Abstract
An important component of severe COVID-19 disease is virus-induced endothelilitis. This leads to disruption of normal endothelial function, initiating a state of failing normal clotting physiology. Massively increased levels of von Willebrand Factor (VWF) lead to overwhelming platelet activation, as well as activation of the enzymatic (intrinsic) clotting pathway. In addition, there is an impaired fibrinolysis, caused by, amongst others, increased levels of alpha-(2) antiplasmin. The end result is hypercoagulation (proven by thromboelastography® (TEG®)) and reduced fibrinolysis, inevitably leading to a difficult-to-overcome hypercoagulated physiological state. Platelets in circulation also plays a significant role in clot formation, but they themselves may also drive hypercoagulation when they are overactivated due to the interactions of their receptors with the endothelium, immune cells or circulating inflammatory molecules. From the literature it is clear that the role of platelets in severely ill COVID-19 patients has been markedly underestimated or even ignored. We here highlight the value of early management of severe COVID-19 coagulopathy as guided by TEG®, microclot and platelet mapping. We also argue that the failure of clinical trials, where the efficacy of prophylactic versus therapeutic clexane (low molecular weight heparin (LMWH)) were not always successful, which may be because the significant role of platelet activation was not taken into account during the planning of the trial. We conclude that, because of the overwhelming alteration of clotting, the outcome of any trial evaluating an any single anticoagulant, including thrombolytic, would be negative. Here we suggest the use of the degree of platelet dysfunction and presence of microclots in circulation, together with TEG®, might be used as a guideline for disease severity. A multi-pronged approach, guided by TEG® and platelet mapping, would be required to maintain normal clotting physiology in severe COVID-19 disease.
Highlights
The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has led to a worldwide, sudden and substantial increase in hospitalizations for pneumonia with multi-organ problems [1,2,3]
To view anomalous clotting of fibrin(ogen) and plasma proteins, in platelet poor plasma (PPP), blood is drawn in citrate tubes, and PPP is collected after a centrifugation step of 15 min at 3000 RPM
We suggest here that an approach of early and close monitoring of clinical parameters of clotting, including TEG® parameters, microclot and platelet mapping, are crucial in the successful management of COVID-19 patients
Summary
The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has led to a worldwide, sudden and substantial increase in hospitalizations for pneumonia with multi-organ problems [1,2,3]. The authors suggest that COVID-19 patients with acute respiratory failure represent the consequence of severe hypercoagulability, that when left untreated results in consumptive coagulopathy (end-stage (DIC)) and that excessive fibrin formation and polymerization may predispose to thrombosis and correlate with a worse outcome [38]. Consumptive coagulopathy is characterized by abnormally increased activation of procoagulant pathways This results in intravascular fibrin(ogen) deposition and decreased levels of hemostatic components, including platelets, soluble fibrinogen, and other clotting factors. If the disease is left to progress until the patient presents with VWF and fibrin(ogen) depletion, and with high D-dimer levels (and even higher P-selectin levels), it will be indicative of a poor prognosis, an imminent cytokine storm and death. We suggest the use of the degree of platelet dysfunction and presence of microclots in circulation, using fluorescence microscopy, as a guideline for disease severity
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