Physiopathology of coagulopathy in haematological malignancies and COVID-19

Coagulopathies in critically ill patients display similar clinical manifestations but have distinctly different underlying pathophysiologies. Prof. Marcel Levi (Chair of the Dutch Research Council; Amsterdam University Medical Centre, the Netherlands) presented the pathophysiology of coagulopathies in patients with cancer and COVID-19 [1].

Excessive blood loss during disseminated intravascular coagulation (DIC) is much more common in cancer patients (10–20%) than in DIC associated with other conditions (1–5%) and associated with higher mortality. The most important contributing cause for coagulopathies in cancer patients is tissue factor (TF) in TF-bearing microparticles of tumour cells. Furthermore, there is direct platelet-cancer interaction as well as thrombotic complications that arise due to anticancer drugs [2].

Coagulopathy in COVID-19 is difficult to classify due to its overlapping features with DIC, thrombotic microangiopathy, catastrophic antiphospholipid syndrome, and cytokine storm syndrome. The coagulation abnormalities and thrombosis in patients with COVID-19 are caused by distinct mechanisms than what is usually seen in patients with severe infections [3]. The presence of D-dimers is associated with disease severity and mortality, as shown by several studies [4,5]. However, it remains unclear whether this is a result of systemic thrombin generation and subsequent fibrin formation and breakdown (D-dimer increase is disproportional to other markers of coagulation), or a result of enhanced fibrin turnover in the lung due to severe pneumonia (fibrin deposition is a hallmark of adult respiratory distress syndrome and macrophage activation). Post-mortem findings in COVID-19 patients are also indicating microvascular thrombosis and haemorrhage in lungs and a massive release of ultra-large von Willebrand factor multimers from injured endothelial cells, which might be unmatched by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif)-cleaving capacity, with low ADAMTS13 plasma levels being predictors of mortality in COVID-19 patients [6]. Furthermore, SARS-CoV-2 can directly infect endothelial cells, increasing the burden of endotheliopathy [7].

Prof. Levi concluded, “Coagulopathies in critically ill patients display similar clinical manifestations but have a distinctly different underlying pathophysiology. Thrombin generation, injured endothelial cells, and abnormal platelet-vessel wall-interaction play a crucial role in both cancer-induced and COVID-19-associated coagulopathies. New insights into coagulopathies in critically ill patients may provide points of impact for better adjunctive treatment.”

1. 
   
   1. Levi M. Physiopathology of coagulopathy in hematological malignancies and in COVID-19. P-202-3, EHA 2021 Virtual Congress, 9–17 June.
   2. Levi M and Sivapalaratnam S. Thromb Res 2020;191(Suppl. 1):S17–S21.
   3. Li H, et al. Lancet 2020;395:1517–20.
   4. Shah S, et al. Cardiol Rev. 2020;28(6):295–302.
   5. Hu Y. P214-1, EHA 2021 Virtual Congress, 9–17 June.
   6. Bazzan M, et al. Intern Emerg Med 2020;15:861–3.
   7. Goshua G, et al. Lancet Haematol 2020;7(8):e575–82.

 

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Posted on 5 August, 20215 August, 2021