血小板低下症的区分及血小板输注合理评估

血小板低下症的区分及血小板输注合理评估 张志升台湾台大医院输血医学科2016/6/26Content 血小板低下症的原因 新生儿血小板低下症 药物诱导血小板低下症 血栓性血小板低下症 特发性血小板减少紫癜 肝素诱导血小板低下症血小板低下症的原因 骨髓制造血小板的功能减少 血小板制造可因放射线、化学治疗或病毒感染等原因受抑制，而骨髓本身疾病，如再生不良性贫血、白血病，骨髓分化不良等皆可引起制造减少。 血小板在周边血液被破坏增加 常见的有经由产生自体免疫抗体来破坏，如全身性红斑性狼疮、特发性血小板减少性紫斑症、某些药物等，而病毒感染也常引起血小板低下，如登革热病毒、人类免疫缺乏病毒等。此外血小板低下也常见于脾脏肿大病人，如肝硬化病人因门脉高压引起脾脏肿大，造成血小板破坏增加。Evaluation of a child with thrombocytopeniaPlatelet count3 mouthsCBC, blood smear evaluationAnemia + thrombocytopeniapancytopeniaPlatelet clumps present pseudothrombocytopeniaIll appearing?No Congenital anomalies? Yes No PMN hypersegmentation RBC macroovalocytosis?B12 or RBC folateB12 or folate deficiencyMedications Immunizations IrradiationToxins?No Yes Macrothrombocytes Drug-induces Live immunizationIrradiation Toxins Yes NoOther morphologic platelet changesNo other platelet changeBone marrowCyanotic heart diseaseFanconi anemiaDyskeratosis congenitaTrisomy 13 or 18Syndromes:Kasabach-MerrittTARAlport variantsSyndromes:May-hegglinHermansky-PudiakGray plateletITPHereditary thrombocytopeniaBernard-SoulierNI megakaryocytesmegakaryocytesLeukemiaAplastic anemiaDrug-induced Amegakaryocytic thrombocytopeniaMyelodysplasiaITP is a diagnosis of exclusionResponse to therapy, if needed (corticosteroid, IVIG, anti-D antibody), confirms the diagnosisYes PTT, PT, TT prolonged DICR/O sepsisSee Consumptional coagulopathyNormal SpleenSigns of portal hypertensionplatelet 50,000+/-pancytopeniaMaleEczemaRecurrent infectionSmall plateletsLymphadenopathyHepatosplenomegalySuperior vena cava syndromeAbdominal massChronically ill appearingAcute, fibrile illnessWBC enzyme assays UltrasonographyThick smearBiopsy of lymph node, mass or bone marrow consider tumor lysis and superior vena cava syndromesHIV assayANAU/ARenal functionBlood culture ? antibioticsMalariaGaucher diseasePortal hypertensionHepatic schistosomiasisCavernoustransformation of the portal veinWiskott-Aldrich syndromeLymphoma:HodgkinNon-Hodkin NeuroblastomaleukemiaMyelodysplasiaHIV Autoimmune or connective tissue diseaseHUS/TTP + other microangiopathies Prosthetic cardiac valveR/O ADMAT-13DATAuto/allo anti-platelet antibody SepsisVaricellaEBVCMVDenque hemorrhagic feverHIVHUSHantavirusParvovirusOther viruses TTPAuto/all anti-platelet antibodies studyHeparin-induced thrombocytopenia Check PF4Thrombocytopenia in the ill neonateAny etiology of thrombocytopenia that occurs in the well childHistory, examination, CBC, blood smear evaluation See Thrombocytopenia in the well neonatePlatelets 100,000149,000/uL Platelets 150,000/uL no further evaluation100,000149,000 continue to fellowPTT, PT, TTHigh Hb Severe jaundice and low HbProlonged PTT, PT and/or TT +/- microangiopathic hemolytic anemia:Consider D-dimer of FSP, and/or fibrinogen +/- factors II, V and VIIIPolycythemiaCyanotic congenital heart diseaseErythroblastosis fetalisExchange transfusion pphototherapyDICEtologiesAcute infectionAsphyxiaRDSMeconium aspirationObstetrical complicationsShockThrombosisSevere hemolytic disease of the newbornSevere hepatic diseaseTP usually mild enough not to require transfusion except in DIC due to erythroblastosis fetalisTreat underlying disease Maintain platelets 50,000 with transfusionsMaintain fibrinogen 1.0g/L and PT WNL with FFP +/- cyrorecipitateNormal PTT, PT, TTRDSPulmonary hypertansionMeconium aspirationMechanical ventilationInfection ViralBacterial FungalPerinatal asphyxiaNo other specific etiology identifiedUnknown etiologyOngoing re-evaluation if platelets 20,000 in stable full term neonates, 50,000 with hemorrhage, surgery, or more extremely preterm infantsObserve for DIC免疫性血小板低下 Neonatal alloimmune thrombocytopenia (NAIT) Platelet transfusion refractoriness (PTR) Post-transfusion thrombocytopenic purpura (PTP) Passive alloimmune thrombocytopenia (PAT) Transplantation-associated alloimmune thrombocytopenia (TAATP) Antigen NAIT PTR PTP PAIT TAATPHPA (+) (+) (+) (+) (+)ABH (+) (+) (-) (?) (?)Class I HLA (+)? (+) (-) (?) (?)CD36 (+) (+) (+)? (?) (?)Alloantigens implicated in allo immune thrombocytopeniaDr. N.H. Tsuno presented in 24th regional congress of ISBT 血小板相关抗体疾病或异常 新生儿免疫性血小板减少症 NAITP 输血后紫斑症 PTP 血小板输血无效症 PTR 免疫性血小板低下紫瘢症 ITP 血栓性血小板低下紫癜 TTP 肝素刺激血小板低下症 HIT 药物抗体血小板低下症 DIT 严重输血相关呼吸窘迫症候群 TRALI即输血小板两次以上无法达到预期血小板的增加数称为 “ 血小板输注无疗效 ” 成因 : 异体免疫 , 自体抗体 , ABO血型不符 , 病人因素 ( 如急性出血或组织移植排斥 等 ), 药物治疗 ( 如抗生素vancomycin)所引起血小板输血后的品质评估 : 1小时后其 “ 校正血小板增加数 ” 7000, 此方法亦为 侦测有无 “ 异体免疫 ” 的间接方式CCI : ( 输血后血小板数 -输血前血小板数 ) X BSA/ 输注血小板量。 血小板输注无效症与血小板抗体有关之疾病：Neonatal alloimmune thrombocytopenia 白种人中此病之报告较多，母体之抗血小板抗体进入胎儿内，造成新生儿之血小板异常低下，此病可以生于第一胎。西方人报告中以HPA-1a 抗体为主 (又名 anti-plA1)，多发生于 HPA-1a阴性且 HLA-DR3*0101之妇人。日本则曾报告过 HPA-4b抗体引起之新生儿血小板减少症 Post-transfusion purpura (PTP)输血后紫斑症，病人输血后发生血小 板异常降低，引起反应的血品包括血小板，红血球等。部份输血病人体内可以验出血小板抗体，文献报告中最多的也是 HPA-1a抗体 (anti-plA1 ) Content 血小板低下症的原因 新生儿血小板低下症 药物诱导血小板低下症 血栓性血小板低下症 特发性血小板减少紫癜 肝素诱导血小板低下症Neonatal Alloimmune Thrombocytopenia (NAIT) NAIT due to anti-HLA antibodiesCase of NAIT suspectedly due to anti-HLA are reported, but the association needs to be confirmed.Class I HLA Abs are found in about one third of multiparous women (1531%), and anti-HPA Abs less frequency; however, platelet destruction is usually caused by the anti-HPA AbsProtective immune mechanism of the placenta : anti-HLA antibodies adsorbed by the stromal cells of placenta expressing paternal antigens; routinely, the infants are born with normal platelet counts. Dr. N.H. Tsuno presented in 24th regional congress of ISBT Specificity of HPA Ab in NAIT(Japan)Antibody specificity Nmber of cases %HPA-1a 1 7500, 24 Hr CCI5000 有效输血小板1Hr CCI7500, 24 Hr CCI7500, 24hrs CCI5000配血相容 , 1 hr CCI7500, 24hrs CCI5000配血相容 , 1 hr CCI7500, 配血不相容 , 1 hr CCI7500, 执行血小板抗体筛检 HPA or HLA class I Ab, or CD36发烧等非免疫因素成功输血 药物诱导型血小板低下跟临床取得药物及查询药物作用浓度配制药物浓度 , 执行药物依赖型检测SPRCA更改药物药物诱导型血小板低下抗体鉴定案例 男性 68岁大肠癌患者，使用 oxaliplastin合并 5-FU化疗使用，每周一次疗程，约使用三星期疗程后发觉血小板从原来 17万 /dL, 不明原因降为 5.8万 /dL, 无出血现象，也无其他败血症及DIC等情形。 其他检查：凝血功能 PT/aPTT正常，血小板交叉配血相容，血小板抗体筛检Pakplus ELISA酶标法无血小板抗体。输血后一小时 CCI 6000.Negative Weak positivePositive疑似药物诱导溶血性贫血与药物诱导血小板低下出血案例 一居住在台湾东部花莲原住民族男性 45岁酒精性肝炎住院患者。 之前的病史及输血史： A型 Rh阳性，年轻时 (30岁左右因工作受伤 )手术曾输过 RBC 6U及 1U机采血小板。三四年前曾因急性肺炎住院接受治疗，长期使用抗生素(泰巴坦 )治疗 此次住院治疗疲倦黄疸，有伤口长期无法愈合不良合并有肾结石发烧出血等症状 实验室检查A/pos 抗筛阴性， Hb 6.5, platelet count 50k, aPTT/PT prolong INR 1.7 blood culture no grow 建议