血小板減少癥的臨床醫(yī)治

1、血小板減少癥的臨床醫(yī)治PlateletsAdult form of the same undifferentiated stem cell as the RBC and the WBCThrombopoietin (hormone) specializes the stem cell into the thrombocyteDisc shaped without a nucleusHelp slow blood loss from damaged vessels by forming a plugAlso excrete a chemical the enhances more clot fo

2、rmationPlateletsLife spanUsually 5-9 daysAged and dead platelets are removed in the liver and spleen by fixed macrophagesNormal amountsBetween 100,000 and 300,000 in each microliter of blood2-4 micrometers in diameter血小板減少的原因 血小板生成減少或無效死亡遺傳性獲得性: 藥物、惡性腫瘤、感染、電離輻射、再障、MDS等損傷造血干細(xì)胞或影響其在骨髓中增殖所致。這些因素可影響多個(gè)造血

3、細(xì)胞系統(tǒng)，常伴有不同程度貧血，白細(xì)胞減少，骨髓巨核細(xì)胞減少(2) 血小板破壞過多先天性獲得性：免疫性和非免疫性。免疫性血小板破壞過多常見的有特發(fā)性血小板減少和藥物性血小板減少。非免疫性血小板減少包括感染、彌漫性血管內(nèi)凝血、血栓性血小板減少等(3)血小板在脾內(nèi)滯留過多：脾功能亢進(jìn) 重癥感染的發(fā)病過程全身炎癥反應(yīng)綜合征（SIRS）膿毒癥（Sepsis）ARDS多器官功能障礙綜合征 （MODS）膿毒癥性休克（Septic Shock）重度膿毒癥（Severe Sepsis)感染感染嚴(yán)重征象-血小板計(jì)數(shù)ICU中，血小板減少的病人住院時(shí)間長且死亡率高有人發(fā)現(xiàn)23%的危重病人至少有一次血小板計(jì)數(shù)10萬/m

4、m3,10%的病人5萬/mm3外科急診ICU血小板減少的病人38%死亡，而對(duì)照組僅為20%嚴(yán)重膿毒癥(Severe sepsis)定義：合并有器官功能障礙、低灌注或低血壓器官功能障礙: 動(dòng)脈氧分壓低(氧合指數(shù)PO2/FIO2 300)；急性少尿(尿量2.0mg/dl；凝血功能異常(INR1.5或APTT60秒)；血小板減少(血小板計(jì)數(shù)2.0mg/dl或35mmol/L)組織灌注指標(biāo):高乳酸鹽血癥(2mmol/L)血液動(dòng)力學(xué)指標(biāo):動(dòng)脈血壓過低(收縮壓SBP 90 mm Hg,平均動(dòng)脈壓MAP 40 mm Hg) 小兒最常見的出血性疾病，也是最常見的血小板異常性疾病。主要臨床特點(diǎn)為血循環(huán)中存在抗血

5、小板抗體，使血小板破壞過多，血小板減少引起皮膚、粘膜自發(fā)性出血；骨髓巨核細(xì)胞數(shù)正?；蛟龆啵鲅獣r(shí)間延長，血塊收縮不良，束臂試驗(yàn)陽性。 免疫性血小板減少性紫癜(ITP) 基本情況 發(fā)病率高（40100/10萬），沒有明顯的地域和種族差別；中國13億人口中每年發(fā)病人數(shù)將超過50萬，其中急性ITP在兒童多見，發(fā)病高峰年齡2-5歲，無性別差異，常在冬春季病毒感染高峰期發(fā)病較多。慢性ITP 則多見于20-50歲的成人，女性較男性發(fā)病率高3-4倍，發(fā)病無季節(jié)性，但近年來兒童慢性ITP的發(fā)病有增多趨勢，研究顯示部分ITP的發(fā)病與幽門螺旋桿菌(HP)、人類巨細(xì)胞病毒(hCMV)等感染有關(guān)。診斷依據(jù) （1）血小

6、板計(jì)數(shù)100109/L（2）骨髓巨核細(xì)胞增多或正常，有成熟障礙。成熟障礙主要表現(xiàn)為幼稚型和（或）成熟型且無血小板釋放的巨核細(xì)胞比例增加，巨核細(xì)胞顆粒缺乏，胞質(zhì)少。（3）皮膚出血點(diǎn)、淤斑和（或）粘膜出血等臨床表現(xiàn)。（4）急性型脾臟多無腫大（5）具有以下4項(xiàng)中任何1項(xiàng)糖皮質(zhì)激素治療有效；脾切除有效；血清血小板相關(guān)抗體（PAIg或PAC3）陽性；血小板壽命縮短（6）排除其他可引起血小板減少的疾病，如再生障礙性貧血、白血病 、骨髓增生異常綜合征（MDS）、其他免疫性疾病以及藥物性因素臨床分型 急性型 起病急，常有發(fā)熱，出血一般較重，血小板計(jì)數(shù)常20109/L，病程6個(gè)月 慢性型 起病隱匿，出血一般較輕

7、，血小板計(jì)數(shù)常為（3080）109/L，病程6個(gè)月病情分度 輕度 血小板計(jì)數(shù)（BPC）50109/L，一般無自發(fā)出血，僅外傷后易發(fā)生出血或術(shù)后出血過多中度 25109/LBPC50109/L，有皮膚粘膜出血點(diǎn)或外傷后淤斑、血腫、外傷出血延長，但無廣泛出血重度（具備下列一項(xiàng)者即可）10109/LBPC25109/L，皮膚廣泛出血、淤斑或多發(fā)血腫，粘膜活動(dòng)性出血（齒齦滲血、口腔血泡、鼻出血）；消化道、泌尿道或生殖道暴發(fā)出血或發(fā)生血腫壓迫；視網(wǎng)膜出血或咽后壁出血；外傷處出血不止，經(jīng)一般治療無效極重度（具備下列一項(xiàng)即可） BPC10109/L或幾乎查不到，皮膚粘膜廣泛自發(fā)性出血、血腫或出血不止；危及生

8、命的嚴(yán)重出血（包括顱內(nèi)出血）等級(jí) 出血嚴(yán)重程度及生活質(zhì)量 臨床干預(yù)一級(jí) 少量出血，紫癜100個(gè)，和/或5個(gè)、 建議觀察 直徑3cm的小瘀斑，無粘膜出血二級(jí) 輕微出血，紫癜100個(gè)，和/或5個(gè)、 觀察或選擇性治療 直徑3cm的小瘀斑，無粘膜出血三級(jí) 中等量出血，明顯的粘膜出血 臨床干預(yù)使患兒 病情達(dá)一/二級(jí) 四級(jí) 粘膜出血或懷疑有內(nèi)部出血 緊急臨床干預(yù)Primary ITP Primary ITP is an autoimmune disorder characterized by isolated thrombocytopenia(peripheral blood platelet count

9、100 x109/L) in the absence of other causes or disorders that maybe associated with thrombocytopenia. The diagnosis of primary ITP remains one of exclusion; no robust clinical or laboratory parameters are currently available to establish its diagnosis with accuracy. The main clinical problem of prima

10、ry ITP is an increased risk of bleeding, although bleeding symptoms may not always be present.Secondary ITP All forms of immune-mediated thrombocytopenia except primary ITP*Proposed definitions of diseaseBLOOD, 12 MARCH 2009 VOLUME 113, NUMBER 11Standardization of terminology, definitions and outcom

11、e criteria in immune thrombocytopenic purpura of adults and children: report from an international working group *The acronym ITP should be followed by the name of the associated disease (for thrombocytopenia after exposure to drugs, the terms “drug-induced” should be used)in parentheses: for exle,

12、“secondary ITP (lupus-associated),” “secondary ITP(HIV-associated),” and “secondary ITP (drug-induced).” For manuscript titles, abstracts,and so on, definitions such as lupus-associated ITP or HIV-associated ITPcan also be used.BLOOD, 12 MARCH 2009 VOLUME 113, NUMBER 11Phases of the disease 1. Newly

13、 diagnosed ITP within 3 months from diagnosis2.Persistent ITP between 3 to 12 months from diagnosis. Includes patients not reachingspontaneous remission or not maintaining complete response off therapy.3.Chronic ITP lasting for more than 12 months4.Severe ITP Presence of bleeding symptoms atpresenta

14、tion sufficient to mandate treatment, or occurrence of new bleeding symptoms requiringadditional therapeutic intervention with a different platelet-enhancing agent or an increased doseBLOOD, 12 MARCH 2009 VOLUME 113, NUMBER 11難治性ITP的診斷標(biāo)準(zhǔn)國際協(xié)作組：脾切除無效或有效后復(fù)發(fā)存在嚴(yán)重的ITP或需要治療(包括但不局限于低劑量的皮質(zhì)激素)的嚴(yán)重出血。僅需單獨(dú)應(yīng)用常規(guī)或附

15、加治療的病人不是難治性的除外其他引起血小板減少的疾病。國內(nèi)采用的標(biāo)準(zhǔn): 病程6個(gè)月, 正規(guī)皮質(zhì)激素治療無效及達(dá)那唑、其它常用免疫抑制劑或脾切除無效, 血小板計(jì)數(shù) 1年 年齡 5歲 血小板持續(xù) 30 109 /L 長期或間斷處于重度出血 藥物治療無效或需長期大劑量激素維持 Individual agents for treatment of ITP and the time to the first and peak responses Agent/treatment Reported dose range Time to initial response* Time to peak respo

16、nse*Pred. 1-4 mg/kg po/dx1-4 w 4-14 d 7-28 dDex. 40 mg po or iv/dx4 d(4-6 courses every 14-28 d) 2-14 d 4-28 dIVIg 0.4-1 g/kg per dose iv (1-5 doses) 1-3 d 2-7 dAnti-D 75 g/kg per dose iv 1-3 d 3-7 dRituximab 375 mg/m2 per dose iv (4 weekly doses) 7-56 d 14-180 dSplenectomy Laparoscopic 1-56 d 7-56 dVincristine up to 2 mg/dose iv (4-6 weekly doses) 7-14 d 7-42 dVinblastine 0.1 mg/kg per dose iv (6 weekly doses) 7-14 d 7-42