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Platelet Transfusion 2013


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Platelet Transfusion 2013

  1. 1. Clinical Case• 04/19/02 61 year old male with myeloma received auto PBSCT• 04/21/02 Fever, LLL pneumonia; Rx with Timentin and Aztreonam• 04/24/02 Vancomycin added• 04/24/02 Developed mild chills with 100 mL pooled plts; transfusiond/c; developed T38.4, BP 60/30, O2 Sat 91%, HR 140 onehour after transfusion d/c; admitted to ICU for presumptiveseptic shock• 04/26/02 Blood Bank notified of subsequent eventsGram stain of saved segment: 2+ Gram-negative rodsCulture of saved segment: 4+ Klebsiella oxytoca, sensitive toTimentin and Aztreonam• 05/30/02 Pt died with multiorgan failureNo post transfusion blood cultures grew KlebsiellaFinal source of contaminated platelet component remainsundetermined
  2. 2. Bacterial Contamination/ Sepsis• usually during transfusion but may occur up to 4-6 h posttransfusion• high fever, severe chill, nausea, vomiting, hypotension,dyspnea• can develop shock, DIC, multiorgan system failure
  3. 3. Septic Transfusion Reaction• Bacterial sepsis has been a long-standing, well-known risk ofmorbidity and mortality related to platelet transfusion therapy• Estimates of incidence vary, but universally acknowledged as mostfrequent infectious transfusion risk in USA• Since the early 1980s, more/most attention paid to transmission ofviral infection• AABB required implementation of methods to limit and detectbacterial contamination in platelet components in March 2004• Since 2004, STR have decreased but have not been eliminated
  4. 4. Sources for bacterial contaminationof platelet components• Phlebotomy– Skin contaminants (inadequate disinfection)– Skin plug (large bore collection needle)• Processing– Contaminated collection bag, tubing, anticoagulant• Asymptomatic donor bacteremia
  5. 5. Bacterial Contamination of PlateletsComponents (05/1993-03/2013)• Coagulase negative Staph – 8• Bacillus spp. – 4• S.aureus – 5• Serratia marcescens – 1• S. viridans – 2• Strep Group A – 1• Klebsiella oxytoca – 1• E.coli – 1• Mixed gram negative - 1
  6. 6. Bacterial SepsisDeterminants of ClinicalSeverity• Organism– Gram-negative organisms elaborating endotoxins– Virulence factors permitting bacterial growth• Bacterial load infused– Time of storage: >3 days for platelets– Volume of component• Host characteristics– Concomitant administration of antibiotic– Degree of immunosuppression– Neutropenia
  7. 7. Preparation of Blood ComponentsRed Cells Platelet-Rich PlasmaRed Cells Platelet Concentrate PlasmaStorage1-6°C 20-24°C -18°C42 days 5 days 1 year
  8. 8. Apheresis Collection1½ - 3 HoursComponentCollectedAnticoagulantReturnBlood FilterSalineBlood CellSeparatorPlateletsStem CellsLymphocytesGranulocytesRBCPlasma
  9. 9. Platelet Preparation Process• Prepared from whole blood or apheresis collection (MSKCC100%, USA 87%)• Diversion of first 30-50 mL• Store at standard condition (20-24oC) for 24-36 h, 8 mL sampleobtained for culture (SCD), culture in FDA approved system 18-24 h, released to available inventory usually day 3 of 5 dayexpiry• Estimated sensitivity for day 1 culture is only 22-40%• Residual risk of bacterial contamination on day of transfusionor outdate is 1:3,000 - 5,000 (clinical significance unknown)
  10. 10. Bacterial Infection byPlateletsFrom “Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2011”
  11. 11. Comparison Across Institutions(Blood suppliers)• ARC Apheresis Collection 12/01/06 – 07/31/08– 781,936 collections– Confirmed positive – 130 (1:6015)– False negative – 9 (1:86,882) reported reactions– One fatality• Canadian Blood Services 03/2004 – 02/2006– 43,732 collections– Confirmed positive – 3 (1:14,577)– False negative – 1 reported reaction, not fatal• Hēma-Quēbec 06/2002 – 02/2006– 33,272 collections– Confirmed positive – 3 (1:11,091)– False negative – 1 reported reaction, possibly fatal
  12. 12. Comparison Across Institutions(Transfusion Services)• Johns Hopkins Passive Surveillance 03/2004 – 08/2007– Two STR in 49,625 SDP transfusion(1:24,813); not fatal• CWRU Active Surveillance 07/1991 – 02/2000 and 03/2004 –12/2006– 1:2,060 culture positive at issue (50 units)– 42 units transfused– 5 reactions with demonstrated bacteremia (1:20,600)– 1 death (1:102,998)
  13. 13. MSKCC Platelet TransfusionTotal STR05/1993-02/2004 121,552 18** 1:6753 1.7/year03/2004-02/2013 124,641 6* 1:20,773 0.7/year* 01/2009 Staph lugdunensis ** two fatal11/2011 Staph aureus12/2011 Strep viridans03/2012 Strep viridans03/2013 Staph aureus (2 recipients)03/2004 – 02/2013- 23,521 collections- confirmed positive – 2 (1:11,761)- False negative - 1
  14. 14. AABB Bulletin # 12-04, October 4, 2012:“Recommendations to Address Residual Risk of Bacterial Contamination ofPlatelets”• Develop a policy to further reduce the residual risk• Improve the recognition and monitoring of STR• Optimize the appropriate transfusion practice
  15. 15. Bacterial Contamination of Platelet ComponentsPossible Future Preventive Measures• Lower storage temperature• Improve culture methods (↑ volume tested, test split units, sample later)• Point-of-issue testing (must be simple, rapid):Culture platelets after the first 24 hours of storage and then retestday four or day five platelets just once with rapid test on the day oftransfusion• Pathogen inactivation (loss of cells, ↓ cell function and survival, toxicity, neo-antigenicity, and expense)• Limit platelet transfusion
  16. 16. MSKCC Platelet Transfusions** Projected0200040006000800010000120001400016000180001997 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012Unitstransfused*
  17. 17. MSKCC Transfusion GuidelinesPLATELETS1. PLT CT <10,000/uL in non-bleeding patientWITHOUT other associated hemostatic defects2. PLT CT <20,000/uL in non-bleeding patient WITHother associated hemostatic defects3. PLT CT <50,000/uL and minor bleeding, severe DIC,invasive procedure or perioperative patient
  18. 18. MSKCC Transfusion GuidelinesPLATELETS4. PLT CT <100,000/uL and clinicallysignificant bleeding (requiring RBC txn orinto closed space) or bleeding risk5. Massive transfusion (>8 units RBC/24hr),continued bleeding and PLT CTunavailable6. Other
  19. 19. Platelet Transfusion Non-indications• ITP or TTP unless clinically significant bleeding• Prophylactic use in massive transfusion
  20. 20. Concept of Patient Blood Management• June 2011, HHS stressed the importance of strengtheningblood management systems to promote the rational use ofblood, cut down on the number of unnecessary transfusions,reduce transfusion risks, improve patient care and savehospital resources• Requires evidence based transfusion guidelines (whenavailable)
  21. 21. Considerations for Risk Reduction inTransfusion• transfusion has never undergone prospective randomizedtesting in the manner expected of a new drug• repletion of elements of hemostasis effective in bleedingpatient• prophylaxis to prevent bleeding in setting of mild-moderateabnormal test result often lacks evidence-based support• associated with unfavorable risk-to-benefit ratio
  22. 22. MSKCC TransfusionGuidelinesPlatelets Inpatient (%) Outpatient (%)PLT CT < 10,000/μL 15 5PLT CT < 20,000/μL 25 12PLT CT < 50,000/μL 31 6PLT CT < 100,000/μL 4 1
  23. 23. Prophylactic Platelet Transfusion• most common use of platelet transfusion• most previous research focused on optimal dose and threshold• effectiveness is uncertain/unproven compared to therapeuticstrategy• previous non-randomized comparisons of therapeuticstrategy with historical prophylactic controls have reported noincrease in major bleeding episodes or RBC transfusion, butsignificant decrease in platelet transfusion• current randomized controlled trial to compare prophylactic vtherapeutic in hematologic malignancies for safety and clinicaleffectiveness• if therapeutic is non-inferior, then potential benefit of decreasedtransfusion: decreased risks, reactions, cost
  24. 24. Prophylactic Platelet Transfusion for Invasive BedsideProcedures• bronchoscopy, endoscopy, LP, paracentesis, thoracentesis,CVC insertion all part of modern medical practice• no published evidence for increased risks of procedure-related hemorrhage and no controlled studies thatindicate what platelet count represents contraindication orthat prophylactic transfusion reduces risk of hemorrhage• no evidence that ASA or NSAIDS increase risk
  25. 25. Relationship between hemorrhage and the platelet count innon-transfused thrombocytopenic patientsSlichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients.Transfus Med Rev. 2004 Jul;18(3):153-167 Gaydos,, 1962
  26. 26. Fecal blood loss inthrombocytopenic patientsSlichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients.Transfus Med Rev. 2004 Jul;18(3):153-167 Slichter:Clin Haem, 1978
  27. 27. Gmur: Lancet, 1991
  28. 28. Slichter: Blood, 1999
  29. 29. Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of Prophylactic Platelet Transfusions andPrevention of Hemorrhage. N Engl J Med. 2010 Feb 18; 362 (7): 600-613.
  30. 30. Friedman: Trans Med Rev, 2002
  31. 31. German Therapeutic v Prophylactic Platelet Transfusion StudyWandt:Lancet,2012• randomized, multicentre, parallel-group trial• stable adults, AML and auto SCT (391 patients)Therapeutic Prophylactic (≤ 10,000/mcL)Platelets transfused (u) 1.6 2.4 33.5% reduction p < 0.0001WHO gr ≥ 2 (% per treat) 42 19 p < 0.0001• 93% of bleeds WHO grade 2• overall survival, RBC transfusion, hospital days, side effects, durations of TCP and time toonset of first bleed did not differ• study not powered to prove significant difference in WHO gr 4 bleeds or lethal events
  32. 32. German Therapeutic v Prophylactic Platelet TransfusionStudyTherapeutic Prophylactic (≤ 10,000/mcL)AML WHO grade 4 bleed 13 41 vaginal bleed 20 myomas (44,000) 4 retinal bleed with visual impairment4 retinal bleed with visual impairment CT not performed after HA6 minor cerebral bleed (CT after HA) 2 plt ct > 10,0002 fatal cerebral bleed(both HA; protocol violations; 1 plt ct < 10,000)6 plt ct >10,000
  33. 33. TOPPS Trial• 600 patients• randomized, non-inferiority trial of therapeutic v prophylactic (<10,000/mcL)• primary outcome: % patients with WHO grade ≥ 2 bleed• non-inferiority margin: 15% difference• adults, hematologic malignancies, chemo or SCT• no difference in period of TCP, hospital days, SAETherapeutic Prohylactic% transfused 59 89total transfusion (u) 1.7 3.0WHO gr ≥ 2 (%) 50 43 non inferiority p = 0.06auto SCT 47 45 p = 0.04bleeding days 1.7 1.2WHO gr 3 – 4* 6/300 1/298 p = 0.13*Only 2 pts with plt ct < 10,000 (median 16,000; range 3 – 42,000)
  34. 34. Platelet Transfusion Guidelines• 1) PLT CT < 10,000/mcL• 2) PLT CT < 20,000/mcL for outpatient• 3) PLT CT < 20,000/mcL for recent hemorrhage (within 5 days)• 4) PLT CT < 20,000/mcL and patient at risk for fall• 5) PLT CT < 50,000/mcL for severe DIC• 6) PLT CT < 50,000/mcL for existing CNS lesion• 7) PLT CT < 50,000/mcL for invasive procedure (except bone marrow biopsy)• 8) PLT CT < 50,000/mcL for active bleeding• 9 PLT CT < 100,000/mcL for CNS invasive procedure (except lumbar puncture)• 10) PLT CT < 100,000/mcL for life threatening bleeding• 11) other