Investigation of Alternative Mechanisms of Collagen - Induced Platelet Activation by Using Monoclonal Antibodies to Glycoprotein IIb-IIIa and Fibrinogen

J M Connellan; P J Thurlow; Bernadette Barlow; Melinda Lowe; I F C McKenzie

doi:10.1055/s-0038-1661512

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1986; 55(02): 153-157
DOI: 10.1055/s-0038-1661512

Original Article

Schattauer GmbH Stuttgart

Investigation of Alternative Mechanisms of Collagen - Induced Platelet Activation by Using Monoclonal Antibodies to Glycoprotein IIb-IIIa and Fibrinogen

J M Connellan

^*The Department of Haematology, Austin Hospital, Melbourne, Australia

,

P J Thurlow

^*The Department of Haematology, Austin Hospital, Melbourne, Australia

,

Bernadette Barlow

^*The Department of Haematology, Austin Hospital, Melbourne, Australia

,

Melinda Lowe

^**The Research Centre for Cancer and Transplantation, Department of Pathology, University of Melbourne, Australia

,

I F C McKenzie

^**The Research Centre for Cancer and Transplantation, Department of Pathology, University of Melbourne, Australia

› Institutsangaben

Abstract

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Summary

Anti-HuPl-ml (reactive with IIIa) and anti-C₂G₇ (reactive with the carboxyl terminal of the a chain of fibrinogen) were used to investigate platelet aggregation, fibrinogen binding and thromboxane synthesis induced by low dose collagen (LDC) or high dose collagen (HDC) in normal or aspirin treated platelets.

Anti-HuPl-ml and anti-C₂G₇ inhibited LDC induced platelet aggregation almost completely whilst abolishing fibrinogen binding; thromboxane production although reduced, still occurred. Thus LDC activation was dependent on fibrinogen binding to Gp IIIa. Aggregation of platelets induced by HDC was inhibited with anti-C₂G₇ or anti-HuPl-ml by 15-35% in association with a modest reduction in thromboxane (TxB₂) production (with anti-HuPl-ml) and total inhibition of fibrinogen binding. When anti-HuPl-ml was added to aspirin treated platelets, aggregation with HDC although substantially reduced was not totally abolished.

Collagen appears to activate platelets in a dose related manner in which there are at least three possible mechanisms via: (i) GpIIb-IIIa and associated fibrinogen binding; (ii) prostaglandin pathway; (iii) an alternate pathway responsible for ∼20%-30% of platelet aggregation.

Key words

Collagen - Fibrinogen binding - Monoclonal antibodies - Mechanism of platelet activation

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Referenzen

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