Shenkman B, Einav Y, Livnat T, Budnik I, Martinowitz U
National Hemophilia Center, Sheba Medical Center, Tel-Hashomer, Israel.
Faculty of Sciences, Holon Institute of Technology, Holon, Israel.
Int J Lab Hematol. 2015 Aug;37(4):521-9. doi: 10.1111/ijlh.12331. Epub 2015 Feb 4.
Bleeding symptoms in severe thrombocytopenia range from mild to severe. The aim of this in vitro study was to improve blood clotting and protect against fibrinolysis in reconstituted severe thrombocytopenia blood.
Thrombocytopenia [(16 ± 4) × 10(6) /mL] was created by high-speed centrifugation of normal blood with subsequent mixing plasma with packed cells. The blood samples were subjected to clotting by CaCl2 and tissue factor and to fibrinolysis by the addition of tissue plasminogen activator. Blood was spiked with fibrinogen, activated prothrombin complex concentrate (FEIBA), thrombin activatable fibrinolysis inhibitor (TAFI), or their combinations. To mimic the situation that may occur in patients subjected to massive transfusion of plasma substitutes, blood was diluted by 40% of TRIS/saline buffer. Clotting time (CT), α-Angle, maximum clot firmness (MCF), and lysis onset time (LOT) were evaluated using rotation thromboelastometry.
Spiking thrombocytopenia blood with FEIBA led to reduction of CT. Fibrinogen and FEIBA enhanced α-Angle and MCF both in the absence and in the presence of tPA. LOT values were prolonged by TAFI and to less extent by FEIBA. Dilution of thrombocytopenia blood was followed by reduction of α-Angle and MCF compared to nondiluted blood which partly reversed by either fibrinogen or FEIBA being higher using fibrinogen and FEIBA together. Clot strength was enhanced, and fibrinolysis was inhibited by TAFI.
The results of this study suggest that combined spiking of blood with fibrinogen and FEIBA may be enough to correct the clot formation disorder in severe thrombocytopenia, whereas in thrombocytopenia and blood dilution, additive inhibition of fibrinolysis may be needed.
严重血小板减少症的出血症状从轻度到重度不等。这项体外研究的目的是改善重组严重血小板减少症血液的凝血功能并防止纤维蛋白溶解。
通过对正常血液进行高速离心,随后将血浆与压积细胞混合,制造出血小板减少症[(16±4)×10⁶/mL]。血液样本通过氯化钙和组织因子进行凝血,并通过添加组织纤溶酶原激活剂进行纤维蛋白溶解。向血液中加入纤维蛋白原、活化凝血酶原复合物浓缩物(FEIBA)、凝血酶激活的纤维蛋白溶解抑制剂(TAFI)或它们的组合。为模拟接受大量血浆代用品输血的患者可能出现的情况,血液用40%的TRIS/生理盐水缓冲液稀释。使用旋转血栓弹力图评估凝血时间(CT)、α角、最大血凝块硬度(MCF)和溶解起始时间(LOT)。
向血小板减少症血液中加入FEIBA可导致CT缩短。无论有无tPA,纤维蛋白原和FEIBA均可增强α角和MCF。TAFI可延长LOT值,FEIBA在较小程度上也有此作用。与未稀释血液相比,血小板减少症血液稀释后α角和MCF降低,使用纤维蛋白原和FEIBA一起可部分逆转这种情况,且使用纤维蛋白原和FEIBA时二者均较高。TAFI可增强血凝块强度并抑制纤维蛋白溶解。
本研究结果表明,血液联合加入纤维蛋白原和FEIBA可能足以纠正严重血小板减少症中的凝血形成障碍,而在血小板减少症和血液稀释的情况下,可能需要额外抑制纤维蛋白溶解。