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Fibrinogen-coated albumin microcapsules reduce bleeding in severely thrombocytopenic rabbits

Nature Medicine volume 5, pages 107–111 (1999)Cite this article

Abstract

Severe thrombocytopenia frequently occurs in patients receiving chemotherapy and in patients with autoimmune disorders. Thrombocytopenia is associated with bleeding, which may be serious and life threatening1,2,3. Current treatment strategies for thrombocytopenia may require transfusion of allogeneic platelets, which is associated with serious drawbacks4. These include the occurrence of anti-platelet antibodies, which may result in refractoriness to further platelet transfusions, and the potential risk of transfer of blood-borne diseases5,6. Therefore, we have recently developed a platelet substitute product (Synthocytes), which is composed of human albumin microcapsules with fibrinogen immobilized on their surface. Here we show that the intravenous administration of these microcapsules not only corrects the prolonged bleeding time in rabbits rendered thrombocytopenic either by anti-platelet antibodies or by chemotherapy, but also reduces bleeding from surgical wounds inflicted in the abdominal skin and musculature. No potential systemic prothrombotic effect of the microcapsules was observed in a model of rabbit venous thrombosis. As for the mechanism of action, experiments with normal and thrombocytopenic human blood in an endothelial cell matrix-coated perfusion chamber demonstrated an interaction between the fibrinogen-coated albumin microcapsules and native platelets. It was shown that the fibrinogen-coated albumin microcapsules could facilitate platelet adhesion to endothelial cell matrix and correct the impaired formation of platelet aggregates in relatively platelet-poor blood. This study indicates that fibrinogen-coated albumin microcapsules can act to improve primary hemostasis under thrombocytopenic conditions and may eventually be a promising agent for prophylaxis and treatment of bleeding in patients with severe thrombocytopenia.

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Figure 1: Effect of the bolus administration of goat antibody against rabbit platelet and the subsequent administration of fibrinogen-coated albumin microcapsules (Synthocytes) or control agents (n = 6 per group).
Figure 2: Effect of the administration of fibrinogen-coated microcapsules
Figure 3
Figure 4

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Acknowledgements

The assistance of A. van de Wardt is acknowledged. M.L. is a fellow of the Royal Dutch Academy of Arts and Sciences.

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Authors and Affiliations

  1. Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam , Meibergdreef 9, Amsterdam, 1105, AZ, The Netherlands

    Marcel Levi, Philip W. Friederich, Bart J. Biemond & Jan Wouter ten Cate

  2. Andaris, 1 Mere Way, Ruddington , NG11 6JS, Nottingham, United Kingdom

    Sarah Middleton & Roy Harris

  3. Department of Hematology, University of Utrecht, P.O. Box 85500, Utrecht, 3508, GA, The Netherlands

    Philip G. de Groot, Ya Ping Wu & Harry F.G. Heijnen

  4. Department of Laboratory Medicine, University of California School of Medicine, and VA Medical Center, 4150 Clement Street , San Francisco, 94121, California, USA

    Jack Levin

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  1. Marcel Levi
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Correspondence to Marcel Levi.

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Levi, M., Friederich, P., Middleton, S. et al. Fibrinogen-coated albumin microcapsules reduce bleeding in severely thrombocytopenic rabbits. Nat Med 5, 107–111 (1999). https://doi.org/10.1038/4795

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