肝素诱导的血小板减少症优秀课件.ppt
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1、肝素肝素肝素肝素诱导诱导的血小板减少症的血小板减少症的血小板减少症的血小板减少症第1页,本讲稿共46页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凝血与抗凝系统第2页,本讲稿共46页Epidemiologythe chance of significant exposure to heparin exceeds 50%in hospitalized patientsacute coronary syndrome (UA/MI)pulmonary embolismdeep ve
2、nous thrombosis and prophylaxisatrial fibrillation/strokeheparinized pulmonary wedge cathetersPCIIABPSemi Thromb Hemost 1999;25 Suppl 1:57-60第3页,本讲稿共46页U.S.Estimated Causes of Accidental Deaths 1000 100040,00040,00090,00090,000Deaths per year第4页,本讲稿共46页Medication Errors Hospital Audit%REFERENCE第5页,本
3、讲稿共46页血小板减少症(血小板减少症(HIT/HITSHIT/HITS)美国每年有美国每年有1200万人因肢体或肺部血栓、心脏病或血管成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型术而接受肝素治疗36万人发生万人发生HIT12万人出现血栓并发症(静脉、动脉)万人出现血栓并发症(静脉、动脉)3.6万人死亡万人死亡 第6页,本讲稿共46页Heparin-induced ThrombocytopeniaHeparin-induced thrombocytopenia(HIT),an antibody-mediated syndrome,is associated with signif
4、icant morbidity and mortalityconsidered 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7页,本讲稿共46页Epidemiologythrombocytopenia is one of the most common laboratory abnormalit
5、ies found among hospitalized patientsserologically proven HIT occurs in 1.5%to 3%of patients with heparin exposureN Engl J Med 1995;332:1330-5第8页,本讲稿共46页Cascade of events leading to formation of HIT antibodies Cascade of events leading to formation of HIT antibodies and prothrombotic componentsand p
6、rothrombotic 第9页,本讲稿共46页Bleeding and Clottingthe most feared consequence in 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10页,本讲稿共46页Throm
7、bosisthrombosis is mostly venous not arterialmay result in bilateral 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:
8、502-7Thromb Haemost 1993;70:554-61第11页,本讲稿共46页Other Clinical FeaturesSkin lesions at heparin injection siteSkin necrosisAcute platelet activation Acute inflammatory reactions(fever,chills,etc.)第12页,本讲稿共46页Skin NecrosisUsed with permission from Warkentin TE.Br J Haematol.1996;92:494497.第13页,本讲稿共46页Ve
9、nous Limb Gangrene Used with permission from Warkentin TE,Elavathil LJ,Hayward CPM,Johnston MA,Russett JI,Kelton JG.Ann Intern Med.1997;127:804812.第14页,本讲稿共46页Morbidity and MortalityHIT-associated mortality is high(about 18%)5%of affected patients require limb amputationOvert bleeding or bruising is
10、 rare even with severe thrombocytopeniaAppropriate management can limit morbidity and mortality第15页,本讲稿共46页HIT SyndromeType Inonimmunologic mechanisms(mild direct platelet activation by heparin)associated with an early(within 4 days)and usually mild decrease in platelet count(rarely 50%)count in the
11、 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17页,本讲稿共46页Risks for HITType Iintravenous high-dose heparinType IIvaries with dose of heparinunfractionated heparin LMW
12、Hbovine porcinesurgical medical patients第18页,本讲稿共46页Diagnosis of HITabsence of another clear cause for thrombocytopeniathe timing of thrombocytopeniathe degree of thrombocytopeniaadverse clinical events(most often thrombocytpenia)positive laboratory tests for HIT antibodies第19页,本讲稿共46页Pathogenesis o
13、f 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 remove the complexes causing severe thrombocytopenia第20页,本讲稿共46页C
14、omparison of HIT and other Drug-Induced Thrombocytopenia HIT Quinine/SulfaFrequency1/1001/10,000Onset5-8 days 7 daysPlatelet count 20-150 x109/L50%that begins after 5 days of heparin therapy,but with the platelet count 150 x 109/L,should also raise the suspicion of HIT 第23页,本讲稿共46页Common Laboratory
15、Tests for HITTestAdvantagesDisadvantagesPAARapid and simpleLow sensitivity-not suitable fortesting multiple samplesSRASensitivity 90%Washed platelet(technicallydemanding),needs radiolabeledmaterial 14CHIPARapid,sensitivity 90%Washed plateletsELISAHigh sensitivity,High cost,lower specificity for clin
16、ically significant HITThromb Haemost 1998;79:1-7platelet aggregation assay(PAA)serotonin release assay(SRA)heparin induced platelet activation(HIPA)第24页,本讲稿共46页Functional AssayPlatelet aggregation assay(PAA)performed by many laboratoriesincubate platelet-rich plasma from normal donors with patient p
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