凝血酶生成试验在遗传性凝血因子缺陷症患者出血评估中的价值

Thrombin generation test in estimating the clinical bleeding of patients with inherited coagulation factor deficiencies

目的探讨遗传性凝血因子V(FV)、X(FX)和XI(FXI)缺陷及FV和凝血因子VⅢ(FVⅢ)联合缺陷(F5F8D)患者的血浆凝血因子活性、凝血酶生成曲线各参数和临床出血症状之间的关系。方法采集遗传性FV(n=24)、FX(n=14)和FXI(n=18)缺陷及F5F8D(n=8)患者及携带者的外周血进行常规出凝血检查及自动校正凝血酶曲线法凝血酶生成试验。结果凝血酶生成曲线的各项参数与FV促凝活性(FV:C)及FX促凝活性(FX:C)存在双曲线趋势关系。FV或FX缺陷患者血浆中缺陷因子的活性只要达到正常人的3%,凝血酶生成潜力和峰值就达到正常值的一半以上。FV:C≤6.9%或FX:C≤2.2%的患者具有出血症状,活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、延迟时间及达峰时间都有不同程度的延长。具有重度出血症状的3例患者的缺陷因子(FV或FX)活性均≤1.5%,APTT、PT、延迟时间和达峰时间都明显延长,且ETP=0。结论凝血酶生成试验的各项参数与凝血因子FV、FX活性及出血症状的发生及严重程度具有相关性,凝血酶生成试验结合APTT、PT及凝血因子活性可以作为评估遗传性凝血因子缺陷症患者出血倾向的有效手段。

Objective We investigated the relation between clotting factor activity,the parameters of the thrombin generation curve（the thrombogram） and the severity of clinically observed bleeding in patients with inherited deficiency of factor V（FV）,factor X（FX） and factor XI（FXI）,and combined deficiency of coagulation factor V and factor VⅢ（F5F8D）.Methods Venous blood samples were collected from the patients and carriers with inherited deficiency of FV（n=24）,FX（n=14） and FXI（n=18） and F5F8D（n=8）,and routine coagulation tests and calibrated automated thrombin generation measurement were conducted.Results The parameters of thrombin generation test varied hyperbolically with the coagulation activity of FV and FX,respectively.Endogenous thrombin potential（ETP） and peak height obtained more than half normal ETP and peak height respectively,in FV deficient patients with FV：C≥3% or FX deficient patients with FX：C≥3%.The patients with FV：C≤6.9% or FX：C≤2.2% had prolonged activated partial thromboplastin time（APTT）,prothrombin time（PT）,lag time and time to peak,and had bleeding symptoms.In all the 3 patients with severe bleeding symptoms,the activity of deficient factor was less than 1.5%,the ETP approached to zero,and APTT,PT,lag time and time to peak all lengthened.Conclusion The properties of the thrombogram were correlated with the levels of clotting factors and the occurrence and severity of bleeding symptoms in patients with inherited deficiencies of FV or FX.The thrombin generation measurement,combined with APTT and PT,can be used as an indicator of the bleeding tendency in rare inherited deficiencies of coagulation factors.