Anticoagulation Options for Coronavirus Disease 2019 (COVID-19)-Induced Coagulopathy

Abstract

As the coronavirus disease 2019 (COVID-19) pandemic is evolving, coagulopathy induced by the disease and its severe complications are raising concerns in the medical community. Because coagulopathy caused by COVID-19 has been difficult to control, it is important to have a better understanding of what therapies have been studied thus far and what therapies have demonstrated better outcomes for hospitalized patients. This review is focused on literature, research, and expert clinical judgments published in 2020 with a few references to articles published earlier. The review introduces the interim guidelines of the International Society of Thrombosis and Haemostasis (ISTH) for management of COVID-19-induced coagulopathy, discusses the efficacy of these guidelines in clinical settings, and summarizes the response of the scientific community to these guidelines and their clinical implications. Due to the failure of patients to respond to the prophylactic doses of heparin recommended by ISTH, higher doses of heparin may be necessary to achieve adequate anticoagulation. Patients' resistance to prophylactic doses of heparin could be due to low levels of anti-thrombin and high levels of fibrinogen, which would reinforce the use of therapeutic doses of heparin in the early stages of hospitalization. The review also compares low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as anticoagulant choices for COVID-19 patients. Given the complications specific to COVID-19, UFH may be a better choice of anticoagulant. Outpatient anticoagulation options are also reviewed. Changing qualified patients from vitamin K antagonists (VKA) to direct-acting oral anticoagulant (DOAC) for the convenience of less frequent monitoring may be appropriate. New anticoagulant, nafamostat, used in Japan is also discussed as a possible potentiate for heparin therapy.

Risk factors for intracerebral hemorrhage in patients with COVID-19

“…There was a significant difference in anticoagulation type in patients who did and did not experience ICH. Again, the fact that a greater percentage of ICH patients were on full dose heparin might be a marker of disease severity rather than represent a difference in ICH risk when on full dose heparin vs full dose enoxaparin [ 43 ]. Only patients with a clear indication and no contraindication should receive anticoagulation and the benefit versus risk of different doses of anticoagulation in hospitalized COVID-19 patients is currently being investigated.…”

Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection

“…47 Based on this pathophysiologic rationale, aspirin 81 mg daily can be administered as an initial antiplatelet and anti-inflammatory agent. 51 , 52 Ambulatory patients can be additionally treated with subcutaneous low-molecular-weight heparin or with short-acting novel anticoagulant drugs in dosing schemes similar to those use in outpatient thromboprophylaxis. In a retrospective study of 2773 inpatients with COVID-19, 28% received anticoagulant therapy within 2 days of admission, and despite being used in more severe cases, anticoagulant administration was associated with a reduction in mortality (HR = 0.86 per day of therapy, 95% CI: 0.82-0.89; P <0.001).…”

A 47-Year-Old Hispanic Man Who Developed Cutaneous Vasculitic Lesions and Gangrene of the Toes Following Admission to Hospital with COVID-19 Pneumonia

“…In a recently published observational study, the use of anticoagulation was associated with better outcomes in severely ill patients with COVID-19 who had elevated D-dimer [ 14 ]. Unfractionated-heparin has been suggested as a better choice for anticoagulation compared with low-molecular-weight heparin [ 15 ]. Our patient was placed on full-dose, weight-based enoxaparin on day 1 of hospitalization after testing revealed an elevated D-dimer level.…”