Figure 1.

Platelet Theory. An invading pathogen binds to platelets either directly (absence of plasma protein) or indirectly (presence of plasma protein). Binding results in platelet activation via Src kinases which results in prostanoid release, cytokine secretion, granule secretion, and activation of GPIIbIIIa. Release of ADP and thromboxane A2 (TXA2) serves to amplify the platelet response. In conjunction with this, activation of GPIIbIIIa allows fibrinogen binding resulting in platelet aggregation. Secretion of platelet cytokines and chemokines activates the vascular endothelium. For example, secreted TNFa activates the TNFR1 receptor on endothelial cells which triggers the death pathway resulting in apoptosis. This results in endothelial cell shrinkage and loss of barrier integrity leading to increased vascular permeability and shock. Separation of endothelial cells allows for pathogens to escape the bloodstream and infect major organs which eventually leads to multi organ failure.