《肝素相关性血小板减少的预防及对策ppt课件.ppt》由会员分享，可在线阅读，更多相关《肝素相关性血小板减少的预防及对策ppt课件.ppt（44页珍藏版）》请在三一办公上搜索。
1、肝素相关性血小板减少的预防及对策,临床实例,73岁，男性2型糖尿病合并肾衰右颈内静脉置管透析普通肝素抗凝第六次导管不畅经处理后无效更换导管继续肝素抗凝/肝素水封管ELISA for HIT(+)随后两次无肝素，生理盐水冲洗，导管压力上升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,认识HIT的必要性和诊断思路HIT的预防措施HIT的治疗对策,血液净化、PCI、CABG、骨科术后,肝素/低分子肝素的广泛应用,预防性,治疗性,肝素广泛应用,基本概念,肝素相关性血
2、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HIT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,“common” (or “frequent”): 1%“infrequent” (or “uncommon”): 0.11%“rare”: 0.1%,Council for International Organization
3、of Medical Sciences(CIOMS). Benefit-risk balance for marketed drugs: evaluating safety signals. Switzerland, 1998,HIT 发生率高-国外,N Engl J Med, 2006; 355:809-17,Heparin: unfractionated heparin,UFH,血小板减少患者血栓事件发生率高,Warkentin TE, et al. N Engl J Med,1995,332:1330-5,Randomized, double-blind clinical trial,
4、prophylaxis after hip surgery,HIT-临床诊断的可能只是冰山一角,Alexander Wahba, MMCTS, 2010.004481,HIT的发生增加住院时间和费用,To evaluate the financial impact of HITA case-control study, 22 case patients and 255 control subjectsHIT case patients: a financial loss of $14,387 per patient an increase in length of stay of 14.5 d
5、ays,Smythe MA, et al. Chest, 2008; 134: 568-573,说明书-法律依据,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HIT!,HIT分型,Cooney NF. Critical Care nurse,2006;26:30-36,免疫型HIT发病机制,Jang IK and Hursting MJ. Circulation, 2005;111:2671-83,Virchows三联症：血流淤滞、血管损伤和高
6、凝状态,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)停用肝素后414天血小板恢复血栓形成,Arepally GM and Ortel TL. N Engl J Med, 2006;355:809-17,罕见出血,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)呼吸心跳骤停(HIT继用肝素),Warkentin TE，et al. Chest, 2005;127:1857-61,HIT 诊断流程,N Engl J Med, 2006,355:
7、809-17,血小板监测,Warkentin TE and Greinacher A. Chest,2004,126:311-337,抗体检测,Cooney NF. Critical Care nurse,2006;26:3036,抗体检测,Warkentin TE and Greinacher A. Chest,2004,126:311-337,#: N Engl J Med, 2006,355:809-17,SRA: “gold standard” Chest 2009;135:1651-1664,下肢B超检查,For patients with strongly suspected or
8、 confirmed HIT, whether or not there is clinical evidence of lower-limb DVTRecommend routine ultrasonography of the lower-limb veins for investigation of DVT (Grade 1C),Chest 2008, 133(suppl):340S-380S,可疑HIT患者“4T”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 Pu
9、lm Med, 2008;14(5): 397-402,Haematologica, 2012;97(1):89-97,“4T”可用于HIT的阴性排除,血小板减少的原因,假性血小板减少 血液稀释血小板生成减少 病毒感染累及骨髓、化放疗、骨髓增生不良血小板破环增加 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 万古,内容概要,认识HIT的必要性和诊断思路HIT的预防措施HIT的治疗对策,HIT预防策略,提高认识和警惕性使用肝素抗凝者监测血小板,提高认识和警惕性使用肝素抗凝者监测血小板,关注HIT发生的危险因素,Warkentin TE
10、, et al. Blood, 2006, 108: 2937-2941,牛UFH猪UFH Ann Thorac Surg, 2003, 75:17-22,HIT预防策略,HIT预防策略,高危患者使用低分子肝素替代普通肝素缩短普通肝素使用的时间(57天)高度怀疑HIT时停用肝素(包括肝素水冲洗)建立HIT档案(HIT card),HIT card,内容概要,认识HIT的必要性和诊断思路HIT的预防措施HIT的治疗对策,基本治疗方案,*Semin Hematol, 1999,36: 29-32 #Hematology, 2004, 390-406,Strategies in heparin-in
11、duced thrombocytopenia,停用所有肝素静脉用非肝素类抗凝剂合适后续口服华发林避免预防性血小板输注,Alexander Wahba, MMCTS, 2011; 2011: 4481,选择性非肝素抗凝剂,Direct thrombin inhibitors lepirudin(重组水蛭素或来匹卢定 ) argatroban(阿加曲班) bivalirudin(比伐卢定)Anti-factor Xa agents danaparoid* (达那肝素) Fondaparinux(磺达肝素),N Engl J Med, 2006,355:809-17Chest 2009, 135:1
12、651-64,Xa Va Ca2+ PL,凝血酶原 凝血酶,纤维蛋白原 纤维蛋白单体 稳定的纤维蛋白,*:美国FDA未批准国内上市：阿加曲班,重组水蛭素 vs 阿加曲班,Cooney NF. Critical Care nurse,2006,26:3036,肾衰并发HIT患者抗凝选择,Argatroban: ideal alternative to heparin not excreted by the kidneys not require dose adjustmentLepirudin: 0.08mg/kg(dialysis) 0.0060.025mg/kg/h(CVVH)Danapar
13、oid: 2500U bolus, 200600U/h(CVVH),Blood,2003, 101(1):31-37,合并HIT患者CPB时抗凝选择,合并HIT患者介入治疗时抗凝选择,J Neurointervent Surg, 2010,58岁男性，慢性肾衰，肝功能不全，DVT，应用肝素3天后发生HIT,Ann Pharmacother,2012;46:000,肝素再应用,For patients with a history of HIT who are HIT antibody negative and require cardiac surgery,we recommend the u
14、se of UFH over anonheparin anticoagulant (Grade 1B). Chest 2008; 133(suppl):340S-380S,243 pats, 144 patients initially had positive tests for heparin-dependent antibodies,N Engl J Med, 2001;344:1286-92,50 days(95%CI 3264),85 days (95%CI 64124),华发林的使用,HIT早期不要单独使用华发林 诱发微血管血栓形成 下肢坏疽（蛋白C、蛋白S水平下降） 等血小板恢复
15、(100150109/L)后使用 与非肝素抗凝剂叠加使用至少45天维持 INR 2.0 连续2天以上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,For patients with strongly suspected or confirmed HIT who do not have active bleeding, we suggest that prophylactic platel
16、et transfusions should not be given (Grade 2C) Chest 2008; 133(suppl):340S-380S HIT 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-延误诊断，导致死亡,73岁，男性2型糖尿病合并肾衰右颈内静脉置管透析普通肝
17、素抗凝第六次导管不畅经处理后无效更换导管继续肝素抗凝/肝素水封管ELISA for HIT(+)随后两次无肝素，生理盐水冲洗，导管压力上升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 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 !,
