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All about platelet immunology
- 1. AAllll aabboouutt ppllaatteelleettiimmmmuunnoollooggyy 張志昇 中華民國一○三年八月廿三日
- 2. 2014/10/5 09:00~09:30 NelsonHirokazu Tsuno Immune-mediated Thrombocytopenia and Detection of Anti-platelet Alloantibodies
- 3. • Platelet antigen • Platelet antibody • Disease associated platelet immunology • Detection of anti-platelet antibodies • Q&A
- 4. RBC antigens (ABO antigens, Rh, Lewis, Duffy ….) Human leukocyte antigen (HLA) Human platelet antigens (HPA) Glycoprotein IV (CD36, Naka )
- 5. Antigens on humanplatelets are categorized according to their biochemical nature into: carbohydrate antigens on glycolipids and glycoproteins (A, B, O, P, Lewis antigens), protein antigens (HLA Class-I; GPIIb/IIIa, GPIb/IX/V) Many platelet antigens are shared with other blood cells, e.g.,ABO and HLA class I antigens, but some of the glycoprotein antigens are expressed predominantly on platelets. These antigens are commonly referred to as platelet-specific alloantigens or human platelet alloantigens (HPAs), although some of these are also present to a lesser extent on other blood cells, e.g., HPA-5 on activated T lymphocytes.
- 6. Platelet-specific alloantigens arelocated on platelet membrane GPs involved in hemostasis through interactions with extracellular matrix proteins in the vascular endothelium and plasma coagulation proteins. CD36 is found on platelets, erythrocytes, monocytes, differentiated adipocytes, skeletal muscle, mammary epithelial cells, spleen cells and some skin microdermal endothelial cells. The majority of these antigens are on the GPIIb/IIIa complex, which plays a central role in platelet aggregation as a receptor for fibrinogen, fibronectin, vitronectin, and von Willebrand factor.
- 7. Other important GPsare GPIb/IX/V,the main receptor for von Willebrand factor involved in platelet adhesion to damaged vascular endothelium; GPIa/IIa, which is involved in adhesion to collagen; and CD109, which also appears to be a collagen receptor. Congenital deficiency of these GPs results in bleeding disorders, e.g., lack of GPIIb/IIIa causes Glanzmanns’ thrombasthenia, and absence of GPIb/IX/V results in Bernard-Soulier syndrome. CD36 is also known as glycoprotein IV (gpIV) or glycoprotein IIIb (gpIIIb) in platelets and gives rise to the Naka antigen.
- 8. 28 systems 34antigens 6 systems with two antigens (a,b) HPA-1~5 and HPA-15 On 6 Glycoproteins 14 systems on GPIIIa 7 systems on GPIIb 4 systems on GPIa 1 system on GP1ba 1 system on GP1bb 1 system on CD109
- 9. 4 7 141 1 1 99660000 mmooll//pplltt 80,000 mol/plt 25,000 mol/plt 1,000 mol/plt British Journal of Haematology Volume 161, Issue 1, pages 3–14,
- 10.
- 11. Platelet membrane glycoprotein(GP) IV (also called CD36 and GPllb) deficiency is associated with Nak"- negative platelets Depending on the nature of the mutation in codon 90 CD36 may be absent either on both platelets and monocytes (type 1) or platelets alone (type 2). The CD36-negative is a phenotype observed in most Asian countries, and the risks associated with alloimmunization to this isoantigen.
- 13. • Platelet antigen • Platelet antibody • Disease associated platelet immunology • Detection of anti-platelet antibodies • Q&A
- 14. Alloantigens implicated inallo immune thrombocytopenia Antigen NAIT PTR PTP PAIT TAATP HPA (+) (+) (+) (+) (+) ABH (+) (+) (-) (?) (?) Class I HLA (+)? (+) (-) (?) (?) CD36 (+) (+) (+)? (?) (?) Neonatal alloimmune thrombocytopenia (NAIT) Platelet transfusion refractoriness (PTR) Post-transfusion thrombocytopenic purpura (PTP) Passive alloimmune thrombocytopenia (PAT) Transplantation-associated alloimmune thrombocytopenia (TAATP) Dr. N.H. Tsuno presented in 24th regional congress of ISBT
- 15. NAIT due toanti-HLA antibodies Case 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. Dr. N.H. Tsuno presented in 24th regional congress of ISBT
- 16. The risk ofICH was the highest with anti-HPA-3 Antibody specificity Nmber of cases % HPA-1a 1 <1 HPA-2a 2 2 HPA-3a 17 15 HPA-3b 1 <1 HPA-3a+5b 1 <1 HPA-4a 8 7 HPA-4b 61 52 HPA-5a 1 <1 HPA-5b 12 10 HPA-6b 7 6 HPA-7b 1 <1 Naka 5 4 Total 117 Dr. N.H. Tsuno presented in 24th regional congress of ISBT
- 17. 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 Taiwa n 1 1 Thaila nd 5 Total 0 5 5 4 1 1 2 43 1 9 3 Dr. G.G. Wu presented in 24th regional congress of ISBT
- 18. Specificity of plateletalloantibodies in 40 alloimmunized patients Specificity No. of PT HLA 12 HLA + Platelet specific 22 Platelet specific 5 Not identified 1 從不同的報告 anti-HLA antibodies : 26-71 % anti-platelet specific antibodies : 8-42%
- 19. Specificity No. WithHLA antibodies IIb/IIIa 2 IIb/IIIa + Ia/IIa 5 IIb/IIIa + Ia/IIa +Ib/IX 2 IIb/IIIa + Ia/IIa + IV 6 Ia/IIa 4 Ia/IIa + IV 1 IIb/IIIa + Ia/IIa + Ib/IX + IV 2 Without HLA antibodies Ib/IX 3 IIb/IIIa + Ia/IIa 2
- 20. Platelet alloantibodies inPakPlus which demonstrated were 38 (64% of 52) for HLA Abs only, 8 (15% of 52) for HPA Abs only and 11 (21% of 52) for HLA + HPA Abs.
- 21. Lin et al. 2003 Chang et al . 2009 Chu et al. 2013 People with Positive Antibody 57 23 51 Positive HLA Antibody Only 38 (66.7%) 8 (34.8%) 7 (13.7%) Positive HLA & HPA Antibody 11 (19.3%) 6 (26.1%) 24 (47.1%) Positive HPA Antibody Only 8 (14.0%) 9 (39.1%) 20 (39.2%)
- 22. 2008 (40 casestudy) 2014 (23 cases study) HLA 12 33.3% 2 8.6% HLA+ platelet specific 22 55% 11 47.8% Platelet specific 5 12.5% 4 17.4% unidentified 1 2.5% 6 Total 40 23
- 24. The riskof 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.
- 25. • Platelet antigen • Platelet antibody • Disease associated platelet immunology • Detection of anti-platelet antibodies • Q&A
- 26. Evaluation of achild with thrombocytopenia Platelet count< 150,000 cells/uL, age>3 mouths CBC, blood smear evaluation Anemia + 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 Irradiation Toxins? Yes No Drug-induces Macrothrombocytes Live immunization Irradiation Toxins Yes No Other morphologic platelet changes No other platelet change Bone marrow Cyanotic heart disease Fanconi anemia Dyskeratosis congenita Trisomy 13 or 18 Syndromes: Kasabach-Merritt TAR Alport variants ITP Hereditary thrombocytopenia Bernard-Soulier Syndromes: May-hegglin Hermansky-Pudiak Gray platelet ↑NI megakaryocytes ↓megakaryocytes Leukemia Aplastic anemia Drug-induced Amegakaryocytic thrombocytopenia Myelodysplasia ITP is a diagnosis of exclusion Response to therapy, if needed (corticosteroid, IVIG, anti-D antibody), confirms the diagnosis Yes PTT, PT, TT prolonged DIC R/O sepsis See Consumptional coagulopathy Normal ↑↑Spleen Signs of portal hypertension platelet > 50,000 +/-pancytopenia Male Eczema Recurrent infection Small platelets Lymphadenopathy Hepatosplenomegaly Superior vena cava syndrome Abdominal mass Chronically ill appearing Acute, fibrile illness WBC enzyme assays Ultrasonography Thick smear Biopsy of lymph node, mass or bone marrow consider tumor lysis and superior vena cava syndromes HIV assay ANA U/A Renal function Blood culture ? antibiotics Malaria Gaucher disease Portal hypertension Hepatic schistosomiasis Cavernous transformation of the portal vein Wiskott-Aldrich syndrome Lymphoma: Hodgkin Non-Hodkin Neuroblastoma leukemia Myelodysplasia R/O ADMAT-13 DAT Auto/allo anti-platelet antibody Sepsis HIV Autoimmune or connective tissue disease HUS/TTP + other microangiopathies Prosthetic cardiac valve Varicella EBV CMV Denque hemorrhagic fever HIV HUS Hantavirus Parvovirus Other viruses TTP Auto/all anti-platelet antibodies study Heparin-induced thrombocytopenia Check PF4
- 27. Thrombocytopenia in thewell neonate Platelet count < 150,000/uL History, examination, CBC, blood smear evaluation, maternal platelet count If there is on obvious etilogy for the TP, bacterial sepsis Congenital anomalies must be considered Maternal history positive Maternal TP Neonatal TP in siblings Maternal drug use Mild TP no bleeding Observe if no change Maternal ITP or SLE Mother acutely ill MASPAT or Capture-P for auto anti-platelet antibodies Preeclampsia HELLP syndrome DIC Hyperthuroidism Viral Illness Platelet <50,000: IVIG ?corticosteroids Random donor platelet transfusions if bleeding( which is unusual ) Blueberry muffin lesions congenital infection hemangiomas Kasabach-Merritt syndrome Purpura fulminans Multiple malformations Trisomy 21,13,18 45XO 11q23.3 deletion TAR syndrome Placenta abnormal Neonatal autoimmune TP Drug adsorption MASPAT or Capture-P Drug-induced TP Placenta infarcts Chorangioma Platelets < 50,000 IVIG < 20,000 Transfuse maternal platelet Platelet Ag and Ab studies on parents and/or baby ( MASPAT or Capture-P cross matching) NAIT Maternal history negative Blood culture, prophylactic antibiotics Abnormal CBC/smear Abnormal Hb, WBC, ANC, RBC indiced or RBC fragments Abnormal platelet size +/- other morphologic changes Bone marrow infiltration Aplastic anemia Pearson syndrome Congenital micro-angiopathic anemia Syndromes Large platelets Bernard-Soulier May-Hegglin Hermansky-Pudiak Gray platelet Small platelet Wiskott-Aldrich NI CBC and smear Platelet > 20,000~30,000 no bleeding Platelet <20,000~30,000 +/- clinical bleeding Careful observation clinically and follow platelet count Count stable or increasing Transfuse random donor platelets Persistent platelets↑ No or transient platelets ↑ Transfuse washed, irradiated maternal platelets IVIG 1g/kg X 1~3 days Persistent platelets post-transfusion ↑ No or only transient platelets↑ Neonatal autoimmune TP Kasabach-Merritt syndrome Early sepsis Viral infection Unknown etilolgy Toxoplasmosis NAIT Drug-induced Amegakaryocytosis Macrothrombocytopenia Familial TP
- 28. Thrombocytopenia in theill 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 Polycythemia Cyanotic congenital heart disease Erythroblastosis fetalis Exchange transfusion p phototherapy DIC Etologies Acute infection Asphyxia RDS Meconium aspiration Obstetrical complications Shock Thrombosis Severe hemolytic disease of the newborn Severe 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 transfusions Maintain fibrinogen > 1.0g/L and PT WNL with FFP +/- cyrorecipitate Normal PTT, PT, TT RDS Pulmonary hypertansion Meconium aspiration Mechanical ventilation Perinatal asphyxia Infection Viral Bacterial Fungal No other specific etiology identified Unknown etiology Ongoing re-evaluation if platelets < 50,000 Acutely ill Usually premature Abdominal signs NEC Acidosis Emesis Lethargy +/- Central venous catheter Hematuria Pulseless extremity Drug use Gancyclovir Heparin Vancomycin Metabolic defects Thrombosis Drug-induced Stop drug Remove catheter when possible LMWH ??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 infants Observe for DIC
- 29. • 新生兒免疫性血小板減少症NAITP •輸血後紫斑症PTP • 血小板輸血無效症PTR • 免疫性血小板低下紫瘢症ITP • 肝素刺激血小板低下症HIT • 藥物抗體血小板低下症DIT • 嚴重輸血相關呼吸窘迫症候群TRALI
- 30. Neonatal alloimmune thrombocytopenia 白種人中此病之報告較多，母體之抗血小板抗體進入胎兒內， 造成新生兒之血小板異常低下，此病可以生於第一胎。西方人報告 中以HPA-1a 抗體為主(又名anti-plA1)，多發生於HPA-1a陰性且 HLA-DR3*0101之婦人。日本則曾報告過HPA-4b抗體引起之新生 兒血小板減少症 Post-transfusion purpura (PTP) 輸血後紫斑症，病人輸血後發生血小 板異常降低，引起反應 的血品包括血小板，紅血球等。部份輸血病人體內可以驗出血小板 抗體，文獻報告中最多的也是HPA-1a抗體(anti-plA1 )
- 31. Heamolytic Disease ofNewborn
- 32. Neonatal Alloimmune Thrombocytopenia Evaluation (NATP)
- 33. NAIT due toanti-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.
- 34. Post-transfusion thrombcytopenia purpura Developed after 1-2 weeks after transfusions Caused by Anti-HPA -1a
- 35. 即輸血小板兩次以上無法達到預期血小板的增加數稱為 “ 血小板輸注無療效” 成因: 異體免疫, 自體抗體, ABO血型不符, 病人因素 ( 如急性出血或組織移植排斥..等 ), 藥物治療 ( 如抗生 素vancomycin..)所引起 血小板輸血後的品質評估: 1 小時後其 “ 校正血小板增加數 ” > 7000, 此方法亦為偵測有無 “ 異體免疫 ” 的間接方式 CCI : ( 輸血後血小板數-輸血前血小板數) X BSA/ 輸注 血小板量。
- 36. 對有抗體的病人 HLA matchedplatelet: for anti-HLA antibody platelet cross-match
- 37. 栓塞性血小板低下紫斑症TTTTPP 形成的原因仍不清楚，多數學者認為是一種病毒傳染後毒素所 造成的反應。其表現的症狀與泛發性血管內凝血症以及溶血性 尿毒症很類似，所以是很容易被忽略的一種急症。但臨床上可 發覺正常金屬蛋白酵素（metalloprotease,ADAMTS-13）可 以分解超大von Willebrand’s體。它具有類似 thrombospondin-1單元（thrombospondin-1–like domains） ，並藉此與內皮細胞上的thrombospondin接受體結合，並由 此固定於內皮細胞上。固定於內皮細胞上的ADAMTS 13，使 可以分解旁邊的超大Von Willebrand's氏因子聚合體。 栓塞性血小板低下紫斑症患者，其金屬蛋白酵素 （metalloprotease－ADAMTS 13）於此時的活性若嚴重通 常趨近於零，無法分解旁邊的超大Von Willebrand's氏因子聚 合體，所導致的微血管內血小板凝集，因而表現出所謂的 pentad：包括微血管病變溶血性貧血、血小板低下、發燒、 神經學症狀、以及腎功能不全等五種特徵。
- 38. HIT is causedby the formation of abnormal antibodies that activate platelets.
- 39. ITP PTR TTPHIT DIT Anti-platelet antibody screen +/- Auto ant-platelet antibody (+) + - - - +drug incubation (+) Special antibodies Auto antibodies Allo antibodies Anti- ADMATS- 13 Anti-PF4 Anti-drug antibodies Platelet specific target GP Ib-IX, IIb-IIIa, Ia-Iia, IV GP Ib-IX, IIb-IIIa, Ia-Iia, IV ( include HLA) ADMATS- 13 PF4–heparin complex on platelet Detection method SPRCA FIPA ELISA MAIPA, SPRCA, ELISA, FIPA, MPHA FRET Gel CAT ELISA SPRCA ( Capture-P or MASPAT)
- 40. Disease Common symptomsDifferential symptoms Hemolytic 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
- 41. Major pathogenesis ofTRALI is known to be related with anti-HLA class I, anti-HLA class II, or anti-HNA in donor's plasma. However, anti-HLA or anti-HNA in recipient against transfused donor's leukocyte antigens also cause TRALI in minor pathogenesis and which comprises about 10% of TRALI.
- 42. SSppeecciiffiicciittiieess ooff lleeuukkooccyytteeaannttiibbooddiieess aassssoocciiaatteedd wwiitthh TTRRAALLII ccaassee Total n=30 Fatalities Leuko-agglutinins HLA class I 6 1 6 HLA class II 13 2 0 HNA-1a,2a 2 0 1 HNA-3a 9 5 9
- 43. • Platelet antigen • Platelet antibody • Disease associated platelet immunology • Detection of anti-platelet antibodies and antigen typing • Q&A
- 44. • Antigen typing • Platelet antibody detection method • Concordance of antibody detection • Other platelet disease associated test • Differential test of platelet disease
- 45. ELISA method e.g.Bio-Rad HPA1a Typing Assay
- 46. Some SSP kitprovided HPA genotype E.g. innotrain HPA-ready gene
- 47. PCR-SSP 5' TCACAGCGAGGTGAGGCCA3' 5' TCACAGCGAGGTGAGGCCG 3' 5' GGAGGTAGAGAGTCGCCATAG 3' HPA-1
- 48. MAPIA Monoclonal Antibody-specificImmobilization of platelet antigens Gold standard method Modified Antigen capture ELlSA (MACE) Commercial kit :GTI diagnostics Purified platelet glycoproteins ELlSA/bead method Commercial kit :GTI diagnostics (Pakplus, PakLx) Specific platelet glycoprotein (IIb/IIIa,Ib/Ix,Ia/IIa,GPIV,HLA)) Flowcytometry or FIPA
- 51. Sample Consensus results% concordance MPHA MAIPA Overall 1 Negative 100 (18/18) 100 (13/13) 100 (18/18) 2 Anti- HLA-class I 83.3 (15/18) 71.4 (10/14) 100 (18/18) 3 Anti-Nak a 100 (18/18) 76.9 (10/13) 100 (18/18) 4 Anti-HPA-5b 88.9(16/18) 100(14/14) 94.4 (17/18) Anti- HLA-class I 50(9/18) 21.4(3/14) 44.4(8/18) 5 Anti-HPA-4b 100(18/18) 53.8(7/13) 100(18/18) 6 Anti-HPA-1a - 100(14/14) 83.3(15/18) For IPIWP workshop, HPA-1b/b and HPA-5b/5b platelets were distributed to the labs by Dr. Santoso
- 52. • By measuringADAMTS13 in plasma, it has been clearly shown that patients with inherited TTP have severe ADAMTS13 deficiency. • However, patients with acquired TTP present with clinical and laboratory heterogeneity, and there are unequivocal cases of acquired TTP with measurable plasma levels of ADAMTS13.
- 54. Test characteristics: •very rapid: result in less than 20 min (including 10 min centrifugation) • very simple procedure • very reliable performance* • economical: unused microtubes in the card can be used at a later time (if the aluminium seal is intact)
- 55. PTR NAITP HITDIT TTP ITP TRALI Test or investig ation CCI CBC, DC CBC,DC Heparin history Drug history DAT BUN CBC,DC DAT BNP CBC X-ray Serologi cal test PRA(class I) ELISA(Pakplus) SPRCA (capture-P, MASPAT):anti-platelet antibody screening, and cross matching PIFA Luminex PRA class I MAIPA MPHA Mother and fetus PRA(class I/II) ELISA(Pakplus) SPRCA (capture-P, MASPAT):anti-platelet antibody screening PIFA Luminex PRA MAIPA MPHA Mother serum Vs. Father/baby plat. SPRCA, PIFA cross matching ELISA (PF4) CAT (PF4) Serum + drug, or eluent SPRCA ( Capture- P, MASPAT) FRET:ADMATS- 13 activity ELISA (Pakauto) ELISA (Pakplus) SPRCA ( Capture-P, MASPAT ): auto antibody and allo antibody PIFA (auto) Donor serum ( and/or patient ) Luminux PRA ( class I/class II/HNA) ELISA PRA (class I/II) flowPRA (class I/II) Leuko-agglutinin test MAIGA GIFA Antigen HLA class I typing HPA typing CD36 typing Parent and fetus: HLA class I/II typing, HPA typing CD 36 typing
- 56. • Platelet antigen • Platelet antibody • Disease associated platelet immunology • Detection of anti-platelet antibodies • Q&A
- 57. 張志昇 Email: [email protected], [email protected] Facebook, Plurk : [email protected] Skype : jschang12 QQ: 1150352697 Line: jschang12 Blog: http://www.jschang.idv.tw Youtube : http://tw.youtube.com/ntuh-tm Website: http://www.jschang,idv.tw Mobilephone -0928825645 Office 0223123456ex65404
Editor's Notes
- #9 System 的概念比較接近是epitope
- #10 血小板上的這些醣蛋白數量也與其臨床影響有關 Anti-HPA-1a 及 anti-HPA-4b都在 GP IIb/III上
- #11 HPA-1b, -2b, -5b 抗原亞洲人都較歐洲人少 相對應的抗體如anti-HPA-1a , anti-HPA-2b,-5b也相對的較少 HPA-4b是日本
- #13 在亞洲區除澳洲外，血小板Naka缺乏可見於各參與國家，發生率在0.62%-7.92%，日本有最高的發生率，泰國的發生率最低。
- #49 使用glycoprotein complex來進行分析， 可以支到抗體作用的目標所在蛋白 也須要以支型別的細胞組來進行鑑定
- #52 MPHA 對於anti-HPA-1a,MAIPA對於 HPA-4b 及 anti-Naka都因無相關的控制組而無法確認