Lawrie Andrew S, Pizzey Arnold, Trompeter Sara, Meiselman Herbert, Mohandas Narla, Dumanski Jan P, Westerman Maxwell P
Department of Haematology, University College London, UK.
Blood Coagul Fibrinolysis. 2012 Jun;23(4):268-70. doi: 10.1097/MBC.0b013e32835187f8.
Patients with sickle cell trait (STr) are usually considered to be asymptomatic. However, complications, including hypercoagulability, increased risk of venous thromboembolism and the exertional exercise syndrome with rhabdomyolysis and sudden death, have been described. The exact cause of these adverse events is unclear. We have investigated two patients, a set of monozygotic twins with STr, to establish their procoagulant activity status as a potential indicator of thrombotic risk. In-vivo thrombin generation was assessed by the measurement of prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT). D-dimer was used as a marker of fibrinolytic activity. The potential to generate thrombin was determined using an ex-vivo thrombin generation test (TGT). The impact of red blood cell (RBC)-derived microparticle shedding and RBC rheology were examined. TAT (>60 μg/l) and F1 + 2 (948 pmol/l) were markedly elevated in patient 2 but within the normal reference range in patient 1 (TAT = 2.5 μg/l; F1 + 2 = 138 pmol/l). D-dimer levels (0.9 mg/l FEU) were similarly elevated in both patients. TGT peak thrombin and endogenous thrombin potential (ETP) were elevated to similar degrees in both patients. Flow cytometric analysis for RBC-derived microparticles showed that both patients had elevated levels on two occasions. RBC deformability, blood viscosity and RBC aggregation were normal and similar in both patients. The results demonstrated different coagulation activity in the patients with one patient in a prothrombotic state, suggesting that there may be two levels of hypercoagulability in STr. Measurement of such differences would allow for separation of high and low-risk patients from serious complications.
镰状细胞性状（STr）患者通常被认为是无症状的。然而，已经描述了包括高凝状态、静脉血栓栓塞风险增加以及伴有横纹肌溶解和猝死的运动性运动综合征等并发症。这些不良事件的确切原因尚不清楚。我们研究了两名患有STr的单卵双胞胎患者，以确定他们的促凝血活性状态作为血栓形成风险的潜在指标。通过测量凝血酶原片段1 + 2（F1 + 2）和凝血酶 - 抗凝血酶复合物（TAT）来评估体内凝血酶生成。D - 二聚体用作纤溶活性的标志物。使用体外凝血酶生成试验（TGT）确定生成凝血酶的潜力。检查了红细胞（RBC）衍生微粒脱落和RBC流变学的影响。患者2的TAT（>60μg/l）和F1 + 2（948pmol/l）明显升高，但患者1在正常参考范围内（TAT = 2.5μg/l；F1 + 2 = 138pmol/l）。两名患者的D - 二聚体水平（0.9mg/l FEU）同样升高。两名患者的TGT峰值凝血酶和内源性凝血酶潜力（ETP）升高程度相似。对RBC衍生微粒的流式细胞术分析表明，两名患者在两个时间点的水平均升高。两名患者的RBC变形性、血液粘度和RBC聚集均正常且相似。结果表明，两名患者具有不同的凝血活性，其中一名患者处于血栓前状态，这表明STr可能存在两种高凝状态水平。测量这些差异将有助于区分高风险和低风险患者与严重并发症。
