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Platelet transfusion

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Platelet transfusion Platelet transfusion Presentation Transcript

  • Platelet Transfusion Magdy El Ekiaby,MD Shabrawishi BTC Shabrawishi BTC
  • PlateletsPlatelets are anucleatedblood cellsThey arise from bonemarrow megakaryocytesThey play key role inblood hemostasisNormal blood plateletcount is 140-450x1000/uL Shabrawishi BTC
  • ThrombocyopeniaHereditary thrombocytopenia as TAR,May-Hegglin,……..etcAcquired as in ITP, TTP, hypersplinism,…etc Shabrawishi BTC View slide
  • ThrombastheniaHereditary as Glanzmann thrombasthenia,Bernard-Soulier Syndrome,…… etcAcquired thrombasthenia as in druginduced cases due to salicylates and non-steroidal anti-inflammatory drugs Shabrawishi BTC View slide
  • Indications of Platelet TransfusionSevere thrombocytopenia <5000/ul inpatients without clinical bleedingThrombocytopenia with clinical bleeding oras supportive therapy duringchemo/radiotherapy and intransplantations Shabrawishi BTC
  • Contraindications of Platelet TransfusionAutoimmune thrombocytopeniaThrombotic Thrombocytopenic Purpura &related syndromes Shabrawishi BTC
  • Platelet Donor CriteriaAge, 18 – 55 yearsSexDonor ScreeningBlood Screening (HBV, HCV, HIV 1&2serology & ID-NAT + Syphilis Ab)Blood group & RhNo Salicylates or non steroidal anti-inflammatory drugs for 7 days Shabrawishi BTC
  • Preparation of Platelet Concentrates From Donated Blood UnitsPlatelets can be prepared from freshly donated bloodunits by deferential centrifugation in cooling centrifugesPrepared units can be stored for 1,3 or 5 days at 22° Cdepending on method of preparationPlatelet content/concentrate = 0.5x10¹¹ platelets in avolume of 40-50 ml Shabrawishi BTC
  • Preparation of Platelet Concentrate Using Cell Separators Blood donors can donate platelets only by cell separators Depending on donor platelet count one can obtain single or double platelet therapeutic dose Platelet therapeutic dose= 3x10¹¹ in 200 ml plasma volume and can be stored for 1,3 or 5 days at 22° C on platelet shaker Ideally it should contain <5x10*6 leucocytes Shabrawishi BTC
  • Dose of Platelet TransfusionIn clinical bleeding, platelet transfusionshould be given untill bleeding is controledIn prophylaxis as in surgery andchemo/radiotherapy, the required level ofplatelets is determined by the clinicianaccording to many factors, eg. Type ofsurgery, clinical condition of the patient,……. etc Shabrawishi BTC
  • Dose ResponseCessation of clinical bleedingCorrected Count Increment (CCI)– CCI at 1 hr = (Platelet Countpost- platelet countpre)-BSA No. of units transfused/No. of platelets transfused– CCI at 1 hr = >4000-5000/ >7000-10000 Shabrawishi BTC
  • Complications of Platelet TransfusionImmunolgicalBacterialViral Shabrawishi BTC
  • Immunologicl ComplicationsAllergy & AnaphylaxisPTPGVHDPlatelet Refractoriness Shabrawishi BTC
  • Platelet ImmunologyPlatelets express HLA class I antigens,ABH, P, Lewis and I5 biallelic platelet specific antigen systemsEach system includes a high frequencyantigen >96% and a low frequencyantigenSome may be detected on other cells Shabrawishi BTC
  • Allo-Antigens in Platelet Glycoproteins Allo-Antigen Synonym Caucasian Japanese GP Location HPA-1a Zw a, PIA1 97.9 99.9 IIIa HPA-1b Zw b, PIA2 26.5 3.7 HPA-2a Kob 99.3 NT Ib HPA-2b Koa, Siba 14.6 25.4 HPA-3a Baka, Leka 87.7 78.9 IIb HPA-3b Bakb 64.1 NT HPA-4a Pena, Yukb 99.9 99.9 IIIa HPA-4b Penb, Yuka 0.2 1.7 HPA-5a Brb, Zavb 99.2 NT Ia HPA-5b Br , Zav , Hc 20.6 a a a NT Shabrawishi BTC
  • Platelet Glycoproteins HPA5 HPA1 HPA2 HPA3 s s ss β α β2M HLA gpIb gpIX gpV gpIaIIa gpIIbIIIaIn NAITP Platelet Allo-Antibodies are directed against HPA1a 78% HPA5b 17% HPA3a 3% others 2%Data from Mueller-Eckhardt et al. 1989 Shabrawishi BTC
  • Platelet AntibodiesA platelet reactive antibody may react againstany antigen on the plateletPlatelet antibodies may be HLA (class I) ,platelet specific antigen, ABH, ... Etc specificantibodiesLike red cell antibodies, they are IgG or Ig M andcause mostly extravascular destructionThe antibodies may be auto or allo-antibodies Shabrawishi BTC
  • Post Transfusion Purpura, PTP• PTP is a rare (1 / 50000) but severe side effect of blood transfusion that resembles DTR due to red cell transfusion• In more than 90% of patients PTP is encountered in women who are HPA1b and have developed anti HPA1a antibodies due to immunization by previous pregnancy• Fall in platelet count 5 to 10 days after transfusion of any of the blood components• Mortality is high, some 5% of PTP cases die• The most effective therapy is plasmapheresis &/or IVIg• Corticosteroids is an essential therapy in combination with other therapies Shabrawishi BTC
  • Graft Versus Host Disease (GVHD) It is reactivity of donor lymphocytes against host tissues in immuno- suppressed patients This causes dermatitis, hepatitis, gastroentritis & if it happens due to transfusion of cellular blood components it is usually fatal It can be prevented by irradiation of RBCs & platelets Shabrawishi BTC
  • Platelet Refractoriness, PR• Platelets are given to thrombocytopenic cancer patients to prevent major hemorrhage• PR is the less than expected increase in platelet count• PR occurs in 10 to 20% of patients who receive prophylactic platelets• 1.4 million platelet concentrates from 5.6 million donations are used each year in the EU• Anti-HLA or anti-HPA antibodies destroy transfused random ABO/RhD-compatible platelets• The refractory state increases the chance of major bleeding, including cerebral bleeding• Treatment of choice is HLA and HPA selected donor platelets or platelet cross matching Shabrawishi BTC
  • Causes of Platelet RefractorinessNon-immunological– Splenomegaly– Drugs (eg amphotricin B)– Accelerated platelet consumption Shabrawishi BTC
  • Management of PRPrevention by leucodepleted cellular bloodcomponents, <5×106 WBCs/bloodproductHLA & HPA matched donorsCross matched platelet concentrates Shabrawishi BTC
  • Leuco-Reduced Cellular ComponentsQC usingflowcytometryStaining of nucleatedcells with propodiumiodide, PISimple equation toobtain residualleucocytes in aconcentrate Shabrawishi BTC
  • Residual Leucocyte Count Residual Leucocyte CountLeucocyte Countx10*6 7 6 5 4 3 2 1 0 1 2 3 4 5 6 7 8 Cell Separator Shabrawishi BTC
  • Platelet Cross Matching Experience6 cases ofimmunologicalrefractorinessOn average 1/9cross-matcheddonors was foundcomp.Delivery time 1 – 2days Shabrawishi BTC
  • Risks Still Exist in Blood Transfusions 1. Bacteria Introduced during collection 5. Leukocytes 2. Emerging/Unknown Adverse immune responses and transfusion reactions Viruses4. Known Pathogens 3. Window Period For which no assay Limits of detection of is available current assays (e.g. false negatives) Transfusion Recipient Shabrawishi BTC
  • Bacterial Contamination  Risk of bacterial contamination in platelet doses can be as high as 1:2,0001  The mortality rate for platelet-related sepsis is one in four 2  A prospective study3 of 3,584 platelet transfusions in 161 bone marrow transplant patients demonstrated risk of symptomatic bacteremia as: • 1 per 16 patients • 1 per 350 transfusions • 1 per 2,100 platelet units  UK SHOT data reported three deaths in UK between 1996 and 1999 as a result of bacterial contamination41 Blajchman MA, The Safety of the Blood Supply, Hillyer CD ed. 1999: 18-27. 3 Chiu EKW et al, Transfusion. 1994:34:950-953.2 Goodnough LT et al, New England Journal of Medicine. 1999; 340/6: 438-447. 4 Love EM et al. The Serious Hazards of Transfusion Annual Report 1999-2000. Published March 2001.
  • Emerging/Unknown Pathogens It is impossible to know if and when emerging pathogens will threaten the safety of the blood supply Impact of previously unknown pathogens is demonstrated through HCV and HIV New viruses continue to emerge at a rate of every 2–3 years with a potentially damaging virus transmitted through blood every 5 years1 1 LEK Consulting. Market research commissioned by Baxter Healthcare Corporation. Boston, MA, USA: January 2001. Shabrawishi BTC
  • Window Period (False Negative) NAT/PCR testing has significantly reduced the window period but it still exists Collection of blood during the window period is likely the most important source of residual HIV infections1 Median Time to NAT/PCR2 Virus Test Seroconversion Positive HIV p-24 antigen 16 days 11 days anti-HIV 22 days HCV anti-HCV 70 days 12 days HBV HBsAg 56 days 40 days 1 Dodd RY, The Safety of the Blood Supply, ed. Hillyer CD. 1999: 1-17. 2 Bush MP, Kleinmann SH, Transfusion. 2000; 40: 143-159.
  • Current Risk of Transfusion Transmitted Virus Risk per Unit Transfused (post-NAT) Virus USA France Germany HIV 1:1,576,000 1:1,000,000 1:1,900,000 HCV 1:223,000 1:200,000 1:<350,000 HBV 1:135,000 1:180,000 1:220,000Cumulative 1:79,808 1:86,505 1:126,121 Risk Stramer SL, Current Opinion in Hematology. 2000; 7: 387-391. Pillonel J et al, Eurosurveillance. 1998; 3: 76-79. Seifried E et al, British Journal of Haematology. 2000; 109: 694-698. Shabrawishi BTC
  • Known Pathogens Transmission There are pathogens that are known, but not routinely screened for of parasites by transfusion, although currently rare in developed countries, does occur Donor demographics may bring change in risk level of transfusion-transmitted agents  Example: Incidence of malaria and Chagas’ disease seems to be increasing • Travel to endemic areas increasing • Climate changes • Immigration Shabrawishi BTC
  • Pathogens Known to be Transmitted by Blood Transfusion Routinely Screened Family Pathogen Disease Yes NoHepatitis viruses HBV, HCV Hepatitis X HEV, HGV Hepatitis XRetroviruses HIV-1 & -2 AIDS X HTLV-I & -II Malignant lymphoproliferative X disorders, neuropathyHerpes viruses CMV CMV retinitis, hepatitis, pneumonia X EBV Epstein-Barr Syndrome X HHV-8 Kaposi’s Sarcoma XParvoviruses B19 Aplastic anemia XBacteria Gram-negative, Gram-positive Sepsis X Treponema pallidum Syphilis X Borrelia burgdorferi Lyme disease X Rickettsia rickettsii Rocky Mountain Spotted Fever X Ehrlichia chafeensis Ehrlichiosis XParasites Trypanosoma cruzi Chagas’ disease X Babesia microti Babesiosis X Leishmania donovani Leishmaniasis X 25/12/2003 Plasmodium spp. Shabrawishi BTC Malaria XBased on US practices
  • Pathogen Inactivation Technology Shabrawishi BTC
  • Nucleic Acids Must “UnZip” During Pathogen Replication Replication of DNA / Strand Separation Nucleic Acids RNA and Pathogen25/12/2003 Shabrawishi BTC
  • Amotosalen Mechanism of ActionAmotosale UVA Illumination n DNA or RNA ofpathogen Docking Permanent Crosslinking25/12/2003 Shabrawishi BTC
  • Psoralen Locks Nucleic Acid and Prevents Replication DNA / RNA No Strand Separation No Replication of Nucleic Acids or Pathogens25/12/2003 Shabrawishi BTC
  • Psoralen Permanently Crosslinks Both Single- and Double-Stranded Nucleic Acids Helical Regions Single-stranded DNA or RNA Double-stranded25/12/2003 Shabrawishi BTC DNA or RNA
  • INTERCEPT Blood System:The Only System in Clinical Trials for All Three Blood Components Platelets Plasma No RBCs Shabrawishi BTC
  • INTERCEPT Blood System: Status Preclinical Phase I Phase II Phase III Regulat Clinical ory use ReviewINTERCEPT Platelets -EUINTERCEPT Platelets -USINTERCEPT Plasma StoppedINTERCEPT Red Cells**Phase I data allowed us to move directly to Phase III Shabrawishi BTC
  • Psoralen Blood System for Platelets and Plasma Use a Similar ProcessThe Psoralen Blood System for plateletsand plasma use the same compoundThis compound, amotosalen, is activatedby UVA lightBoth systems use the same UVA device(the Illuminator) Shabrawishi BTC
  • ConclusionPlatelet transfusion is an importanttherapeutic modality in transfusionmedicineGMP, proper prescription and accuratemonitoring are all essential factors for safeand effective outcome Shabrawishi BTC
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