The factor XIII-A Val34Leu polymorphism decreases whole blood clot mass at high fibrinogen concentrations.
The factor XIII-A Val34Leu polymorphism decreases whole blood clot mass at high fibrinogen concentrations.
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DOI：
10.1111/jth.14744
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发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
Wolberg AS
中科院分区：
文献类型：
--
作者：
Kattula S;Bagoly Z;Tóth NK;Muszbek L;Wolberg AS
因子XIII （FXIII）促进纤维蛋白交联和红细胞（RBC）在凝块中的保留。FXIII-A多态性Val34Leu与预防静脉血栓形成有关。这种效应被假设是由纤维蛋白原浓度依赖性的纤维蛋白结构变化引起的。FXIII-A Val34Leu多态性在全血凝块中的影响尚未研究。表征FXIII-A Val34Leu多态性和纤维蛋白原对全血凝块的影响。我们从人类供体（FXIIIVal/Val, FXIIIVal/Leu, fxiiieu /Leu）中分离出血小板缺乏的血浆，用血小板和红细胞重建血浆，并触发凝血。我们评估了性别、年龄、凝血时间、凝血酶生成、FXIII活性、FXIII- a Val34Leu多态性和纤维蛋白原对凝块的影响。我们还用血小板、红细胞、纯化的FXIIIVal/Val或fxiiieu /Leu、不同的纤维蛋白原重建了fxiiiii耗尽的血浆，并表征了对凝块的影响。凝块与年龄、纤维蛋白原、凝血酶原时间和凝血酶生成有关。用FXIII-ALeu/ Val和fxiii - alval /Leu患者的血浆重建的血块与FXIII-ALeu/Leu患者的血块在质量上没有差异。然而，含有34Val等位基因的血块表现出纤维蛋白原浓度依赖性的质量增加，而纯合子34Leu的血块则没有。在高纤维蛋白原的血浆中，携带34Val等位基因的血块比携带纯合子34Leu的血块质量更高。在用纯化的FXIII重组的血块中，纤维蛋白原的增加增加了34Val存在时的血块质量，但减少了34Leu存在时的血块质量。FXIII 34Leu可减轻纤维蛋白原升高对全血凝块的影响。Val34Leu多态性可能通过减少血栓块来预防静脉血栓形成。
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. Characterize effects of FXIII-A Val34Leu polymorphism and fibrinogen on whole blood clots. We isolated platelet-poor plasmas from human donors (FXIIIVal/Val, FXIIIVal/Leu, FXIIILeu/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 FXIIIVal/Val or FXIIILeu/Leu, varied fibrinogen, and characterized effects on clot mass. Clot mass was associated with age, fibrinogen, prothrombin time, and thrombin generation. Clots reconstituted with plasmas from individuals with FXIII-AVal/Val and FXIII-AVal/Leu did not differ in mass from clots with FXIII-ALeu/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 to 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. 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.
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5.6
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