By: Veeraya White, PharmD Candidate 2022 – University of Health Sciences and Pharmacy in St. Louis
Mentor: Brooke E. Gengler, PharmD, BCCP; Pharmacy Clinical Specialist, Cardiology, SSM Health Saint Louis University Hospital
IntroductionCoronavirus disease 2019 (COVID-19) is a viral respiratory infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which has become a significant threat worldwide. The infection triggers host defense systems resulting in activation of coagulation and thrombin generation, called thromboinflammation.1 As a result, some patients with COVID-19 encounter complications associated with cytokine overproduction, hypercoagulability, and thrombosis. Thromboinflammation may lead to a life-threatening condition, disseminated intravascular coagulopathy (DIC), a condition in which blood clots throughout the body use up available clotting factors thereby increasing the risk of bleeding.2,3 Anticoagulants (ACs), such as low molecular weight heparin (LMWH), and unfractionated heparin (UFH), are used to prevent thrombosis.2 This article will discuss the appropriate criteria for anticoagulant venous thromboembolism (VTE) prophylaxis in patients with COVID-19.
Literature ReviewEarly in the pandemic, clinicians identified that DIC was commonly associated with severe cases of COVID-19 that resulted in death.4 Upon closer examination, many of these patients experienced microvascular thrombosis or venous thromboembolism.5 As a result, several studies attempted to find an association between various biomarkers such as D-dimer and risk of thrombosis. One retrospective study from Wuhan, China found that patients with sepsis-induced coagulopathy scores (SIC) ≥4 or elevated D-dimers who were given prophylactic doses of LMWH had reduced mortality compared to those without.6
Larger, prospective, randomized controlled trials have explored whether prophylactic anticoagulation is enough to prevent thrombosis or if intermediate intensity, doses between prophylactic and therapeutic anticoagulation, should be used instead. The ACTION study evaluated extended duration therapeutic anticoagulation with rivaroxaban or enoxaparin during admission followed by rivaroxaban for 30 days after discharge in acutely ill COVID-19 patients. Compared to standard VTE prophylaxis, therapeutic anticoagulation increased the risk of bleeding without improving clinical outcomes.7 In critically ill patients, receipt of early therapeutic anticoagulation within two days of admission was not associated with reduced mortality.8 Preliminary data from the multi-platform randomized controlled trial (mpRCT) also indicate that therapeutic anticoagulation did not improve survival or days free from organ support compared to standard pharmacologic prophylaxis. This trial was stopped early due to futility.9 Based on currently available evidence, most COVID-19 patients admitted to the hospital should be initiated on standard VTE prophylaxis rather than an intensified regimen.
Application in Practice
Thrombosis prophylaxis in hospitalized COVID-19 patients
Recommended standard prophylaxis doses of anticoagulants (dose adjustments for renal function and obesity not included)10,12,13
Recommended intermediate doses of anticoagulants17
Duration of VTE prophylaxis after hospital discharge10