Effect of glycoprotein IIb/IIIa antagonists on the HIT serum induced activation of platelets.

Abstract

Heparin-induced thrombocytopenia is an increasingly common side effect associated with heparin usage. In the more severe manifestation of the syndrome, patients can develop thrombosis; a 10% mortality is associated with heparin induced thrombocytopenia. To date, the therapeutic options for patients with heparin-induced thrombocytopenia are limited. Glycoprotein IIb/IIIa inhibitors have been shown to block platelet aggregation induced by a wide variety of agonists. The ability of antibody and synthetic small molecule inhibitors of glycoprotein IIb/IIIa to block in vitro activation and aggregation of platelets in response to heparin-induced thrombocytopenia positive serum/heparin was examined using flow cytometry, platelet aggregometry, and luminescence aggregometry. Abciximab, YM 337, and SR 121566A were each found to inhibit platelet microparticle formation and P-selectin expression in whole blood, in response to heparin-induced thrombocytopenia positive serum/heparin. In a platelet rich plasma system, the platelet aggregation response was inhibited by all three agents. The IC50 for inhibition of heparin-induced thrombocytopenia positive serum/heparin induced platelet aggregation by SR 121566A was 18 nM, a concentration which was 4 to 8 fold lower than that observed for collagen and arachidonic acid induced aggregation. Adenosine triphosphate release from activated platelets, as measured by luminescence aggregometry, was concentration-dependently inhibited by SR 121566A. These results suggest that glycoprotein Ilb/IIIa inhibitors may be beneficial in the management of heparin-induced thrombocytopenia and warrant further investigation.

• Authors: W P Jeske, J M Walenga, E Szatkowski, M Ero, J M Herbert, S Haas, M Bakhos
• Journal: Thrombosis research (Thromb Res) Vol. 88 Issue 3 Pg. 271-81 (Nov 01 1997) ISSN: 0049-3848 [Print] United States
• PMID: 9526947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzylamines
• Blood Proteins
• Immunoglobulin Fab Fragments
• Piperidines
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• SR 121566
• Thiazoles
• Heparin

Topics

• Benzylamines
• Blood Platelets (physiology)
• Blood Proteins (pharmacology)
• Drug Interactions
• Heparin (adverse effects)
• Humans
• Immunoglobulin Fab Fragments (immunology, pharmacology)
• Piperidines
• Platelet Activation (drug effects)
• Platelet Aggregation Inhibitors (pharmacology)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors, immunology)
• Thiazoles
• Thrombocytopenia (blood, chemically induced)