Lincz Lisa F, Lonergan Amy, Scorgie Fiona E, Rowlings Phillip, Gibson Richard, Lawrie Andrew, Seldon Michael
Hunter Haematology Research Group, Newcastle Mater Misericordiae Hospital, Waratah, Australia.
Pathophysiol Haemost Thromb. 2006;35(6):435-9. doi: 10.1159/000102050.
Measurement of endogenous thrombin potential (ETP) detects hypercoagulability and can be used to identify activated protein C resistance due to factor V Leiden (FVL). However, not all carriers of FVL suffer thrombosis and therefore we sought to determine if the test for ETP could be modified in such a way as to enable detection of FVL patients who were at increased risk of venous thromboembolism. Protac, an activator of both protein C and factor V, was incorporated into the traditional thrombin generation reaction and ratios (reaction with Protac:reaction without Protac) were calculated. Plasma samples from 42 FVL heterozygotes (12 with a history of thrombosis and 30 with no prior thrombosis) and 38 controls (non-FVL with no history of thrombosis) were analysed. The mean ETP ratio was significantly higher in FVL heterozygotes (0.90 +/- 0.06) compared to normal controls (0.41 +/- 0.10; p = 0.00004). Multivariate analysis indicated that the average ETP ratio was significantly and inversely correlated with factor V levels in FVL heterozygotes (p = 0.002) but not controls. Within the FVL group, patients with a history of thrombosis had higher ETP ratios (0.92 +/- 0.06) compared to those without (0.89 +/- 0.05), however, this did not reach statistical significance (p = 0.09). Further investigation into the use of ETP for detecting risk of thrombosis in people who are genetically predisposed is warranted. The recent introduction of diagnostic ETP measurements in the form of the calibrated automated thrombin generation from Thrombinoscope and the TechnoThrombin from Baxter should facilitate such studies.
内源性凝血酶潜力（ETP）的测定可检测高凝状态，并可用于识别因因子V莱顿（FVL）导致的活化蛋白C抵抗。然而，并非所有FVL携带者都会发生血栓形成，因此我们试图确定ETP检测是否可以通过某种方式进行改进，以便能够检测出静脉血栓栓塞风险增加的FVL患者。将蛋白C和因子V的激活剂Protac纳入传统的凝血酶生成反应中，并计算比率（与Protac反应：不与Protac反应）。分析了42名FVL杂合子（12名有血栓形成病史，30名无既往血栓形成病史）和38名对照（无血栓形成病史的非FVL）的血浆样本。与正常对照（0.41±0.10；p = 0.00004）相比，FVL杂合子的平均ETP比率（0.90±0.06）显著更高。多变量分析表明，FVL杂合子的平均ETP比率与因子V水平呈显著负相关（p = 0.002），而对照中无此相关性。在FVL组中，有血栓形成病史的患者的ETP比率（0.92±0.06）高于无血栓形成病史的患者（0.89±0.05），然而，这未达到统计学显著性（p = 0.09）。有必要进一步研究ETP在检测遗传易感性人群血栓形成风险中的应用。最近以Thrombinoscope的校准自动凝血酶生成和Baxter的TechnoThrombin形式引入的诊断性ETP测量应该有助于此类研究。
