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1、肝素诱导的血小板减少症 史旭波 首都医科大学同仁医院,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,Epidemiology,the chance of significant exposure to heparin exceeds 50% in hospitalized patients acute coronary syndrome (UA / MI) pulmonary embolism deep venous thrombosis a
2、nd prophylaxis atrial fibrillation / stroke heparinized pulmonary wedge catheters PCI IABP,Semi Thromb Hemost 1999;25 Suppl 1:57-60,U.S. Estimated Causes of Accidental Deaths, 1000,40,000,90,000,Deaths per year,Medication Errors Hospital Audit,%,REFERENCE,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
3、 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,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
4、 confirm until recently there was no therapeutic options other than discontinuation of heparin,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 M
5、ed 1995;332:1330-5,Cascade of events leading to formation of HIT antibodies and prothrombotic components,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 ecchymos
6、es to life-threatening gastrointestinal and intracranial hemorrhage,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
7、thrombosis limb ischemia and amputation,Circulation 1999;100:587-93 Am J Med 1996;101:502-7 Thromb Haemost 1993;70:554-61,Other Clinical Features,Skin lesions at heparin injection site Skin necrosis Acute platelet activation Acute inflammatory reactions (fever, chills, etc.),Skin Necrosis,Used with
8、permission from Warkentin TE. Br J Haematol. 1996;92:494497.,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.,Morbidity and Mortality,HIT-associated mortality is high (about 18%) 5% of affecte
9、d patients require limb amputation Overt bleeding or bruising is rare even with severe thrombocytopenia Appropriate management can limit morbidity and mortality,HIT Syndrome,Type I nonimmunologic mechanisms (mild direct platelet activation by heparin) associated with an early (within 4 days) and usu
10、ally mild decrease in platelet count (rarely 100 x 109/L) typically recovers within 3 days despite continued use of heparin not associated with any major clinical sequelae occurs primarily with high dose iv heparin,HIT Syndrome,Type II induced by immunologic mechanisms substantial fall in platelet c
11、ount ( 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,Risks for HIT,Type I intravenous high-dose heparin Type II varies with dose of heparin unf
12、ractionated heparin LMWH bovine porcine surgical medical patients,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,Patho
13、genesis 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 thrombocytop
14、enia,Comparison of HIT and other Drug-Induced Thrombocytopenia,HIT Quinine/Sulfa Frequency 1/100 1/10,000 Onset 5-8 days 7 days Platelet count 20-150x109/L 20x109/L Sequelae Thrombosis Bleeding Laboratory Immunoassay Platelet- (heparin/PF4) associated IgG,Unusual Clinical Events Suspicious for HIT,m
15、ild to moderate thrombocytopenia, often in conjunction with thrombosis adrenal hemorrhagic infarction (caused by adrenal vein thrombosis) warfarin-induced venous limb gangrene fever, chills, beginning 5 to 30 minutes after an IV heparin bolus heparin-induced skin lesions associated with HIT antibodi
16、es, even in the absence of thrombocytopania,Other Clinical Features Suspicious for HIT,a rapid drop in platelets may also be indicative of HIT, particularly if the patients received heparin within the previous 3 months a fall in platelet count of 50% 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 HIT,Test Advantages Disadvantages PAA Rapid and simple
