Table 4 Overview of the pharmacological interventions under investigation targeting hypercoagulability and platelet activation in COVID-19 patients.
Pharmacological intervention Sample size and criteria Treatment protocol Key findings Conclusion Reference
• Heparin anticoagulant treatment in sepsis-induced coagulopathy • Retrospective cohort study
• ≥ 18 years of age
• Severe COVID-19 infection
• Evaluation of 28-day mortality in heparin and non-heparin users
• 48.5% comorbid hypertension and/or heart disease
•  N = 99 heparin
•  N = 350 no heparin • Unfractionated (10, 000–15, 000 U/day) or low molecular weight heparin (40–60 mg enoxaparin/day) for 7 days or longer • No difference in 28-day mortality endpoint between heparin and non-heparin users.
• Lower 28-day mortality in patients with sepsis-induced coagulopathy (SIC) score of ≥4 in stratified analysis
• Odd Ratio (OR) 0.372 (95% CI 0.154–0.901) • Heparin may be associated with a lower 28-day mortality rate only in patients with enhanced coagulopathy risk such as SIC score of 4 or greater (Tang, Bai, et al., 2020)
• Antiplatelet and anticoagulant combination therapy for hypoxemia, respiratory failure, and cardiac adverse events • Case control, proof-of-concept study
• Adult patients with hypoxemic respiratory failure
• N = 5 ASA + clopidogrel + tirofiban + fondaparinux + standard care
•  N = 5 matched controls given low molecular weight heparin
• Secondary outcome included major and minor cardiac adverse events 1. Single dose of acetylsalicylic acid (ASA) 250 mg i.v. and single loading dose of oral clopidogrel 300 mg2. ASA and clopidogrel continued at 75 mg orally for 30 days3. Tirofiban 25 μg/kg as bolus i.v. injection, then 0.15 μg/kg/min continuous i.v. infusion for 48 h4. Fondaparinux 2.5 mg/day s.c. for the duration of the hospital stay • Significant improvement in alveolar-arterial oxygen gradient
• Significant improvement in CRP and lymphocyte count
• Patients in treatment group did not experience any cardiac adverse events • Small study and not a randomized controlled trial (RCT)
• Intensive antithrombotic therapy may be useful in patients with severe respiratory distress with prothrombotic state at risk for acute cardiac events (Viecca, Radovanovic, Forleo, & Santus, 2020)