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1、1抗凝治疗 的实验室监测上海交通大学医学院附属瑞金医院王学锋2A Cell-Based Model of Coagulation and A Cell-Based Model of Coagulation and Potential Targets Potential Targets 3AT+ Xa + IIa (1:1 ratio)普通肝素1930sAT + Xa静脉间接 Xa抑制剂2002IIa口服直接 凝血酶抑制剂2004AT + Xa + IIa (Xa IIa)低分子量肝素1980sII, VII, IX, X (Protein C,S)华法林1940sXa口服直接 Xa抑制剂200
2、8抗凝药物发展史IIa静脉直接 凝血酶抑制剂1990sOAT药物个体差异性v遗传性因素: Hereditary resistance to warfarin 遗传性华法林 抵抗(rare) Race种族 v获得性因素 Variations in the metabolisms of vitamin K, OAT and coagulation factors 维生素K，口服抗凝药和 凝血因子的代谢差异 Pathologies (e.g. renal insufficiency)疾病（肾 功能不全等） Age and weight 年龄和体重 Drugs and diet 药物和饮食AVK 监测
3、PT (1935): w 多种试剂 w 缺乏统一标准 w 室间差异大INR (1984): w 结果的标准化：统一使用ISI w 有所改善，然而vThe goal of the monitoring is to maintain the patient within a narrow therapeutic range 监测目标：维持病人PT在一个狭窄的治疗范围内 PT监测OATApproximate therapeutic rangeRisk of thrombosisSafety / efficacy zone Risk of bleedingPTTherapeutic ranges 有效
4、浓度范围vTherapeutic ranges have been recommended in INR by different representative groups不同的机构推荐使用INR作为治疗范围的监测指标The most widely used come from the ACCP1, the BSCH2 or the GEHT3 Therapeutic ranges given in range or in “target INR” 1. American College of Chest Physicians 2. British Committee for Standar
5、ds in Haematology 3. Groupement dEtude Hmostase et ThromboseTherapeutic ranges OAT适应证及有效浓度范围适用于需长期持续 抗凝的患者 CAP survey 2007 CG-2CSame reagent / Different instruments00,20,40,60,811,2ABCDEFGHIJKLMINR00,511,522,533,5ABCDEFGHIJKLMINRINR 监测- OAT10肝素治疗的实验室监测问题11肝素与低分子量肝素肝素诱导的血小板减少症肝素抵抗常见问题常见问题12OOOOHOCOOO
6、HO OOOHOOHHNSO3HNSO3OCOO -OSO3OSO3OSO3HNSO3OSO3OSO3O OH肝 素 Anticoagulant activity of AT is then enhanced by 1 000AT binds through the pentasaccharideAT-Heparin complex inhibits serine proteases (Xa 134: 3-19目前市场上的3种口服，单一剂量，无需 监测的抗凝药物：两种直接Xa因子抑制剂一种直接IIa因子抑制剂实验室监测或无需实验室监测实验室监测或无需实验室监测无需监测 但 需要检测抗凝活性者
7、特殊人群 v敏感人群，老年人，肾功能受损，肥胖患者 威胁生命的情况 v出血，药物过量可以使用哪些方法全球通用方法 PT APTT特殊方法w 依赖于抗凝靶点 anti-Xa anti-IIaEffect of Rivaroxaban, anti-Xa, on hemostasis testsEffect of Rivaroxaban, anti-Xa, on hemostasis teststesttesteffecteffectPTPT, , Sensitivity depending of the reagent; NO INRSensitivity depending of the rea
8、gent; NO INRaPTTaPTTProlongation Prolongation dependent of the reagent; not sensitivedependent of the reagent; not sensitiveFibrinogen Fibrinogen Clauus: no effect; fromPT: UnderestimationClauus: no effect; fromPT: UnderestimationTTTTNo effectNo effectCoagulant activity of factorsCoagulant activity
9、of factorsUnderestimation of factors level for high concentration of Underestimation of factors level for high concentration of Rivaroxaban; depending of reagentsRivaroxaban; depending of reagents Immunological assays: D-D, Immunological assays: D-D, FDP, factors, inhibitors, FDP, factors, inhibitor
10、s, No effect on measurementNo effect on measurementAT activityAT activityReagents based on anti-Xa: overestimationReagents based on anti-Xa: overestimation Reagents based on anti-IIa: no effect Reagents based on anti-IIa: no effect PC and PS anticoag. activityPC and PS anticoag. activityOverestimati
11、onOverestimationAnti-Xa activityAnti-Xa activitySpecific testSpecific testActivated PC resistanceActivated PC resistancecoagulation timecoagulation time Over estimation of ratio: should not be usedOver estimation of ratio: should not be used F V Leiden, FII 20210A F V Leiden, FII 20210A No effectNo
12、effectAnticardiolipin ABAnticardiolipin AB And anti-And anti- 2GP1 (ELISA)2GP1 (ELISA)Coagulation tests: prolongedCoagulation tests: prolonged Elisa: no effectElisa: no effectEffect of Dabigatran, anti-IIa, on hemostasis testsEffect of Dabigatran, anti-IIa, on hemostasis teststesttesteffecteffectPTP
13、T, , Sensitivity depending of the reagent; NO INRSensitivity depending of the reagent; NO INRaPTTaPTTProlongation Prolongation dependent of the reagent; not sensitivedependent of the reagent; not sensitiveFibrinogen Fibrinogen Underestimation (Clauss +/-, from PT +)Underestimation (Clauss +/-, from
14、PT +)TTTT, , Sensitivity+Sensitivity+Coagulant activity of factorsCoagulant activity of factorsUnderestimation for high concentration of Dabigatran; Underestimation for high concentration of Dabigatran; depending of reagentsdepending of reagents Immunological assays: D-D, Immunological assays: D-D,
15、FDP, factors, inhibitors, FDP, factors, inhibitors, No effect on measurementNo effect on measurementAT activityAT activityReagents based on anti-Xa (amidolytic): no effectReagents based on anti-Xa (amidolytic): no effect Reagents based on anti-IIa: overestimationReagents based on anti-IIa: overestim
16、ation PC and PS anticoag. activityPC and PS anticoag. activityOverestimation of levelsOverestimation of levelsAnti-IIa activityAnti-IIa activitySpecific testSpecific testActivated PC resistanceActivated PC resistancecoagulation timecoagulation time Over estimation of ratio: should not be usedOver estimation of ratio: should not be used F V Leiden, FII 20210A F V Leiden, FII 20210A No effectNo effectAnticardiolipin ABAnticardi
