COVID Coagulopathy and Thrombosis: A Systematic Review

Introduction: Since the onset of the SARS-CoV-2 pandemic, haematological laboratory abnormalities and thrombotic complications have been observed among infected patients. We aimed to highlight key pathophysiological mechanisms of COVID-19-associated coagulopathy and to summarize incidence rates of venous and arterial thrombotic events, comorbidities conferring risk, and current treatment guidelines including data from ongoing clinical trials. Methods: A systematic review was performed according to PRISMA recommendations of case-control studies, cohort studies, observational studies and randomized clinical trials (RCTs) published between 1 December 2019 and 30 September 2021 within PubMed and Web of Science. Inclusion criteria were English language, adult patients and at least one coagulation parameter described. Results: 2,554 records were screened, from which 59 studies were included. Abnormalities in several laboratory parameters were associated with worse clinical outcomes including elevations in prothrombin time, activated partial thromboplastin time, D-dimer, fibrinogen, von Willebrand factor antigen/activity and lupus anticoagulant antibodies. Rates of venous and arterial thromboembolism varied significantly among studies performed early in the pandemic and across different nations. Pathophysiological mechanisms included vascular endotheliopathy, increased inflammation and macrophage activation, neutrophil extracellular traps, antiphospholipid antibody production and obesity/adipose tissue signalling. Current recommendations for management of COVID coagulopathy from various societies include the use and dosing of systemic anticoagulation to prevent thrombotic sequelae in the outpatient, inpatient and critical care settings. The optimal anticoagulant dose for thromboprophylaxis in the inpatient and critical care settings is currently not well established. Conclusions: SARS-CoV-2 infection can cause a distinct form of coagulopathy, with thromboembolic complications leading to significant morbidity and mortality. The optimal treatment requires further refinement pending the results from key ongoing RCTs.