20160626血小低下

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2016/6/26

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

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 count< 150,000 cells/uL, age>3 mouths

CBC, blood smear evaluationAnemia + thrombocytopenia

pancytopenia

Platelet clumps present pseudothrombocytopenia

Ill appearing?No

Congenital anomalies?

Yes No

PMN hypersegmentation RBC macroovalocytosis?↓B12 or ↓RBC folate

B12 or folate deficiency

Medications Immunizations IrradiationToxins?

No Yes

Macrothrombocytes Drug-induces Live immunizationIrradiation Toxins Yes No

Other morphologic platelet changes

No other platelet change

Bone marrow

Cyanotic heart diseaseFanconi anemiaDyskeratosis congenitaTrisomy 13 or 18Syndromes: Kasabach-Merritt TAR Alport variants

Syndromes:

May-hegglinHermansky-PudiakGray platelet

ITPHereditary thrombocytopeniaBernard-Soulier

↑NI megakaryocytes

↓megakaryocytes

LeukemiaAplastic anemiaDrug-induced Amegakaryocytic thrombocytopeniaMyelodysplasia

ITP is a diagnosis of exclusionResponse to therapy, if needed (corticosteroid, IVIG, anti-D antibody), confirms the diagnosis

Yes PTT, PT, TT prolonged DICR/O sepsis

See Consumptional coagulopathy

Normal

↑↑SpleenSigns of portal hypertensionplatelet > 50,000+/-pancytopenia

MaleEczemaRecurrent infectionSmall platelets

LymphadenopathyHepatosplenomegalySuperior vena cava syndromeAbdominal mass

Chronically ill appearing

Acute, fibrile illness

WBC enzyme assays UltrasonographyThick smear

Biopsy of lymph node, mass or bone marrow consider tumor lysis and superior vena cava syndromes

HIV assayANAU/ARenal function

Blood culture ? antibiotics

MalariaGaucher diseasePortal hypertensionHepatic schistosomiasisCavernoustransformation of the portal vein

Wiskott-Aldrich syndrome

Lymphoma: Hodgkin Non-Hodkin NeuroblastomaleukemiaMyelodysplasia

HIV Autoimmune or connective tissue diseaseHUS/TTP + other microangiopathies Prosthetic cardiac valve

R/O ADMAT-13DATAuto/allo anti-platelet antibody Sepsis

VaricellaEBVCMVDenque hemorrhagic feverHIVHUSHantavirusParvovirusOther viruses TTP

Auto/all anti-platelet antibodies study

Heparin-induced thrombocytopenia Check PF4

Thrombocytopenia in the ill neonate

Any etiology of thrombocytopenia that occurs in the well child

History, examination, CBC, blood smear evaluation See Thrombocytopenia in the well neonate

Platelets 100,000~149,000/uL Platelets < 100,000/uL If platelets < 50,000? Cranial ultrasound to R/O intracranial hemorrhage resulting from severe TP of any etology

Follow platelet count >150,000/uL no further evaluation

100,000~149,000 continue to fellow

PTT, PT, TT

High Hb Severe jaundice and low Hb

Prolonged PTT, PT and/or TT +/- microangiopathic hemolytic anemia:Consider D-dimer of FSP, and/or fibrinogen +/- factors II, V and VIII

PolycythemiaCyanotic congenital heart disease

Erythroblastosis fetalisExchange transfusion pphototherapy

DIC

EtologiesAcute infectionAsphyxiaRDSMeconium aspirationObstetrical complicationsShockThrombosisSevere hemolytic disease of the newbornSevere hepatic disease

TP usually mild enough not to require transfusion except in DIC due to erythroblastosis fetalis

Treat underlying disease Maintain platelets > 50,000 with transfusionsMaintain fibrinogen > 1.0g/L and PT WNL with FFP +/- cyrorecipitate

Normal PTT, PT, TT

RDSPulmonary hypertansionMeconium aspirationMechanical ventilation

Infection

ViralBacterial

Fungal

Perinatal asphyxia

No other specific etiology identified

Unknown etiology

Ongoing re-evaluation if platelets < 50,000

Acutely ill Usually premature Abdominal signs

NEC

AcidosisEmesisLethargy

+/- Central venous catheterHematuriaPulseless extremity

Drug useGancyclovirHeparinVancomycin

Metabolic defects

Thrombosis

Drug-induced

Stop drug

Remove catheter when possibleLMWH??Thrombolytic therapy

Supportive care- Platelet transfusions to maintain count > 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 TAATP

HPA (+) (+) (+) (+) (+)

ABH (+) (+) (-) (?) (?)

Class I HLA (+)? (+) (-) (?) (?)

CD36 (+) (+) (+)? (?) (?)

Alloantigens implicated in allo immune thrombocytopenia

Dr. 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 )

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 (15~31%), and anti-HPA Abs less frequency; however, platelet destruction is usually caused by the anti-HPA Abs

Protective 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.


Specificity of HPA Ab in NAIT(Japan)

Antibody specificity Nmber of cases %

HPA-1a 1 <1

HPA-2a 2 2HPA-3a 17 15HPA-3b 1 <1

HPA-3a+5b 1 <1

HPA-4a 8 7HPA-4b 61 52HPA-5a 1 <1HPA-5b 12 10

HPA-6b 7 6HPA-7b 1 <1

Naka 5 4

Total 117


• The risk of ICH was the highest with anti-HPA-3

血小板抗体的特异性 70 NAITP案例Area(5)

Anti-HPA-1

Anti-HPA-3

Anti-HPA-4

Anti-HPA-5

Anti-HPA-7bw

Anti-HPA-15

Anti-HPA-21bw

Anti-HLA

Anti-A

Anti-CD36

Un-known

China 1 1 4 3

Japan 3 5 3 1 1 2 37 1

Korea 5

Taiwan 1 1

Thailand

5

Total 0 5 5 4 1 1 2 43 1 9 3

Dr. G.G. Wu presented in 24th regional congress of ISBT

2013 ISBT IPIWP-AR

The risk of ICH was the highest with anti-HPA-3 Anti-HPA-4a/4b is the highest rate in NAIT in Japan

( anti-HPA-4a 7%, anti-HPA-4b 52%) HPA-4 incompatible may cause rejection rection

reactions in solid organ transplantation.(Vox Sanguinis, 2010 july, Supplement1,Vol 99)

More than 0.5% of CD36 type I deficient individuals are at risk to be immunized through blood transfusion or pregnancy in China.

The frequency of CD36 negative

新生儿免疫血小板低下症 (NAIT)

• NAIT due to anti-HLA antibodies• Case of NAIT suspectedly due to anti-HLA are

reported, but the association needs to be comfirmed• Class I HLA Abs are found in about one third of

multiparous women (15~31%), and anti-HPA Abs less frequently; however, platelet destruction is usually caused by the anti-HPA Abs.

• Protective 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.

新生儿血小板低下的评估 (NATP)

新生儿免疫血小板低下症的评估诊断• 母体血清验血小板抗体

– PIFT– ELISA 法

• 母体血清和患儿血小板交叉– SPRCA, FCM

• 母体血清和父亲血小板交叉– SPRCA, 流式细胞仪

This assay can detect HLA, ABO, and platelet specific IgG antibodies. But weak reactions give immediate results.

Solid- phase red cell adherence assay (SPRCA)

输血后紫斑症• Post-transfusion thrombcytopenia purpura• Developed after 1-2 weeks after transfusions• Caused by Anti-HPA -1a

药物诱导血小板低下症抗体• 大部份药物诱导血小板低下的症状轻微，但偶而有危及生命的出血状况产生。• 病理原因较药物诱导红细胞溶血性贫血复杂，至少有六种以上的机转• 主要临床意义在于排除血小板低下原因

J Thromb Haemost. 2009 Jun; 7(6): 911–918.

DIT药物诱导血小板低下抗体鉴定• 血小板交叉配血相容， 1Hr CCI>7500, 24 Hr

CCI>5000 有效输血小板1Hr CCI>7500, 24 Hr CCI<5000 infection, fever, non-immune1Hr CCI<7500, 药物诱导型血小板低下 .

• 血小板抗体筛检阴性，自身血小板抗体阳性( flowcytometry, SPRCA, 近日内输过血小板也可能自身血小板抗体阳性 )

• 使用 SPRCA 法鉴定：血清 + 药物及血小板 +药物培温

Drug induced thrombocytopenia

药物诱导型血小板低下抗体鉴定流程血小板低下

筛查血小板骨髓制作功能及最近用药史血小板抗体筛检交叉配血 , 1Hr /24 Hrs

CCI,

配血相容 , 1 hr CCI>7500, 24hrs CCI>5000

配血相容 , 1 hr CCI>7500, 24hrs CCI<5000

配血相容 , 1 hr CCI<7500,

配血不相容 , 1 hr CCI<7500,

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 positive

Positive

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

• 建议抗生素及输血治疗

疑似 DIHA合并 DIT输血治疗案例• 临床医师建议输给 RBC 4U, 机采血小板 1U, FFP 6U 及泰巴坦治疗 , 抗筛阴性输血科给予随机 A型 RBC 相叉相容 RBC 4U 及 A 型机采血小板 1U, FFP6U 输注。

• 输血后第一天 Hb 7.2 直抗转阳 , Plt 45K 溶血三症明显， LDH↑↑ ，疑输血后溶血症，输血科启动输血反应调查 SOP 。

• 输血科输血反应调查：输血后样本抗筛阴性，直抗转阳，放散液抗筛阴性和原献血者样本交叉相容，重复输血后样本对照输血前样本交叉配血，输血后样本的主侧配血 AHG有 1+凝集，凝聚胺配血相合，输血前样本配血均相容。临床医师建议再次输血 RBC 4U, Plt 1 机采血小板 . 输血科再次配血相容 RBC 4U及 1U 机采血小板输注。

• 输血后第二天溶血评估加剧，疑似引发 DIC ( D-dimer, FDP 上升 ) Hb5.0, plt 8k, 无大量出血现象 .

疑似 DIHA合并 DIT输血治疗案例 -cont.

• 输血科再次启动输血反应调查作业，同时间病患出现 EV bleeding 输血科紧急供应交叉配血相容 RBC 及机采血小板 , FFP, Cryo 。• 最后输血不及 , 病患死亡• 事后调查 : 血小板抗体筛检阴性 ( Genprobe

Pakplus ELISA), auto-platelet Ab. 阳性( FIPA, Flowcytometry 流式细胞仪 )DAT : polyAHG 3+, IgG AHG 3+, C3d negative, 放散液抗筛阴性重测抗筛阴性 , 红细胞主交叉 : 相容 .

DITP的治疗• 立即停药；• 血小板输注；• 大剂量 IVIG；• 短期使用糖皮质激素；• 避免再次使用该药物

栓塞性血小板低下紫斑症 TTP• 形成的原因仍不清楚，多数学者认为是一种病毒传染后毒素所造成的反应。但临床上可发觉正常金属蛋白酵素（metalloprotease,ADAMTS-13）可以分解超大 von Willebrand’s 体。它具有类似 thrombospondin-1单元（ thrombospondin-1–like domains），并藉此与内皮细胞上的 thrombospondin 接受体结合，并由此固定于内皮细胞上。固定于内皮细胞上的 ADAMTS 13 ，使可以分解旁边的超大 Von Willebrand's氏因子聚合体。

• 栓塞性血小板低下紫斑症患者，其金属蛋白酵素（metalloprotease－ ADAMTS 13）于此时的活性若严重通常趋近于零，无法分解旁边的超大 Von Willebrand's氏因子聚合体，所导致的微血管内血小板凝集，因而表现出所谓的 pentad：包括微血管病变溶血性贫血、血小板低下、发烧、神经学症状、以及肾功能不全等五种特征。

• The ADAMTS-13 assay is based on fluorescence resonance energy transfer (FRET) technology. A synthetic fragment of the von Willebrand Factor protein is used as the Substrate. Cleavage of this peptide between two modified residues releases the fluorescence quenching capabilities.

• This assay is based on quantifying the cleavage of a small fragment of von Willebrand Factor by the ADAMTS-13 protease. The cleavage of this synthetic substrate is detected by reading the fluorescence that results when the substrate is cleaved.

测定 ADAMTS-13的原理

TECHNOZYM® ADAMTS-13 ACTIVITY

PE 对 TTP的疗效• 一般血浆交换术 PE对 TTP的临床反应可谓是十分之迅速且明确。 Bukowski报告 2-3天， Petitt报告约 36小时。• 血小板约 2~5 PE可见成效，但血色素较略显缓慢

。 LDH恢复则较慢。• 对不同病因的 TTP之临床反应速度快慢差异颇大，有约连续 5 天疗程即完成疗效，有近一个月或以上连续 QD PE才完成疗效。• 以大量血浆﹝新鲜血浆，新鲜冷冻血浆，冷冻血

浆﹞补充效果较佳，开始 PE疗程 QD实施，超过一个 blood volume的血浆置换术﹝急性期治疗常使用 120%﹞ ，以 platelet count评估成效。

PE & PI 对 TTP的疗效• Plasma infusion (PI)bas been used as an

alternative to PE.• Studies observed no difference in

response or survival between PE and PI.• The risks of fluid overload with PI and the

potential for PE to remove ADAMTS13 have resulted in PE being preferred to PI

TTP之血浆疗法• 自 1977 年血浆疗法的临床应用已显着地改善血栓性血小板减少性紫斑症 (TTP) 之愈后。使用血液成份分离机及血浆分离术或者是血浆输注法 plasma infusion 可治愈大部分的

TTP 病人。• 唯此两种血浆疗法之相互优劣比较及引发 TTP 之致病假说，仍尚无定论。• 1997 年新光医院温武庆 / 叶建宏等发表一例 TTP ，交互使用双重过滤血浆分离术 DFPP 配合血浆输注疗法，及血浆交换术的案例报告：初期以连续 16 次 DFPP 配合每天之血浆输注疗法，病人之临床征状却依然持续恶化，只得改用传统血浆交换术。结果在二天之内血小板数目及神智状态明显进步。比较此二种血浆疗法之个别差异，发现血浆交换术中每次使用之血浆量大约是血浆输注法之三倍，因此，大量的血浆输注应是治疗成功的主因。﹝台湾医学 Formosan J

Med 1997;6:710-5﹞

Cryo-poor plasma(cryosupernatant)

• laboratory indices of complete and stable response (platelet count, serum lactate dehydrogenase level) did not normalize in concert with clinical improvement.

PE of TTP in NTUH• 2006.01.~2008 计十五名疑似 TTP﹝如下一张

slide﹞。• 其中一名 E 先生，症状十分疑似，但 ADAMTS-

13 测出达 80%normal ，执行四次 PE 换血浆64U 后停止 PE 治疗，使用传统 platelet transfusion 可回复到 180k 。

• 其他十二名 , 男 3 名﹝平均 52.5 岁﹞，女 9 名﹝平均 32.1 岁﹞• H 女士只执行一次 PE ，临床症状十分吻合，原高度怀疑为 TTP ，但 ADAMTS-13 测出达 78%最后确认是 Trousseaus syndrome 。

2005~2008 TTP案例报告A 吳秋媚4226XXX F 50B 王薇晴4352XXX F 27 15~26%C 干慧蘭5167XXX F 32 60~80%D 古明巧4512XXX F 22E 何維發5291XXX M 52 80%F 沈佩蓉4131XXX F 23 35%G 洪素美3686XXX F 68H 梁淑媛5170XXX F 40 78%I 陳季和4584XXX F 36 32%J 曾建中1461XXX M 62 <15%K 董至綱5252XXX M 43 10. 20%L 蔡妙貞5159XXX F 55 8. 30%M 姜壽峰3122XXX M 24 40%N 李崇煦2543XXX M 24 18%I 向泓霖5365XXX M 9 normal

ADAMTS-13 对 TTP的鉴别• H女士： Poor prognosis was informed. Pupil

dilate, unconsciousness and no gag reflex were found. Held PLT transfusion due to suspect TTP. FFP was kept as hematologist suggestion. However, vaginal bleeding and oral bleeding persisted.

• The ADAMT13 was about 80%. TTP was not likely. Elevated CA 125 was found.

• The abdomen CT showed ovarian cancer and endometrial hyperplasia. Trousseaus syndrome was suspected.

ADAMTS-13 对 TTP的鉴别( 二 )•某君从新店慈济转入本院急诊，疑似 TTP的案例。•临床症状及实验室检查疑似 TTP ： LDH↑

， Bilirubin↑ ， Hb↓ ， Platelet↓,Coombs’test: negative, unconsciousness , 唯 PT, aPTT prolong,留检体评估 ADAMTS-13。

•病人随即 CPR ， ADAMTS-13 assay: 5%,suspected terminal TTP.

血栓性血小板低下的区分 (TTP) Disease Common symptoms Differential symptomsHemolytic uremic syndrome

Thrombocytopenia, hemolytic anemia with schistocytosis

Gastrointestinal infections: E. coli 0157:H7,Shigella dysenteria Hemorrhagic colitis High serum creatinine

HELLP syndrome Hemolytic anemia, thrombocytopenia

Elevated liver enzymes

Pre-eclampsia, eclampsia Thrombocytopenia, proteinuria

Hypertension Peripheral edema Proteinuria Increased D-dimer

Disseminated intravascular coagulation

Thrombocytopenia Markedly increased D-dimer Prolonged prothrombin time

Catastrophic antiphospholipid syndrome

Thrombocytopenia Positive lupus-like anticoagulant

Antinuclear and antiphospholipid antibodies

Evans syndrome Hemolytic anemia, thrombocytopenia

Positive Coombs test Usually absence of end-organ ischemic symptoms

Heparin-induced thrombocytopenia

Thrombocytopenia Thrombosis mainly in large arteries and veins Antiplatelet antibodies

ITP特发性血小板减少症• ITP 的治疗主要是在降低临床重大出血的风险。• 严重出血的 ITP 患者，输血仍是最直接有效的，但缺乏评估输血 1 小时后的有效的血小板数的循证• IVIG 1g/kg (<5000/mL, 每日追踪 )• Glucocorticoids (1g IV, 每日 3dose)

ITP的实验室诊断• 取 auto platelet 测 auto antibody• ELISA PakAuto kit, flowcytometry,

SPRCA• 最近无施打 IVIG, 无输过血小板，采 SPRCA: ,<50000 plat count, 抽 40cc EDTA ，制成 PRP

This assay can detect HLA, ABO, and platelet specific IgG antibodies. But weak reactions give immediate results.

Solid- phase red cell adherence assay (SPRCA)

肝素介导的血小板减少（ HIT）•机制：肝素与血小板因子 4(PF4) 结合形成抗原结构，抗体通过 Fab 段识别 PF4/ 肝素结合于血小板， Fc 段连接单核细胞，迅速、猛烈地引起血小板激活以及促凝微粒的释放。•类似机制的药物：鱼精蛋白鱼精蛋白 - 肝素 -IgG- 血小板 FcγRIIa

EDTA依赖假性血小板低下Vs.HIT

HIT 的抗体侦测：血清素释放试验 serotonin release assay SRA( 高特异性 ,低敏感性 ), 抗体 - 肝素 -PF4 免疫复合体试测酶标法 ( 高敏感性低特异性性 )

血小板输血参考指标 IPF• IPF是 Immature platelet fraction(未成熟血小板比例 ), 可作为评估骨髓造血小板功能恢复的参考指标• 化疗或干细胞移植后 , IPF开始上升代表骨髓造血小板功能逐渐恢复，约一周内血小板会显着上升。• 降低不必要的血小板输血

IPF与造血小板功能

IPF可早期评估骨髓造血小板功能

• 评估停上血小板输血时机• 降低输血成本• 降低输血造成感染的风险

美国红十字会与英国输血组织移植联盟血小板配型流程Crossmatch with 8 random donors

All donors negative: Use random donors

for PLT Tx8 Crossmatch positive

Positive and negative donors

Select negative donor for PLT TXHLA/HPA antibody test

Anti-HPA +Anti-HLA -

Anti-HPA -Anti-HLA +

Anti-HPA +Anti-HLA +

HPA typing of recipient

HLA-identical or compatible PLT

Crossmatch with HPA compatible

donor

HPA typing of recipient

Crossmatch with HLA/HPA compatible donor

二次以上输随机血小板无效

HLA class I 筛查positive

Negative 或持续对 HLA 相容血小板输注无效病患的 HLA-I 分型

提供 HLA 相容配型血小板持续对HLA及HPA 配血相容血小板输注无效

考虑非免疫问题或药物诱导型抗体或HPA专一性筛检

阳性阴性执行 HPA 抗体筛检

提供 HPA 相容配型血小板

区分血小板相关疾病PTR NAITP HIT DIT TTP ITP TRALI

Test or investigation

CCI CBC,DCHeparin history

Drug history DATBUN

CBC,DC

DAT BNPCBCX-ray

Serological test

PRA(class I) ELISA(Pakplus)SPRCA (capture-P, MASPAT):anti-platelet antibody screening, and cross matching PIFALuminux PRA class IMAIPAMPHA

Mother and fetusPRA(class I/II) ELISA(Pakplus)SPRCA (capture-P, MASPAT):anti-platelet antibody screeningPIFALuminux PRAMAIPAMPHA

Mother serum Vs. Father/baby plat.SPRCA, PIFA cross matching

ELISA (PF4)CAT (PF4)

Serum + drug, or eluentSPRCA ( Capture-P, MASPAT)

FRET:ADMATS-13 activity

ELISA (Pakauto)ELISA (Pakplus)SPRCA ( Capture-P, MASPAT ): auto antibody and allo antibodyPIFA (auto)

Donor serum ( and/or patient )Luminux PRA ( class I/class II/HNA)ELISA PRA (class I/II)flowPRA (class I/II)Leuko-agglutinin testMAIGAGIFA

Antigen HLA class I typingHPA typingCD36 typing

Parent and fetus:HLA class I/II typing, HPA typingCD 36 typing

区分各种血小板低下 ITP, PTR, TTP, HIT, DIT

ITP特发性血小板低下 PTR血小板输注无效 TTP血栓性血小板低下HIT肝素诱导血小板低下

DIT药物诱导型血小板低下血小板抗体筛查 +/-

Auto ant-platelet antibody (+)

+ - - -+drug incubation (+)

特异性抗体Auto antibodies

Allo antibodiesAnti-HLA class IAnti-HPA, CD36

ADMATS-13

Anti-PF4-heparin-plt Cpx

Anti-drug antibodies

血小板上最主要的目标GP Ib-IX, IIb-IIIa,Ia-Iia,IV

GP Ib-IX, IIb-IIIa,Ia-Iia,IV( include HLA)

ADMATS-13

PF4–heparincomplex on platelet

检测的方法 SPRCAFIPAELISA

MAIPA, SPRCA, ELISA, FIPA, MPHA

FRETELISA

Gel CATELISA

SPRCA( Capture-P or MASPAT)

张志升Email: [email protected], [email protected], facebook, Plurk : [email protected] : jschang12QQ: 1150352697Line: jschang12Wechat:Jschang12Blog: http://www.jschang.idv.twYoutube : http://tw.youtube.com/ntuh-tm Website: http://www.jschang,idv.twMobilephone -0928825645Office 0223123456ex65404

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20160626血小低下

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