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CC BY 4.0 · TH Open 2021; 05(03): e273-e285
DOI: 10.1055/s-0041-1725976
Original Article

Fibers Generated by Plasma Des-AA Fibrin Monomers and Protofibril/Fibrinogen Clusters Bind Platelets: Clinical and Nonclinical Implications

Dennis K. Galanakis
1   Department of Pathology, Stony Brook University School of Medicine, Stony Brook, New York
,
Anna Protopopova
2   Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
,
Liudi Zhang
3   Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
,
Kao Li
3   Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
,
Clement Marmorat
3   Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
,
Tomas Scheiner
2   Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
,
Jaseung Koo
3   Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
,
Anne G. Savitt
4   Department of Microbiology and Immunology, Stony Brook University School of Medicine, Stony Brook, New York
,
Miriam Rafailovich
3   Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
,
John Weisel
2   Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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Funding This work was supported by grants from NSF DMR 0606387 and NIH RO1-HL135254.
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Abstract

Objective Soluble fibrin (SF) is a substantial component of plasma fibrinogen (fg), but its composition, functions, and clinical relevance remain unclear. The study aimed to evaluate the molecular composition and procoagulant function(s) of SF.

Materials and Methods Cryoprecipitable, SF-rich (FR) and cryosoluble, SF-depleted (FD) fg isolates were prepared and adsorbed on one hydrophilic and two hydrophobic surfaces and scanned by atomic force microscopy (AFM). Standard procedures were used for fibrin polymerization, crosslinking by factor XIII, electrophoresis, and platelet adhesion.

Results Relative to FD fg, thrombin-induced polymerization of FR fg was accelerated and that induced by reptilase was markedly delayed, attributable to its decreased (fibrinopeptide A) FpA. FR fg adsorption to each surface yielded polymeric clusters and co-cryoprecipitable solitary monomers. Cluster components were crosslinked by factor XIII and comprised ≤21% of FR fg. In contrast to FD fg, FR fg adsorption on hydrophobic surfaces resulted in fiber generation enabled by both clusters and solitary monomers. This began with numerous short protofibrils, which following prolonged adsorption increased in number and length and culminated in surface-linked three-dimensional fiber networks that bound platelets.

Conclusion The abundance of adsorbed protofibrils resulted from (1) protofibril/fg clusters whose fg was dissociated during adsorption, and (2) adsorbed des-AA monomers that attracted solution counterparts initiating protofibril assembly and elongation by their continued incorporation. The substantial presence of both components in transfused plasma and cryoprecipitate augments hemostasis by accelerating thrombin-induced fibrin polymerization and by tightly anchoring the resulting clot to the underlying wound or to other abnormal vascular surfaces.

Keywords

fibrin fibers - fibrinogen adsorption - soluble fibrin - cryoprecipitate fibrinogen - protofibril/fibrinogen clusters - platelet adhesion

Authors' Contributions

D.K.G. isolated the fibrinogen fractions, designed most experiments, and wrote the manuscript. A.P. prepared the modified graphite microplates and performed AFM experiments using them. C.M. and K.L. prepared the PS-coated wafers and performed the AFM scans, light microscopy, and rheometer experiments. L.Z. designed and conducted transmission and electron microscopy and confocal microscopy experiments. A.S. conducted fibrinopeptide measurements. M.R. designed AFM and light microscopy experiments. J.K. prepared the TOMA wafers and conducted the FG adsorption and AFM experiments. J.W. participated in the design of the modified graphite adsorption experiments and the scanning electron microscopy of clots.




Publikationsverlauf

Eingereicht: 21. Oktober 2020

Angenommen: 26. Januar 2021

Artikel online veröffentlicht:
06. Juli 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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