1. BLOOD TRANSFUSION Ferdi Menda,M.D. Assistant Prof of Anesthesiology Yeditepe University

2. Today’sTopics AvailableBloodProducts CurrentEstimatesofTransfusionRisks FatalTransfusionReactions TransfusionReactions IndicationsforAdultBloodTransfusions

3. IndicationsforTransfusion(Adults)

4. Defining Quality Administeringthe  Right  Rightquantity component way time patient  Right  Right  Right  Right  Right  Right  Right  Rightreason withinformedconsentandadequate documentationofprocess&outcomes  Right

5. PackedRedBloodCells SymptomaticAnemia: AnginaClaudicationDiaphoresis DyspneaFatigueTIA SyncopeTachycardiaPosturalHypotension AsymptomaticanemiawithHgb<7g/dl Pre-orPost-operativeHgb<10g/dlorHct<30% Acutebloodloss>15%ofestimatedbloodvolumeor estimatedbloodlossof750ml Acutebloodlosswithevidenceofinadequateoxygen delivery Hgb<9g/dlinpatientonachronictransfusionregimen

6. Study compared “ restrictive ” (Hgb<7) to “ liberal ” (Hgb<10) transfusion strategies among critically ill patients. The “ restrictive ” strategy was as effective and superior to the “ liberal ” transfusion strategy among patients less than 55 and without cardiac disease. Patients had an overall greater decrease in mortality and less complications. They concluded that a transfusion threshold of 7 g/dl is safe in critically ill patients, including those with minimal cardiopulmonary disease.

7. Platelets >100,000/mm 3 Bleedingwithfunctional plateletdefect Neonates 50-100,000/mmabovebaseline 3 Bleedingpatient>50,000/mm 3 >100,000/mm 3 Neurosurgicalor ophthalmologicprocedure Invasiveprocedure>50,000/mm 3 Marrowfailure>10-20,000/mm 3 Patient…Maintainplateletct.above…

8. FreshFrozenPlasma PTT>50secorINR>1.5(PT>20sec) Diffusemicrovascularbleedinginmassive transfusion(>1bloodvolume)withabnormal parameters EmergencyreversalofWarfarin(Coumadin) anticoagulationwhenevidenceofbleeding presentoremergencysurgeryrequired Deficiencyofspecificfactorsofthe coagulationsystemwhenvirus-inactivated concentratesnotavailable

9. Cryoprecipitate Fibrinogen<100mg/dl FactorXIIIdeficiency Diffusemicrovascularbleedingandfibrinogen <120mg/dl VonWillebrand’sdiseaseorhemophilia unresponsivetoDDAVPandnoappropriate factorconcentratesavailable Uremicbleeding(ifDDAVPisineffective)

10. RisksofTransfusion

11. Thesafesttransfusionistheonenotgiven Medicine

13. TransfusionRisks:Infectious CurrentRisksofInfectionfrom“TestNegative” BloodComponents(USA) AgentRisk HIV-1/21in2.1million HCV1in1.9million HBV1in205,000-488,000 WNV1in12million Bacteria(culturedapheresis1in75,000 platelets,2004-2006ARC)

14. TransfusionRisks:Non-Infectious,EarlyOnset PublishedRates Febrile,nonhemolyticnonsepticreactionRBC:1per100-500units Platelets:1-1.5% Circulatoryoverload(TACO)1per100-2,000units HemolysisofincompatibleRBCs1per13,000-200,000 1per1.3-1.7million(fatal) Hemolysisfromincompatibleplasma1per46,000(21%plasma incompatible) TRALI1per1,000-5,000 Allergicreaction,mild1per4,000RBC,3-5%plts Allergicreaction,severe;anaphylactic1per25,000(RBC), 1per2,000plts Risk NoninfectiousRisksofTransfusion,EarlyOnset(withinhrs)

15. TransfusionRisks,LateOnset RiskPublishedRates Formationredcellantibody(s)1per200RBCunits(9%pts) Delayedhemolyticreaction1per5,000-10,000 IronoverloadEssentiallyallchronically transfusedpatients ImmunesuppressionAllshowvariablesuppression FormationofHLAantibodies7-15%ifmultiplytransfused Formationofanti-plateletAb0.85%ofpatients Graft-versus-hostdisease<1per1million NoninfectiousRisksofTransfusion,LateOnset (daystomonths)

16. TransfusionReactions

17. Transfusionreactions Timing:acuteversusdelayedreaction Severity:fatalversusnon-fatal Cause:immunologic,infectious, cardiovascularoverload Allreactionsmustbereportedtothe labforinvestigationanddocumentation

18. TransfusionReactions-Common Febrile Allergic CardiovascularOverload

19. TransfusionReactions-Serious TRALI(transfusion-relatedacutelunginjury) Hemolytic Bacterialcontamination Anaphylactic Graftvs.hostdisease

20. LeadingCausesofFatalReactions: CasesReportedtoFDA,FY07-08 TRALI(51%) Incompatibleblood(23%) Patientmis-identification:50-75% Clericalerrors:10-15% Technicalerrors:10-15% Bacterialcontamination(13%) Anaphylaxis(5%)

21. TransfusionFatalityUpdate Transfusion-RelatedFatalitiesReportedinFY2005thruFY2008 Source:FatalitiesReportedtoFDAFollowingBloodCollectionand Transfusion,AnnualSummaryforFiscalYear2008,March2009

22. TransfusionFatalityUpdate Transfusion-RelatedFatalitiesReportedinFY2005thruFY2008 Source:FatalitiesReportedtoFDAFollowingBloodCollectionand Transfusion,AnnualSummaryforFiscalYear2008,March2009

23. AllergicReaction Frequency: RBCs:1per4,000,Platelets:3-5% Hivesorrash Few/localized–slowinfusionrate,antihistaminesRx GeneralizedorcardiorespiratoryS/Sx–D/Cinfusion Triggeredbydonorproteinsormedications Candevelopbronchospasm,GIsymptoms Rx:antihistamines;steroids(severerxns)

24. Volumeoverload Frequency: 1per100-2,000units Toorapidortoolargeavolumetransfused Usuallypre-existinghistoryofheartorlung disease Rx:slowinfusionrate,diuretics Mayneedto“split”aunitofbloodiftransfusion timewillexceed4hours

25. HemolyticReactions,Acute Frequency RBCs:1per13,000-200,000 1per1.3-1.7million(fatal) ABOincompatibility(usually) Misidentifiedpatientorclericalerror Rx:Supportive(treatshock,DIC)

26. HemolyticReactions,Delayed Frequency– 1per5,000-10,000RBCs PatienthasRBCantibodies Chronicallytransfusedpatients(10-40%) Multiparousfemales UnexplaineddropinHgb3-10days aftertransfusion Rx:Antigennegativeblood

27. SepticTransfusionReaction Bacterialcontaminationofbloodproduct Frequency–1in75,000 Platelettransfusionsmostcommoncause Roomtemperaturestorage Contaminationduringbloodcollection,processingor pooling StrepandStaph;gramnegativebacteria PlateletproductsculturedbeforereleasebySBB Rx:Supportive,antibiotics

28. AnaphylacticReaction(SevereAllergic) Frequency RBCs:1per25,000,Platelets:1per2,000 IgAdeficientpatientwithanti-IgA antibodies Symptomsareimmediate(1-2ml) Hypotension,shock,bronchospasm Rx:Supportive;washedRBCs/platelets

29. TRALI: Transfusion-RelatedAcuteLungInjury Donororpatienthascytotoxicwhitecell antibodies(HLAorHNA) Patientordonorhascognantantigen Symptomswithin6hoursoftransfusion Acuteinjurytocapillary-alveolarmembraneof lungs Protein-richfluidleaksintoalveolarairspaces Hypoxemia,fever,pulmonaryedema AllrequireO2therapy,mayrequiremechanical ventilation Chestx-ray:pulmonaryedemafluidwithoutCHF changes

30. TRALI:Treatment&Diagnosis Supportivecare: O 2 AVOIDdiuretics,steroids? Diagnosis:,mechanicalventilation,inotropicagents DemonstrateHLAand/orHNAantibodiesand matchingantigeninpatientanddonor DifferentialDiagnosis: congestiveheartfailure,acuteleftventricularfailure acutecirculatory(volume)overload pulmonaryembolism rapidlyprogressivepneumonia acuterespiratorydistresssyndrome(ARDS)

31. TRALIPrevention FrequencyofTRALIrelatedtoamountofplasmain bloodproduct PlateletsandFFP>RBC Donorswithhistoryofpriorpregnancies,transfusion, tissuetransplantathigherriskforHLA/HNAantibodies Bloodsupplier(SBB)providesmale-onlyFFP beprovidedifemergencyFFP FemaleABFFPmay inventoryshortage Bloodprovidersconsideringscreeningofplateletand FFPdonors Historyofpriorpregnancies,transfusion,tissue transplants HLA/HNAantibodies

32. TRALIandBloodProducts Source:FatalitiesReportedtoFDAFollowingBloodCollectionand Transfusion,AnnualSummaryfor2006,March2009

33. TRALIEdemaFluid

35. TRALIChestX-Ray

36. SuspectedTransfusionReaction STOPtransfusion;KeepIVopenwithNS PromptlynotifylaboratoryandattendingMD Verifyclericalinformation; PatientID,bagtagandlabel Completetransfusionreactionreport OrdertransfusionreactionworkupinCareCast Sendreportwithbag(tubingattached)tolab Labwilldeterminewhatsamplesneedtobe collectedandcontactpathologiston-call

37. Massive Blood Transfusion

38. Replacement by transfusion of more than 50 % of a patient's blood volume in 12 - 24 hours

39. Hypothermia, acidosis, coagulopathy, usually occurs after uncontrolled bleeding often at 16 units. It exemplifies the issues associated with massive bleeding and volume and blood product replacement

40. Reduces the enzymatic activity of plasma coagulation proteins Has a greater effect by preventing the activation of platelets via traction on the glycoprotein Ib/IX/V complex by von Willebrand factor. In tests of shear-dependent platelet activation, this pathway stops functioning in 50 percent of individuals at 30 º C, and is markedly diminished in most of the rest.

41. Interferes with the assembly of coagulation factor complexes involving calcium and negatively- charged phospholipids. The activity of the factor Xa/Va/prothrombinase complex is reduced by 50, 70, and 90 percent at a pH of 7.2, 7.0, and 6.8, respectively.

42. Large amounts of citrate are given with massive blood transfusion, since blood is anticoagulated with sodium citrate and citric acid. Metabolic alkalosis Decline in the plasma free calcium concentration

43. Citrate binding of ionized calcium can lead to a clinically significant fall in the plasma free calcium concentration. This change can lead to paresthesias and/or cardiac arrhythmias in some patients

44. Maintain Hb >8 g/dl Maintain platelet count >75 · 10 9 /LMaintain platelet count >75 · 10 9 /L Maintain PT & APTT < 1.5 · mean controlMaintain PT & APTT < 1.5 · mean control Maintain Fibrinogen > 1.0 g/L

45. The coagulation system should be frequently monitored with measurements of the PT, aPTT and platelet count, preferably after each 5 units of blood replaced. If the PT and PTT exceed 1.5 times the control value, the patient should be transfused with 2 units of fresh frozen plasma. If the platelet count falls below 50,000/microL, 6 units of platelets should be given.

46. A blood warmer should be used whenever more than three units are transfused. Hypothermia should be either avoided or minimized. Acid – base balance and the plasma ionized calcium and potassium levels should be periodically monitored, particularly in patients with coexistent liver or renal disease or in those with massive hemorrhage and low cardiac output