1、血小板减少症血小板减少症血小板减少症2PlateletsnAdult form of the same undifferentiated stem cell as the RBC and the WBCnThrombopoietin(hormone)specializes the stem cell into the thrombocytenDisc shaped without a nucleusnHelp slow blood loss from damaged vessels by forming a plugnAlso excrete a chemical the enhances m
2、ore clot formation血小板减少症3PlateletsnLife spannUsually 5-9 daysnAged and dead platelets are removed in the liver and spleen by fixed macrophagesnNormal amountsnBetween 100,000 and 300,000 in each microliter of bloodn2-4 micrometers in diameter血小板减少症4血小板减少的原因 血小板生成减少或无效死亡遗传性获得性:药物、恶性肿瘤、感染、电离辐射、再障、MDS等损
3、伤造血干细胞或影响其在骨髓中增殖所致。这些因素可影响多个造血细胞系统，常伴有不同程度贫血，白细胞减少，骨髓巨核细胞减少(2)血小板破坏过多先天性获得性：免疫性和非免疫性。免疫性血小板破坏过多常见的有特发性血小板减少和药物性血小板减少。非免疫性血小板减少包括感染、弥漫性血管内凝血、血栓性血小板减少等(3)血小板在脾内滞留过多：脾功能亢进 血小板减少症5 重症感染的发病过程重症感染的发病过程全身炎症反应综合征（全身炎症反应综合征（SIRSSIRS）脓毒症（脓毒症（SepsisSepsis）ARDS多器官功能障碍综合征（MODS）脓毒症性休克（Septic Shock）重度脓毒症（Severe Se
4、psis)感染感染血小板减少症6感染严重征象感染严重征象-血小板计数血小板计数nICU中，血小板减少的病人住院时间长且死亡率高n有人发现23%的危重病人至少有一次血小板计数10万/mm3,10%的病人5万/mm3n外科急诊ICU血小板减少的病人38%死亡，而对照组仅为20%血小板减少症7严重脓毒症严重脓毒症(Severe sepsis)n定义：合并有器官功能障碍、低灌注或低血压n器官功能障碍:动脉氧分压低(氧合指数PO2/FIO2 300)；急性少尿(尿量2.0mg/dl；凝血功能异常(INR1.5或APTT60秒)；血小板减少血小板减少(血小板计数血小板计数100,000/ml)2.0mg/
5、dl或35mmol/L)n组织灌注指标:高乳酸盐血症(2mmol/L)n血液动力学指标:动脉血压过低(收缩压SBP 90 mm Hg,平均动脉压MAP 40 mm Hg)血小板减少症8 小儿最常见的出血性疾病，也是最常见的血小板异常性疾病。主要临床特点为血循环中存在抗血小板抗体，使血小板破坏过多，血小板减少引起皮肤、粘膜自发性出血；骨髓巨核细胞数正常或增多，出血时间延长，血块收缩不良，束臂试验阳性。免疫性血小板减少性紫癜免疫性血小板减少性紫癜(ITP)(ITP)血小板减少症9 基本情况基本情况 发病率高（发病率高（4040100/10100/10万），没有明显的地域和万），没有明显的地域和种族
6、差别；中国种族差别；中国1313亿人口中每年发病人数将超过亿人口中每年发病人数将超过5050万，其中急性万，其中急性ITPITP在儿童多见，发病高峰年龄在儿童多见，发病高峰年龄2-52-5岁，岁，无性别差异，常在冬春季病毒感染高峰期发病较多。无性别差异，常在冬春季病毒感染高峰期发病较多。慢性慢性ITP ITP 则多见于则多见于20-5020-50岁的成人，女性较男性发病岁的成人，女性较男性发病率高率高3-43-4倍，发病无季节性，但近年来儿童慢性倍，发病无季节性，但近年来儿童慢性ITPITP的发病有增多趋势，研究显示部分的发病有增多趋势，研究显示部分ITPITP的发病与幽门的发病与幽门螺旋杆菌
7、螺旋杆菌(HP)(HP)、人类巨细胞病毒、人类巨细胞病毒(hCMV)(hCMV)等感染有关。等感染有关。血小板减少症10诊断依据诊断依据（1）血小板计数）血小板计数100109/L（2）骨髓巨核细胞增多或正常，有成熟障碍。成熟障）骨髓巨核细胞增多或正常，有成熟障碍。成熟障碍主要表现为幼稚型和（或）成熟型且无血小板释放碍主要表现为幼稚型和（或）成熟型且无血小板释放的巨核细胞比例增加，巨核细胞颗粒缺乏，胞质少。的巨核细胞比例增加，巨核细胞颗粒缺乏，胞质少。（3）皮肤出血点、淤斑和（或）粘膜出血等临床表现。）皮肤出血点、淤斑和（或）粘膜出血等临床表现。（4）急性型脾脏多无肿大）急性型脾脏多无肿大（5
8、）具有以下）具有以下4项中任何项中任何1项项糖皮质激素治疗有效；糖皮质激素治疗有效；脾切除有效；血清血小板相关抗体（脾切除有效；血清血小板相关抗体（PAIg或或PAC3）阳性；血小板寿命缩短阳性；血小板寿命缩短（6）排除其他可引起血小板减少的疾病，如再生障碍）排除其他可引起血小板减少的疾病，如再生障碍性贫血、白血病性贫血、白血病、骨髓增生异常综合征（、骨髓增生异常综合征（MDS）、）、其他免疫性疾病以及药物性因素其他免疫性疾病以及药物性因素血小板减少症11临床分型临床分型 n急性型急性型 起病急，常有发热，出血一般较起病急，常有发热，出血一般较重，血小板计数常重，血小板计数常202010109
9、 9/L/L，病程，病程66个月个月 n慢性型慢性型 起病隐匿，出血一般较轻，血小起病隐匿，出血一般较轻，血小板计数常为（板计数常为（30803080）10109 9/L/L，病程，病程6 6个个月月血小板减少症12病情分度病情分度 n轻度轻度 血小板计数（血小板计数（BPCBPC）505010109 9/L/L，一般无自发出血，仅，一般无自发出血，仅外伤后易发生出血或术后出血过多外伤后易发生出血或术后出血过多n中度中度 25 2510109 9/L/LBPC50BPC5010109 9/L/L，有皮肤粘膜出血点或外，有皮肤粘膜出血点或外伤后淤斑、血肿、外伤出血延长，但无广泛出血伤后淤斑、血肿
10、、外伤出血延长，但无广泛出血n重度（具备下列一项者即可）重度（具备下列一项者即可）101010109 9/L/LBPC25BPC2510109 9/L/L，皮肤广泛出血、淤斑或多发血肿，粘膜活动性出血（齿龈渗皮肤广泛出血、淤斑或多发血肿，粘膜活动性出血（齿龈渗血、口腔血泡、鼻出血）；消化道、泌尿道或生殖道暴发出血、口腔血泡、鼻出血）；消化道、泌尿道或生殖道暴发出血或发生血肿压迫；视网膜出血或咽后壁出血；外伤处出血血或发生血肿压迫；视网膜出血或咽后壁出血；外伤处出血不止，经一般治疗无效不止，经一般治疗无效n极重度（具备下列一项即可）极重度（具备下列一项即可）BPC10 BPC1010109 9/
11、L/L或几乎查不到，或几乎查不到，皮肤粘膜广泛自发性出血、血肿或出血不止；危及生命的严皮肤粘膜广泛自发性出血、血肿或出血不止；危及生命的严重出血（包括颅内出血）重出血（包括颅内出血）血小板减少症13等级 出血严重程度及生活质量 临床干预一级 少量出血，紫癜100个，和/或5个、建议观察 直径3cm的小瘀斑，无粘膜出血二级 轻微出血，紫癜100个，和/或5个、观察或选择性治疗 直径3cm的小瘀斑，无粘膜出血三级 中等量出血，明显的粘膜出血 临床干预使患儿 病情达一/二级 四级 粘膜出血或怀疑有内部出血 紧急临床干预血小板减少症14Primary ITPPrimary ITP Primary IT
12、P is an autoimmune disorder Primary ITP is an autoimmune disorder characterized by isolated thrombocytopeniacharacterized by isolated thrombocytopenia(peripheral blood platelet count(peripheral blood platelet count100 x10100 x109 9/L)in the/L)in the absence of other causes or disorders that mayabsen
13、ce of other causes or disorders that maybe associated with thrombocytopenia.The diagnosis of be associated with thrombocytopenia.The diagnosis of primary ITP remains one of exclusion;no robust primary ITP remains one of exclusion;no robust clinical or laboratory parameters are currently clinical or
14、laboratory parameters are currently available to establish its diagnosis with accuracy.available to establish its diagnosis with accuracy.The The main clinical problem of primary ITP is an increased main clinical problem of primary ITP is an increased risk of bleeding,risk of bleeding,although bleed
15、ing symptoms may not although bleeding symptoms may not always be present.always be present.Secondary ITPSecondary ITP All forms of immune-mediated All forms of immune-mediated thrombocytopenia except primary ITPthrombocytopenia except primary ITP*Proposed definitions of diseaseBLOOD,12 MARCH 2009 V
16、OLUME 113,NUMBER 11Standardization of terminology,definitions and outcome criteria in immune thrombocytopenic purpura of adults and children:report from an international working group15 *The acronym ITP should be followed by the The acronym ITP should be followed by the name of the associated diseas
17、e(for name of the associated disease(for thrombocytopenia after exposure to drugs,thrombocytopenia after exposure to drugs,the terms“drug-induced”should be used)the terms“drug-induced”should be used)in parentheses:for example,“secondary ITP in parentheses:for example,“secondary ITP(lupus-associated)
18、,”“secondary ITP(lupus-associated),”“secondary ITP(HIV-associated),”and“secondary ITP(HIV-associated),”and“secondary ITP(drug-induced).”For manuscript titles,(drug-induced).”For manuscript titles,abstracts,and so on,definitions such as abstracts,and so on,definitions such as lupus-associated ITP or
19、HIV-associated ITPlupus-associated ITP or HIV-associated ITPcan also be used.can also be used.BLOOD,12 MARCH 2009 VOLUME 113,NUMBER 11血小板减少症16Phases of the disease 1.Newly diagnosed ITP1.Newly diagnosed ITP within 3 months from within 3 months from diagnosisdiagnosis2.Persistent ITP2.Persistent ITP
20、between 3 to 12 months from between 3 to 12 months from diagnosis.Includes patients not reachingdiagnosis.Includes patients not reachingspontaneous remission or not maintaining complete spontaneous remission or not maintaining complete response off therapy.response off therapy.3.Chronic ITP3.Chronic
21、 ITP lasting for more than 12 months lasting for more than 12 months4.Severe ITP4.Severe ITP Presence of bleeding symptoms at Presence of bleeding symptoms atpresentation sufficient to mandate treatment,or presentation sufficient to mandate treatment,or occurrence of new bleeding symptoms requiringo
22、ccurrence of new bleeding symptoms requiringadditional therapeutic intervention with a different additional therapeutic intervention with a different platelet-enhancing agent or an increased doseplatelet-enhancing agent or an increased doseBLOOD,12 MARCH 2009 VOLUME 113,NUMBER 11血小板减少症17难治性难治性ITPITP
23、的诊断标准的诊断标准n国际协作组：国际协作组：1.1.脾切除无效或有效后复发脾切除无效或有效后复发2.2.存在严重的存在严重的ITPITP或需要治疗或需要治疗(包括但不局限于低剂量的皮包括但不局限于低剂量的皮质激素质激素)的严重出血。仅需单独应用常规或附加治疗的的严重出血。仅需单独应用常规或附加治疗的病人不是难治性的病人不是难治性的3.3.除外其他引起血小板减少的疾病。除外其他引起血小板减少的疾病。n国内采用的标准国内采用的标准:病程病程66个月个月,正规皮质激素治疗无效正规皮质激素治疗无效及达那唑、其它常用免疫抑制剂或脾切除无效及达那唑、其它常用免疫抑制剂或脾切除无效,血小板血小板计数计数
24、30 1 1年年 年龄年龄 5 5岁岁 血小板持续血小板持续 30 30 10 109 9/L/L 长期或间断处于重度出血长期或间断处于重度出血 药物治疗无效或需长期大剂量激素维持药物治疗无效或需长期大剂量激素维持 血小板减少症34Individual 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 response*Pred.1-4 mg/kg po
25、/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
26、 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 dDanazo 400-800 mg po daily 14-90 d 28-180 dAzathioprine 2 mg/kg po daily 30-90 d 30-180 dAMG5316 3-10 g/kg weekly sc 5-14 d 14-60 dEltrombopag 50-75 mg po daily 7-28 d 14-90 d BLOOD,12 MARCH 2009 VOLUME 113,NUMBER 11血小板减少症35nThank you very much for your attention！武汉协和医院儿童血液科血小板减少症36
