肝素诱导的血小板减少症课件.ppt
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- 肝素 诱导 血小板 减少 课件
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1、肝素诱导的血小板减少症肝素诱导的血小板减少症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Epidemiology the chance of significant exposure to heparin exceeds 50%in hospitalized patients acute coronary syndrome (UA/MI)pulmonary embolism deep venous thrombosis and prophylaxis atria
2、l fibrillation/stroke heparinized pulmonary wedge catheters PCI IABPSemi Thromb Hemost 1999;25 Suppl 1:57-60020000400006000080000100000AirplanesCarsMedical ErrorsDeaths per year4025201001020304050HeparinInsulinAntibioticsNarcotics%REFERENCE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
3、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HIT 12万人出现血栓并发症(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 Heparin-induced Thrombocytopenia Heparin-induced thrombocytopenia(HIT),an antibody-mediated syndrome,is associated with significant morbidity and mortality considered a rarity in the past unrecognized
4、 by many clinicians diagnoses can be difficult to confirm until recently there was no therapeutic options other than discontinuation of heparinEpidemiology thrombocytopenia is one of the most common laboratory abnormalities found among hospitalized patients serologically proven HIT occurs in 1.5%to
5、3%of patients with heparin exposureN Engl J Med 1995;332:1330-5Cascade of events leading to formation of HIT antibodies and prothrombotic Bleeding and Clotting the most feared consequence in these patients with a low platelet count is not bleeding but clotting present with mucocutaneous bleeding,ran
6、ging from petechiae and ecchymoses to life-threatening gastrointestinal and intracranial hemorrhageThrombosis thrombosis is mostly venous not arterial may result in bilateral deep venous thrombosis of the legs pulmonary embolism venous gangrene of fingers,toes,penis,or nipples myocardial infarction,
7、stroke mesenteric arterial thrombosis limb ischemia and amputationCirculation 1999;100:587-93Am J Med 1996;101:502-7Thromb Haemost 1993;70:554-61Other Clinical Features Skin lesions at heparin injection site Skin necrosis Acute platelet activation Acute inflammatory reactions(fever,chills,etc.)Used
8、with permission from Warkentin TE.Br J Haematol.1996;92:494497.Used with permission from Warkentin TE,Elavathil LJ,Hayward CPM,Johnston MA,Russett JI,Kelton JG.Ann Intern Med.1997;127:804812.HIT-associated mortality is high(about 18%)5%of affected patients require limb amputation Overt bleeding or b
9、ruising is rare even with severe thrombocytopenia Appropriate management can limit morbidity and mortalityHIT Syndrome Type I nonimmunologic 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 th
10、e 50,000-80,000/mm range typical onset of 4-14 days occurs with any dose by any route potential for development of life-threatening thromboembolic complications rarely causes bleedingRisks for HIT Type I intravenous high-dose heparin Type II varies with dose of heparin unfractionated heparin LMWH bo
11、vine porcine surgical medical patientsDiagnosis of HIT absence of another clear cause for thrombocytopenia the timing of thrombocytopenia the degree of thrombocytopenia adverse clinical events(most often thrombocytpenia)positive laboratory tests for HIT antibodiesPathogenesis of Drug-induced thrombo
12、cytopenia Certain drugs(quinine,quinidine,sulfa antibiotics)link non-covalently to platelet membrane glycoproteins very rarely,IgG antibodies are produced that recognize these drug-glycoprotein complexes macrophages remove the complexes causing severe thrombocytopeniaComparison of HIT and other Drug
13、-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 x 109/L,should also raise the suspicion of HIT Common Laboratory Tests for HITTestAdvantagesDisadvantagesPAAR
14、apid and simpleLow sensitivity-not suitable fortesting multiple samplesSRASensitivity 90%Washed platelet(technicallydemanding),needs radiolabeledmaterial 14CHIPARapid,sensitivity 90%Washed plateletsELISA High sensitivity,High cost,lower specificity for clinically significant HITThromb Haemost 1998;7
15、9:1-7platelet aggregation assay(PAA)serotonin release assay(SRA)heparin induced platelet activation(HIPA)Platelet aggregation assay(PAA)performed by many laboratories incubate platelet-rich plasma from normal donors with patient plasma and heparin limited by poor sensitivity and specificity because
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