standard thromboprophylaxis&#44; but the INSPIRATION trial<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> failed to demonstrate a reduction in thromboembolic events with intermediate-dose prophylactic anticoagulation compared to standard prophylactic anticoagulation&#44; without taking into account anti-Xa measurements&#46; Probably&#44; the main outcome of these studies should not have been standard&#44; intermediate or high-dose thromboprophylaxis&#44; but rather targeted anti-Xa activity&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">The message from our study is that we should not only anticoagulate patients with severe COVID-19 according to weight and renal function&#44; but also individualize anticoagulation &#40;prophylactic and therapeutic&#41; according to proper monitoring&#44; as we do in routine clinical practice with other drugs such as antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Our study revealed that many new thromboembolic events were diagnosed during the first three anti-Xa adjustments&#46; If we did not monitor the anti-Xa level&#44; we would not have changed the enoxaparin dose&#44; and more thromboses would likely have been diagnosed&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Most anti-Xa levels were within range after the third measurement&#44; so it may not have been necessary to monitor anti-Xa levels throughout ICU stay&#44; if the patient remained stable&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Because anti-Xa monitoring may be important for reducing the incidence of thromboembolic events in severe COVID-19 patients&#44; a second analysis from this study will be performed to determine which factors were related to anti-Xa activity below range&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">In this study&#44; the cumulative incidence of thromboembolic events was high &#40;37&#46;3&#37;&#59; 95&#37; CI&#44; 31&#46;3&#8211;43&#46;7&#41;&#44; as were the incidence of new thromboembolic events diagnosed &#40;28&#46;9&#37;&#59; 95&#37;&#44; CI 23&#46;4&#8211;35&#46;1&#41;&#46; These results agree with other reports &#40;30&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> 42&#46;6&#37;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and 40&#37; in a cohort of 100 COVID-19 autopsies<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#41;&#46; In our cohort&#44; arterial thrombosis &#40;2&#46;6&#37;&#41; was only related to the catheter line&#44; differing from other studies that reported up to 3&#37; myocardial or cerebral thromboses&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">As other authors reported&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> the crude relative risk of thrombosis in COVID-19 patients receiving ECMO therapy was high &#40;RR&#44; 3&#46;06&#59; 95&#37; CI&#44; 1&#46;2&#8211;7&#46;77&#41; because of their inflammatory state and the absence of filter clotting during therapy&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">New thromboembolic events were also related to increased fibrinogen degradation products &#40;D-Dimer&#41;&#44; reflecting the hypercoagulation state of patients with severe COVID-19&#44;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6&#44;8&#44;10</span></a> and to classical inflammatory biomarkers&#44; such as C-reactive protein&#44; leading to heparin-resistance because of inflammation and impaired enoxaparin absorption due to vasoconstriction induced by shock and vasopressors&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23&#44;27&#44;33</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Our study had several limitations&#46; The results should be viewed with caution&#44; as an observational study is unable to control potentially confounding variables&#46; Furthermore&#44; the multivariable analysis could have been influenced by other unknown variables related to severe COVID-19&#46; In addition&#44; there was only one treatment group because we did not consider it ethical to conduct the study with a control group without anti-Xa monitoring&#44; because it was a usual clinical practice&#44; and we did not consider it appropriate to conduct the study with a retrospective control group because data collection in previous COVID-19 waves was not strictly reported&#46; Moreover&#44; mortality was not considered a competing endpoint and PE may be underdiagnosed&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Purposely designed clinical trials should be carried out to confirm the benefit of anti-Xa monitoring&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">Conclusions</span><p id="par0285" class="elsevierStylePara elsevierViewall">In conclusion&#44; anti-Xa activity below range&#44; increased C-reactive protein and D-dimer levels were the independent factors related to new thromboembolic events in patients with severe COVID-19&#46;</p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0250">Author contributions</span><p id="par0290" class="elsevierStylePara elsevierViewall">Study design&#58; PMN&#44; CMI&#44; MFC&#44; TTI&#44; LBL&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Data acquisition&#58; PMN&#44; CMI&#44; VRA&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Analysis and interpretation of data&#58; PMN&#44; CMI&#44; MAFC&#44; LBL&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">Quality assessment&#58; CMI&#44; MFC&#44; TTI&#44; LBL&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Drafting the manuscript&#58; PMN&#44; CMI&#44; MFC&#44; TTI&#44; VRA&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Revision for important intellectual content&#58; PMN&#44; CMI&#44; MFC&#44; LBL&#44; TTI&#46;</p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0255">Funding</span><p id="par0320" class="elsevierStylePara elsevierViewall">The current work was not funded&#46;</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0260">Competing interest</span><p id="par0325" class="elsevierStylePara elsevierViewall">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper&#46;</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0265">Author contributions</span><p id="par0330" class="elsevierStylePara elsevierViewall">Study design&#58; Pilar Marcos-Neira&#44; Cristian Morales-Indiano&#44; Mariana Fern&#225;ndez-Caballero&#44; Teresa Tomasa-Irriguible&#44; Luisa Bordej&#233;-Laguna&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">Data acquisition&#58; Pilar Marcos-Neira&#44; Cristian Morales-Indiano&#44; V&#237;ctor Ru&#237;z-Artola&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Analysis and interpretation of data&#58; Pilar Marcos-Neira&#44; Cristian Morales-Indiano&#44; Mariana Fern&#225;ndez-Caballero&#44; Luisa Bordej&#233;-Laguna&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">Quality assessment&#58; Cristian Morales-Indiano&#44; Mariana Fern&#225;ndez-Caballero&#44; Teresa Tomasa-Irriguible&#44; Luisa Bordej&#233;-Laguna&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">Drafting the manuscript&#58; Pilar Marcos-Neira&#44; Cristian Morales-Indiano&#44; Mariana Fern&#225;ndez-Caballero&#44; Teresa Tomasa-Irriguible&#44; V&#237;ctor Ru&#237;z-Artola&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Revision for important intellectual content&#58; Pilar Marcos-Neira&#44; Cristian Morales-Indiano&#44; Mariana Fern&#225;ndez-Caballero&#44; Luisa Bordej&#233;-Laguna&#44; Teresa Tomasa-Irriguible&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper&#46;</p></span></span>"
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            1 => "ICU"
            2 => "LMWH"
            3 => "GFR"
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            5 => "MDW"
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            7 => "LDH"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">We aimed to anlayse the relationship between anti-Xa activity below range and thomboembolic events&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Single center prospective observational longitudinal cohort study &#40;February&#8211;November 2021&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Setting</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Patients admitted to the ICU of a University Hospital&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Participants</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Patients with severe COVID-19 pneumoniae&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Interventions</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Enoxaparin was used for prophylactic and therapeutic anticoagulation&#46; Enoxaparin dosing and dose adjustment were based on anti-Xa activity according to the hospital protocol&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Main variables of interest</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Target&#58; thomboembolic events&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Predictors&#58; demographics&#44; pharmacotherapy&#44; anti-Xa measurements&#44; clinical data&#44; and laboratory results&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Logistic regression was used to identify independent risk factors for thomboembolic events&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Data were available for 896 serum anti-Xa measurements from 228 subjects&#46; Overall&#44; 71&#46;9&#37; were male&#44; with a median age of 62&#46; Most patients needed invasive mechanical ventilation &#40;87&#46;7&#37;&#41; and mortality was 24&#46;1&#37;&#46; A total of 28&#46;9&#37; new thomboembolic events were diagnosed&#46; There were 27&#46;1&#37; anti-Xa measesurements below range&#46; When multivariable logistic regression analysis was performed anti-Xa activity below range &#40;RR&#44; 4&#46;2&#59; p&#160;&#61;&#160;0&#46;000&#41;&#44; C-reactive protein &#40;25&#160;mg&#47;L increase&#41; &#40;RR&#44; 1&#46;14&#59; p&#160;&#61;&#160;0&#46;005&#41; and D-dimer &#40;1000&#160;ng&#47;L increase&#41; &#40;RR&#44; 1&#46;06&#59; p&#160;&#61;&#160;0&#46;002&#41; were the independent factors related to new thomboembolic events in patients with severe COVID-19&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Anti-Xa activity below range&#44; C-reactive protein and D-dimer were the independent factors related to thomboembolic events in patients with severe COVID-19&#46; Purposely designed clinical trials should be carried out to confirm the benefit of an anti-Xa monitoring&#46;</p></span>"
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        "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Analizar la relaci&#243;n entre los niveles de anti-Xa por debajo del rango objetivo con los eventos tromb&#243;ticos&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Dise&#241;o</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohortes&#44; unic&#233;ntrico&#44; prospectivo&#44; longitudinal y observacional &#40;Febrero&#8211;Noviembre 2021&#41;&#46;</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">&#193;mbito</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Pacientes ingresados en la UCI de un Hospital Universitario&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Participantes</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Pacientes cr&#237;ticos con neumon&#237;a COVID-19&#46;</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intervenciones</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">La enoxaparina se utiliz&#243; como anticoagulaci&#243;n profil&#225;ctica y terap&#233;utica&#46; Su dosificaci&#243;n y ajuste de dosis se bas&#243; en la actividad anti-Xa seg&#250;n el protocolo hospitalario&#46;</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Variables de inter&#233;s principals</span><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Objetivo&#58; eventos tromb&#243;ticos&#46;</p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Predictores</span><p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">demogr&#225;ficos&#44; farmacoterapia&#44; mediciones de anti-Xa&#44; datos cl&#237;nicos y resultados de laboratorio&#46;</p><p id="spar0130" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un an&#225;lisis de regresi&#243;n log&#237;stica para identificar los factores de riesgo independientes de trombosis&#46;</p></span> <span id="abst0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Resultados</span><p id="spar0135" class="elsevierStyleSimplePara elsevierViewall">Se realizaron 896 mediciones s&#233;ricas de anti-Xa en 228 pacientes&#46; La mayor&#237;a fueron varones &#40;71&#44;9&#37;&#41;&#44; con una edad mediana de 62 a&#241;os&#46; La mayor&#237;a precisaron de ventilaci&#243;n mec&#225;nica invasiva &#40;87&#44;7&#37;&#41; y la mortalidad fue del 24&#44;1&#37;&#46; Se diagnostic&#243; un 28&#44;9&#37; de nuevos eventos tromb&#243;ticos&#46; El 27&#44;1&#37; de las mediciones se encontraron por debajo del rango objetivo&#46; El an&#225;lisis de regresi&#243;n log&#237;stica demostr&#243; que la actividad anti-Xa por debajo del rango objetivo &#40;RR&#58; 4&#44;2&#59; p&#160;&#61;&#160;0&#44;000&#41;&#44; la PCR &#40;incremento de 25&#160;mg&#47;L&#41; &#40;RR&#58;1&#44;14&#59; p&#160;&#61;&#160;0&#44;005&#41; y&#44; el d&#237;mero D &#40;incremento de 1000&#160;ng&#47;L&#41; &#40;RR&#58; 1&#44;06&#59; p&#160;&#61;&#160;0&#44;002&#41; fueron los factores predictores independientes relacionados con nuevos eventos tromb&#243;ticos&#46;</p></span> <span id="abst0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusiones</span><p id="spar0140" class="elsevierStyleSimplePara elsevierViewall">La actividad anti-Xa por debajo del rango objetivo&#44; la PCR y&#44; el d&#237;mero D fueron los factores independientes que se relacionaron con eventos tromb&#243;ticos en pacientes con neumon&#237;a grave por COVID-19&#46; Se deber&#237;an realizar ensayos cl&#237;nicos al respecto para confirmar el beneficio de la monitorizaci&#243;n de la actividad anti-Xa&#46;</p></span>"
        "secciones" => array:9 [
          0 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Objetivo"
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          1 => array:2 [
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            "titulo" => "Dise&#241;o"
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          2 => array:2 [
            "identificador" => "abst0055"
            "titulo" => "&#193;mbito"
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          3 => array:2 [
            "identificador" => "abst0060"
            "titulo" => "Participantes"
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          4 => array:2 [
            "identificador" => "abst0065"
            "titulo" => "Intervenciones"
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          5 => array:2 [
            "identificador" => "abst0070"
            "titulo" => "Variables de inter&#233;s principals"
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          6 => array:2 [
            "identificador" => "abst0075"
            "titulo" => "Predictores"
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          7 => array:2 [
            "identificador" => "abst0080"
            "titulo" => "Resultados"
          ]
          8 => array:2 [
            "identificador" => "abst0085"
            "titulo" => "Conclusiones"
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        ]
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        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0375" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0165"
          ]
        ]
      ]
    ]
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      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
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            "Tamanyo" => 332439
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            "identificador" => "at0005"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flow chart of the study and descriptive study population according to thromboembolic events&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">TE&#58; Thromboembolic events&#46; Angio-CT&#58; Computed tomography angiography&#46; US&#58; Ultrasound&#46; AT&#58; Arterial thrombosis&#46; PE&#58; Pulmonary embolism&#46; DVT&#58; Deep vein thrombosis&#46;</p>"
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      1 => array:8 [
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        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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            "identificador" => "at0010"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">ROC curve predicting new thromboembolic events&#46;</p>"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">APACHE II&#58; Acute physiology and chronic health evaluation II&#46; ECMO&#58; Extracorporeal membrane oxygenation&#46; ARC&#58; Augmented renal clearance &#40;GFR above 130&#160;ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#160;&#61;&#160;228 patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estimated 95&#37; CI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Age&#44; years&#44; mean&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#8722;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex &#40;Male&#41;&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">164 &#40;71&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#46;7&#8722;77&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Body-mass index &#62; 30 Kg&#47;m<span class="elsevierStyleSup">2</span>&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">118 &#40;51&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;2&#8722;58&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APACHE II&#44; mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#8722;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vaccination&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;15&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;2&#8722;20&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypertension&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102 &#40;44&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#46;4&#8722;51&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diabetes mellitus&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 &#40;30&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#8722;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chronic renal dysfunction&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;6&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;7&#8722;10&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immunosuppression&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#46;2&#8722;11&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atrial Fibrillation&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;4&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;7&#8722;8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Antiplatelet therapy&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;5&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#8722;9&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Therapies</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ECMO therapy&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;7&#8722;13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Invasive Mechanical Ventilation&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">200 &#40;87&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82&#46;8&#8722;91&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tocilizumab&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;24&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#8722;30&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dexamethasone&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">160 &#40;70&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#46;8&#8722;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tocilizumab and dexamethasone&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;13&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;7&#8722;18&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prophylactic enoxaparin&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">151 &#40;66&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;9&#8722;72&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Therapeutic enoxaparin&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#8722;10&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prophylactic &#40;first&#41;&#44; therapeutic &#40;second&#41; enoxaparin&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#40;27&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#46;8&#8722;33&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Outcomes</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Shock&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;15&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;2&#8722;20&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acute Kidney Injury&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;19&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;7&#8722;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ARC&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78 &#40;34&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;3&#8722;40&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bleeding complications&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;4&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;7&#8722;8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Length of ICU stay &#40;days&#41;&#44; median&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#8722;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Death&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;24&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#8722;30&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            "identificador" => "at0020"
            "detalle" => "Table "
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        "tabla" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Anticoagulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&#47;Total Anti-Xa measurements &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estimated 95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Prophylactic anticoagulation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">591&#47;896 &#40;66&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#46;2&#8722;69&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subprophylactic &#40;anti-Xa &#60;0&#46;2 IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">164&#47;591 &#40;27&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;7&#8211;31&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prophylactic &#40;anti-Xa 0&#46;2&#8722;0&#46;4 IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">349&#47;591 &#40;59&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55-62&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Supraprophylactic &#40;anti-Xa &#62;0&#46;4 IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#47;591 &#40;13&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;7-16&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Therapeutic anticoagulation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">305&#47;896 &#40;34&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#8722;37&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subtherapeutic &#40;anti-Xa &#60;0&#46;5 IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#47;305 &#40;25&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#46;3-31&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Therapeutic &#40;anti-Xa 0&#46;5&#8722;1 IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">207&#47;305 &#40;67&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#46;9&#8211;72&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Supratherapeutic &#40;anti-Xa &#62;1 IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#47;305 &#40;6&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4-9&#46;5&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estimated 95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#47;896 &#40;7&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Below range&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">45&#47;243 &#40;18&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;4&#8722;10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Within range&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#47;556 &#40;2&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Prophylactic anticoagulation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#47;591 &#40;5&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subprophylactic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#47;164 &#40;17&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;4&#8722;19&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prophylactic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#47;349 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Therapeutic anticoagulation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#47;305 &#40;10&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subtherapeutic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#47;79 &#40;21&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;2&#8722;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Therapeutic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#47;207 &#40;5&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">New Pulmonary embolism</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#47;896 &#40;1&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Below range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#47;243 &#40;4&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;9&#8722;39&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;005&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Prophylactic anticoagulation</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subprophylactic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;5&#8722;144&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prophylactic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#47;349 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Therapeutic anticoagulation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#47;305 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subtherapeutic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#47;79 &#40;3&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;6&#8722;143&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Therapeutic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#47;207 &#40;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">New Deep Vein Thrombosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">44&#47;896 &#40;4&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Below range&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">30&#47;234 &#40;12&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;8&#8722;10&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;000&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Within range&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">11&#47;556 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Prophylactic anticoagulation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25&#47;591 &#40;4&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subprophylactic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">19&#47;164 &#40;11&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">6&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">2&#46;6&#8722;17&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prophylactic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#47;349 &#40;1&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Therapeutic anticoagulation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">19&#47;305 &#40;6&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  "referenciaCompleta" => "WHO Director-General&#8217;s opening remarks at the media briefing on COVID-19-11 March 2020&#44; <a target="_blank" href="https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19-11-march-2020#:&amp;sim;:text=WHO%20has%20been%20assessing%20this,to%20use%20lightly%20or%20carelessly">https&#58;&#47;&#47;www&#46;who&#46;int&#47;director-general&#47;speeches&#47;detail&#47;who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19-11-march-2020&#35;&#58;&#8764;&#58;text&#61;WHO&#37;20has&#37;20been&#37;20assessing&#37;20this&#44;to&#37;20use&#37;20lightly&#37;20or&#37;20carelessly</a>&#59; 2024 &#91;accessed el 14 de abril 2024&#93;&#46;"
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Original article
Available online 25 July 2024
Anti-Xa activity below range is related to thrombosis in patients with severe COVID-19
La actividad anti-Xa por debajo del rango objetivo se relaciona con los eventos trombóticos en pacientes con neumonía grave por COVID-19
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Pilar Marcos-Neiraa,
Corresponding author
pmarcos.germanstrias@gencat.cat

Corresponding author.
, Cristian Morales-Indianob, Mariana Fernández-Caballeroc, Teresa Tomasa-Irriguiblea, Luisa Bordejé-Lagunaa, Víctor Ruíz-Artolaa
a Intensive Care Unit, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain
b Department of Clinical Analysis and Biochemistry, Laboratori Clínic Metropolitana Nord, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain
c Hematology Laboratory, ICO-Badalona, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain
This item has received
Received 16 April 2024. Accepted 25 June 2024
Article information
Abstract
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Figures (2)
Tables (4)
Table 1. Patient baseline characteristics at ICU enrolment.
Table 2. Descriptive ranges of anti-Xa levels.
Table 3. Incidence and RR of new thromboembolic events when anti-Xa is below range.
Table 4. Multivariable logistic regression for new thromboembolic events.
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Additional material (1)
Abstract
Objective

We aimed to anlayse the relationship between anti-Xa activity below range and thomboembolic events.

Design

Single center prospective observational longitudinal cohort study (February–November 2021).

Setting

Patients admitted to the ICU of a University Hospital.

Participants

Patients with severe COVID-19 pneumoniae.

Interventions

Enoxaparin was used for prophylactic and therapeutic anticoagulation. Enoxaparin dosing and dose adjustment were based on anti-Xa activity according to the hospital protocol.

Main variables of interest

Target: thomboembolic events.

Predictors: demographics, pharmacotherapy, anti-Xa measurements, clinical data, and laboratory results.

Logistic regression was used to identify independent risk factors for thomboembolic events.

Results

Data were available for 896 serum anti-Xa measurements from 228 subjects. Overall, 71.9% were male, with a median age of 62. Most patients needed invasive mechanical ventilation (87.7%) and mortality was 24.1%. A total of 28.9% new thomboembolic events were diagnosed. There were 27.1% anti-Xa measesurements below range. When multivariable logistic regression analysis was performed anti-Xa activity below range (RR, 4.2; p = 0.000), C-reactive protein (25 mg/L increase) (RR, 1.14; p = 0.005) and D-dimer (1000 ng/L increase) (RR, 1.06; p = 0.002) were the independent factors related to new thomboembolic events in patients with severe COVID-19.

Conclusions

Anti-Xa activity below range, C-reactive protein and D-dimer were the independent factors related to thomboembolic events in patients with severe COVID-19. Purposely designed clinical trials should be carried out to confirm the benefit of an anti-Xa monitoring.

Keywords:
Anti-Xa monitoring
Severe COVID-19
Thomboembolic events
Venous thromboembolism
Pulmonary embolism
Enoxaparin
Intensive care unit
Abbreviations:
COVID-19
ICU
LMWH
GFR
PCT
MDW
IL-6
LDH
ECMO
DVT
PE
AT
Angio-CT
US
RR
APACHE II
95% CI
ROC curve
ARC
VIF
Resumen
Objetivo

Analizar la relación entre los niveles de anti-Xa por debajo del rango objetivo con los eventos trombóticos.

Diseño

Estudio de cohortes, unicéntrico, prospectivo, longitudinal y observacional (Febrero–Noviembre 2021).

Ámbito

Pacientes ingresados en la UCI de un Hospital Universitario.

Participantes

Pacientes críticos con neumonía COVID-19.

Intervenciones

La enoxaparina se utilizó como anticoagulación profiláctica y terapéutica. Su dosificación y ajuste de dosis se basó en la actividad anti-Xa según el protocolo hospitalario.

Variables de interés principals

Objetivo: eventos trombóticos.

Predictores

demográficos, farmacoterapia, mediciones de anti-Xa, datos clínicos y resultados de laboratorio.

Se realizó un análisis de regresión logística para identificar los factores de riesgo independientes de trombosis.

Resultados

Se realizaron 896 mediciones séricas de anti-Xa en 228 pacientes. La mayoría fueron varones (71,9%), con una edad mediana de 62 años. La mayoría precisaron de ventilación mecánica invasiva (87,7%) y la mortalidad fue del 24,1%. Se diagnosticó un 28,9% de nuevos eventos trombóticos. El 27,1% de las mediciones se encontraron por debajo del rango objetivo. El análisis de regresión logística demostró que la actividad anti-Xa por debajo del rango objetivo (RR: 4,2; p = 0,000), la PCR (incremento de 25 mg/L) (RR:1,14; p = 0,005) y, el dímero D (incremento de 1000 ng/L) (RR: 1,06; p = 0,002) fueron los factores predictores independientes relacionados con nuevos eventos trombóticos.

Conclusiones

La actividad anti-Xa por debajo del rango objetivo, la PCR y, el dímero D fueron los factores independientes que se relacionaron con eventos trombóticos en pacientes con neumonía grave por COVID-19. Se deberían realizar ensayos clínicos al respecto para confirmar el beneficio de la monitorización de la actividad anti-Xa.

Palabras clave:
Anti-Xa
COVID-19 grave
Eventos trombóticos
Trombosis venosa
Embolia pulmonar
Enoxaparina
Unidad de cuidados intensivos

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