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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
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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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