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

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Abstract
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.