肝素相关性血小板减少的预防及对策.ppt

肝素相关性血小板减少肝素相关性血小板减少的预防及对策的预防及对策临床实例临床实例n73岁，男性n2型糖尿病合并肾衰n右颈内静脉置管透析n普通肝素抗凝n第六次导管不畅经处理后无效更换导管n继续肝素抗凝/肝素水封管nELISA for HIT(+)n随后两次无肝素，生理盐水冲洗，导管压力上升n第三次无肝素透析几分钟后突发血压下降，紫绀，心跳骤停，复苏无效 Davenport A.Nephrol Dial Transplant,2006;21:1721-24内容概要内容概要n认识认识HIT的必要性和诊断思路的必要性和诊断思路nHIT的预防措施的预防措施nHIT的治疗对策的治疗对策血液净化、血液净化、PCI、CABG、骨科术后、骨科术后肝素肝素/低分子肝素的广泛应用低分子肝素的广泛应用预防性预防性治疗性治疗性肝素广泛应用肝素广泛应用基本概念基本概念n肝素相关性血小板减少肝素相关性血小板减少(Heparin-Induced Thrombocytopenia,HIT)指患者使用肝素后不久或在肝素治疗过程中出现的血小板减少 (150109/L 或 比基础值下降 50%)可引起血栓形成，造成肢体及器官血栓栓塞，严重者危及生命nHIT伴血栓形成综合征伴血栓形成综合征(HIT with thrombosis syndrome,HITTS)药物不良事件发生频率的判断药物不良事件发生频率的判断“common”(or“frequent”):1%“infrequent”(or“uncommon”):0.11%“rare”:0.1%Council for International Organization of Medical Sciences(CIOMS).Benefit-risk balance for marketed drugs:evaluating safety signals.Switzerland,1998HIT 发生率高发生率高-国外国外TherapyClinical Population at RiskIncidenceof PF4HeparinAntibodies（）Incidenceof HIT（）Heparinnew or remote(100 days)exposure Patients undergoing orthopedic surgery1435Adults undergoing cardiac surgery255012General medical patients8200.83.0LMWHnew or remote(100 days)exposure Medical patientsPatients undergoing surgical or orthopedic procedures2800.9N Engl J Med,2006;355:809-17Heparin:unfractionated heparin,UFH血小板减少患者血栓事件发生率高血小板减少患者血栓事件发生率高Warkentin TE,et al.N Engl J Med,1995,332:1330-5Randomized,double-blind clinical trial,prophylaxis after hip surgeryHIT-临床诊断的可能只是冰山一角临床诊断的可能只是冰山一角Alexander Wahba,MMCTS,2010.004481HIT的发生增加住院时间和费用的发生增加住院时间和费用nTo evaluate the financial impact of HITnA case-control study,22 case patients and 255 control subjectsnHIT case patients:a financial loss of$14,387 per patient an increase in length of stay of 14.5 days Smythe MA,et al.Chest,2008;134:568-573说明书说明书-法律依据法律依据n肝素：不良反应中在用药后8天左右有时可发生明显血小板减少，与抗体产生免疫反应相关，后期可合并脏器栓塞n低分子肝素：不良反应中也偶见血小板减少 有肝素诱导的血小板减少症史患者禁用有必要认识和重视有必要认识和重视HIT!HIT!HIT分型分型Cooney NF.Critical Care nurse,2006;26:30-36免疫型免疫型HIT发病机制发病机制Jang IK and Hursting MJ.Circulation,2005;111:2671-83Virchows三联症：血流淤滞、血管损伤和高凝状态三联症：血流淤滞、血管损伤和高凝状态 临床表现临床表现-1接触肝素或低分子肝素一般510天后血小板下降 (100109/L 或 比基础值下降 50%)(如近期曾用过肝素，发病时间提前)n停用肝素后414天血小板恢复n血栓形成血栓形成Arepally GM and Ortel TL.N Engl J Med,2006;355:809-17罕见出血罕见出血临床表现临床表现-2急性炎症反应 发热、寒战、皮肤潮红肝素导致的皮肤损害肾上腺出血性梗死(肾上腺静脉血栓形成肾上腺静脉血栓形成)呼吸心跳骤停(HIT继用肝素)Warkentin TE，et al.Chest,2005;127:1857-61HIT 诊断流程诊断流程N Engl J Med,2006,355:809-17血小板监测血小板监测Warkentin TE and Greinacher A.Chest,2004,126:311-337抗体检测抗体检测Cooney NF.Critical Care nurse,2006;26:3036抗体检测抗体检测 Diagnostic AssaySensitivity,%Specificity,%EarlyPlatelet FallLatePlatelet FallPF4/heparin ELISA97#955093Platelet SRA9098958097Heparin-induced platelet aggregation assay9098958097Combination of sensitive platelet activation and PF4-dependent antigen assay100958097Warkentin TE and Greinacher A.Chest,2004,126:311-337#:N Engl J Med,2006,355:809-17SRA:“gold standard”Chest 2009;135:1651-1664下肢下肢B超检查超检查nFor patients with strongly suspected or confirmed HIT,whether or not there is clinical evidence of lower-limb DVTnRecommend routine ultrasonography of the lower-limb veins for investigation of DVT (Grade 1C)Chest 2008,133(suppl):340S-380S可疑可疑HIT患者患者“4T”评分系统评分系统中国心血管病研究杂志,2006;4(5):389-390Nephrol Dial Transplant,2006;21:1721-1724Curr Opin Pulm Med,2008;14(5):397-402Haematologica,2012;97(1):89-97“4T”可用于可用于HIT的阴性排除的阴性排除血小板减少的原因血小板减少的原因n假性血小板减少假性血小板减少 血液稀释n血小板生成减少血小板生成减少 病毒感染累及骨髓、化放疗、骨髓增生不良n血小板破环增加血小板破环增加 输血或移植后反应、传染性单核细胞增多症、球囊反搏、药物导致的血小板破环增加、抗心磷脂抗体综合征等利奈唑胺利奈唑胺 万古万古内容概要内容概要n认识认识HIT的必要性和诊断思路的必要性和诊断思路nHIT的预防措施的预防措施nHIT的治疗对策的治疗对策HIT预防策略预防策略n提高认识和警惕性提高认识和警惕性n使用肝素抗凝者监测血小板使用肝素抗凝者监测血小板n提高认识和警惕性提高认识和警惕性n使用肝素抗凝者监测血小板使用肝素抗凝者监测血小板n关注关注HIT发生的危险因素发生的危险因素Overall effect of different typeCommon OR for HIT95%CICommon ORP-valueLowerUpperUFH vs LMHW 5.292.849.86 0.0001Surgical vs Medical3.251.985.35猪UFH Ann Thorac Surg,2003,75:17-22 HIT预防策略预防策略HIT预防策略预防策略n高危患者使用低分子肝素替代普通肝素高危患者使用低分子肝素替代普通肝素n缩短普通肝素使用的时间缩短普通肝素使用的时间(2.0 连续2天以上n疗程取决于是否发生血栓(血小板恢复后24周/36月或更长)Am J Health-Syst Pharm 2008,65:1144-7 Chest,2004,126:311-337N Engl J Med,2006,355:809-17血小板输注血小板输注nFor patients with strongly suspected or confirmed HIT who do not have active bleeding,we suggest that prophylactic platelet transfusions should not be given(Grade 2C)Chest 2008;133(suppl):340S-380S nHIT is a hypercoagulable state driven by intense platelet activation.Infusing platelets into a patient with HIT is akin to adding fuel to a raging fire.Chest,2009;135:1651-64 临床实例临床实例-延误诊断，导致死亡延误诊断，导致死亡n73岁，男性n2型糖尿病合并肾衰n右颈内静脉置管透析n普通肝素抗凝n第六次导管不畅经处理后无效更换导管n继续肝素抗凝/肝素水封管nELISA for HIT(+)n随后两次无肝素，生理盐水冲洗，导管压力上升n第三次无肝素透析几分钟后突发血压下降，紫绀，心跳骤停，复苏无效 Davenport A.Nephrol Dial Transplant,2006;21:1721-24小小 结结使用肝素的高危患者应警惕HIT，常规监测血小板计数，低分子肝素发生HIT风险低于普通肝素HIT患者血小板可逆性降低，多伴有血栓形成，肝素-PF4抗体阳性，“4T”评分有助于临床诊断一旦诊断HIT，应停用肝素或低分子肝素，视情况使用非肝素抗凝剂，以及后续口服抗凝剂治疗Thank you!