肝素诱导的血小板减少症课件

Click to edit Master title style,Click to edit Master text styles kbb,Second level,Third level,Fourth level,Fifth level,肝素诱导的血小板减少症,史旭波,首都医科大学同仁医院,肝素诱导的血小板减少症,XIa,XIIa,IXa,VIIa-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,Xa,VIIIa,Va,内源性凝血系统,外源性凝血系统,凝血与抗凝系统,XIaXIIaIXaVIIa-III组织因子途径抑制物抗,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,atrial fibrillation/stroke,heparinized pulmonary wedge catheters,PCI,IABP,Semi Thromb Hemost 1999;25 Suppl 1:57-60,Epidemiologythe chance of sign,U.S.Estimated Causes of Accidental Deaths,1000,40,000,90,000,Deaths per year,U.S.Estimated Causes of Accid,Medication Errors Hospital Audit,%,REFERENCE,Medication Errors Hospital A,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,HIT,12,万人出现血栓并发症（静脉、动脉）,3.6万人死亡,血小板减少症（HIT/HITS）,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 by many clinicians,diagnoses can be difficult to confirm,until recently there was no therapeutic options other than discontinuation of heparin,Heparin-induced Thrombocytopen,Epidemiology,thrombocytopenia is one of the most common laboratory abnormalities found among hospitalized patients,serologically proven HIT occurs in 1.5%to 3%of patients with heparin exposure,N Engl J Med,1995;332:1330-5,Epidemiologythrombocytopenia i,Cascade of events leading to formation of HIT antibodies and prothrombotic components,Cascade of events leading to f,Bleeding and Clotting,the most feared consequence in these patients with a low platelet count is not bleeding but,clotting,present with mucocutaneous,bleeding,ranging from petechiae and ecchymoses to life-threatening gastrointestinal and intracranial hemorrhage,Bleeding and Clottingthe most,Thrombosis,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,stroke,mesenteric arterial thrombosis,limb ischemia and amputation,Circulation 1999;100:587-93Am J Med 1996;101:502-7Thromb Haemost 1993;70:554-61,Thrombosisthrombosis is mostly,Other Clinical Features,Skin lesions at heparin injection site,Skin necrosis,Acute platelet activation,Acute inflammatory reactions(fever,chills,etc.),Other Clinical FeaturesSkin le,Skin Necrosis,Used with permission from Warkentin TE.,Br J Haematol,.1996;92:494497.,Skin NecrosisUsed with permiss,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.,Venous Limb Gangrene Used with,Morbidity and Mortality,HIT-associated mortality is high(about 18%),5%of affected patients require limb amputation,Overt bleeding or bruising is rare even with severe thrombocytopenia,Appropriate management can limit morbidity and mortality,Morbidity and MortalityHIT-ass,HIT 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 the 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 bleeding,HIT SyndromeType II,Risks for HIT,Type I,intravenous high-dose heparin,Type II,varies with dose of heparin,unfractionated heparin LMWH,bovine porcine,surgical medical patients,Risks for HITType I,Diagnosis 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 antibodies,Diagnosis of HITabsence of ano,Pathogenesis of Drug-induced thrombocytopenia,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 thrombocytopenia,Pathogenesis of Drug-induced,Comparison of HIT and other Drug-Induced Thrombocytopenia,HIT,Quinine/Sulfa,Frequency1/1001/10,000,Onset5-8 days,7 days,Platelet count20-150 x10,9,/L50%that begins after 5 days of heparin therapy,but with the platelet count 150 x 10,9,/L,should also raise the suspicion of HIT,Other Clinical Features,Common Laboratory Tests for HIT,TestAdvantagesDisadvantages,PAARapid and simpleLow sensitivity-not suitable for,testing multiple samples,SRASensitivity 90%Washed platelet(technically,demanding),needs radiolabeled,material,14,C,HIPARapid,sensitivity 90%Washed platelets,ELISA,High sensitivity,High cost,lower specificity for,clinically significant HIT,Thromb Haemost 1998;79:1-7,platelet aggregation assay(PAA),serotonin release assay(SRA),hepari