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

Dennis K. Galanakis; Anna Protopopova; Liudi Zhang; Kao Li; Clement Marmorat; Tomas Scheiner; Jaseung Koo; Anne G. Savitt; Miriam Rafailovich; John Weisel

doi:10.1055/s-0041-1725976

TH Open, Table of Contents

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

Authors

Dennis K. Galanakis

¹Department of Pathology, Stony Brook University School of Medicine, Stony Brook, New York
Anna Protopopova

²Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Liudi Zhang

³Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
Kao Li

³Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
Clement Marmorat

³Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
Tomas Scheiner

²Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Jaseung Koo

³Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
Anne G. Savitt

⁴Department of Microbiology and Immunology, Stony Brook University School of Medicine, Stony Brook, New York
Miriam Rafailovich

³Department of Materials Science and Engineering, Stony Brook University, Stony Brook, New York
John Weisel

²Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

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

Full Text

References

References
1 Galanakis DK. Plasma cryoprecipitation studies: major increase in fibrinogen yield by albumin enrichment of plasma. Thromb Res 1995; 78 (04) 303-313
2 Shainoff JR, Page IH. Significance of cryoprofibrin in fibrinogen-fibrin conversion. J Exp Med 1962; 116: 687-707
3 Saadoun D, Elalamy I, Ghillani-Dalbin P, Sene D, Delluc A, Cacoub P. Cryofibrinogenemia: new insights into clinical and pathogenic features. Am J Med 2009; 122 (12) 1128-1135
4 Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 2012; 34 (01) 43-62
5 Cost CR, Journeycake JM. Deep venous thrombosis screening in patients with inherited bleeding disorders and central venous catheters. Haemophilia 2011; 17 (06) 890-894
6 Galanakis DK. Afibrinogenemia and dysfibrinogenemia. In: Hemostasis and Thrombosi-Basic Principles and Clinical Practice. 6th ed.. Philadelphia: Lippincott Williams & Wilkins; 2012: 693-708
7 Goel R, Patel EU, Cushing MM. et al. Association of perioperative red blood cell transfusions with venous thromboembolism in a North American Registry. JAMA Surg 2018; 153 (09) 826-833
8 Koo J, Rafailovich MH, Medved L. et al. Evaluation of fibrinogen self-assembly: role of its αC region. J Thromb Haemost 2010; 8 (12) 2727-2735
9 Zhang L, Casey B, Galanakis DK. et al. The influence of surface chemistry on adsorbed fibrinogen conformation, orientation, fiber formation and platelet adhesion. Acta Biomater 2017; 54: 164-17
10 Weisel JW. Fibrinogen and fibrin. Adv Protein Chem 2005; 70: 247-299
11 Litvinov RI, Yakovlev S, Tsurupa G, Gorkun OV, Medved L, Weisel JW. Direct evidence for specific interactions of the fibrinogen alphaC-domains with the central E region and with each other. Biochemistry 2007; 46 (31) 9133-9142
12 Chernysh IN, Nagaswami C, Weisel JW. Visualization and identification of the structures formed during early stages of fibrin polymerization. Blood 2011; 117 (17) 4609-4614
13 Smith EL, Cardinali B, Ping L, Ariëns RAS, Philippou H. Elimination of coagulation factor XIII from fibrinogen preparations. J Thromb Haemost 2013; 11 (05) 993-995
14 Protopopova AD, Barinov NA, Zavyalova EG, Kopylov AM, Sergienko VI, Klinov DV. Visualization of fibrinogen αC regions and their arrangement during fibrin network formation by high-resolution AFM. J Thromb Haemost 2015; 13 (04) 570-579
15 Sit PS, Marchant RE. Surface-dependent conformations of human fibrinogen observed by atomic force microscopy under aqueous conditions. Thromb Haemost 1999; 82 (03) 1053-1060
16 Tang L. Mechanisms of fibrinogen domains: biomaterial interactions. J Biomater Sci Polym Ed 1998; 9 (12) 1257-1266
17 Evans-Nguyen KM, Fuierer RR, Fitchett BD, Tolles LR, Conboy JC, Schoenfisch MH. Changes in adsorbed fibrinogen upon conversion to fibrin. Langmuir 2006; 22 (11) 5115-5121
18 Geer CB, Rus IA, Lord ST, Schoenfisch MH. Surface-dependent fibrinopeptide A accessibility to thrombin. Acta Biomater 2007; 3 (05) 663-668
19 Whitlock PW, Clarson SJ, Retzinger GS. Fibrinogen adsorbs from aqueous media to microscopic droplets of poly(dimethylsiloxane) and remains coagulable. J Biomed Mater Res 1999; 45 (01) 55-61
20 Smolarczyk K, Boncela J, Szymanski J, Gils A, Cierniewski CS. Fibrinogen contains cryptic PAI-1 binding sites that are exposed on binding to solid surfaces or limited proteolysis. Arterioscler Thromb Vasc Biol 2005; 25 (12) 2679-2684
21 Tang L, Ugarova TP, Plow EF, Eaton JW. Molecular determinants of acute inflammatory responses to biomaterials. J Clin Invest 1996; 97 (05) 1329-1334
22 Ugarova TP, Budzynski AZ, Shattil SJ, Ruggeri ZM, Ginsberg MH, Plow EF. Conformational changes in fibrinogen elicited by its interaction with platelet membrane glycoprotein GPIIb-IIIa. J Biol Chem 1993; 268 (28) 21080-21087
23 Galanakis DK, Neerman-Arbez M, Brennan S. et al. Thromboelastographic phenotypes of fibrinogen and its variants: clinical and non-clinical implications. Thromb Res 2014; 133 (06) 1115-1123
24 Koo J, Galanakis D, Liu Y. et al. Control of anti-thrombogenic properties: surface-induced self-assembly of fibrinogen fibers. Biomacromolecules 2012; 13 (05) 1259-1268
25 Peerschke EI, Galanakis DK. The synthetic RGDS peptide inhibits the binding of fibrinogen lacking intact alpha chain carboxyterminal sequences to human blood platelets. Blood 1987; 69 (03) 950-952
26 Galanakis DK, Neerman-Arbez M, Kudryk B, Henschen A. Decreased plasmin resistance by clots of a homophenotypic Aalpha R 16H fibrinogen (Kingsport, slower fibrinopeptide A than fibrinopeptide B release). Blood Coagul Fibrinolysis 2010; 21 (02) 135-139
27 Mosesson MW, Sherry S. The preparation and properties of human fibrinogen of relatively high solubility. Biochemistry 1966; 5 (09) 2829-2835
28 Larsen ML, Abildgaard U, Teien AN, Gjesdal K. Assay of plasma heparin using thrombin and the chromogenic substrate H-D-Phe-Pip-Arg-pNA (S-2238). Thromb Res 1978; 13 (02) 285-288
29 Mosesson MW, Galanakis DK, Finlayson JS. Comparison of human plasma fibrinogen subfractions and early plasmic fibrinogen derivatives. J Biol Chem 1974; 249 (14) 4656-4664
30 Galanakis DK, Mosesson MW. The A alpha chain composition of plasma fibrinogen catabolites. Thromb Res 1979; 15 (1-2): 287-289
31 Kudryk BJ, Collen D, Woods KR, Blombäck B. Evidence for localization of polymerization sites in fibrinogen. J Biol Chem 1974; 249 (10) 3322-3325
32 Nakashima A, Sasaki S, Miyazaki K, Miyata T, Iwanaga S. Human fibrinogen heterogeneity: the COOH-terminal residues of defective A alpha chains of fibrinogen II. Blood Coagul Fibrinolysis 1992; 3 (04) 361-370
33 Siebenlist KR, Meh DA, Mosesson MW. Protransglutaminase (factor XIII) mediated crosslinking of fibrinogen and fibrin. Thromb Haemost 2001; 86 (05) 1221-1228
34 Galanakis DK, Lane BP, Simon SR. Albumin modulates lateral assembly of fibrin polymers: evidence of enhanced fine fibril formation and of unique synergism with fibrinogen. Biochemistry 1987; 26 (08) 2389-2400
35 Klinov DV, Protopopova AD, Andrianov DS, Litvinov RI, Weisel JW. An improved substrate for superior imaging of individual biomacromolecules with atomic force microscopy. Colloids Surf B Biointerfaces 2020; 196: 111321
36 Woodhead JL, Nagaswami C, Matsuda M, Arocha-Piñango CL, Weisel JW. The ultrastructure of fibrinogen Caracas II molecules, fibers, and clots. J Biol Chem 1996; 271 (09) 4946-4953
37 Hansen MS, Bang NU, Barton RD, Mattler LE. Enhancement of blood coagulation by soluble fibrin complexes. J Exp Med 1975; 141 (05) 944-961
38 Riedel T, Suttnar J, Brynda E, Houska M, Medved L, Dyr JE. Fibrinopeptides A and B release in the process of surface fibrin formation. Blood 2011; 117 (05) 1700-1706
39 Li W, Sigley J, Pieters M. et al. Fibrin fiber stiffness is strongly affected by fiber diameter, but not by fibrinogen glycation. Biophys J 2016; 110 (06) 1400-1410
40 Cheresh DA, Berliner SA, Vicente V, Ruggeri ZM. Recognition of distinct adhesive sites on fibrinogen by related integrins on platelets and endothelial cells. Cell 1989; 58 (05) 945-953
41 Safiullin R, Christenson W, Owaynat H. et al. Fibrinogen matrix deposited on the surface of biomaterials acts as a natural anti-adhesive coating. Biomaterials 2015; 67: 151-159
42 Tsai WB, Grunkemeier JM, McFarland CD, Horbett TA. Platelet adhesion to polystyrene-based surfaces preadsorbed with plasmas selectively depleted in fibrinogen, fibronectin, vitronectin, or von Willebrand's factor. J Biomed Mater Res 2002; 60 (03) 348-359
43 Jirousková M, Dyr JE, Suttnar J, Holada K, Trnková B. Platelet adhesion to fibrinogen, fibrin monomer, and fibrin protofibrils in flowing blood -- the effect of fibrinogen immobilization and fibrin formation. Thromb Haemost 1997; 78 (03) 1125-1131
44 Litvinov RI, Farrell DH, Weisel JW, Bennett JS. The platelet integrin αIIbβ3 differentially interacts with fibrin versus fibrinogen. J Biol Chem 2016; 291 (15) 7858-7867
45 García X, Seyve L, Tellier Z. et al. Aggregates dramatically alter fibrin ultrastructure. Biophys J 2020; 118 (01) 172-181
46 Dardik BN, Shainoff JR. Kinetic characterization of a saturable pathway for rapid clearance of circulating fibrin monomer. Blood 1985; 65 (03) 680-688