Fibrinogen-coated albumin microcapsules reduce bleeding in severely thrombocytopenic rabbits

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

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our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS IMPACT OF G FORCE AND TIMING ON THE CHARACTERISTICS OF PLATELET-RICH FIBRIN MATRICES Article Open access 16 March

2021 THERAPEUTIC POTENTIAL OF FIBRINOGEN Γ-CHAIN PEPTIDE-COATED, ADP-ENCAPSULATED LIPOSOMES AS A HAEMOSTATIC ADJUVANT FOR POST-CARDIOPULMONARY BYPASS COAGULOPATHY Article Open access 09 July

2020 HEMOSTATIC CAPABILITY OF ULTRAFILTRATED FRESH FROZEN PLASMA COMPARED TO CRYOPRECIPITATE Article Open access 07 December 2023 REFERENCES * Roy, A.J., Jaffe, N. & Djerassi, I.

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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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * Andaris, 1 Mere Way, Ruddington , NG11 6JS, Nottingham, United Kingdom Sarah Middleton & Roy Harris * 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 * Department of Laboratory Medicine, University

of California School of Medicine, and VA Medical Center, 4150 Clement Street , San Francisco, 94121, California, USA Jack Levin Authors * Marcel Levi View author publications You can also

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Bart J. Biemond View author publications You can also search for this author inPubMed Google Scholar * Harry F.G. Heijnen View author publications You can also search for this author

inPubMed Google Scholar * Jack Levin View author publications You can also search for this author inPubMed Google Scholar * Jan Wouter ten Cate View author publications You can also search

for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Marcel Levi. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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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