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Lytic resistance of fibrin containing red blood cells

journal contribution
posted on 2023-05-19, 20:43 authored by Wohner, N, Sotonyi, P, Machovich, R, Szabo, L, Kiril TenekedjievKiril Tenekedjiev, Silva, MMCG, Longstaff, C, Kolev, K

Objective: Arterial thrombi contain variable amounts of red blood cells (RBCs), which interact with fibrinogen through an eptifibatide-sensitive receptor and modify the structure of fibrin. In this study, we evaluated the modulator role of RBCs in the lytic susceptibility of fibrin.

Methods and Results: If fibrin is formed at increasing RBC counts, scanning electron microscopy evidenced a decrease in fiber diameter from 150 to 96 nm at 40% (v/v) RBCs, an effect susceptible to eptifibatide inhibition (restoring 140 nm diameter). RBCs prolonged the lysis time in a homogeneous-phase fibrinolytic assay with tissue plasminogen activator (tPA) by up to 22.7±1.6%, but not in the presence of eptifibatide. Confocal laser microscopy using green fluorescent protein–labeled tPA and orange fluorescent fibrin showed that 20% to 40% (v/v) RBCs significantly slowed down the dissolution of the clots. The fluorescent tPA variant did not accumulate on the surface of fibrin containing RBCs at any cell count above 10%. The presence of RBCs in the clot suppressed the tPA-induced plasminogen activation, resulting in 45% less plasmin generated after 30 minutes of activation at 40% (v/v) RBCs.

Conclusion: RBCs confer lytic resistance to fibrin resulting from modified fibrin structure and impaired plasminogen activation through a mechanism that involves eptifibatide-sensitive fibrinogen-RBC interactions.

History

Publication title

Arteriosclerosis, Thrombosis, and Vascular Biology

Volume

31

Issue

10

Pagination

2306-2313

ISSN

1079-5642

Department/School

Australian Maritime College

Publisher

Lippincott Williams & Wilkins

Place of publication

USA

Rights statement

Copyright 2011 American Heart Association, Inc.

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the health sciences; Expanding knowledge in the information and computing sciences

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