Abstract：
BACKGROUND: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB.
METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test.
RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001).
CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.
METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test.
RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001).
CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.
摘要：
背景：最近建议将低剂量氨甲环酸（TXA）用于体外循环（CPB），以减少相关并发症。尽管无法进行TXA浓度的即时实验室测试，在ClotPro®系统上进行的新型TPA测试可以测量TXA诱导的纤维蛋白溶解抑制。我们评估了TPA测试在体外和需要CPB的手术患者中的性能。
方法：从六名志愿者中获取血液样本，用于体外评估组织纤溶酶原激活物（tPA）触发的纤维蛋白溶解和TXA的作用。随后在20名心脏手术患者中进行了一项观察性研究，以评估TXA对TPA测试的临床影响。
结果：TXA≥2mgL-1以浓度依赖的方式抑制tPA诱导的纤溶亢进，并在TXA≥10mgL-1时完全抑制。在接受CPB的患者中，在CPB结束时0.1g推注TXA后，对TPA测试参数可检测到抗纤维蛋白溶解作用，TXA≥0.5g时，纤溶完全抑制。1gTXA对TPA测试参数的抗纤溶作用在术后18小时内逐渐减弱。然而,在估计肾小球滤过率(eGFR)≤30mlmin-11.73m-2的4例患者中,纤溶抑制持续.eGFR与术后18h的TPA检测参数有很强的相关性(r=0.86-0.92;P<0.0001)。
结论：TPA试验对低浓度的TXA敏感，可作为心脏手术患者术后纤溶活性的实用监测工具。该测试可能对严重肾功能损害的患者特别有用。
方法：从六名志愿者中获取血液样本，用于体外评估组织纤溶酶原激活物（tPA）触发的纤维蛋白溶解和TXA的作用。随后在20名心脏手术患者中进行了一项观察性研究，以评估TXA对TPA测试的临床影响。
结果：TXA≥2mgL-1以浓度依赖的方式抑制tPA诱导的纤溶亢进，并在TXA≥10mgL-1时完全抑制。在接受CPB的患者中，在CPB结束时0.1g推注TXA后，对TPA测试参数可检测到抗纤维蛋白溶解作用，TXA≥0.5g时，纤溶完全抑制。1gTXA对TPA测试参数的抗纤溶作用在术后18小时内逐渐减弱。然而,在估计肾小球滤过率(eGFR)≤30mlmin-11.73m-2的4例患者中,纤溶抑制持续.eGFR与术后18h的TPA检测参数有很强的相关性(r=0.86-0.92;P<0.0001)。
结论：TPA试验对低浓度的TXA敏感，可作为心脏手术患者术后纤溶活性的实用监测工具。该测试可能对严重肾功能损害的患者特别有用。
