The Interaction of the Factor Vlll/von Willebrand Factor Complex with Hematin

David Green; Fiona H Furby; Michael C Berndt

doi:10.1055/s-0038-1661666

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1986; 56(03): 277-282
DOI: 10.1055/s-0038-1661666

Original Article

Schattauer GmbH Stuttgart

The Interaction of the Factor Vlll/von Willebrand Factor Complex with Hematin

David Green

The Department of Medicine, University of Sydney, Westmead Centre, Sydney, Australia, and the Atherosclerosis Program, Department of Medicine, Northwestern University Medical School and the Rehabilitation Institute, Chicago, Illinois, USA

,

Fiona H Furby

The Department of Medicine, University of Sydney, Westmead Centre, Sydney, Australia, and the Atherosclerosis Program, Department of Medicine, Northwestern University Medical School and the Rehabilitation Institute, Chicago, Illinois, USA

,

Michael C Berndt

The Department of Medicine, University of Sydney, Westmead Centre, Sydney, Australia, and the Atherosclerosis Program, Department of Medicine, Northwestern University Medical School and the Rehabilitation Institute, Chicago, Illinois, USA

› Author Affiliations

Abstract

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Summary

Intravenous infusion of hematin, used in the treatment of acute porphyria, induces a decline in the plasma factor VIH/von Willebrand factor complex (VIII/vWF) and thrombocytopenia. We investigated this problem by studying the interaction between hematin, purified VIII/vWF, and platelets in vitro. Hematin was labeled with either ⁵⁹Fe or ³H and characterized by gel chromatography. Hematin self-aggregated, forming a complex with an average molecular weight of approximately 10,000 daltons. When incubated with VIII/vWF for 30 min at 37° C and applied to Sepharose CL-4B, the hematin eluted with the VIII/vWF in the void volume. Hematin inhibited the dissociation of factor VIII antigen (VIII :Ag) from the von Willebrand antigen (vWF:Ag) in 0.25 M CaCl₂, and reversed the aggregation of VIII:Ag induced by 0.1 M 6-aminocaproic acid. Both hematin and the hematin-VIII/vWF complex bound to washed normal platelets and to platelets from a patient with Bemard-Soulier syndrome. Thromb-asthenic platelets were not aggregatable by hematin, and bound significantly less hematin-VIII/vWF than normal platelets suggesting that hematin-induced platelet activation was required for binding. Likewise, binding was inhibited by PGE₁ which also prevented aggregation. We conclude that hematin forms complexes with VIII/vWF, alters the functional activity and dissociation of this compound, and participates in the binding of VIII/vWF to platelets.

Keywords

Factor VIII/vWF - Hematin - Platelets - Porphyria

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References

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