Post doc Stony Brook University kolkata, West Bengal, India
Background: Hypofibrinolysis, is the underlying reason behind hypercoagulability in severe COVID-19. Hypertension, cardiovascular diseases and diabetes are the prime comorbidities . Blood clotting, maintained by regulatory balance between procoagulants and anticoagulants, lead to equilibrium between coagulation and fibrinolysis. Fibrin clots made of meshwork of polymerised fibrin threads, generated by proteolysis of fibrinogen by thrombin, play a cardinal role in thrombosis . RBC, WBC and platelets get embroiled in the meshwork of fibrin thread to form "clot”. Clots made up thin, highly branched fibrin fibers with smaller pores are less susceptible to fibrinolysis, on the contrary clots with thick fibers, less branched with larger pores are prone to lysis . Factor VIIIa crosslinks to fibrin , also crosslinks α2-antiplasmin, TAFI, and PAI-2 to fibrin, to increase resistance to fibrinolysis and enhancing thrombosis risk .
Aims: How COVID-19 comorbidities escalate hypofibrinolysis?
Methods: Methods are from published literatures.
Results: Fibrinogen levels are found to be enhanced in diabetes, with fibrin clots denser and resistant to fibrinolysis. Glycation of fibrinogen attributes to increased fibrin polymerisation and crosslinkings, ensuing in abnormal clots. Altered fibrin structures, resistant to fibrinolysis are also observed in patients with coronary artery diseases and peripheral arterial diseases .Hypertension has also contributed to altered fibrin structures, with antihypertensive treatment increasing the clot susceptibility to lysis . Interestingly, platelet derived polyphosphate has been known to induce higher mass-length ratio of fibrin threads making it fibrinolysis resistant. More so, thromboembolic COVID-19 patients reported of elevated factor VIII, in comparison to patients without thromboembolisms. Severe COVID-19 patients also reported of elevated anticoagulant proteins as SERPINS, PAI-1, α2-antiplasmin and TAFI, reflective of impaired fibrinolysis .Supportively, expression of PAI-1 and TAFI are known to be enhanced in comorbidities.
Conclusion(s): Altered fibrin structures coupled with enhanced anticoagulant production, can lead to hypofibrinolysis, which predisposes to thromboembolisms in some severe COVID-19 patients with comorbidities.
