1、關(guān)于肝素誘導(dǎo)的血小板減少癥第一張，PPT共四十五頁，創(chuàng)作于2022年6月XIaXIIaIXaVIIa - III組織因子途徑抑制物抗凝血酶IIa纖維蛋白原纖維蛋白蛋白C，蛋白S系統(tǒng)XaVIIIaVa內(nèi)源性凝血系統(tǒng)外源性凝血系統(tǒng)凝血與抗凝系統(tǒng)第二張，PPT共四十五頁，創(chuàng)作于2022年6月Epidemiologythe chance of significant exposure to heparin exceeds 50% in hospitalized patientsacute coronary syndrome (UA / MI)pulmonary embolismdeep venous

2、thrombosis and prophylaxisatrial fibrillation / strokeheparinized pulmonary wedge cathetersPCIIABPSemi Thromb Hemost 1999;25 Suppl 1:57-60第三張，PPT共四十五頁，創(chuàng)作于2022年6月U.S. Estimated Causes of Accidental Deaths 100040,00090,000Deaths per year第四張，PPT共四十五頁，創(chuàng)作于2022年6月Medication Errors Hospital Audit%REFERENCE

3、第五張，PPT共四十五頁，創(chuàng)作于2022年6月血小板減少癥（HIT/HITS） 美國每年有1200萬人因肢體或肺部血栓、心臟病或血管成型術(shù)而接受肝素治療36萬人發(fā)生HIT12萬人出現(xiàn)血栓并發(fā)癥（靜脈、動脈）3.6萬人死亡 第六張，PPT共四十五頁，創(chuàng)作于2022年6月Heparin-induced ThrombocytopeniaHeparin-induced thrombocytopenia (HIT), an antibody-mediated syndrome, is associated with significant morbidity and mortalityconsidere

4、d a rarity in the pastunrecognized by many cliniciansdiagnoses can be difficult to confirmuntil recently there was no therapeutic options other than discontinuation of heparin第七張，PPT共四十五頁，創(chuàng)作于2022年6月Epidemiologythrombocytopenia is one of the most common laboratory abnormalities found among hospitaliz

5、ed patientsserologically proven HIT occurs in 1.5% to 3% of patients with heparin exposureN Engl J Med 1995;332:1330-5第八張，PPT共四十五頁，創(chuàng)作于2022年6月Cascade of events leading to formation of HIT antibodies and prothrombotic components第九張，PPT共四十五頁，創(chuàng)作于2022年6月Bleeding and Clottingthe most feared consequence in

6、 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第十張，PPT共四十五頁，創(chuàng)作于2022年6月Thrombosisthrombosis is mostly venous not arterialmay result in bila

7、teral 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;101:502-7Thromb Haemost 1993;70:554-61第十一張，PPT共四十五頁，創(chuàng)作于2022年6月O

8、ther Clinical FeaturesSkin lesions at heparin injection siteSkin necrosisAcute platelet activation Acute inflammatory reactions (fever, chills, etc.)第十二張，PPT共四十五頁，創(chuàng)作于2022年6月Skin NecrosisUsed with permission from Warkentin TE. Br J Haematol. 1996;92:494497.第十三張，PPT共四十五頁，創(chuàng)作于2022年6月Venous Limb Gangrene

9、 Used with permission from Warkentin TE, Elavathil LJ, Hayward CPM, Johnston MA, Russett JI, Kelton JG. Ann Intern Med. 1997;127:804812.第十四張，PPT共四十五頁，創(chuàng)作于2022年6月Morbidity and MortalityHIT-associated mortality is high (about 18%)5% of affected patients require limb amputationOvert bleeding or bruising

10、 is rare even with severe thrombocytopeniaAppropriate management can limit morbidity and mortality第十五張，PPT共四十五頁，創(chuàng)作于2022年6月HIT SyndromeType Inonimmunologic mechanisms (mild direct platelet activation by heparin)associated with an early (within 4 days) and usually mild decrease in platelet count (rare

11、ly 50%)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第十七張，PPT共四十五頁，創(chuàng)作于2022年6月Risks for HITType Iintravenous high-dose heparinType IIvaries with dose of

12、 heparinunfractionated heparin LMWHbovine porcinesurgical medical patients第十八張，PPT共四十五頁，創(chuàng)作于2022年6月Diagnosis of HITabsence of another clear cause for thrombocytopeniathe timing of thrombocytopeniathe degree of thrombocytopeniaadverse clinical events (most often thrombocytpenia)positive laboratory tes

13、ts for HIT antibodies第十九張，PPT共四十五頁，創(chuàng)作于2022年6月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 r

14、emove the complexes causing severe thrombocytopenia第二十張，PPT共四十五頁，創(chuàng)作于2022年6月Comparison of HIT and other Drug-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

15、x 109/L, should also raise the suspicion of HIT 第二十三張，PPT共四十五頁，創(chuàng)作于2022年6月Common Laboratory Tests for HITTestAdvantagesDisadvantagesPAARapid and simpleLow sensitivity - not suitable fortesting multiple samplesSRASensitivity 90%Washed platelet (technicallydemanding), needs radiolabeledmaterial 14CHIPA

16、Rapid, sensitivity 90% Washed plateletsELISAHigh sensitivity,High cost, lower specificity for clinically significant HITThromb Haemost 1998;79:1-7platelet aggregation assay (PAA)serotonin release assay (SRA)heparin induced platelet activation (HIPA)第二十四張，PPT共四十五頁，創(chuàng)作于2022年6月Functional AssayPlatelet a

17、ggregation assay (PAA)performed by many laboratoriesincubate platelet-rich plasma from normal donors with patient plasma and heparinlimited by poor sensitivity and specificity because heparin can activate platelets under these conditions, even in the absence of HIT antibodies第二十五張，PPT共四十五頁，創(chuàng)作于2022年6

18、月Antigen AssayAntibodies against heparin/PF4 complexes (the major antigen of HIT) are measured by colorimetric absorbanceTwo ELISA have been developedStagoGTIlimited by high cost第二十六張，PPT共四十五頁，創(chuàng)作于2022年6月Management of HITrisk for thrombosis is high in HIT, prevention of thrombosis is the goal of inte

19、rventionheparin is contraindicated in patients with HITdiscontinuation of heparin - all sources of heparin must be eliminatedmost patients will require treatment with an alternate anticoagulant forinitial clinical problemHIT induced thrombosis第二十七張，PPT共四十五頁，創(chuàng)作于2022年6月HIT 處理措施藥物 可用 禁用 評價華法令 xwarfarin

20、 in the absence of an anticoagulantcan precipitate venous limb gangrene補(bǔ)充血小板 xinfusing platelets merely “adds fuel to the fire”靜脈濾器 xoften results in devastating caval, pelvic, andlower leg venous thrombosis低分子肝素 xlow molecular weight heparin usually cross-react with unfractionated heparin after HIT

21、 or HITTS (HIT thrombosis syndrome) has occurred水蛭素/阿加曲班 xBeware renal insufficiency, antibody formation血漿置換 xremoves micro-particles formed from plateletactivation; not a standard indication 阿司匹林 x can inhibit platelet activation by HIT 氯吡格雷 x antibodies Gp2b/3a受體 x 阻滯劑第二十八張，PPT共四十五頁，創(chuàng)作于2022年6月Step

22、s to Prevent HITporcine heparin preferred over bovine heparinLMWH preferred over unfractionated heapirnoral anticoagulation should be started as early as possible to reduce the duration of heparin exposureintravenous adapters should not be flush with heparinmonitoring serial plate counts for develop

23、ing thrombocytopenia第二十九張，PPT共四十五頁，創(chuàng)作于2022年6月第七次ACCP抗栓和溶栓會議肝素誘導(dǎo)的血小板減少癥防治指南第三十張，PPT共四十五頁，創(chuàng)作于2022年6月HIT監(jiān)測血小板計數(shù)接受治療劑量UFH患者，建議隔日血小板計數(shù)，直到第14天或直至停用UFH(2C級)100天內(nèi)接受過UFH治療的患者或既往是否使用過UFH的病史不詳者，再次開始使用UFH或LMWH時，建議先進(jìn)行血小板計數(shù)，隨后在肝素治療后的24小時以內(nèi)再次血小板計數(shù)(2C級)第三十一張，PPT共四十五頁，創(chuàng)作于2022年6月HIT監(jiān)測血小板計數(shù) 靜脈UFH注射后30min內(nèi)出現(xiàn)發(fā)熱、寒戰(zhàn)、呼吸困難、

24、或其他不常見的癥狀體征，建議立即進(jìn)行血小板計數(shù)，并與先前的計數(shù)值進(jìn)行比較(1C級) 第三十二張，PPT共四十五頁，創(chuàng)作于2022年6月HIT監(jiān)測血小板計數(shù) HIT發(fā)生率不高患者（0.1-1%）下列患者建議術(shù)后4-14天，至少隔2-3天進(jìn)行血小板計數(shù)（或直到停用UFH）(2C級) 內(nèi)科/產(chǎn)科患者預(yù)防性使用UFH 術(shù)后患者預(yù)防性使用LMWH UFH沖洗穿刺導(dǎo)管 或內(nèi)科/產(chǎn)科患者使用過UFH后接受LMWH治療第三十三張，PPT共四十五頁，創(chuàng)作于2022年6月HIT監(jiān)測血小板計數(shù) HIT發(fā)生率很低患者（0.1%）僅接受LMWH治療的內(nèi)科/產(chǎn)科患者或僅在血管內(nèi)介入治療中使用UFH的患者（HIT危險0.1

25、%），建議臨床醫(yī)師不常規(guī)使用血小板監(jiān)測(2C級) 第三十四張，PPT共四十五頁，創(chuàng)作于2022年6月HIT監(jiān)測血小板計數(shù) HIT抗體篩查使用肝素的患者，如果無血小板減少癥、血栓形成、肝素誘發(fā)的皮膚改變或其他HIT相關(guān)的情況，不建議常規(guī)監(jiān)測HIT抗體(1C級)第三十五張，PPT共四十五頁，創(chuàng)作于2022年6月HIT治療 非肝素類抗凝藥物治療HIT高度懷疑（或確診）HIT，無論是否合并血栓栓塞，建議選用另外一種非肝素抗凝劑，如來匹盧定（1C級），阿加曲班（1C級），比伐盧定（2C級），或達(dá)那肝素（1B級）,而不是繼續(xù)使用UFH或LMWH，也不建議不使用抗凝劑（有或無下腔靜脈濾器）。第三十六張，PPT共四十五頁，創(chuàng)作于2022年6月HIT治療 非肝素類抗凝藥物治療HIT高度懷疑（或確診）HIT，無論是否有下肢DVT的臨床證據(jù)，建議常規(guī)下肢靜脈超聲以明確是否存在DVT（IC級） 第三十七張，PPT共四十五頁，創(chuàng)作于2022年6月HIT治療 VKAs 高度懷疑或確診HIT的患者建議不使用維生素K拮抗劑（香豆素），直至血小板計數(shù)明顯恢復(fù)（如至少100109/L，最好150109/L）VKA僅用于替換抗凝劑時的重疊期（最少重疊5天），起始劑量小，替換使用的抗凝劑直到血小板計數(shù)恢復(fù)至穩(wěn)定狀態(tài)時，或至少最近2天的INR達(dá)到靶治療目標(biāo)范圍內(nèi)才能停用（IC級）第三十八張，PPT共四十五頁，創(chuàng)作于