Incorporation of Fibrin, Platelets, and Red Blood Cells into a Coronary Thrombus in Time and Space

Author:

Maly Martin1,Riedel Tomas23,Stikarova Jana2ORCID,Suttnar Jiri2,Kotlin Roman2,Hajsl Martin1,Tousek Petr4,Kaufmanova Jirina25,Kucerka Ondrej1,Weisel John W.6,Dyr Jan E.2

Affiliation:

1. First Faculty of Medicine, Department of Medicine, Charles University in Prague and Military University Hospital, Prague, Czech Republic

2. Department of Biochemistry, Institute of Hematology and Blood Transfusion, Prague, Czech Republic

3. Chemistry and Physics of Surfaces and Biointerfaces, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic

4. Cardiocenter, University Hospital Kralovske Vinohrady and Third Medical Faculty, Charles University, Prague, Czech Republic

5. Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Prague, Czech Republic

6. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Abstract

AbstractWe describe the internal structure, spatial organization and dynamic formation of coronary artery thrombi from ST-segment elevation myocardial infarction patients. Scanning electron microscopy (SEM) revealed significant differences among four groups of patients (<2 hours; 2–6 hours; 6–12 hours, and >12 hours) related to the time of ischemia. Coronary artery thrombi from patients presenting less than 2 hours after the infarction were almost entirely composed of platelets, with small amounts of fibrin and red blood cells. In contrast, thrombi from late presenters (>12 hours) consisted of mainly platelets at the distal end, where clotting was initiated, with almost no platelets at the proximal end, while the red blood cell content went from low at the initiating end to more than 90% at the proximal end. Furthermore, fibrin was present mainly on the outside of the thrombi and older thrombi contained thicker fibers. The red blood cells in late thrombi were compressed to a close-packed, tessellated array of polyhedral structures, called polyhedrocytes. Moreover, there was redistribution from the originally homogeneous composition to fibrin and platelets to the outside, with polyhedrocytes on the interior. The presence of polyhedrocytes and the redistribution of components are signs of in vivo clot contraction (or retraction). These results suggest why later thrombi are resistant to fibrinolytic agents and other treatment modalities, since the close-packed polyhedrocytes form a nearly impermeable seal. Furthermore, it is of particular clinical significance that these findings suggest specific disparate therapies that will be most effective at different stages of thrombus development.

Funder

Ministry of Health, Czech Republic

Czech Science Foundation

European Regional Development Fund and the state budget of the Czech Republic

Ministry of Education, Youth and Sports

National Institutes of Health grant

University of Pennsylvania Research Foundation

Publisher

Georg Thieme Verlag KG

Subject

Hematology

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