GPIIb/IIIa receptor
Summary
GPIIb/IIIa (integrin αIIbβ3) is a platelet surface receptor that binds fibrinogen and von Willebrand factor, mediating platelet-platelet aggregation—the final common pathway of primary hemostasis. Congenital deficiency causes Glanzmann thrombasthenia, and the receptor is the target of antiplatelet drugs like abciximab, eptifibatide, and tirofiban.
Detail
GPIIb/IIIa is a calcium-dependent integrin heterodimer expressed abundantly on the platelet surface. After platelet activation (via ADP, thromboxane A2, thrombin, collagen exposure, etc.), the receptor undergoes a conformational change (inside-out signaling) that increases its affinity for fibrinogen and von Willebrand factor. Fibrinogen cross-links adjacent platelets by binding GPIIb/IIIa receptors on neighboring platelets, forming platelet aggregates—this is the final step of primary hemostasis, following platelet adhesion (via GPIb-vWF interaction) and activation.
Clinical significance: - Glanzmann thrombasthenia: autosomal recessive disorder due to GPIIb/IIIa deficiency or dysfunction, causing impaired platelet aggregation. Presents with mucocutaneous bleeding (epistaxis, gingival bleeding, menorrhagia), normal platelet count and morphology, but abnormal aggregation studies (no aggregation with ADP, collagen, epinephrine, thrombin, but normal with ristocetin since GPIb-vWF interaction is intact). - Differentiated from Bernard-Soulier syndrome (GPIb deficiency), which shows abnormal ristocetin-induced aggregation. - Pharmacologic target: GPIIb/IIIa inhibitors (abciximab—monoclonal antibody; eptifibatide—cyclic peptide; tirofiban—non-peptide small molecule) block the receptor, used in acute coronary syndromes and during percutaneous coronary intervention (PCI) to prevent platelet aggregation and thrombus formation. Risk of thrombocytopenia and bleeding is a key side effect.
Testing: Platelet aggregation studies and flow cytometry can confirm GPIIb/IIIa deficiency. Bleeding time/PFA-100 closure time is prolonged.
Sources
- First Aid for the USMLE Step 1
- Robbins Basic Pathology
- Goldman-Cecil Medicine
- UpToDate: Glanzmann thrombasthenia
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.