肝素诱导血小板减少症

1、关于肝素诱导的血小板减少症第一张，PPT共四十五页，创作于2022年6月XIaXIIaIXaVIIa - III组织因子途径抑制物抗凝血酶IIa纤维蛋白原纤维蛋白蛋白C，蛋白S系统XaVIIIaVa内源性凝血系统外源性凝血系统凝血与抗凝系统第二张，PPT共四十五页，创作于2022年6月Epidemiologythe chance of significant exposure to heparin exceeds 50% in hospitalized patientsacute coronary syndrome (UA / MI)pulmonary embolismdeep venous

2、thrombosis and prophylaxisatrial fibrillation / strokeheparinized pulmonary wedge cathetersPCIIABPSemi Thromb Hemost 1999;25 Suppl 1:57-60第三张，PPT共四十五页，创作于2022年6月U.S. Estimated Causes of Accidental Deaths 100040,00090,000Deaths per year第四张，PPT共四十五页，创作于2022年6月Medication Errors Hospital Audit%REFERENCE

3、第五张，PPT共四十五页，创作于2022年6月血小板减少症（HIT/HITS） 美国每年有1200万人因肢体或肺部血栓、心脏病或血管成型术而接受肝素治疗36万人发生HIT12万人出现血栓并发症（静脉、动脉）3.6万人死亡 第六张，PPT共四十五页，创作于2022年6月Heparin-induced ThrombocytopeniaHeparin-induced thrombocytopenia (HIT), an antibody-mediated syndrome, is associated with significant morbidity and mortalityconsidere

4、d a rarity in the pastunrecognized by many cliniciansdiagnoses can be difficult to confirmuntil recently there was no therapeutic options other than discontinuation of heparin第七张，PPT共四十五页，创作于2022年6月Epidemiologythrombocytopenia is one of the most common laboratory abnormalities found among hospitaliz

5、ed patientsserologically proven HIT occurs in 1.5% to 3% of patients with heparin exposureN Engl J Med 1995;332:1330-5第八张，PPT共四十五页，创作于2022年6月Cascade of events leading to formation of HIT antibodies and prothrombotic components第九张，PPT共四十五页，创作于2022年6月Bleeding and Clottingthe most feared consequence in

6、 these patients with a low platelet count is not bleeding but clottingpresent with mucocutaneous bleeding, ranging from petechiae and ecchymoses to life-threatening gastrointestinal and intracranial hemorrhage第十张，PPT共四十五页，创作于2022年6月Thrombosisthrombosis is mostly venous not arterialmay result in bila

7、teral deep venous thrombosis of the legspulmonary embolismvenous gangrene of fingers, toes, penis, or nipplesmyocardial infarction, strokemesenteric arterial thrombosislimb ischemia and amputationCirculation 1999;100:587-93Am J Med 1996;101:502-7Thromb Haemost 1993;70:554-61第十一张，PPT共四十五页，创作于2022年6月O

8、ther Clinical FeaturesSkin lesions at heparin injection siteSkin necrosisAcute platelet activation Acute inflammatory reactions (fever, chills, etc.)第十二张，PPT共四十五页，创作于2022年6月Skin NecrosisUsed with permission from Warkentin TE. Br J Haematol. 1996;92:494497.第十三张，PPT共四十五页，创作于2022年6月Venous Limb Gangrene

9、 Used with permission from Warkentin TE, Elavathil LJ, Hayward CPM, Johnston MA, Russett JI, Kelton JG. Ann Intern Med. 1997;127:804812.第十四张，PPT共四十五页，创作于2022年6月Morbidity and MortalityHIT-associated mortality is high (about 18%)5% of affected patients require limb amputationOvert bleeding or bruising

10、 is rare even with severe thrombocytopeniaAppropriate management can limit morbidity and mortality第十五张，PPT共四十五页，创作于2022年6月HIT SyndromeType Inonimmunologic mechanisms (mild direct platelet activation by heparin)associated with an early (within 4 days) and usually mild decrease in platelet count (rare

11、ly 50%)count in the 50,000 - 80,000 /mm range typical onset of 4-14 days occurs with any dose by any routepotential for development of life-threatening thromboembolic complicationsrarely causes bleeding第十七张，PPT共四十五页，创作于2022年6月Risks for HITType Iintravenous high-dose heparinType IIvaries with dose of

12、 heparinunfractionated heparin LMWHbovine porcinesurgical medical patients第十八张，PPT共四十五页，创作于2022年6月Diagnosis of HITabsence of another clear cause for thrombocytopeniathe timing of thrombocytopeniathe degree of thrombocytopeniaadverse clinical events (most often thrombocytpenia)positive laboratory tes

13、ts for HIT antibodies第十九张，PPT共四十五页，创作于2022年6月Pathogenesis of Drug-induced thrombocytopeniaCertain drugs (quinine, quinidine, sulfa antibiotics) link non-covalently to platelet membrane glycoproteinsvery rarely, IgG antibodies are produced that recognize these drug-glycoprotein complexesmacrophages r

14、emove the complexes causing severe thrombocytopenia第二十张，PPT共四十五页，创作于2022年6月Comparison of HIT and other Drug-Induced Thrombocytopenia HIT Quinine/SulfaFrequency1/1001/10,000Onset5-8 days 7 daysPlatelet count20-150 x109/L50% that begins after 5 days of heparin therapy, but with the platelet count 150

15、x 109/L, should also raise the suspicion of HIT 第二十三张，PPT共四十五页，创作于2022年6月Common Laboratory Tests for HITTestAdvantagesDisadvantagesPAARapid and simpleLow sensitivity - not suitable fortesting multiple samplesSRASensitivity 90%Washed platelet (technicallydemanding), needs radiolabeledmaterial 14CHIPA

16、Rapid, sensitivity 90% Washed plateletsELISAHigh sensitivity,High cost, lower specificity for clinically significant HITThromb Haemost 1998;79:1-7platelet aggregation assay (PAA)serotonin release assay (SRA)heparin induced platelet activation (HIPA)第二十四张，PPT共四十五页，创作于2022年6月Functional AssayPlatelet a

17、ggregation assay (PAA)performed by many laboratoriesincubate platelet-rich plasma from normal donors with patient plasma and heparinlimited by poor sensitivity and specificity because heparin can activate platelets under these conditions, even in the absence of HIT antibodies第二十五张，PPT共四十五页，创作于2022年6

18、月Antigen AssayAntibodies against heparin/PF4 complexes (the major antigen of HIT) are measured by colorimetric absorbanceTwo ELISA have been developedStagoGTIlimited by high cost第二十六张，PPT共四十五页，创作于2022年6月Management of HITrisk for thrombosis is high in HIT, prevention of thrombosis is the goal of inte

19、rventionheparin is contraindicated in patients with HITdiscontinuation of heparin - all sources of heparin must be eliminatedmost patients will require treatment with an alternate anticoagulant forinitial clinical problemHIT induced thrombosis第二十七张，PPT共四十五页，创作于2022年6月HIT 处理措施药物 可用 禁用 评价华法令 xwarfarin

20、 in the absence of an anticoagulantcan precipitate venous limb gangrene补充血小板 xinfusing platelets merely “adds fuel to the fire”静脉滤器 xoften results in devastating caval, pelvic, andlower leg venous thrombosis低分子肝素 xlow molecular weight heparin usually cross-react with unfractionated heparin after HIT

21、 or HITTS (HIT thrombosis syndrome) has occurred水蛭素/阿加曲班 xBeware renal insufficiency, antibody formation血浆置换 xremoves micro-particles formed from plateletactivation; not a standard indication 阿司匹林 x can inhibit platelet activation by HIT 氯吡格雷 x antibodies Gp2b/3a受体 x 阻滞剂第二十八张，PPT共四十五页，创作于2022年6月Step

22、s to Prevent HITporcine heparin preferred over bovine heparinLMWH preferred over unfractionated heapirnoral anticoagulation should be started as early as possible to reduce the duration of heparin exposureintravenous adapters should not be flush with heparinmonitoring serial plate counts for develop

23、ing thrombocytopenia第二十九张，PPT共四十五页，创作于2022年6月第七次ACCP抗栓和溶栓会议肝素诱导的血小板减少症防治指南第三十张，PPT共四十五页，创作于2022年6月HIT监测血小板计数接受治疗剂量UFH患者，建议隔日血小板计数，直到第14天或直至停用UFH(2C级)100天内接受过UFH治疗的患者或既往是否使用过UFH的病史不详者，再次开始使用UFH或LMWH时，建议先进行血小板计数，随后在肝素治疗后的24小时以内再次血小板计数(2C级)第三十一张，PPT共四十五页，创作于2022年6月HIT监测血小板计数 静脉UFH注射后30min内出现发热、寒战、呼吸困难、

24、或其他不常见的症状体征，建议立即进行血小板计数，并与先前的计数值进行比较(1C级) 第三十二张，PPT共四十五页，创作于2022年6月HIT监测血小板计数 HIT发生率不高患者（0.1-1%）下列患者建议术后4-14天，至少隔2-3天进行血小板计数（或直到停用UFH）(2C级) 内科/产科患者预防性使用UFH 术后患者预防性使用LMWH UFH冲洗穿刺导管 或内科/产科患者使用过UFH后接受LMWH治疗第三十三张，PPT共四十五页，创作于2022年6月HIT监测血小板计数 HIT发生率很低患者（0.1%）仅接受LMWH治疗的内科/产科患者或仅在血管内介入治疗中使用UFH的患者（HIT危险0.1

25、%），建议临床医师不常规使用血小板监测(2C级) 第三十四张，PPT共四十五页，创作于2022年6月HIT监测血小板计数 HIT抗体筛查使用肝素的患者，如果无血小板减少症、血栓形成、肝素诱发的皮肤改变或其他HIT相关的情况，不建议常规监测HIT抗体(1C级)第三十五张，PPT共四十五页，创作于2022年6月HIT治疗 非肝素类抗凝药物治疗HIT高度怀疑（或确诊）HIT，无论是否合并血栓栓塞，建议选用另外一种非肝素抗凝剂，如来匹卢定（1C级），阿加曲班（1C级），比伐卢定（2C级），或达那肝素（1B级）,而不是继续使用UFH或LMWH，也不建议不使用抗凝剂（有或无下腔静脉滤器）。第三十六张，PPT共四十五页，创作于2022年6月HIT治疗 非肝素类抗凝药物治疗HIT高度怀疑（或确诊）HIT，无论是否有下肢DVT的临床证据，建议常规下肢静脉超声以明确是否存在DVT（IC级） 第三十七张，PPT共四十五页，创作于2022年6月HIT治疗 VKAs 高度怀疑或确诊HIT的患者建议不使用维生素K拮抗剂（香豆素），直至血小板计数明显恢复（如至少100109/L，最好150109/L）VKA仅用于替换抗凝剂时的重叠期（最少重叠5天），起始剂量小，替换使用的抗凝剂直到血小板计数恢复至稳定状态时，或至少最近2天的INR达到靶治疗目标范围内才能停用（IC级）第三十八张，PPT共四十五页，创作于