Table 4.

Potential mechanisms of immune thrombocytopenia secondary to COVID-19

Pathogenesis	Mechanisms of thrombocytopenia
Molecular mimicry • Host generation of cross-reactive anti-platelet antibodies (anti-GP IIb/IIIa, GP-Ib/IX, or GP-V)	• Immune complex formation on platelet surface leading to clearance by reticuloendothelial system • Inhibit the development of bone marrow megakaryocytes and promote their apoptosis
Direct viral infection Local inflammatory milieu	• Expression of cryptic antigen on platelets leading to recognition by the immune system
Release of self-antigens following tissue damage Local cytokine effects Role of B cells	• Epitope spreading: no single anti-platelet antibody specificity to a particular glycoprotein
Role of T cells Immune dysregulation	• Direct effect of cytotoxic CD8+ T cells on platelets • Low or dysfunctional regulatory CD4+ T cells
Homology between SARS-CoV-2 immunogenetic proteins (one-third) and proteins essential to adaptive immune system	• Cross-presentation of exogenous antigens • PD-1 signaling
Increased C-reactive protein (CRP) in COVID-19-associated hyperinflammatory state (perpetuating role)	CRP can bind to platelet phosphorylcholine residues, thereby facilitating IgG-mediated phagocytic responses against platelets
Heterozygous SOCS 1 loss of function mutations (susceptibility locus)	Enhanced interferon signaling and increased immune cell activation, thereby predisposing to immune cytopenias

GP, glycoprotein; SARS-CoV-2, severe acute respiratory syndrome corona virus-2; PD-1, programmed cell death protein 1; IgG, immunoglobulin G; SOCS 1, suppressor of cytokine signaling 1