Venous thromboembolism (VTE) is a frequent, preventable, and potentially fatal complication in critically ill patients.1–3 The presence of active cancer, such as hematologic malignancy (HM), further increases thromboembolic risk.4,5 Patients with HM are at risk for both thrombosis and bleeding, which may be further increased in the setting of critical illness.4–6

Many patients with hematologic malignancy require admission to the Intensive Care Unit (ICU). Ferreyro et al. observed a 13.9% 1-year incidence of ICU admission for this population, with a median time from diagnosis to ICU admission of 35 days.7 In addition, Carini et al. recently highlighted a higher incidence of venous thromboembolism in critically ill patients with hematologic malignancy compared with those not requiring an ICU admission (3.7% vs 1.2% respectively).8 Clinical Practice Guidelines recommend pharmacological VTE prophylaxis in critically ill patients except in cases of high bleeding risk, when they recommend mechanical prophylaxis.9–13 Severe thrombocytopenia (platelets<50×109/L) is a frequent complication both in patients with HM and in critically ill patients, and is associated with worse outcomes and complications (i.e., higher bleeding risk).14–16 Regarding mechanical prophylaxis, it is not recommended as monotherapy except when pharmacological methods are contraindicated (grade 2A).9 Regarding bleeding, the same study by Carini et al. reported that 3.8% of included patients had at least one episode of major bleeding in the cohort, with a higher incidence in ICU patients compared to non-ICU hospitalized controls (7.6% vs 2.4%, OR 3.33; 95% CI 3.09–3.58).8 The balance between preventing VTE and minimizing bleeding complications underscores the complexity of managing thromboprophylaxis in critically ill patients with HM.

Given the increasing number of patients with hematologic malignancy who develop critical illness, it is imperative to understand the incidence and risk factors for venous thromboembolism, as well as the efficacy and risks associated with both chemical and mechanical thromboprophylaxis. Our objectives are to describe the: 1) use, type (mechanical or pharmacological) and timing of thromboprophylaxis; 2) incidence of catheter and non-catheter related VTE (deep venous thrombosis and pulmonary embolism) according to type of thromboprophylaxis (pharmacological or mechanical); and 3) incidence of bleeding episodes according to type of thromboprophylaxis (pharmacological or mechanical). We also described outcomes related to critical illness including ICU/hospital mortality.

The study was approved by the Research Ethics Boards at Mount Sinai Hospital (MSH) (#21-0109-C) and the University Health Network (#21-5476), who waived the need for consent. The study is registered with ClinicalTrials.gov (NCT05396157).

We conducted a single-center retrospective cohort study of adult patients (≥18 years) with a diagnosis of HM admitted to the ICU at MSH between January 1st, 2014, and January 31st, 2022. MSH is a tertiary care center which provides critical care services to Princess Margaret Cancer Center, the largest cancer center in Canada. There were no exclusion criteria. Each patient's relevant data was retrieved from the Electronic Health Record (EHR). Each ICU admission between hospital admission and discharge was included as a separate episode. Patients were followed until hospital discharge or death, whichever occurred first.

We report study findings in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist (eTable 1).17

This cohort study of 813 unique patients (accounting for 862 unique hospital admissions) represents the largest analysis of the incidence of and risk factors associated with VTE and bleeding among patients with HM admitted to ICU, and on thromboprophylaxis strategies in this population. Remarkably, we found that in more than one third of episodes prophylaxis was not used or not documented and that there was a non-negligible incidence of VTE and/or bleeding during ICU admission.

Effectively implementing DVT prophylaxis is challenging in some clinical settings. In a previous multinational cross-sectional survey only 37% of patients with active malignancy received adequate prophylaxis, with thrombocytopenia as one of the associated factors with inadequate prophylaxis.28 In the ICU, there is a reported 70% adherence to guideline recommendations, however there is also a lack of mechanical devices in cases where pharmacological prophylaxis is contraindicated as reported by García-Olivares.29,30

Thrombocytopenia does not appear to be strictly protective against VTE, and previous studies document the safety of prophylactic enoxaparin even in patients with platelets lower than 10×109/L.5,31 In addition, the omission of thromboprophylaxis within the first 24h of ICU admission without clinical reasons has been associated with increased mortality in critically ill adults.32 A notable finding in our study is the substantial proportion of patients not receiving any prophylaxis or in which there was no mention of it. There is extensive literature around inadequate VTE prophylaxis that helps to better frame this issue. In a previous cross-sectional study, the factors associated with an increased risk for inadequate VTE prophylaxis included the presence of a contraindication to pharmacological prophylaxis (OR 3.9, 95% CI 2.5–6.1), and ICU admission for a non-medical pathology (OR 11.1; 95% CI 7.6–16.1).33 In a retrospective analysis of 1.4 million critically ill patients, 4% did not receive thromboprophylaxis within the first 24h after ICU admission, without obvious reason.29 This is a lower proportion than our study, where thromboprophylaxis was withheld in 21% of admissions because of thrombocytopenia; and there was no mention of prophylaxis in 14%. In the ENDORSE study, platelet count<100×109/L was a contraindication for VTE prophylaxis.28 Furthermore, up to 50% of all hospitalized patients at risk for VTE were not receiving appropriate prophylaxis. The use of prophylaxis protocols has been proven to be feasible and could potentially reduce the risk of VTE in this population.34,35

Finally, we found a non-negligible incidence of bleeding (7% minor bleeding and 14% major bleeding). This rate is higher than the reported in a previous population study that found a higher incidence of bleeding in ICU patients compared to non-ICU hospitalized controls (7.6% vs 2.4%, OR 3.33; 95% CI 3.09–3.58).8 In an analysis of factors associated with bleeding risk in medical patients, Decousus et al. reported a cumulative 3.2% incidence of major and nonmajor in-hospital bleeding within 14 days of admission. Active gastroduodenal ulcer (OR, 4.15; 95% CI, 2.21–7.77), prior bleeding (OR, 3.64; 95% CI, 2.21–5.99), and low platelet count (<50×109/L) (OR, 3.37; 95% CI, 1.84–6.18) were the strongest independent risk factors at admission for bleeding.36

As a retrospective analysis, this study has several limitations. Detection of events was done by individual chart review, subjected to human error. Also, there was lack of documentation for prophylaxis in 14% of cases which could potentially influence the results, either underestimating or overestimating the thromboprophylaxis use. Furthermore, despite being conducted at Canada’s largest HM centre, this was a single-center study. Further, VTE events are limited to those where the diagnosis was clinically suspected and a confirmatory test done, possibly leading to under-detection compared with active surveillance ultrasound for DVT.37 Finally, we lack data on some risk factors for VTE, such as previous chemotherapy. The strengths of our study include the large HM population, and the detailed and comprehensive data collection, including information regarding ICU-related treatments (i.e., mechanical ventilation, vasopressor requirements, etc.) and severity scores. By examining individual patient records instead of solely relying on administrative data, we could determine details about VTE timing and platelet counts.

We anticipated a low VTE risk in patients with HM and thrombocytopenia, however we found a considerable rate of thrombosis considering that this was a non-surveillance scenario. The risk of thrombosis was similar to that observed in a non-HM population of critically ill patients receiving chemical thromboprophylaxis.38 Additionally, our study revealed a high risk of bleeding, surpassing rates observed in general ICU populations, where studies report rates of major bleeding closer to 5%.39

The risk of VTE in critically ill patients with HM should be considered even in patients with thrombocytopenia. The risk of bleeding was considerably higher than expected. Our results should inform future prospective studies on this topic to try and better define the risk of thrombosis and bleeding in this population in a surveillance context.

The authors have no relevant financial or non-financial interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article.

FCC was awarded the Hold’em for Life Oncology Fellowship 2021-2022 for the completion of this project.

• a

  Poster presentation at Critical Care Canada Forum 2022 (Carini FC, Dozois G, Novitzky-Basso I, Munshi L, Ferreyro B, Mehta S. Critical Care Canada Forum 2022 Abstracts. Canadian Journal of Anesthesia/Journal canadien d’anesthésie. 2023;70(1):s175-s177. doi:https://doi.org/10.1007/s12630-023-02445-y).

• b

  Presented as a poster at the Virtual Art Slutsky Research Day, Interdepartmental Division of Critical Care Medicine, University of Toronto, June 21, 2022.

The study was approved by the Research Ethics Boards at Mount Sinai Hospital (#21-0109-C) and the University Health Network (#21-5476). We requested a full waiver of consent and Personal Information Protection and Electronic Document Act (PIPEDA) authorization for the patients identified in this study.

During the preparation of this work, the author used ChatGPT, an AI language model developed by OpenAI, in order to improve readability and to check grammar and spelling. After using this tool, the author reviewed and edited the text and assume full responsibility for the content of the publication.