Gantioqui Jorell, Stevic Ivan, Atkinson Helen, Chan Anthony K C
Thrombosis and Atherosclerosis Research Institute.
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Blood Coagul Fibrinolysis. 2018 Sep;29(6):521-527. doi: 10.1097/MBC.0000000000000751.
Current recommendations for treating patients with thromboembolism and concomitant thrombocytopenia are based on anecdotal data and expert opinion, rather than clinical studies. Our aim was to use an in-vitro model employing thromboelastography (TEG) to evaluate clot formation as a surrogate indicator of clinical tendency to hemorrhage, and investigate the interactions of plasma at varying concentrations of platelets in the presence of anticoagulants.
Platelet-rich and platelet-poor plasma isolated from whole blood were mixed together to obtain platelet concentrations ranging from less than 10-150 × 10 platelets/l. Clotting was initiated with tissue factor and measured by TEG.
Different tissue factor concentrations were required to model clinical clotting profiles for plasma that contained heparin (UFH), low molecular weight heparin (LMWH), or fondaparinux. No tissue factor was required for rivaroxaban or dabigatran-clotting reactions. The time to initiate coagulation (R) was significantly delayed at platelet concentrations less than 30 × 10/l for UFH and LMWH, less than 20 × 10/l for fondaparinux, and less than 10 × 10/l for rivaroxaban and dabigatran. The strength of the clot was significantly compromised at all platelet concentrations in the presence of UFH, LMWH or fondaparinux. In contrast, rivaroxaban and dabigatran compromised clot strength at platelet concentrations less than 10 × 10/l.
All anticoagulants tested compromised coagulation at specific platelet concentration thresholds. Rivaroxaban and dabigatran had reduced impact on clot formation at low-platelet concentrations compared with heparinoids, suggesting that the factor-specific inhibitors may be more favorable than traditional heparin-based treatment of thromboembolism in the presence of thrombocytopenia.
目前针对血栓栓塞合并血小板减少症患者的治疗建议是基于轶事性数据和专家意见，而非临床研究。我们的目的是使用一种采用血栓弹力图（TEG）的体外模型来评估凝血形成，将其作为临床出血倾向的替代指标，并研究在存在抗凝剂的情况下不同血小板浓度的血浆之间的相互作用。
从全血中分离出富含血小板和血小板减少的血浆，将它们混合在一起，以获得血小板浓度范围为低于10 - 150×10⁹血小板/升。用组织因子启动凝血，并通过TEG进行测量。
对于含有普通肝素（UFH）、低分子量肝素（LMWH）或磺达肝癸钠的血浆，需要不同的组织因子浓度来模拟临床凝血曲线。利伐沙班或达比加群凝血反应不需要组织因子。对于UFH和LMWH，血小板浓度低于30×10⁹/升时，凝血起始时间（R）显著延迟；对于磺达肝癸钠，低于20×10⁹/升时显著延迟；对于利伐沙班和达比加群，低于10×10⁹/升时显著延迟。在存在UFH、LMWH或磺达肝癸钠的情况下，所有血小板浓度下的血凝块强度均显著受损。相比之下，利伐沙班和达比加群在血小板浓度低于10×10⁹/升时会损害血凝块强度。
所有测试的抗凝剂在特定的血小板浓度阈值下都会损害凝血功能。与类肝素相比，利伐沙班和达比加群在低血小板浓度下对凝血形成的影响较小，这表明在存在血小板减少症的情况下，因子特异性抑制剂可能比传统的基于肝素的血栓栓塞治疗更有利。
