GPIIb/IIIa

GPIIb/IIIa is a calcium-dependent integrin receptor expressed on the platelet surface that mediates the final common pathway of platelet aggregation. After vascular injury, platelets adhere to exposed subendothelial collagen via GPIb interacting with von Willebrand factor (vWF). Platelet activation then occurs via thromboxane A2, ADP, and thrombin, causing a conformational change in GPIIb/IIIa that increases its affinity for fibrinogen and vWF. Fibrinogen cross-links adjacent platelets via GPIIb/IIIa receptors, forming platelet aggregates and completing the platelet plug (primary hemostasis).

Clinical relevance: - Glanzmann thrombasthenia: autosomal recessive disorder due to GPIIb/IIIa deficiency or dysfunction, resulting in impaired platelet aggregation despite normal platelet count and morphology. Presents with mucocutaneous bleeding, normal platelet count, prolonged bleeding time, and absent platelet aggregation in response to all agonists except ristocetin (since GPIb-vWF interaction is intact). - Differentiate from Bernard-Soulier syndrome, which involves GPIb deficiency (impaired platelet adhesion, abnormal ristocetin-induced aggregation, giant platelets). - Pharmacology: GPIIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) are IV antiplatelet agents used in acute coronary syndromes and during percutaneous coronary intervention (PCI) to prevent platelet aggregation and thrombus formation. They block fibrinogen binding to GPIIb/IIIa, inhibiting the final common pathway of platelet aggregation regardless of the activating stimulus. - Lab correlation: Platelet aggregometry testing is used to assess GPIIb/IIIa function; absence of aggregation with multiple agonists (ADP, collagen, epinephrine, thrombin) but normal response to ristocetin suggests Glanzmann thrombasthenia.