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

2. Today’sTopics AvailableBloodProducts CurrentEstimatesofTransfusionRisks FatalTransfusionReactions TransfusionReactions IndicationsforAdultBloodTransfusions

3. IndicationsforTransfusion(Adults)

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

5. 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.

6. 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…

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

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

9. RisksofTransfusion

10. Thesafesttransfusionistheonenotgiven Medicine

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

13. 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)

14. 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)

15. TransfusionReactions

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

17. TransfusionReactions-Common Febrile Allergic CardiovascularOverload

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

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

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

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

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

23. Allergic Reaction Evaluate the patient in respect of Ig A deficiency in a serious reaction (2 % of the population) In following transfusions washed eritrocytes may be required

24. Volumeoverload Frequency: 1per100-2,000units Toorapidortoolargeavolumetransfused Usuallypre-existinghistoryofheartorlung disease Rx:slowinfusionrate,diuretics

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

26. HemolyticReactions,Acute Clinical signs: chest pain shortness of breath fever titreme

27. HemolyticReactions,Acute Pathophysiology: 1- Cardiovascular collaps 2- Oliguric renal failure 3- Disseminated intravascular coagulation Primary mechanisms: - Activation of the coagulation cascade - Activation of the vasoactive substances - ATN due to myoglobinuria

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

30. SepticTransfusionReaction Bacterialcontaminationofbloodproduct Frequency–1in75,000 Platelettransfusionsmostcommoncause Roomtemperature storage Contaminationduringbloodcollection,processingor pooling StrepandStaph;gramnegativebacteria Rx:Supportive,antibiotics

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

32. TRALI: Transfusion-RelatedAcuteLungInjury Donororpatienthascytotoxicwhitecell antibodies(HLAorHNA) Patientordonorhascognantantigen Symptomswithin 6hoursoftransfusion Acuteinjurytocapillary-alveolarmembraneof lungs Protein-richfluidleaks intoalveolarairspaces Hypoxemia,fever,pulmonaryedema AllrequireO2therapy,mayrequire mechanical ventilation Chestx-ray:pulmonaryedemafluid withoutCHF changes

33. TRALI Triad of severe TRALI: 1-Hypoxia 2-Hypotension 3- Protein rich tracheal exuda

34. TRALI Types: Immune type: - Antileucocytes antigens ( HLA,HNA) - Activation of granulocytes - Secestration of leucoaglutinates in pulmonary capillaries Non-immune type: - Antileucocytes antigens ( HLA,HNA ) only 3.6 % - Activation of granulocytes

35. TRALI Consensus definitions: 1-Acute lung injury 2-Acute onset 3- Bilateral infiltrates in chest X-Ray 4-No pre-existing acute lung injury 5-Pulmonary edema not related to left atrial hypertension

36. TRALI:Treatment&Diagnosis Supportivecare: O 2 AVOIDdiuretics,steroids? Diagnosis:,mechanicalventilation,inotropicagents DemonstrateHLAand/orHNAantibodies and matching antigenin patient and donor DifferentialDiagnosis: Congestive heartfailure,acuteleftventricularfailure Acute circulatory(volume)overload pulmonaryembolism rapidlyprogressivepneumonia acuterespiratorydistresssyndrome(ARDS)

37. TRALIPrevention FrequencyofTRALIrelatedtoamountofplasmain bloodproduct FFP>RBC and PLT Donorswithhistoryofpriorpregnancies,transfusion, tissuetransplantathigherriskforHLA/HNAantibodies Bloodsupplier(SBB)providesmale-onlyFFP Bloodprovidersconsideringscreeningofplateletand FFPdonors Historyofpriorpregnancies,transfusion,tissue transplants HLA/HNAantibodies -S/D FFP

38. TRALIandBloodProducts Source:FatalitiesReportedtoFDAFollowingBloodCollectionand Transfusion,AnnualSummaryfor2006,March2009

39. TRALIEdemaFluid

41. TRALIChestX-Ray

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

43. Massive Blood Transfusion

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

45. 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

46. 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.

47. 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.

48. 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

49. 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

50. 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

51. 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.

52. 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