肝素诱导的血小板减少症课件.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,此课件共43页哦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,此课件共43页哦Epidemiologythe chance of significant exposure to heparin exceeds 50%in hospitalized patientsacute coronary syndrome (UA/MI)pulmonary embolismdeep
2、venous thrombosis and prophylaxisatrial fibrillation/strokeheparinized pulmonary wedge cathetersPCIIABPSemi Thromb Hemost 1999;25 Suppl 1:57-60第3页,此课件共43页哦U.S.Estimated Causes of Accidental Deaths 1000 100040,00040,00090,00090,000Deaths per year第4页,此课件共43页哦Medication Errors Hospital Audit%REFERENCE第
3、5页,此课件共43页哦血小板减少症(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,此课件共43页哦Heparin-induced ThrombocytopeniaHeparin-induced thrombocytopenia(HIT),an antibody-mediated syndrome,is associated with
4、significant 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,此课件共43页哦Epidemiologythrombocytopenia is one of the most common laboratory abn
5、ormalities 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,此课件共43页哦Cascade of events leading to formation of HIT Cascade of events leading to formation of HIT antibodies and prothrombotic componentsantibodi
6、es and prothrombotic 第9页,此课件共43页哦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,此课件
7、共43页哦Thrombosisthrombosis 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
8、 1996;101:502-7Thromb Haemost 1993;70:554-61第11页,此课件共43页哦Other Clinical FeaturesSkin lesions at heparin injection siteSkin necrosisAcute platelet activation Acute inflammatory reactions(fever,chills,etc.)第12页,此课件共43页哦Skin NecrosisUsed with permission from Warkentin TE.Br J Haematol.1996;92:494497.第1
9、3页,此课件共43页哦Venous 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,此课件共43页哦Morbidity and MortalityHIT-associated mortality is high(about 18%)5%of affected patients require limb amputationOvert bleeding
10、or bruising is rare even with severe thrombocytopeniaAppropriate management can limit morbidity and mortality第15页,此课件共43页哦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 5
11、0%)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17页,此课件共43页哦Risks for HITType Iintravenous high-dose heparinType IIvaries with dose of heparinunfraction
12、ated heparin LMWHbovine porcinesurgical medical patients第18页,此课件共43页哦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,此课件共
13、43页哦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 remove the complexes causing severe thrombocyto
14、penia第20页,此课件共43页哦Comparison 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,此课件共43
15、页哦Common Laboratory 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
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