Download PDF
Thromb Haemost 1996; 75(01): 161-167
DOI: 10.1055/s-0038-1650237
Original Article
Schattauer GmbH Stuttgart

Promotion of the Crosslinking of Fibrin and α2-antiplasmin by Platelets

Zsuzsa Hevessy
1   The Department of Clinical Chemistry, University of Debrecen, Medical School, Debrecen, Hungary
,
Gizella Haramura
1   The Department of Clinical Chemistry, University of Debrecen, Medical School, Debrecen, Hungary
,
Zoltán Boda
2   The IInd Department of Medicine, University of Debrecen, Medical School, Debrecen, Hungary
,
Miklós Udvardy
2   The IInd Department of Medicine, University of Debrecen, Medical School, Debrecen, Hungary
,
László Muszbek
1   The Department of Clinical Chemistry, University of Debrecen, Medical School, Debrecen, Hungary
› Author Affiliations
Further Information

Publication History

Received 18 January 1995

Accepted after resubmission 18 September 1995

Publication Date:
10 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Factor XIII (FXIII) is of high importance in the regulation of fibrinolysis. It crosslinks α2-antiplasmin (α2AP) and fibrin and by this way protects fibrin from the prompt elimination by plasmin. Although FXIII of platelets has been implicated in this protective mechanism, the role of platelets and platelet FXIII in the crosslinking process is far from being elucidated. As demonstrated by SDS PAGE and by immunoblotting for α2AP, intact normal platelets resuspended in FXIII-free plasma or FXIII-free fibrinogen solution catalyzed the crosslinking of fibrin chains and also the crosslinking of α2AP to fibrin α-chains. With FXIII-deficient platelets no crosslinking reaction could be observed indicating that the crosslinking with normal platelets was, indeed, due to platelet FXIII and not to another, putative platelet transglutaminase. However, the crosslinking of α2AP to fibrin induced by the FXIII of intact platelets resuspended in FXIII-free plasma was considerably less extensive than the crosslinking carried out by the FXIII of normal plasma in the presence of FXIII-free platelets. Furthermore, the replacement of FXIII-free platelets by normal platelets in normal FXIII-containing plasma resulted in little, if any, difference in the crosslinking process. When crosslinking was induced by highly purified plasma FXIII the presence of intact FXIII-free platelets significantly accelerated the formation of α-chain polymers as well as the incorporation of α2AP-fibrin α-chain hetero-dimer into these polymers. The results indicate that, in physiological conditions, platelet FXIII plays only a minor role in the crosslinking of α2AP and fibrin; however, platelets, independently of their FXIII content, promote the crosslinking reaction by providing a catalytic surface on which the formation of highly crosslinked fibrin polymers is accelerated.

 

  • References

  • 1 Folk JA, Finlayson JS. The epsilon(γ-glutamyl)lysine crosslink and the catalytic role of transglutaminases. Adv Protein Chem 1977; 31: 001-133
    PubMedGoogle Scholar
  • 2 Haverkate F. Lysis of crosslinked and non-crosslinked purified fibrin. Thromb Diath Haemorrh 1975; 34: 584-585
    PubMedGoogle Scholar
  • 3 Sakata Y, Aoki N. Crosslinking of α2-plasmin inhibitor to fibrin by fibrin-stabilizing factor. J Clin Invest 1980; 65: 290-297
    CrossrefPubMedGoogle Scholar
  • 4 Tamaki T, Aoki N. Cross-linking of α2-plasmin inhibitor and fibronectin to fibrin by fibrin-stabilizing factor. Biochim Biophys Acta 1981; 661: 280-286
    CrossrefPubMedGoogle Scholar
  • 5 Ichinose A, Aoki N. Reversible crosslinking of α2-plasmin inhibitor to fibrinogen by fibrin-stabilizing factor. Biochim Biophys Acta 1982; 706: 158-164
    CrossrefPubMedGoogle Scholar
  • 6 Mimuro J, Kimura S, Aoki N. Release of α2-plasmin inhibitor from plasma fibrin clots by activated coagulation factor XIII. J Clin Invest 1986; 77: 1006-1013
    CrossrefPubMedGoogle Scholar
  • 7 Sakata Y, Aoki N. Significance of cross-linking of α2-plasmin inhibitor to fibrin in inhibition of fibrinolysis and in hemostasis. J Clin Invest 1982; 69: 536-542
    CrossrefPubMedGoogle Scholar
  • 8 Kimura S, Tamaki T, Aoki N. Acceleration of fibrinolysis by the amino-terminal peptide of α2-plasmin inhibitor. Blood 1985; 66: 157-160
    CrossrefPubMedGoogle Scholar
  • 9 Jansen JWCM, Haverkate F, Koopman J, Nieuwenhuis HK, Kluft C, Boschman TAC. Influence of factor XIIIa activity on human whole blood clot lysis in vitro. Thromb Haemost 1987; 57: 171-175
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 van Giezen JJJ, Minkema J, Bouma BN, Jansen JWCM. Cross-linking of α2-antiplasmin to fibrin is a key factor in regulating blood clot lysis: species differences. Blood Coag Fibrinolysis 1993; 4: 869-875
    CrossrefPubMedGoogle Scholar
  • 11 Francis CW, Marder VJ. Increased resistance to plasmic degradation of fibrin with highly crosslinked α-polymer chains formed at high factor XIII concentrations. Blood 1988; 71: 1361-1365
    PubMedGoogle Scholar
  • 12 Francis CW, Marder VJ. Rapid formation of large molecular weight α-polymers in cross-linked fibrin induced by high factor XIII concentrations. Role of platelet factor XIII. J Clin Invest 1987; 80: 1459-1465
    CrossrefPubMedGoogle Scholar
  • 13 Sakata Y, Mimuro J, Aoki N. Differential binding of plasminogen to crosslinked and non-crosslinked fibrin: its significance in hemostatic defect in factor XIII deficiency. Blood 1984; 63: 1393-1401
    PubMedGoogle Scholar
  • 14 Reed GL, Matsueda GR, Haber E. Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of α2-antiplasmin to fibrin. Thromb Haemost 1992; 68: 315-320
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Aoki N. Clot retraction increases clot resistance to fibrinolysis by condensing α2-plasmin inhibitor crosslinked to fibrin. Thromb Haemost 1993; 70: 376
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Lorand L, Credo RB, Janus TJ. Factor XIII (fibrin stabilizing factor). Meth Enzymol 1981; 80: 333-341
    PubMedGoogle Scholar
  • 17 Muszbek L, Polgár J, Boda Z. Platelet Factor XIII becomes active without the release of activation peptide during platelet activation. Thromb Haemost 1993; 69: 282-285
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Boda Z, Pfliegler G, Muszbek L, Tóth A, Ádány R, Hársfalvi J, Papp Z, Tomai I, Rák K. Congenital Factor XIII deficiency with multiple benign breast tumors and successful pregnancy with substitutive therapy. Haemostasis 1989; 19: 348-352
    PubMedGoogle Scholar
  • 19 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
    CrossrefPubMedGoogle Scholar
  • 20 Buluk K. An unknown function of blood platelets. Pol Tyg Lek 1955; 10: 191
    PubMedGoogle Scholar
  • 21 Lüscher EF. Ein fibrinstabilisierender Faktor aus Thrombozyten. Schweiz Med Wschr 1957; 87: 1220-1221
    PubMedGoogle Scholar
  • 22 Bohn H. Isolierung und Charakterisierung des fibrinstabilisierenden Faktors aus menschlichen Thrombozyten. Thromb Diath Haemorrh 1970; 23: 455-468
    PubMedGoogle Scholar
  • 23 McDonagh J, McDonagh RP. Factor XIII from human platelets: effect on fibrin crosslinking. Thromb Res 1972; 1: 147-160
    CrossrefPubMedGoogle Scholar
  • 24 Puszkin EG, Raghuraman V. Catalytic properties of a calmodulin-regulated transglutaminase from human platelets and chicken gizzard. J Biol Chem 1985; 260: 16012-16020
    PubMedGoogle Scholar
  • 25 Muszbek L, Adany R, Kavai M, Boda Z, Lopaciuk S. Monocytes of patients congenitally deficient in plasma factor XIII lack factor XIII subunit A antigen and transglutaminase activity. Thromb Haemost 1988; 59: 231-235
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Lopaciuk S, Lovette KM, McDonagh J, Chuang HYK, McDonagh RP. Subcellular distribution of fibrinogen and factor XIII in human blood . platelets. Thromb Res 1974; 8: 453-465
    PubMedGoogle Scholar
  • 27 Broekman MJ, Handin RJ, Cohen P. Distribution of fibrinogen and platelet factor 4 and XIII in subcellular fractions of human platelets. Br J Haematol 1975; 31: 51-55
    CrossrefPubMedGoogle Scholar
  • 28 Sixma JJ, Van den Berg A, Schiphorst M, Geuze HJ, McDonagh J. Immunocytochemical localization of albumin and factor XIII in thin cryo sections of human blood platelets. Thromb Haemost 1984; 51: 388-391
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Joist JH, Niewiarowski S. Retention of platelet fibrin stabilizing factor during the platelet release reaction and clot retraction. Thromb Diath Haemorrh 1973; 29: 679-683
    PubMedGoogle Scholar
  • 30 Marx G, Korner G, Mou X, Gorodetsky R. Packaging zinc, fibrinogen and factor XIII in platelet α-granules. J Cell Physiol 1993; 156: 437-442
    CrossrefPubMedGoogle Scholar
  • 31 Kreager JA, Devine DV, Greenberg CS. Cytofluorometric identification of plasmin-sensitive factor XIIIa binding to platelets. Thromb Haemost 1988; 60: 88-93
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Holme PA, Brosstadt F, Solum NO. The difference between platelet and plasma FXIII used to study the mechanism of platelet microvesicle formation. Thromb Haemost 1993; 70: 681-686
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Greenberg CS, Shuman MA. Specific binding of blood coagulation factor XIIIa to thrombin-stimulated platelets. J Biol Chem 1984; 259: 14721-14727
    PubMedGoogle Scholar
  • 34 Devine DV, Andestad G, Nugent D, Carter CJ. Platelet-associated factor XIII as a marker of platelet activation in patients with peripheral vascular disease. Arterioscler Thromb 1993; 13: 857-862
    CrossrefPubMedGoogle Scholar
  • 35 Cox AD, Devine DV. Factor XIIIa binding to activated platelets is mediated through activation of glycoprotein IIb-IIIa. Blood 1994; 83: 1006-1016
    PubMedGoogle Scholar