1止凝血产品线移转移转沃芬中国08 May 2012HemosIL Diluted Russell Viper Venom TimedRVVT ScreendRVVT Confirm狼疮抗凝物试剂（DRVVT)HemosIL Diluted Russell Viper Venom TimedRVVT ScreendRVVT Confirm狼疮抗凝物（DRVVT)4/17/20133内容内容 前言 产品说明 主要特点 研究数据 竞争比较前言前言 狼疮抗凝物（LA）检测对抗磷脂综合征起着举足轻重的作用，当患者体内出现中高滴度的抗心磷脂抗体和抗2糖蛋白I抗体时可被确定为高血栓形成风险。 APS是一种由于体内出现抗磷脂抗体（aPL）导致的自身免疫失调，与血栓和/或妊娠发病率相关。 LA能延长磷脂依赖性凝血实验的凝固时间，从而预示着某种抑制物的存在。4前言前言 最新的LA指南指出，检测LA应该依赖于监测、混合和确诊实验。应分别采用不同的方法学检测两个项目。1.dRVVT被认为对高风险易栓症患者LA具有特异性2.基于硅的APTT需要低浓度的磷脂保证敏感性 LA阳性结果必须在12周后复检，以排除APL的瞬态性。5前言前言 LA阳性结果应考虑在APS的背景下识别高风险的患者。 IL提供两个完整的检测项目，满足国际血栓与止血学会委员会发布的针对狼疮抗凝/磷脂依赖性抗体的LA检测标准*. HemosIL dRVVT Silica Clotting Time LA Positive and Negative Controls ( Mixing Study)*Pengo V, Tripodi A, Reber G, Rand H, Ortel T.L, Galli M and DeGroot P.G. Update of the guidelines for lupus anticoagulant detection. Thromb Haemost 2009;7:1737-17406前言前言 NEW HemosIL dRVVT Screen (PN 0020301500) NEW HemosIL dRVVT Confirm (PN 0020301600)将会取代原来的： HemosIL LAC Screen (PN 0020008000) HemosIL LAC Confirm (PN 0020008200)7产品说明和规格产品说明和规格 dRVVT Screen和dRVVTConfirm是改进的dRVVT试剂用于简化和规范LA的临床评估。DRVVT Screen缺少磷脂, 使其对LA敏感。dRVVT Confirm 添加额外的磷脂 ( bi-layers)，抵消LA，缩短凝固时间。 dRVVT Screen 10 x 2 mL (Lyophilized) dRVVT Confirm 10 x 2 mL (Lyophilized)8dRVVT Screen and Confirm特点特点 在ACL全自动血凝仪上检测 和原来的LAC有相似的性能 和原来的LAC试剂盒的配置一样 使用IL的4ml试剂瓶，每试剂盒比LAC能增加大约30%的检测量（从160到210测试/盒 ACL TOP，扣除死腔量） 条码标签的使用使ACL TOP Family的试剂装载过程进一步自动化，且具有能够跟踪试剂效期等相关功能。9dRVVT 特点特点 提升了 2 8 C 的存储时间，15 days vs 48 hours with LAC 改进了机载稳定性，3 days on TOP Family vs 2 days with LAC. 10In House Method Comparison11In House Method Comparison ACL TOP12差异差异 在in house 研究中，正常与异常LA样本的确定没有差异，这批样本无论是参照CLSI文件使用95% 置信区间或者参照ISTH推荐的99%，两者的cut-off值都有一个特别的正常样本在cut-off值之上，此样本NR对LAC是1.14，对dRVVT是1.15，所以这个样本在LAC和dRVVT NR cut-off 之上，包括95% Cl和99%.13方法学比较方法学比较: dRVVT Screen vs LAC Screen14y = 1.0482x - 3.4966r = 0.992040608010012014016020406080100120140160HemosILLAC(sec)dRVVT(sec)结论结论: 新的dRVVT 与LAC Screen具有优异的相关性， 斜率在10% 以内，r 0.95.方法学比较方法学比较: dRVVT Confirm vs LAC Confirm15y = 0.967x - 0.4431r = 0.972025303540455020253035404550HemosILLAC(sec)dRVVT(sec).结论结论:新的dRVVT Confirm与LAC Confirm具有优异的相关性， 合适的斜率和相关系数方法学比较方法学比较: dRVVT N.R. vs LAC N.R16y = 1.1212x - 0.1303r = 0.980.801.001.201.401.601.802.002.202.402.602.803.003.203.403.603.804.000.801.001.201.401.601.802.002.202.402.602.803.003.203.403.603.804.00HemosILLAC(NR)dRVVT(NR)Conclusion:总体来说新的与LAC 的具有相同的结果临床试验临床试验95 % CI99th383 正常样本253 阳性样本144 非-LA 干扰样本9/383 正常 cut-off = 3744/383 Cut-off = 37996/253 LA 阳性 cut-off = 157111/253 1.23 and LAC is 1.24 The following table shows that LAC has more positives in the NR range of 1.24 and 1.24 to 1.4021943%1.40 136 133 98% Above an NR of 1.40 we have excellent agreement. Incorporating the 99th percentile we see a similar pattern. NR dRVVT 1.33 and LAC 1.32 In the NR range of 1.32 and 1.32 to 1.40 7 3 43% 1.40 136 130 96% Samples above the NR range of 1.40 correlate excellently. Cut-Off at EU Launch cut-off 基于 central 95% ，应用 95% 置信区间. ( 2.5 97.5 percentile, n=153) Noramlized Ratio cut-off 1.13 建议用户应该建立自己的cut-off. 如果遵循ISTH N= 40 ( 50岁) 99thPercentile.21竞争对比竞争对比22HemosILdRVVT ScreendRVVT ConfirmHemosILLAC ScreenLAC ConfirmStagoDRVV ScreenDRVV ConfirmSiemensLA 1 Screen &LA 2 ConfirmAmerican DiagnosticaDVVtest &DVVconfirmPrincipledRVVTdRVVTdRVVTdRVVTdRVVTPackagingdRVVT Screen10 x 2 mLdRVVT Confirm10 x 2 mLLAC Screen10 x 2 mLLAC Confirm10 x 2 mLDRVV Screen12 x 5 mLDRVV Confirm12 x 2 mLLA 1 Screen10 x 2 mLLA 2 Confirm10 x 1 mLDVV test10 x 5 mL10 x 2 mLDVV Confirm10 x 2 mL10 x 1 mLPreparationCLSI Type CLR Water CLSI Type CLR WaterDistilled WaterDistilled WaterDe-ionized WaterReconstitutedStability15 days at 2-8C3 days at 15COn-board ACL TOP Family48 hours at 2-8C3 days at 15COn-board ACL TOP Family1 month at -20 C72 hours On-board7 days 2-8C2 days at 15C8 hours at 37C1 month at -20C24 hours at 20 - 25 C7 days at 2 - 8 C1 month at -20 CInterference ClaimsHeparin (UF and LMW) up to 1 U/mLHemoglobin up to 200 mg/dLTriglycerides up to 500 mg/dLBilirubin up to 10 mg/dLHeparin (UF and LMW) up to 1 U/mLHemoglobin up to 125 mg/dLTriglycerides no claimBilirubin up to 13 mg/dLNo specific interference claims supplied by the manufacturer on the specific package insertNo specific interference claims supplied by the manufacturer on the specific package insertUF Heparin up to 1 U/mLLMW Heparin up to 2 U/mL总结总结 相近的性能与目前的HemosIL LAC Screen PN 0002000800 and HemosIL LAC Confirm PN 0020008200. 相同的规格与目前的HemosIL LAC Screen and HemosIL LAC Confirm: dRVVT Screen : 10 x 2 mL (lyophilized) dRVVT Confirm: 10 x 2 mL (lyophilized) HemosIL dRVVT Screen and HemosIL dRVVT Confirm使用IL的4ml试剂瓶，每试剂盒能增加大约30%的检测量（从160到210测试/盒 ACL TOP，扣除死腔量）23总结总结 条形码管理 稳定性改进 15 days at 2 8 C. 推荐使用质控：HemosIL LA Positive Control PN 0020012500 and HemosIL LA Negative Control PN 0020012600.24材料和要求材料和要求 HemosIL dRVVT Screen PN 0020301500 lot number N0803551 expires May 2012 HemosIL dRVVT Confirm PN 0020301600 lot number N0502703 expires February 2012 TOP Parameters 14.609 is required2526ScreeningConfirmatoryScreeningConfirmatory整合的LA检测项目dRVVT ScreendRVVT ConfirmSCT ScreenSCT ConfirmN.R. cut-off: LA (-)N.R. cut-off: LA (+)N.R. cut-off: SCT (-)N.R. cut-off: SCT (+)PlateletPoor PlasmadRVVT and SCT Results AnalysisdRVVT (-) & SCT (-)dRVVT (+) & SCT (+)dRVVT (+) & SCT (-)dRVVT (-) & SCT (+)No Lupus Anticoagulants-排除因子缺乏或者因子抑制物存在对Normalized ratios的影响的影响-排除肝素对排除肝素对Normalized Ratios.的影响的影响.参阅说明书中肝素的影响细节参阅说明书中肝素的影响细节-口服抗凝药样本可能对口服抗凝药样本可能对Normalized Ratios产生影响产生影响如果以上情况均不存在，患者存在如果以上情况均不存在，患者存在LA的概率极高的概率极高Screen and ConfirmClotting Times 2 SDRangeScreen and Confirm Clotting Times 2 SDRange Mixing studies necessary to investigate factor deficiencies or inhibitors. If mixing test is still prolonged it indicates that some anticoagulant other than LA is present272013携手发展携手发展