Normandie Univ, UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit, F 76000, Rouen, France.
Service d'Hématologie Biologique, Centre Hospitalier Universitaire Charles Nicolle, 1 rue de Germont, 76031, Rouen, France.
J Thromb Thrombolysis. 2019 Apr;47(3):473-477. doi: 10.1007/s11239-019-01821-0.
Factor V Leiden (FVL) mutation is the most common genetic risk factor for venous thromboembolism. In families with a history of thrombosis, FVL can be present in 18%. Thrombin generation test is commonly used as an evaluation tool of thrombotic risk. The objective of this study was to evaluate the thrombogenic potential of FVL in asymptomatic carriers and in patients with personal or familial history of thrombosis. This was a retrospective single center study including 160 patients. Among them, 43 had personal history of thrombosis and 117 had familial history of thrombosis. Thrombin generation (TG) was realized in frozen platelet poor plasma with 1 pM of tissue factor and 4 µM of phospholipid. FVL mutation was associated with a global increase of TG. No difference was observed between patients with provoked thrombosis and patients with first-degree familial history of thrombosis (endogenous thrombin potential (ETP): 1501.0 ± 316.4 nM min and thrombin peak: 253.4 ± 71.5 nM vs. 1520.4 ± 283.8 nM min and 268.6 ± 68.0 nM). An increase of TG was observed in patients with unprovoked thrombosis (n = 23) and in patients with provoked thrombosis (n = 20) (ETP: 1819.5 ± 319.8 nM min and peak: 332.3 ± 55.8 nM). In the unprovoked thrombosis group, patients with a pulmonary embolism had a higher ETP than patients with deep vein thrombosis (DVT) (2036 ± 343 nM min vs. 1707 ± 261 nM min). With a predictive score formula (s = 0.1315 × Age + 0.0105 × ETP) with a threshold of 22.1 as risk to develop an unprovoked thrombosis among patients with second-degree familial history. The results of our analysis suggest that measurement of thrombin generation in patients with FVL mutation may identify subjects with an increased risk of unprovoked thrombosis. Further studies are needed to examine the usefulness of predicting thrombotic presentation in asymptomatic carriers.
凝血酶原第五因子 Leiden 突变（FVL）是静脉血栓栓塞症最常见的遗传风险因素。在有血栓形成家族史的家庭中，FVL 的发生率为 18%。凝血酶生成试验通常被用作血栓形成风险评估的工具。本研究的目的是评估无症状携带者和有个人或家族血栓形成史的患者中 FVL 的血栓形成潜力。这是一项回顾性的单中心研究，共纳入 160 名患者。其中，43 名患者有个人血栓形成史，117 名患者有家族血栓形成史。凝血酶生成（TG）是在含有 1 pM 组织因子和 4 µM 磷脂的冷冻血小板贫浆中实现的。FVL 突变与 TG 的整体增加有关。有诱发性血栓形成的患者和有一级家族血栓形成史的患者之间没有差异（内源性凝血酶潜能（ETP）：1501.0±316.4 nM min 和凝血酶峰：253.4±71.5 nM vs. 1520.4±283.8 nM min 和 268.6±68.0 nM）。无诱因血栓形成的患者（n=23）和有诱发性血栓形成的患者（n=20）中观察到 TG 的增加（ETP：1819.5±319.8 nM min 和峰值：332.3±55.8 nM）。在无诱因血栓形成组中，患有肺栓塞的患者的 ETP 高于患有深静脉血栓形成（DVT）的患者（2036±343 nM min vs. 1707±261 nM min）。使用预测评分公式（s=0.1315×年龄+0.0105×ETP），阈值为 22.1，用于评估二级家族史患者发生无诱因血栓形成的风险。我们的分析结果表明，在 FVL 突变患者中测量凝血酶生成可能有助于识别无诱因血栓形成风险增加的患者。需要进一步研究来检验预测无症状携带者血栓形成表现的有用性。
