Thromboembolic and bleeding events in ICU patients with COVID-19: A nationwide, observational study

Abstract

Background: Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and bleeding events in all ICU patients with COVID-19 in Denmark during the first and second waves of the pandemic.

Methods: This was a sub-study of the Danish Intensive Care Covid database, in which all patients with SARS-CoV-2 admitted to Danish ICUs from 10th March 2020 to 30th June 2021 were included. We registered coagulation variables at admission, and all thromboembolic and bleeding events, and the use of heparins during ICU stay. Variables associated with thrombosis and bleeding and any association with 90-day mortality were estimated using Cox regression analyses.

Results: We included 1369 patients in this sub-study; 158 (12%, 95% confidence interval 10-13) had a thromboembolic event in ICU and 309 (23%, 20-25) had a bleeding event, among whom 81 patients (6%, 4.8-7.3) had major bleeding. We found that mechanical ventilation and increased D-dimer were associated with thrombosis and mechanical ventilation, low platelet count and presence of haematological malignancy were associated with bleeding. Most patients (76%) received increased doses of thromboprophylaxis during their ICU stay. Thromboembolic events were not associated with mortality in adjusted analysis (hazard ratio 1.35 [0.91-2.01, p = .14], whereas bleeding events were 1.55 [1.18-2.05, p = .002]).

Conclusions: Both thromboembolic and bleeding events frequently occurred in ICU patients with COVID-19. Based on these data, it is not apparent that increased doses of thromboprophylaxis were beneficial.

Keywords: COVID-19; bleeding; thromboprophylaxis; thrombosis.

FIGURE 1

Thrombosis prophylaxis in the Danish intensive care unit (ICU) COVID cohort during the first week in ICU. The figure shows the number of patients receiving therapeutic doses of low molecular weight heparin (LMWH), intermediate (twice daily) doses of LMWH or standard thrombosis prophylaxis with LMWH. A small number of patients received unfractionated heparin (UFH) doses unknown. (Therapeutic dose LMWH: Enoxaparin 1 mg/kg/daily or tinzaparin 175 units/kg/daily or equivalent; Intermediate dose LMWH: Enoxaparin 40 mg × 2 or tinzaparin 4500 units × 2 or equivalent; Standard dose LMWH: Enoxaparin 40 mg or lower or tinzaparin 4500 units or lower once daily.)

FIGURE 2

Kaplan–Meier curves with 95% confidence intervals showing survival from intensive care unit (ICU) Day 7 and onwards in (A) Patients with and without thrombotic events during the first week in the ICU. Log‐rank test score 0.59; p = .44. (B) Patients with and without bleeding during the first week in the ICU. Log‐rank test score 17.2; p < .0001. Exactly 117 patients died during the first week in ICU and were not included in the survival analyses, leaving 1250 patients in the analyses. The follow‐up is the same in both groups (thin lines), but the length of confidence intervals (broad markings) differs depending on time of the last event.