The incidence of thrombotic complications in patients with coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) appears to be “remarkably high,” according to the authors of a recent study published in Thrombosis Research.

Frederikus A. Klok, MD, PhD, of the department of thrombosis and hemostasis at the Leiden University Medical Center in the Netherlands, and colleagues evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep vein thrombosis, ischemic stroke, myocardial infarction, or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 university hospitals and 1 teaching hospital in the Netherlands. They also estimated the incidence of venous and arterial thrombotic complications separately. Between March 7, 2020, and April 5, 2020, admitted patients were followed until ICU discharge, death, or April 5, 2020.

In total, 184 patients (mean age, 64 years; 76% men) with confirmed COVID-19 pneumonia were admitted to the ICU. At admission, therapeutic anticoagulation was administered to 9.2% of patients; 38% of patients had coagulopathy, and 13% of patients had renal replacement therapy.

 At the study completion date, 13% of patients had died, 12% had been discharged, and 76% were still in the ICU. During admission, all patients had received at least standard doses of thromboprophylaxis, though the local protocols at each center differed and dose increased with time.


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The cumulative incidence of the composite outcome was 31%. Of the events, 27% were confirmed as venous thromboembolism (VTE) and 3.7% were confirmed as arterial thrombotic events using computed tomography pulmonary angiography and/or ultrasonography.

The most frequent thrombotic complication was PE, comprising 81% of events. Two independent predicators of thrombotic complications were identified: age (adjusted hazard ratio [aHR], 1.05/per year) and coagulopathy (aHR, 4.1).

The authors acknowledged that these estimates were likely underestimations for several reasons. First, most of the patients were still in the ICU and may have experienced more thrombotic events. Second, intubated patients had a higher threshold before diagnostic imaging could be performed, therefore VTE was difficult to diagnose in these patients. Third, VTE screening had not be implemented. They also noted that they could not study the effects of the different nadroparin dosing regimens across institutions and time.

“In view of this, our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are suggestive of increasing the prophylaxis towards high-prophylactic doses, e.g. going from enoxaparin 40 mg [once daily] to 40 mg [twice daily], even in the absence of randomized evidence,” wrote the authors.

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“Finally, we propose that, rather than treating all patients with COVID-19 infections at the ICU with therapeutic anticoagulation, physicians should be vigilant for signs of thrombotic complications, and order appropriate diagnostic tests at a low threshold,” the investigators concluded.

Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19 [published online April 10, 2020]. Thromb Res. doi: 10.1016/j.thromres.2020.04.013