Hemostasis Branch, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, 20993, Silver Spring, MD, USA.
Department of Pathology, The Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, University of Maryland, Baltimore, MD, USA.
J Thromb Thrombolysis. 2023 Apr;55(3):566-570. doi: 10.1007/s11239-022-02742-1. Epub 2022 Dec 12.
Assessing simultaneous generation of thrombin (TG) and plasmin (PG) is an approach to evaluate the balance between coagulation and fibrinolysis with sensitivity to predict endogenous thrombin and plasmin generation. The addition of thrombomodulin (TM), provides the essential component for thrombin activation of protein C and thrombin-activatable fibrinolysis inhibitor. However, the influence of sex on the balance between TG and PG with and without TM addition has not been investigated to date.
To investigate the possible sex-based differences in TG and PG in the presence and absence of TM.
Simultaneous TG and PG were measured in plasma samples obtained from 17 males and 17 females upon tissue factor and tissue plasminogen activator addition. Thrombin- and plasmin-specific fluorogenic substrates Z-Gly-Gly-Arg-AMC and Boc-Glu-Lys-Lys-AMC were used in the study. Thrombin and plasmin peak height (TPH and PPH) and production rate (TPR and PPR) values were determined. To evaluate the balance between TG and PG, the ratios between TPH and PPH (TPH/PPH) and TPR and PPR (TPR/PPR) were calculated.
TPH between males and females demonstrated significant difference regardless of TM addition. TPR demonstrated differences between males and females only upon TM addition, while PG parameters was not dependent on the sex of the donor. TM significantly lowered TPH/PPH in males, and enhanced TPR/PPR in females. Thus, TPH/PPH and TPR/PPR significantly differed between men and women. Our results indicate that TM may act differently in males and females by shifting the underlying TG/PG balance to fibrinolysis in males and to coagulation in females.
评估凝血酶 (TG) 和纤溶酶 (PG) 的同时生成是一种评估凝血和纤溶平衡的方法，其敏感性可预测内源性凝血酶和纤溶酶的生成。添加血栓调节蛋白 (TM) 为蛋白 C 的凝血酶激活和凝血酶激活的纤溶抑制物提供了必需的成分。然而，迄今为止，尚未研究性别对添加和不添加 TM 时 TG 和 PG 平衡的可能影响。
研究在存在和不存在 TM 的情况下 TG 和 PG 可能存在的性别差异。
在组织因子和组织纤溶酶原激活物添加后，从 17 名男性和 17 名女性的血浆样本中测量同时的 TG 和 PG。研究中使用了凝血酶和纤溶酶特异性荧光底物 Z-Gly-Gly-Arg-AMC 和 Boc-Glu-Lys-Lys-AMC。确定了凝血酶和纤溶酶的峰值高度 (TPH 和 PPH) 和生成率 (TPR 和 PPR) 值。为了评估 TG 和 PG 之间的平衡，计算了 TPH 和 PPH 之间的比值 (TPH/PPH) 和 TPR 和 PPR 之间的比值 (TPR/PPR)。
无论是否添加 TM，男性和女性之间的 TPH 均存在显著差异。仅在添加 TM 时，TPR 表现出男性和女性之间的差异，而 PG 参数不依赖于供体的性别。TM 显著降低了男性的 TPH/PPH，并增强了女性的 TPR/PPR。因此，TPH/PPH 和 TPR/PPR 在男性和女性之间存在显著差异。我们的结果表明，TM 可能通过将潜在的 TG/PG 平衡向男性的纤溶和女性的凝血转移，在男性和女性中发挥不同的作用。
