National Haemophilia Centre, Chaim Sheba Medical Centre, Tel-Hashomer, Israel.
Faculty of Sciences, Holon Institute of Technology, Holon, Israel.
Blood Transfus. 2014 Jan;12(1):78-84. doi: 10.2450/2013.0068-13. Epub 2013 Nov 29.
The treatment options in severe thrombocytopenia (platelet count ≤20×10(9)/L) are limited. The aim of this study was to investigate ways of improving blood clotting and stability in reconstituted thrombocytopenia.
Thrombocytopenia (platelets [16±4]×10(9)/L) was created by differential centrifugation of normal blood followed by reconstitution of whole blood which was subjected to clotting in a rotation thromboelastometer by CaCl2 and tissue factor, and to fibrinolysis by tissue plasminogen activator (tPA). In separate experiments, blood was diluted by 40% with TRIS/saline solution. Blood was treated with fibrinogen (fib), factor XIII (FXIII), and thrombin-activatable fibrinolysis inhibitor (TAFI).
The maximum clot firmness of thrombocytopenic blood was approximately 2-fold less than that of intact blood. Supplementation of blood with fib and FXIII improved clot formation. In the presence of tPA, among fib, FXIII and TAFI, only fib stimulated clot propagation whereas each of these agents increased clot strength. There was a synergistic effect when fib was added together with FXIII or TAFI. Fibrinolysis was inhibited by TAFI and to a greater extent by TAFI + FXIII. Fourty percent dilution of blood reduced clot strength and increased susceptibility to tPA. Clot strength was increased by the treatments in the following order: fib/FXIII/TAFI > fib/TAFI > fib > TAFI > FXIII. In the presence of tPA, TAFI and FXIII lysed the clots significantly more slowly. This effect was stronger when blood was treated with the combination of fib/FXIII/TAFI. Doubling the fib concentration, alone or together with other agents, did not improve clot strength or stability.
Augmentation of clot formation and anti-fibrinolysis by combining fib, FXIII and TAFI may be beneficial for the treatment of patients with severe thrombocytopenia especially when complicated by haemodilution following introduction of fluids to compensate for massive blood loss.
严重血小板减少症（血小板计数≤20×10(9)/L）的治疗选择有限。本研究旨在探讨改善再生成血小板减少症中血液凝结和稳定性的方法。
通过正常血液的差速离心创建血小板减少症（血小板[16±4]×10(9)/L），然后用氯化钙和组织因子在旋转血栓弹性图中对全血进行凝结，并通过组织纤溶酶原激活物（tPA）进行纤维蛋白溶解。在单独的实验中，用 TRIS/盐水溶液将血液稀释 40%。用纤维蛋白原（fib）、因子 XIII（FXIII）和凝血酶激活的纤溶抑制物（TAFI）处理血液。
血小板减少症血液的最大凝块硬度约为完整血液的 2 倍。用 fib 和 FXIII 补充血液可改善凝血形成。在 tPA 的存在下，在 fib、FXIII 和 TAFI 中，只有 fib 刺激凝块传播，而这些药物中的每一种都增加了凝块强度。当 fib 与 FXIII 或 TAFI 一起添加时，存在协同作用。TAFI 抑制纤维蛋白溶解，而 TAFI+FXIII 的抑制作用更大。血液稀释 40%会降低凝块强度并增加对 tPA 的敏感性。凝块强度的增加顺序为：fib/FXIII/TAFI>fib/TAFI>fib>TAFI>FXIII。在 tPA 的存在下，TAFI 和 FXIII 显著更缓慢地溶解凝块。当血液用 fib/FXIII/TAFI 联合处理时，这种效果更强。单独或与其他药物一起加倍 fib 浓度并不能改善凝块强度或稳定性。
通过结合 fib、FXIII 和 TAFI 增强凝血形成和抗纤维蛋白溶解可能有益于治疗严重血小板减少症患者，特别是在引入液体以补偿大量失血后出现血液稀释时。
