Figure 1.

Putative mechanism of complement-mediated microvascular thrombosis and vaso-occlusive disease in SCD and COVID-19: SARS-CoV-2 infection and sickle cell disease induce complement activation and formation of membrane attack complex leading to necrosis and pyroptosis of endothelial cells, platelets, and monocytes and accumulation of IL-1α. IL-1α stimulates the IL-1 receptor expressed on endothelial cells leading to thromboxane synthesis. Thromboxane A₂ via the TP receptor activates platelets leading to platelet activation, platelet neutrophil partnership, neutrophil activation, and the release of neutrophil extracellular traps (NETs), thrombo-inflammation, oxidative stress, and subsequent end-organ damage and failure. The current review article is primarily focused on eicosanoid signaling in platelets; therefore, other receptors and pathways were excluded from Figure 1 for the reader’s convenience. COX, cyclooxygenase; IL, interleukin; NETs, neutrophil extracellular traps; TP, thromboxane prostanoid receptor; MAC, membrane attack complex; VTE, venous thromboembolism; TMA, thrombotic microangiopathy; DIC, disseminated intravascular thrombosis; ARDS, acute respiratory distress syndrome; AKI, acute kidney injury.