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The factor XIII‐A Val34Leu polymorphism decreases whole blood clot mass at high fibrinogen concentrations
Author(s) -
Kattula Sravya,
Bagoly Zsuzsa,
Tóth Noémi Klára,
Muszbek László,
Wolberg Alisa S.
Publication year - 2020
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14744
Subject(s) - fibrinogen , fibrin , factor xiii , platelet , chemistry , whole blood , coagulation , immunology , medicine , biochemistry
Background Factor XIII (FXIII) promotes fibrin crosslinking and red blood cell (RBC) retention in clots. The FXIII‐A polymorphism, Val34Leu, is associated with protection against venous thrombosis. This effect is hypothesized to result from fibrinogen concentration‐dependent changes in fibrin structure. Effects of the FXIII‐A Val34Leu polymorphism in whole blood clots have not been investigated. Aim Characterize effects of FXIII‐A Val34Leu polymorphism and fibrinogen on whole blood clots. Methods We isolated platelet‐poor plasmas from human donors (FXIII Val/Val , FXIII Val/Leu , FXIII Leu/Leu ), reconstituted plasmas with platelets and RBCs, and triggered clotting. We assessed contributions of gender, age, clotting times, thrombin generation, FXIII activity, FXIII‐A Val34Leu polymorphism, and fibrinogen to clot mass. We also reconstituted FXIII‐depleted plasma with platelets, RBCs, and purified FXIII Val/Val or FXIII Leu/Leu , varied fibrinogen, and characterized effects on clot mass. Results Clot mass was associated with age, fibrinogen, prothrombin time, and thrombin generation. Clots reconstituted with plasmas from individuals with FXIII‐A Val/Val and FXIII‐A Val/Leu did not differ in mass from clots with FXIII‐A Leu/Leu . However, clots containing a 34Val allele demonstrated a fibrinogen concentration‐dependent increase in mass, whereas clots with homozygous 34Leu did not. In plasmas with high fibrinogen, mass was higher for clots with 34Val alleles compared with clots with homozygous 34Leu. In clots reconstituted with purified FXIII, increasing fibrinogen enhanced clot mass in the presence of 34Val, but decreased mass in the presence of 34Leu. Conclusions FXIII 34Leu mitigates the effect of elevated fibrinogen on whole blood clot mass. The Val34Leu polymorphism may protect against venous thrombosis by reducing clot mass.