Thromboprophylaxis in COVID-19 - Rationale and considerations

Abstract

The Corona Virus Disease-2019 (COVID-19) pandemic is associated with a very high incidence of thrombotic complications. The exact mechanisms for this excess risk for clots have not been elucidated although one of the often-quoted pathophysiological entity is immunothrombosis. Recognition of thrombotic complications early on in this pandemic led to an over-explosion of studies which looked at the benefits of anticoagulation to mitigate this risk. In this review, we examine the rationale for thromboprophylaxis in COVID-19 with particular reference to dosing and discuss what may guide the decision-making process to consider anticoagulation. In addition, we explore the rationale for thrombosis prevention measures in special populations including outpatient setting, pregnant females, children, those with high body mass index and those on extracorporeal membrane oxygenation.

Keywords: COVID-19; Corona virus; Heparin; Thromboprophylaxis; Thrombosis.

Fig. 1

Pathophysiology of COVID-19 disease -related coagulopathy. There is a bi-directional interaction of the immune system (including the complement cascade) and the haemostatic system in COVID-19 disease. Endothelial dysfunction facilitates the crosstalk between them and its role is pivotal in the development of thrombotic complications. NET-osis: Neutrophil Extracellular Traps formation; PAMPS: Pathogen-Associated Molecular Patterns; DAMPS: Damage-Associated Molecular Patterns; MP: MicroParticles; TF: Tissue Factor; ROS: Reactive Oxygen Species; AGEs: Advanced Glycosylated End products; VWF: Von Willebrand Factor; PAI-1: Plasminogen Activator Inhibitor-1; t-PA: tissue Plasminogen Activator; u-PA: urokinase Plasminogen Activator; CRP: C-Reactive Protein; IL-1/6: Interleukin 1/6. Permission for use of picture is granted from Dr. Dawn Swan.

Fig. 2

Suggested thromboprophylaxis in COVID-19 disease in relation with disease severity. Heparin, either Low Molecular Weight Heparin or Unfractioned Heparin (if Creatinine Clearance < 30 ml/min) is the first-line anticoagulant due to drug interactions of alternative anticoagulants with treatments for COVID-19 disease. DOACS (Direct Oral Anticoagulants) or Warfarin can be used instead for post-discharge thromboprophylaxis. ¹Limited data exist to guide the need and the intensity of anticoagulation in these circumstances;² Level of Evidence: 5;³ If diagnosed with thrombosis, consider the possibility of being pre-existing and undiagnosed, ensure optimal dosing (according to Anti-Xa levels), assess for Heparin-Induced Thrombocytopaenia (HIT) or Heparin Resistance and consider Thrombophilia screen. ^3,4If HIT/Heparin Resistance confirmed, change to Fondaparinux or Direct Thrombin Inhibitors. Please refer to (Goshua et al., 2020) for calculation of IMPROVE-VTE score. Permission for use of the picture granted from Dr. Sofia Zacharioudaki.