Fig. 4.

This model illustrates potential mechanisms associated with thrombocytopenia in COVID-19 patients. Coagulopathy is a major risk factor in severe COVID-19 patients. This is characterized by the formation of platelet aggregates resulting in platelets consumption at the site of infection. It has also been reported that plasma thrombopoietin (TPO) levels are declining in COVID-19 patients either because of the direct infection of liver cells by SARS-CoV-2 or drug toxicities as another potential factor in thrombocytopenia. Moreover, considering the reports of HSPCs susceptibility to the virus, it is possible to speculate that SARS-CoV-2 may impair HSPCs differentiation to megakaryocytes or make them dysfunctional. The cytokine storm in particularly elevated levels of plasma TGF-β and IFN-α can impair HSPCs differentiation into megakaryocytes. Another element that may imply the mechanism underlying thrombocytopenia in COVID-19 patients could be related to pathological damage to the lungs tissue. It is demonstrated that under steady physiological conditions, megakaryocytes are recruited to the lungs where they differentiate into platelets in mice. If this is the case for humans, then pathological alterations in the lungs following COVID-19 disease may impair/prevent this process