Background: Hypercoagulability can lead to serious thromboembolic events. The aim of this study was to assess the perioperative coagulation status in liver transplant recipients with a tendency to hypercoagulability. Methods: In a prospective observational study (South African Cochrane Registry 201405000814129), 151 potential liver transplant recipients were screened for thrombophilic factors from October 2014 to June 2017, and 57 potential recipients fulfilled the inclusion criterion of presenting two or more of the following thrombophilic factors: low protein C, low protein S, low anti-thrombin, increased homocystein, increased antiphospholipid IgG/IgM antibodies, increased lupus anticoagulant, and positive Factor V Leiden mutation. Seven patients were excluded from the study because they fulfilled the exclusion criteria of cancelling the liver transplantation, oral anticoagulation, or intraoperative treatment with rFVIIa. Accordingly, 50 patients were included in the final analysis. Thromboelastometry (ROTEM) (EXTEM, INTEM and FIBTEM) and conventional coagulation tests (CCT) were performed preoperatively, during the anhepatic phase, post reperfusion, and on postoperative days (POD) 1, 3 and 7. ROTEM was used to guide blood product transfusion. Heparin was infused (60-180 U/kg/day) postoperatively for 3 days and then was replaced by low-molecular-weight heparin (20 mg/12 h). Results: FIBTEM MCF significantly increased postoperatively above reference range on POD 7 despite normal fibrinogen plasma concentrations (p < 0.05). Both EXTEM and INTEM demonstrated significant changes with the phases of transplantation (p < 0.05), but with no intra- or postoperative hypercoagulability observed. INTEM CT (reference range, 100-240 s) normalized on POD 3 and 7 (196.1 ± 69.0 and 182.7 ± 63.8 s, respectively), despite prolonged aPTT (59.7 ± 18.7 and 46.4 ± 15.7 s, respectively; reference range, 20-40 s). Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) were reported in 12.0% and 2.0%, respectively, mainly after critical care discharge and with high FIBTEM MCF values in 57% on POD 3 and 86% on POD 7. Receiver operating characteristics curve analyses of FIBTEM MCF were significant predictors for thromboembolic events with optimum cut-off, area under the curve and standard error on POD 3 (>23 mm, 0.779 and 0.097; p = 0.004) and POD 7 (>28 mm, 0.706 and 0.089; p = 0.020). Red blood cells (mean ± SD, 8.68 ± 5.81 units) were transfused in 76%, fresh frozen plasma (8.26 ± 4.14 units) in 62%, and cryoprecipitate (12.0 ± 3.68 units) in 28% of recipients. None of the recipients received intraoperative platelet transfusion or any postoperative transfusion. Main transplant indication was hepatitis C infection in 82%. 76% of recipients included in this highly selected patient population showed increased lupus anticoagulant, 2% increased antiphospholipid IgG/IgM antibodies, 20% increased homocysteine, 74% decreased anti-thrombin, 78% decreased protein C, 34% decreased protein S, and 24% a positive Factor V Leiden mutation. Overall 1-year survival was 62%. Conclusion: A significant postoperative step-wise increase in FIBTEM MCF beyond the reference range was observed despite normal fibrinogen plasma concentrations, and FIBTEM MCF was a predictor for thromboembolic events in this study population, particularly after POD 3 and 7 on surgical wards when CCTs failed to detect this condition. However, the predictive value of FIBTEM MCF for postoperative HAT and PVT needs to be confirmed in a larger patient population. A ROTEM-guided anticoagulation regime needs to be developed and investigated in future studies.

中文翻译：

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具有高凝倾向的成人活体肝移植受者围手术期血栓弹力图：一项前瞻性观察性队列研究

背景：高凝状态可导致严重的血栓栓塞事件。本研究的目的是评估具有高凝倾向的肝移植受者的围手术期凝血状态。方法：在一项前瞻性观察研究（南非 Cochrane Registry 201405000814129）中，从 2014 年 10 月到 2017 年 6 月，对 151 名潜在的肝移植受者进行了血栓形成因素筛查，其中 57 名潜在的接受者满足了呈现以下两种或更多血栓形成因素的纳入标准：低蛋白 C、低蛋白 S、抗凝血酶低、同型半胱氨酸升高、抗磷脂 IgG/IgM 抗体升高、狼疮抗凝剂升高、因子 V Leiden 突变阳性。7名患者被排除在研究之外，因为他们符合取消肝移植、口服抗凝剂或术中rFVIIa治疗的排除标准。因此，最终分析包括 50 名患者。在术前、无肝期、再灌注后和术后第 1、3 和 7 天（POD）进行血栓弹力图 (ROTEM)（EXTEM、INTEM 和 FIBTEM）和常规凝血测试 (CCT)。ROTEM 用于指导血液制品输血。术后输注肝素（60-180 U/kg/天）3天，然后换用低分子肝素（20 mg/12 h）。结果：尽管纤维蛋白原血浆浓度正常（p < 0.05），但术后 POD 7 时，FIBTEM MCF 显着高于参考范围（p < 0.05）。EXTEM 和 INTEM 都表现出随着移植阶段的显着变化（p < 0.05），但未观察到术中或术后高凝状态。INTEM CT（参考范围，100-240 s）在 POD 3 和 7（分别为 196.1 ± 69.0 和 182.7 ± 63.8 s）归一化，尽管 aPTT 延长（分别为 59.7 ± 18.7 和 46.4 ± 15.7 s；参考范围，20- 40 秒）。据报道，肝动脉血栓形成 (HAT) 和门静脉血栓形成 (PVT) 分别为 12.0% 和 2.0%，主要是在重症监护出院后，并且在 POD 3 和 POD 7 分别有 57% 和 86% 的高 FIBTEM MCF 值。接收操作FIBTEM MCF 的特征曲线分析是血栓栓塞事件的重要预测因子，具有最佳截止值、曲线下面积和 POD 3（>23 mm，0.779 和 0.097；p = 0.004）和 POD 7（>28 mm，0.706）的标准误差和 0。089; p = 0.020)。76% 的受者输注红细胞（平均值 ± SD，8.68 ± 5.81 单位），62% 的受者输注新鲜冷冻血浆（8.26 ± 4.14 单位），28% 的受者输注冷沉淀（12.0 ± 3.68 单位）。没有接受者接受术中血小板输注或任何术后输血。主要移植适应症是 82% 的丙型肝炎感染。在这个高度选择的患者群体中，76% 的受者显示狼疮抗凝剂增加，抗磷脂 IgG/IgM 抗体增加 2%，同型半胱氨酸增加 20%，抗凝血酶减少 74%，蛋白 C 减少 78%，蛋白 S 减少 34%，和24% 为阳性因子 V Leiden 突变。总体 1 年生存率为 62%。结论：尽管纤维蛋白原血浆浓度正常，但观察到 FIBTEM MCF 术后显着逐步增加超出参考范围，并且 FIBTEM MCF 是该研究人群中血栓栓塞事件的预测因子，特别是在手术病房的 POD 3 和 7 后，当 CCT 未能检测到时这种情况。然而，FIBTEM MCF 对术后 HAT 和 PVT 的预测价值需要在更大的患者群体中得到证实。在未来的研究中需要开发和研究 ROTEM 指导的抗凝方案。