Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Abstract

Introduction: COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. Methods: We 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 Dutch university hospitals and 1 Dutch teaching hospital. Results: We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. Conclusion:The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

COVID-19 — Toward a comprehensive understanding of the disease

“…Thus, the extrinsic pathway of coagulation is activated in plasma throughout the pulmonary vasculature, resulting in the clinical picture of local coagulation [59]. Obstruction of pulmonary capillaries by thrombi and local inflammatory vasodilation contributes to veno-arterial shunt and profound hypoxia observed in the severe COVID-19 patients [15,42,59,60]. The process is limited by the immune status of the patient as the mechanisms described above accelerate into vicious positive feedback loops.…”

“…Initial reports from China, reported patients suffering from a severe or fatal COVID-19 disease course, with slightly lower platelet count and a higher level of d-dimer [41,62]. But it was the first reports from Italy and other European countries, which emphasized the remarkably high incidence of pulmonary embolism and thrombosis in the most severe and fatal cases [59,60,63]. At present, there is an awareness of a few clinical and laboratory features of patients with COVID-19, which is thrombocytopenia, elevated d-dimer level, prothrombin time prolongation and disseminated intravascular coagulation [64,65].…”

“…Klok et al [60] reviewed 184 patients with COVID-19 admitted to an intensive care unit (ICU), of whom 31% experienced thrombotic events -particularly pulmonary embolism [80]. Surprisingly, the majority of infected individuals remained resistant to high doses of both lowmolecular-weight heparin (LMWH) and unfractionated heparin (UFH) [60].…”

“…Klok et al [60] reviewed 184 patients with COVID-19 admitted to an intensive care unit (ICU), of whom 31% experienced thrombotic events -particularly pulmonary embolism [80]. Surprisingly, the majority of infected individuals remained resistant to high doses of both lowmolecular-weight heparin (LMWH) and unfractionated heparin (UFH) [60]. Although it was speculated that it might result from a decreased antithrombin level, it appears that the failure to achieve therapeutic prolongation of activated partial thromboplastin time results from abnormally high levels of factor VIII [81].…”

The renin–angiotensin system – a therapeutic target in COVID-19?

“…Moreover, the expression of ACE2 in the lining of blood vessels is of note, as it could contribute to the risk of thrombotic events in patients with COVID-19, potentially via virion entry causing endothelial inflammation. 6 In addition, the interaction between ACE2 and the coronavirus virion could act as a target for vaccines. For example, a recent study characterising the receptor-binding domain of the viral spike protein, which interacts with ACE2, suggested that this protein could be used as a vaccine target which would prevent COVID-19 infection.…”