Thromb Haemost 1987; 57(02): 171-175
DOI: 10.1055/s-0038-1651088
Original Article
Schattauer GmbH Stuttgart

Influence of Factor Xllla Activity on Human Whole Blood Clot Lysis In Vitro

J W C M Jansen
*   The Duphar B. V., Dept. Pharmacology, Weesp, The Netherlands
,
F Haverkate
**   The Gaubius Institute TNO, Leiden, The Netherlands
,
J Koopman
**   The Gaubius Institute TNO, Leiden, The Netherlands
,
H K Nieuwenhuis
***   The Dept. Haematology, University Hospital Utrecht, Utrecht, The Netherlands
,
C Kluft
**   The Gaubius Institute TNO, Leiden, The Netherlands
,
Th A C Boschman
*   The Duphar B. V., Dept. Pharmacology, Weesp, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 26 September 1986

Accepted after revision 18 December 1986

Publication Date:
28 June 2018 (online)

Summary

We studied the influence of Factor XIII a (F XIII a) activity on the lysis rate of fresh whole human blood clots, without using anticoagulants. Clotting was induced by exogenous thrombin, lysis by tissue-type Plasminogen Activator (t-PA) added before clotting. After various periods of time, lysis rates were determined by measuring the radioactivity in the supernatant of the clot originating from 125I-Fibrinogen added before clotting.

Lysis rates were determined in the presence of endogenous F XHIa and compared with those obtained after specific inhibition of F XIII a activity. We used an IgG fraction of an antiserum quenching the F XIII a activity. Addition of increasing amounts of the antibodies to normal blood resulted in a dramatic increase in clot lysis rate, concomitant with loss of F XIII activity. Lysis of blood clots from a patient with a congenital, homozygous, functional α2-Antiplasmin (α2-AP) deficiency (α2-AP-Enschede) was not or slightly increased by the anti F XIII antibodies indicating that fibrin-fibrin crosslinking per se does not contribute essentially to resistance of the blood clot against fibrinolysis. Both active α2-AP and F XIII a are required for the major part of the F XIII-dependent resistance of whole blood clots against lysis.

 
  • References

  • 1 Lorand L, Losowsky MS, Miloszewski K JM. Human factor XIII: fibrin stabilizing factor. In Progress in Hemostasis and thrombosis. Spaet Th H (Ed) Grune & Stratton; New York: 1980. 5 245-290
  • 2 Duckert F. Documentation of the plasma Factor XIII deficiency in man. Ann New York Acad Sci 1972; 202: 190-199
  • 3 McDonagh RP, McDonagh J, Duckert F. The influence of fibrin crosslinking on the kinetics of urokinase-induced clot lysis. Brit J Haemat 1971; 21: 323-332
  • 4 Kirkpatrick JP, Mclntire LV, Moake JL. Streptokinase induced degradation of crosslinked and uncrosslinked clots. Thromb Res 1978; 13: 569-575
  • 5 Henderson KW, Nussbaum M. The mechanism of enhanced streptokinase induced clot lysis following in-vitro Factor XIII inactivations. Brit J Haemat 1969; 17: 445-453
  • 6 Gormsen J, Fedderson C. Degradation of stabilized and non-stabilized fibrin clots by plasmin. Immunological study. Ann New York Acad Sci 1972; 202: 329-334
  • 7 Folk JE, Finlayson JS. The Epsilon (y-Glutamyl) lysine crosslink and the catalytic role of transglutaminases. Adv Protein Chem 1977; 31: 1-133
  • 8 Haverkate F. Lysis of crosslinked and non-crosslinked purified fibrin. Thromb Diath Haemorrh 1975; 34: 584-585
  • 9 Sakata Y, Aoki N. Crosslinking of α2-plasmin inhibitor of fibrin by fibrin-stabilizing factor. J Clin Invest 1980; 65: 290-297
  • 10 Sakata Y, Aoki N. Significance of crosslinking of α2-plasmin inhibitor to fibrin in inhibition of fibrinolysis and haemostasis. J Clin Invest 1982; 69: 536-542
  • 11 Van Ruijven-Vermeer I AM, Nieuwenhuizen W. Purification of rat fibrinogen and its constituent chains. Biochem J 1978; 169: 653-658
  • 12 Fraker PJ, Speck JC. Protein and cell membrane iodinations with a sparingly soluble chloroamide 1, 3, 4, 6 tetrachloro-3a, 6a-diphenylglycoluril. Biochem Biophys Res Commun 1978; 80: 849-857
  • 13 Nieuwenhuizen W, Emeis JJ, Vermond A, Kurver P, Van der Heide D. Studies on the catabolism and distribution of fibrinogen in rats. Application of the iodogen labelling technique. Biochem Biophys Res Commun 1980; 97: 49-55
  • 14 Kluft C, Van Wezel AL, Van der Velden C AM, Emeis JJ, Verheijen JH, Wijngaards G. Large-scale production of extrinsic (tissue-type) plasminogen activator from human melanoma cells. In Advances in Biotechnological processes. Mizrahi A, Van Wezel AL. (Eds) Alan R Liss; New York: 1983. 2 97-110
  • 15 Haverkate F, Brakman P. Fibrin plate assay. In Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Samama MM, Desnoyers PC. (Eds) Raven Press; New York: 1975. 1 151-159
  • 16 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
  • 17 Haverkate F, Timan G. Protective effect of calcium in the plasmin degradation of fibrinogen and fibrin fragments D. Thromb Res 1977; 10: 803-812
  • 18 Koopman J, Haverkate F. Formation of fibrin degradation products from a non-anticoagulated whole blood clot. In Fibrinogen, Structure, Functional aspects, Metabolism. Haverkate F, Henschen A, Nieuwenhuizen W, Straub PW. (Eds) Walter de Gruyter; Berlin-New York: 1983: 255-260
  • 19 Inoshita K, Shanberge JN. A rapid quantitative assay method for fibrinstabilizing factor (Factor XIII). Am J Clin Pathol 1974; 61: 85-91
  • 20 Kröninger A, Egbring R. Long-term treatment (12 years) with Factor-XIII concentrate in a patient with congenital Factor XIII deficiency. In Factor XIII and fibronectin. Egbring R, Klingemann HG. (Eds) Mediz Verlagsgesellschaft, Marburg/Lahn; W. Germany: 1983: 41-44
  • 21 Nieuwenhuis HK, Kluft C, Wijngaards G, Van Berkel W, Sixma JJ. α2-Antiplasmin Enschede: an autosomal recessive hemorrhagic disorder caused by a dysfunctional a2-antiplasmin molecule. Thromb Haemostas 1983; 50: 170
  • 22 Kluft C, Nieuwenhuis HK, Vellenga E. Congenital deficiencies in α2-antiplasmin. La Ricerca Clin Lab 1984; 14: 507-513
  • 23 Ferguson EW, Sander GE. Fibrin Epsilon (y-glutamyl) lysine crosslink acceleration by red blood cells. Nature 1979; 278: 183-185
  • 24 Taylor FB, Carroll RC, Gerrard J, Esmon CT, Radcliffe RD. Lysis of clots prepared from whole blood and plasma. Fed Proc 1981; 40: 2092-2098
  • 25 Gaffney PJ, Whitaker AN. Fibrin crosslinks and lysis rates. Thromb Res 1979; 14: 85-94
  • 26 Rasche H. Influence of fibrin subunit structure on the resistance of clots to streptokinase-induced fibrinolytic activity. In Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Samama MM, Desnoyers PC. (Eds) Raven Press; New York: 1985. 1 79-84
  • 27 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
  • 28 Schwartz ML, Pizzo SV, Hill RL, McKee PA. Human factor XIII from plasma and platelets. J Biol Chem 1973; 248: 1395-1407
  • 29 Hartert H. Rheo-stimulation: a new method for the assay of clotting process and Factor XIII. A preliminary report. Biorheology 1974; 11: 355-360
  • 30 Duckert F, Jung E, Schnerling DH. A hitherto undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency. Thromb Diath Haemorrh 1960; 5: 179-186
  • 31 Britton A FH. Congenital deficiency of factor XIII (fibrin-stabilizing factor). Am J Med 1967; 43: 751-761