In medicine, glycoprotein IIb/IIIa (GPIIb/IIIa, also known as integrin α_IIbβ₃) is an integrin complex found on platelets. It is a receptor for fibrinogen^[1] and von Willebrand factor and aids platelet activation. The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence.^[2][3] Platelet activation by ADP (blocked by clopidogrel) leads to the aforementioned conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen.^[1] The gpIIb/IIIa receptor is a target of several drugs including abciximab, eptifibatide, and tirofiban.

gpIIb/IIIa complex formation

Once platelets are activated, granules secrete clotting mediators, including both ADP and TXA2. These then bind their respective receptors on platelet surfaces, in both an autocrine and paracrine fashion (binds both itself and other platelets). The binding of these receptors result in a cascade of events resulting in an increase in intracellular calcium (e.g. via G_q receptor activation leading to Ca²⁺ release from platelet endoplasmic reticulum Ca²⁺ stores, which may activate PKC). Hence, this calcium increase triggers the calcium-dependent association of gpIIb and gpIIIa to form the activated membrane receptor complex gpIIb/IIIa, which is capable of binding fibrinogen (factor I), resulting in many platelets “sticking together” as they may connect to the same strands of fibrinogen, resulting in a clot. The coagulation cascade then follows to stabilize the clot, as thrombin (factor IIa) converts the soluble fibrinogen into insoluble fibrin strands. These strands are then cross-linked by factor XIII to form a stabilized blood clot.

Pathology

Defects in glycoprotein IIb/IIIa cause Glanzmann’s thrombasthenia.^[4]

Autoantibodies against IIb/IIIa can be produced in immune thrombocytopenic purpura.^[5]

Medicine

Glycoprotein IIb/IIIa inhibitors can be used to prevent blood clots in an effort to decrease the risk of heart attack or stroke.

See also

• Glycoprotein IIb/IIIa inhibitors

In medicine, glycoprotein IIb/IIIa inhibitors, also GpIIb/IIIa inhibitors, is a class of antiplatelet agents.

Several GpIIb/IIIa inhibitors exist:

• abciximab (abcixifiban) (ReoPro)
• eptifibatide (Integrilin)
• tirofiban (Aggrastat)
• roxifiban
• orbofiban

Use

Glycoprotein IIb/IIIa inhibitors are frequently used during percutaneous coronary intervention (angioplasty with or without intracoronary stent placement).

They work by preventing platelet aggregation and thrombus formation. They do so by inhibition of the GpIIb/IIIa receptor on the surface of the platelets.

They may also be used to treat acute coronary syndromes, without percutaneous coronary intervention, depending on TIMI risk.

They should be given intravenously. The oral form is associated with increased mortality and hence should not be given.

In integrin nomenclature glycoprotein IIb/IIIa is called αIIbβ3.

History

Their development arose from the understanding of Glanzmann’s thrombasthenia, a condition in which the GpIIb/IIIa receptor is deficient or dysfunctional. ^{[Seligsohn U. Glanzmann thrombasthenia: a model disease which paved the way to powerful therapeutic agents. Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):216-7. doi:10.1159/000073569 PMID 13679645. Free Full Text.]}

References

1. ^ Jump up to:^a b Vickers JD (July 1999). “Binding of polymerizing fibrin to integrin alpha(IIb)beta(3) on chymotrypsin-treated rabbit platelets decreases phosphatidylinositol 4,5-bisphosphate and increases cytoskeletal actin”. Platelets. 10 (4): 228–37. doi:10.1080/09537109976077. PMID 16801097.
2. ^ Calvete JJ (April 1995). “On the structure and function of platelet integrin alpha IIb beta 3, the fibrinogen receptor”. Proceedings of the Society for Experimental Biology and Medicine. 208 (4): 346–60. doi:10.3181/00379727-208-43863a. PMID 7535429. S2CID 9298838.
3. ^ Shattil SJ (August 1999). “Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways”. Thrombosis and Haemostasis. 82 (2): 318–25. doi:10.1055/s-0037-1615849. PMID 10605720.
4. ^ Bellucci S, Caen J (September 2002). “Molecular basis of Glanzmann’s Thrombasthenia and current strategies in treatment”. Blood Reviews. 16 (3): 193–202. doi:10.1016/S0268-960X(02)00030-9. PMID 12163005.
5. ^ McMillan R (October 2007). “The pathogenesis of chronic immune thrombocytopenic purpura”. Seminars in Hematology. 44 (4 Suppl 5): S3–S11. doi:10.1053/j.seminhematol.2007.11.002. PMID 18096470.

External links

• Glycoproteins+IIb-IIIa at the US National Library of Medicine Medical Subject Headings (MeSH)