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Platelet transfusion
This document provides information about platelet transfusion. It discusses what platelets are, their role in hemostasis, normal platelet counts, causes of thrombocytopenia, indications for platelet transfusion, contraindications, donor criteria, preparation of platelet concentrates, dosing, response to transfusion, complications including immunological and non-immunological issues, and methods to reduce complications like use of leukoreduced products. The document contains detailed information about platelet immunology, causes of refractoriness, its management, and methods to improve safety and availability of platelet transfusion like use of matched donors and crossmatching.
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Overview of platelet transfusion and the presenter.
Platelets are anucleated blood cells crucial for hemostasis. Normal count: 140-450 x 1000/uL.
Thrombocytopenia types: hereditary (TAR, May-Hegglin) and acquired (ITP, TTP).
Thrombasthenia includes hereditary (Glanzmann) and acquired types due to drugs.
Platelet transfusion is indicated for severe thrombocytopenia and clinical bleeding.
Autoimmune thrombocytopenia and TTP are contraindications for platelet transfusion.
Donor criteria includes age, health, and medication history (no NSAIDs for 7 days).
Preparation from blood by centrifugation, stored for 1-5 days at 22°C, typical content 0.5x10¹¹.
Platelets can be obtained using cell separators for therapeutic doses; stored similarly.
Doses depend on clinical context; continued until bleeding stops, varies by patient.
Corrected Count Increment (CCI) is key to evaluating platelet transfusion success.
Platelet transfusions can lead to immunological, bacterial, and viral complications.
Allergic reactions, PTP, GVHD, and platelet refractoriness as immunological issues.
Platelets have antigens (HLA, ABH systems) influencing immunological responses.
Data on allo-antigens in platelet glycoproteins, their prevalence in populations.
Platelet antibodies may be anti-HLA or specific antigens; lead to severe reactions.
PTP is a serious complication post-transfusion; most common in women after pregnancy.
GVHD occurs in immunosuppressed patients post-transfusion; can be fatal.
Definition, prevalence (10-20%), and the significance of using matched platelets.
Non-immunological causes like splenomegaly and drug interactions leading to PR.
Management strategies include using leukodepleted components and matched donors.
QC techniques using flow cytometry for assessing leukocyte levels in blood products.
Graphical presentation of residual leucocyte counts in blood concentrates.
Experience in cross-matching for immunological refractoriness cases and success rates.
Potential risks include bacterial infection, immune responses, and unknown pathogens.
Bacterial contamination in platelets poses severe risks; significant mortality rates reported.
Emerging viruses challenge blood safety; new pathogens appear regularly.
NAT/PCR testing reduces but does not eliminate the window period for HIV/HCV exposure.
Statistics on transfusion-transmitted viral risks in different countries post-NAT.
List of known pathogens, both screened and unscreened, linked to blood transfusions.
Introduction to pathogen inactivation technologies in blood component safety.
Description of psoralen's action in inhibiting pathogen replication during blood processing.
Status of INTERCEPT Blood System trials for various blood components.
Shared process for psoralen systems used in platelet and plasma safety.
Emphasizes the importance of GMP and monitoring in effective platelet transfusion.
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Platelet transfusion
- 1. Platelet Transfusion Magdy El Ekiaby,MD Shabrawishi BTC Shabrawishi BTC
- 2. Platelets Platelets are anucleated bloodcells They arise from bone marrow megakaryocytes They play key role in blood hemostasis Normal blood platelet count is 140-450x1000/uL Shabrawishi BTC
- 3. Thrombocyopenia Hereditary thrombocytopenia asTAR, May-Hegglin,……..etc Acquired as in ITP, TTP, hypersplinism,… etc Shabrawishi BTC
- 4. Thrombasthenia Hereditary as Glanzmannthrombasthenia, Bernard-Soulier Syndrome,…… etc Acquired thrombasthenia as in drug induced cases due to salicylates and non- steroidal anti-inflammatory drugs Shabrawishi BTC
- 5. Indications of PlateletTransfusion Severe thrombocytopenia <5000/ul in patients without clinical bleeding Thrombocytopenia with clinical bleeding or as supportive therapy during chemo/radiotherapy and in transplantations Shabrawishi BTC
- 6. Contraindications of Platelet Transfusion Autoimmune thrombocytopenia Thrombotic Thrombocytopenic Purpura & related syndromes Shabrawishi BTC
- 7. Platelet Donor Criteria Age,18 – 55 years Sex Donor Screening Blood Screening (HBV, HCV, HIV 1&2 serology & ID-NAT + Syphilis Ab) Blood group & Rh No Salicylates or non steroidal anti- inflammatory drugs for 7 days Shabrawishi BTC
- 8. Preparation of PlateletConcentrates From Donated Blood Units Platelets can be prepared from freshly donated blood units by deferential centrifugation in cooling centrifuges Prepared units can be stored for 1,3 or 5 days at 22° C depending on method of preparation Platelet content/concentrate = 0.5x10¹¹ platelets in a volume of 40-50 ml Shabrawishi BTC
- 9. Preparation of PlateletConcentrate 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
- 10. Dose of PlateletTransfusion In clinical bleeding, platelet transfusion should be given untill bleeding is controled In prophylaxis as in surgery and chemo/radiotherapy, the required level of platelets is determined by the clinician according to many factors, eg. Type of surgery, clinical condition of the patient, ……. etc Shabrawishi BTC
- 11. Dose Response Cessation ofclinical bleeding Corrected 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
- 12. Complications of PlateletTransfusion Immunolgical Bacterial Viral Shabrawishi BTC
- 13. Immunologicl Complications Allergy &Anaphylaxis PTP GVHD Platelet Refractoriness Shabrawishi BTC
- 14. Platelet Immunology Platelets expressHLA class I antigens, ABH, P, Lewis and I 5 biallelic platelet specific antigen systems Each system includes a high frequency antigen >96% and a low frequency antigen Some may be detected on other cells Shabrawishi BTC
- 15. Allo-Antigens in PlateletGlycoproteins 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
- 16. Platelet Glycoproteins HPA5 HPA1 HPA2 HPA3 s s ss β α β2M HLA gpIb gpIX gpV gpIaIIa gpIIbIIIa In NAITP Platelet Allo-Antibodies are directed against HPA1a 78% HPA5b 17% HPA3a 3% others 2% Data from Mueller-Eckhardt et al. 1989 Shabrawishi BTC
- 17. Platelet Antibodies A plateletreactive antibody may react against any antigen on the platelet Platelet antibodies may be HLA (class I) , platelet specific antigen, ABH, ... Etc specific antibodies Like red cell antibodies, they are IgG or Ig M and cause mostly extravascular destruction The antibodies may be auto or allo-antibodies Shabrawishi BTC
- 18. 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
- 19. Graft Versus HostDisease (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
- 20. 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
- 21. Causes of PlateletRefractoriness Non-immunological – Splenomegaly – Drugs (eg amphotricin B) – Accelerated platelet consumption Shabrawishi BTC
- 22. Management of PR Preventionby leucodepleted cellular blood components, <5×106 WBCs/blood product HLA & HPA matched donors Cross matched platelet concentrates Shabrawishi BTC
- 23. Leuco-Reduced Cellular Components QCusing flowcytometry Staining of nucleated cells with propodium iodide, PI Simple equation to obtain residual leucocytes in a concentrate Shabrawishi BTC
- 24. Residual Leucocyte Count Residual Leucocyte Count Leucocyte Countx10*6 7 6 5 4 3 2 1 0 1 2 3 4 5 6 7 8 Cell Separator Shabrawishi BTC
- 25. Platelet Cross MatchingExperience 6 cases of immunological refractoriness On average 1/9 cross-matched donors was found comp. Delivery time 1 – 2 days Shabrawishi BTC
- 26. Risks Still Exist in Blood Transfusions 1. Bacteria Introduced during collection 5. Leukocytes 2. Emerging/Unknown Adverse immune responses and transfusion reactions Viruses 4. 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
- 27. 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 contamination4 1 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.
- 28. 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
- 29. Window Period (FalseNegative) 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.
- 30. Current Risk ofTransfusion 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 1:220,000 Cumulative 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
- 31. 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
- 32. Pathogens Known tobe Transmitted by Blood Transfusion Routinely Screened Family Pathogen Disease Yes No Hepatitis viruses HBV, HCV Hepatitis X HEV, HGV Hepatitis X Retroviruses HIV-1 & -2 AIDS X HTLV-I & -II Malignant lymphoproliferative X disorders, neuropathy Herpes viruses CMV CMV retinitis, hepatitis, pneumonia X EBV Epstein-Barr Syndrome X HHV-8 Kaposi’s Sarcoma X Parvoviruses B19 Aplastic anemia X Bacteria 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 X Parasites Trypanosoma cruzi Chagas’ disease X Babesia microti Babesiosis X Leishmania donovani Leishmaniasis X 25/12/2003 Plasmodium spp. Shabrawishi BTC Malaria X Based on US practices
- 33. Pathogen Inactivation Technology Shabrawishi BTC
- 34. Nucleic Acids Must“UnZip” During Pathogen Replication Replication of DNA / Strand Separation Nucleic Acids RNA and Pathogen 25/12/2003 Shabrawishi BTC
- 35. Amotosalen Mechanism of Action Amotosale UVA Illumination n DNA or RNA of pathogen Docking Permanent Crosslinking 25/12/2003 Shabrawishi BTC
- 36. Psoralen Locks NucleicAcid and Prevents Replication DNA / RNA No Strand Separation No Replication of Nucleic Acids or Pathogens 25/12/2003 Shabrawishi BTC
- 37. Psoralen Permanently CrosslinksBoth Single- and Double-Stranded Nucleic Acids Helical Regions Single-stranded DNA or RNA Double-stranded 25/12/2003 Shabrawishi BTC DNA or RNA
- 38. INTERCEPT Blood System: TheOnly System in Clinical Trials for All Three Blood Components Platelets Plasma No RBCs Shabrawishi BTC
- 39. INTERCEPT Blood System:Status Preclinical Phase I Phase II Phase III Regulat Clinical ory use Review INTERCEPT Platelets - EU INTERCEPT Platelets - US INTERCEPT Plasma Stopped INTERCEPT Red Cells* *Phase I data allowed us to move directly to Phase III Shabrawishi BTC
- 40. Psoralen Blood Systemfor Platelets and Plasma Use a Similar Process The Psoralen Blood System for platelets and plasma use the same compound This compound, amotosalen, is activated by UVA light Both systems use the same UVA device (the Illuminator) Shabrawishi BTC
- 41. Conclusion Platelet transfusion isan important therapeutic modality in transfusion medicine GMP, proper prescription and accurate monitoring are all essential factors for safe and effective outcome Shabrawishi BTC
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Editor's Notes
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