Blood transfusion complication

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1. PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINEJuly 2017
BLOOD TRANSFUSION
COMPLICATIONS

2. IMMEDIATE DELAYED
IMMUNOLOGIC
•Acute hemolytic transfusion
reactions
•Febrile nonhemolytic transfusion
reactions
•Allergic, anaphylaticreaction
•TRALI
•Delayedhemolytic
transfusion reactions
•TaGVHD
•Posttransfusion purpura
NON-IMMUNOLOGIC
•Transfusion-transmittedinfections
•TACO
•Massive transfusion related
•Viral infection
•Iron overload
CLASSIFICATION

3. Dzieczkowski J. S., Anderson K. C. (2016), Harrison's Principles of Internal Medicine, Anthony S. Fauci Dennis L. Kasper, Stephen L. Hauser, Editor, McGraw Hill Education, pp. 138e1-6

4. OVERVIEW
•Risksassociatedwiththetransfusionofanyspecificunitofblood:low
•Risksmustbeweighedagainstthebenefitsatthetimeeachtransfusion
•Classification:immunologicandnonimmunologic;immediateanddelayed
•Severecomplications(includingdeath):developwithinafewminutesofinitiatingtransfusion
closeattentionandearlyvitalsignassessments:atthebeginningandwithin15
minutesofstartingatransfusion

5. Isbister J. P. (2014), Oh’s Intensive Care Manual, Andrew D Bersten , Neil Soni, Editors, Elsevier, pp. 973-986

6. IMMUNOLOGIC REATIONS
•Stimulationofantibodyproductionbyforeignalloantigens(transfusedredcells,leukocytes,
platelets,orplasmaproteins)immunologicallymediatedreactionsinthefuture.
•Hemolyticreactions:redcellincompatibility
•Febrileorpulmonaryreactions:leukocytesandplateletantigens
•Allergicoranaphylacticreactions:antibodiesreactingwithsolubleantigens(plasma
proteins,intransfusedmaterial)
•GVHD:engraftmentoftransfusedlymphocytesinimmunosuppressedrecipients

7. NON-IMMUNOLOGIC REACTIONS
•Physicalorchemicalpropertiesofthetransfusedbloodproducts
•Contaminatinginfectiousagents

8. Coil C. J., Santen S. A. (2016), Tintinalli’s Emergency Medicine -A Comprehensive Study Guide, Judith E. TintinalliJ, Stephan Stapczynski, O. John Ma, Editors, McGraw Hill, pp. 1518-1523.

9. Acute hemolytic reactions (AHTR)
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

10. OVERVIEW
•Mostseriousandimmediatelylife-threatening
•Rare,humanerrorrelated
•Soon(<24h),intravascularhemolysis
•ABOincompatibility,otherredcellantigens(Jk
a
,K,Fy
a
)
•anti-Aandanti-Bantibodies:predominantlyIgM,bindingcomplement
•Havebeenreportedinassociationwithapheresisplatelets(containingabnormallyhightiter
(>1:250)antiAoranti-Bantibodiesintheplasma)

11. SEVERITY
•47%:noeffects(evenaferreceivingawholeunit)
•41%:symptomsofAHTR
•Mortality:~2%
Severity~volumeofredcellsinfused

12. PATHOPHYSIOLOGY
•Interactionbetweenantibodyandredcellmembraneimmunecomplexes,activationof
complementreleaseofC3a,C5a(anaphylatoxicactivity,coagulationmechanismviacytokines
IL-1,6,8,TNF-αandfactorXIIbothconsumptivecoagulopathyandgenerationof
bradykinin)
•Vasomotormediatorsimplicatedinthetransfusionreaction:histamine,serotonin,cytokines
shock
•Renalfailure:poorlyunderstoodetiology(primarilyischemichypotension,vasoconstrictionvia
nitricoxideinactivationbyHb,intravascularcoagulation,antigen-antibodycomplexdeposition)
•Freehemoglobinoncethoughttobethemajorcauseofrenalfailure(precipitatinginand
obstructingtherenaltubules):adequateevidencetodiscountthishypothesis!!

13. MANIFESTATION
•Suddenchangeclinically
•Feverwithorwithoutchills:mostcommon
•Hypotension,shock
•Anaphylaxis
•Anxiety,chestorbackpain,flushing,dyspneawithwheezing(bronchospasm),tachycardia
•Hematuriaorhemoglobinuria
•Bleeding(consumptivecoagulopathy)
Acuterenalfailure,shock,andintravascularcoagulation

14. LABORATORY
•DAT:detectantibody-coatedredcells(NegativeDAToccursinrarecaseswhenall
transfusedRBCsarelysed)
•RepeatABOandRhtypingofthepatientandthetransfusedblood
•Repeatantibodyscreenandcrossmatchmaybehelpful.
•Intravascularcoagulation(espDIC)
•Renalfunction
•Urinaryhemosiderinorfreehemoglobin(post‐transfusionsampleofurine)
•Reducedserumhaptoglobin,orhyperbilirubinemia
•Furthersamplesofblood(6hoursand/or24hoursaftertransfusion):bloodcount,
bilirubin,freehaemoglobin,methaemalbumin

15. Galel S. A., fontaine M. J., Viele M. K., et al. (2014), Wintrobe's Clinical Hematology, John P. Greer, Daniel A. Arber, Bertil Glader, Editors, Wolster Kluwer, pp. 547-586

16. MANAGEMENT
(1)
•Transfusionmustbediscontinuedimmediately(onanysuspicious!)
•GeneralABCs,cardiacandoxygenmonitoring
•Maintainingvascularaccess(slowlyNaClinfusion)
•Recheckofthepatient’sidentity+informationonthediscontinuedbloodunitruleout
bedsideidentificationerrors
•Reporttothebloodbankwithoutdelay(aposttransfusionbloodsampleandthe
discontinuedbagofbloodsenttothebloodbankforinvestigation)

17. •Hydration(immediately)preventrenalfailure
•Infusionofnormalsaline:maintainBP,urineflowrateto100ml/hin24hours(without
contraindications)
•Diuretics
•Severecasesofhypotension:IVdopamine(dilatesrenalvasculatureandincreases
cardiacoutput)
•Renalfailure:fluidrestriction,managementofelectrolytebalance,dialysis.
•Coagulopathyandactivebleeding:platelets,fresh-frozenplasma,orcryoprecipitate
•Shockoranaphylaxis:Hydrocortisone100mg(IV),antihistamine(parenteral),
epinephrine(0.3mLof1:1000SC),AcetaminophenPO/IV
•ExcretionoffreeHb:alkalinizationofurine(pH≥7.5)
MANAGEMENT
(2)

18. Mosley J. C., Blinder M. A. (2012), The Washington Manual of Critical Care Marin H. Kollef ,
Warren Isakow, Editors, Lippincott Williams & Wilkins, pp. 505-510

19. PREVENTION
MostcommonbasisforAHTRsisaclericalerrorresultingfrom
•mistakesinidentifyingthepatient
•labelingthepretransfusionssample
•identifyingthecorrectredcellunitforthepatient

20. Delayed hemolytic reactions (DHTR)
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

21. OVERVIEW
•Muchmilder
•Predominantlyextravascular:IgG-coatedredcellsareremovedbythereticuloendothelial
system
•2to10daysafteratransfusion
•DAT:oftenpositive(transient,maybemissedifperformedtoolate,revertstonegativeasthe
incompatibleredcellsareremovedfromthecirculation)
•Almostalwaysrepresentsecondary,oranamnestic,antibodyresponses(secondary
exposuretoantigens)=Asubsequenttransfusioncausesrecalloftheantibodyfollowedbya
fallinghematocrit5to10dayslater
•AntibodiestoKidd(Jk)antigensandtoantigensoftheRh:majoroffenders(anti-Kelland
anti-Duffy(Fy)implicatedinmostotherdelayedreactions)

22. MANIFESTATION
•Usuallynosymptoms
•NewredcellantibodyandpositiveDATdetectedincidentally
•Fever,fallinghematocrit,jaundice,and,infrequently,hemoglobinemia and
hemoglobinuria
•Rarelydramatic:renalfailureuncommon,butfatalitiesbeenreported
•Hemolysismaybenotedonlybyamorerapiddeclinethanusualinthepatient’s
hemoglobinlevelorbyanabsenceoftheexpectedriseinhemoglobin

23. INVESTIGATION
•DATantibodiesshouldbeelutedfromtheredcellsandidentified
•Givepatientacardindicatingthepresenceoftheantibody

24. MANAGEMENT
•Nospecifictherapyisnecessary
•Crossmatch-compatiblebloodnegativefortheoffendingantigen(s)forfurthertransfusion
•Physicianandpatientshouldbeinformed
•Prednisone(1to2mg/kg/day)isindicatedformoreseverereactions

25. PSEUDOHEMOLYTIC TRANSFUSION REACTIONS
•Conditionsthatmimichemolytictransfusionreactions:clinicalsyndromeconsistentwith
intravascularhemolysis><nobloodgroupincompatibilitycanbeidentified
•ETIOLOGY:
•BacterialcontaminationwithorganismssuchasYersinia
•Resorptionoflargehematomas
•Hemolysiscausedbydrugreactionsorvascularprostheses
•Pretransfusionhemolysisofdonorblood(mechanicaltrauma,freezing,heat,orhypotonic
solutions)
Beauregard P., Blajchman M. A. (1994), Transfus Med Rev, 8 (3), pp. 184-99

26. Febrile Nonhemolytic Transfusion
Reactions (FNHTRs)
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

27. OVERVIEW
•0.5-3.0%transfusion
•Mostcommonlyencounteredtransfusionreactions
•Morecommoninmultiplytransfusedpatients,multiparouswomen(exposedtoforeign
bloodantigens)
•MorelikelytooccurfollowingtransfusionofplateletsthanRBCs
•Typical:chillfeverof1°Corgreater,duringorwithinafewhoursofthetransfusion(upto
4-6hours)
•Headache,nausea,andvomiting:mayoccur
•Usuallymild,resolvecompletelywithin1to2hoursaferthetransfusionisdiscontinued
•Diagnosedwhenothercausesoffeverinthetransfusedpatientareruledout(underlying
patientcondition,bacterialcontaminationoftheunit,acutehemolytictransfusionreaction)

28. Triulzi D. J. (2009), Anesth Analg, 108 (3), pp. 770-6

29. ETIOLOGY
•Alloimmunizationtoantigensonleukocytesandplatelets:
•mostcommon
•HLAantibodies,platelet-specificantibodies,granulocyte-specificantibodies:in
commonorder
•Activationofdonorleukocytesbyanti-HLAorotherantibodiesintherecipient,activation
ofrecipientleukocyteandendothelialcellsbytransfuseddonorleukocytesorplasma
constituents
•Transfusionofcytokinesdevelopedduringproductstorage(withtheageoftheplatelet
concentrateandtheleukocyteconcentrationintheproduct)apheresisplatelets:
leukoreducedreducedcytokinelevels
•Bacterialcontamination

30. MANAGEMENT
•Febriletransfusionreactiontransfusionshouldbediscontinueduntilthepatienthasbeen
carefullyassessedbyaphysicianandthebloodbankalerted(hemolyticorbacterially
contaminatedtransfusionruledout)
•Ifafebrilereactionoccursinafirst-timetransfusion:shouldbetreatedasanextravascular
hemolyticreactionuntilprovenotherwise
•Antipyreticsuchasacetaminophen
•Hydrocortisone:severereactions
•Meperidine:decreaseorstopsevereshakingchills
•Antihistamines:onlyifallergicsymptoms

31. PREVENTION
•TransfusingleukoreducedRBCsand/orplateletsstoredinadditivesolution
•Prestorageleukocytereduction
•Premedicationwithantipyretics(acetaminophen):NOThelpful
•Marti-Carvajal A. J., Sola I., Gonzalez L. E., et al. (2010), Cochrane Database Syst Rev, (6), pp. CD007539
•Tobian A. A., King K. E., Ness P. M. (2008), Transfusion, 48 (11), pp. 2274-6

32. Transfusion-related Acute Lung Injury
(TRALI)
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

33. OVERVIEW
•Leadingcauseoftransfusion-relateddeaths
•Severerespiratorydistressofsuddenonset
•Within6hoursoftransfusion
•Asyndromeofnoncardiogenicpulmonaryedema
•Usuallyresolveswithsupportivecarewithin48to96hourswithoutsequelae(80-90%
patients)
•Usuallyacomplicationoffreshfrozenplasmaorplatelettransfusion

34. PATHOGENESIS
•‘Two-hit’hypothesis
•Transfusionofpotentialgranulocyteprimersthatbindrecipientleukocytes(inflammatory
cytokines,activelipids,and/oralloantibodies)
•Eventlinkedtothepatient(i.e.,underlyingsepsis,hematologicdisease,and/orpostsurgical
status,mechanicalventilation,chronicalcoholabuse,severeliverdisease)anecessaryfirst
hit,leadingtoadherenceofprimedneutrophilstothepulmonaryendothelium
•Agglutinationofgranulocytesandcomplementactivationinpulmonaryvascularbed
capillaryendothelialdamage,fluidleakintothealveoli
•Mostcommonmediators:antibodiesspecificforeitherclassIIHLAorforhuman
neutrophilantigens(HNAs)

35. •Triulzi D. J. (2009), Anesth Analg, 108 (3), pp. 770-6
•Silliman C. C., Ambruso D. R., Boshkov L. K. (2005), Blood, 105 (6), pp. 2266-73

36. MANIFESTATION
•Chills,fever,chestpain,hypotension,andcyanosis,aswellastheusualmanifestations
ofpulmonaryedema
•ALI(acutelunginjury):PaO
2/FiO
2≤300mmHg
•Bilateralinfiltratesonfrontalchestradiograph
•NOevidenceofcirculatoryoverload

37. Kleinman S., Caulfield T., Chan P., et al. (2004), Transfusion, 44 (12),
pp. 1774-89

38. Marino P. L. (2014), Marino's the ICU Book, Wolters Kluwer, pp. 349-368

39. MANAGEMENT
•Stoptransfusionimmediatelyatthefirstsignsofrespiratorydifficulty
•Supportivemeasuresforthepulmonaryedemaandhypoxia,includingventilatorysupportif
required
•Hemodynamicfluidoverload(ifnot,diuretics:noprovenvalue)
•IVfluidandvasopressorsforhypotension(ifindicated)
•Glucocorticoidsmayprovidebeneft

40. PREVENTION
•Avoidfurthertransfusionofplasma-containingproductsfromimplicateddonorsfoundto
haveanti-HLAorantigranulocyteantibodies
•Minimizetheproductionofhigh-plasma-contentcomponents(plasmaproducts,pheresis
platelets)fromdonorsatriskforalloimmunization(e.g.,womenwithahistoryofpregnancy)

41. Allergic transfusion reactions (ATR)
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

42. OVERVIEW
•Common
•Widerange:urticariallesions(hives),otherskinrashes,bronchospasm,angioedema,
anaphylacticshock
•Wholebloodandplasma>concentratedredcells
•Doserelated,incidence~volumeofplasmatransfused
•RecipientIgEtoproteinsorothersolublesubstancesindonorplasmareleaseof
histaminefrommastcellsandbasophils
•Usuallybeginduringorwithinanhourofstartingatransfusion,butmaynotbecomeevident
untilseveralhourslater.
•Feverisusuallyabsent

43. IgA-RELATED
•Severeanaphylactoidoranaphylacticreactions:antibodiesreactingwithIgAindonorplasma
shouldbeconsidered
•IncidenceofgeneticallydeterminedIgAdeficiency(normalpopulation):high,1:400-500
•20%to25%ofsuchpatientsproduceantibodiestoIgA,generallyclass-specific(i.e.,
reactingwithallIgAmolecules)
•ManypatientswithnormalIgAlevelshaveantibodiesthatreactwithsome,butnotall,IgA
molecules(incidencemaybehigherinmultiplytransfusedpatients)

44. GRADING
•GradeI:
oskinmanifestations
•GradeII:
omildtomoderatehypotension
ogastrointestinaldisturbances(nausea)
orespiratorydistress
•GradeIII:
oseverehypotension,shock
obronchospasm
•GradeIV:
ocardiacand/orrespiratoryarrest
Isbister J. P. (2014), Oh’s Intensive Care Manual, Andrew D Bersten , Neil Soni, Editors, Elsevier, pp. 973-986

45. MANAGEMENT
•MostATRs:mild,self-limitedandrespondwelltotransfusiondiscontinuation
•Maintainingvascularaccess
•Antihistamine
•Steroids:usuallyNOThelpfulinacutecrises±requiredinseverecases
•Incaseslimitedtourticaria:transfusionmayberesumedimmediatelyaftersymptoms
resolve
•Severesymptoms:epinephrine,bronchodilators
•Forpatientswithrepeatedallergicreactions:premedicationwithanH1-blocking
antihistamine
•Reducingtheplasmacontentofthetransfusedbloodproduct(centrifugingtheproduct
andremovingalmostalltheplasmaorbyredcellwashing)
•SevereIgAdeficiency:onlyIgA-deficientplasmaandwashedcellularbloodcomponents

46. Posttransfusion Purpura (PTP)
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

47. OVERVIEW
•Rare
•Developmentoflife-threateningthrombocytopenia
•Formationofallowantibodiesagainstplateletantigens
•Boththetransfusedandrecipientplateletsaredestroyedbytheimmunecomplexes
•Mostcommon:HPA-1a(polymorphicepitopeofGPIIIa)
•HPA-1a/1bnegativemultiparouswomenorpreviouslytransfusedpatients
•Within7-10daysoftransfusion
•Confirmation:detectionofplateletalloantibodies
•Spontaneousplateletrecoveryeventually

48. MANAGEMENT
•IVIG(neutrolizeantibodies)
•Highdosecorticosteroid
•Plasmapheresis(removeantibodies)
•Additionalplatelettransfusions:canworsenthethrombocytopeniashouldbeavoided

49. Transfusion-associated Graft-versus-
Host Disease (TaGVHD)
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

50. OVERVIEW
•Mostcellularbloodproducts(redcell,platelet,granulocyteproducts):containviable,
immunocompetentTlymphocytes
•Occurin:
•Immunoincompetentrecipients
•Alsobeenreportedinimmunocompetentpatients(espreceivetransfusionsfromfamily
membersorfromrandomdonorswhoshareHLAantigensrecipientnotrecognize
donorcellsasforeignallowingthetransfusedlymphocytestoproliferate
•Mostcases:transfusionofleukocyteorplateletconcentratesorfreshblood
•Afewreportsofspontaneousresolution
•Fatalinapproximately90%ofaffectedpatients

51. Galel S. A., fontaine M. J., Viele M. K., et al. (2014), Wintrobe's Clinical
Hematology, John P. Greer, Daniel A. Arber, Bertil Glader, Editors,
Wolster Kluwer, pp. 547-586

52. PRESENTATION
•Mostcommon:fever
•Typicalerythematous,maculopapularskinrash(beginscentrallyandspreadsperipherallyto
thehandsandfeet)
•Abnormalitiesofhepaticfunction
•Nausea
•Bloodydiarrhea
•Leukopeniafollowedbypancytopeniaduetomarrowfailure:quitecommoninTA-GVHD,
mostoften2to3weeksaftertheonsetofsymptoms

53. PRESENTATION
•Histologicalconfirmation:skinbiopsy
•Laboratoryconfirmation:demonstratingthepresenceofdonorlymphocytesinthepatient
(HLAtyping,cytogeneticanalysis,analysisofDNAmicrosatellitepolymorphismsor
variable-numbertandemrepeats)
•Mostcommoncauseofdeath:severesystemicinfections(within3to4weeksfromthe
timeoftheimplicatedtransfusion)

54. MANAGEMENT
•Corticosteroids,antithymocyteglobulin,cyclosporine,growthfactors:minimal
success
•Currentapproach:combinationsofimmunosuppressantmedicationswithlymphocyte-
directedantibodytherapy(anti-CD3,anti–interleukin-2receptor,antithymocyteglobulin)
•Prevention:pretransfusionirradiationofallbloodproductsadministeredtopatientsatrisk
•inhibitsproliferationofdonorlymphocyteswithlittlesignificantadverseeffectonredcell,
platelet,orgranulocytefunction
•Changesintheredcellmembraneincreasedlossofpotassiumfromthecelllimiting
thestoragetimeofirradiatedredcellsto28days
•2,500cGy(centeroftheirradiationfield),minimumdoseof1,500cGy(anypointinthe
field)

55. Hoffbrand A. V., Moss P. A. H. (2016), Hoffbrand’s Essential Haematology, John Wiley & Sons, pp. 333-345

56. Transfusion-associated Circulatory
Overload (TACO)
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

57. •Bloodcomponents:excellentvolumeexpanders(comparedtosimilarvolumesofcrystalloid
fluids)
•Atrisk:
•Elderlypatientswithlimitedcardiacreserve
•Severelyanemicpatientsincongestiveheartfailure
•Affectby:infusionsrates,thevolumeofinfusedbloodproduct,and/oranunderlying
cardiac,renal,and/orpulmonarypathology
•Fluidvolumetransfused:maybelessimportantthantheinfusionflowrateandthepatient’s
abilitytoprocessthefluid
•Signssuchasrales,hypertension,andjugularveindistentiondifferentiateTACOfrom
TRALI
OVERVIEW

58. •Supplementaloxygen
•Diuretictherapyandothermeasurestomanageheartfailure
•Partialexchangetransfusion
•Transfusion:slowly(1to4mlofblood/kg/hour)
•Mechanicalventilationmayberequired(non-invasive,invasive)
•Closemonitoringofthepatient’svitalsigns
MANAGEMENT

59. Transfusion-Related Sepsis
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

60. •Usuallyfromplateletunitsthatarestoredatroomtemperature(Staphylococcus,
Enterobacteriaceae)
•Redcells,storedatrefrigeratortemperatures,areveryrarelycontaminatedbyunusualcold-
growingorganisms(e.g.,Yersinia,Serratia,Pseudomonas,Acinetobacter,andEscherichia)
•Potentialsources:
•asymptomaticbacteremiainthedonor
•bacteriafromthedonor’sskin
•Fever(>38.5°C),rigors,markedhypotension,abdominalpain,vomiting,diarrhea,andthe
developmentofprofoundshock
•Gr(-)>Gr(+):severity
•Gramstain,cultureofthetransfusedcomponent

61. Viral Infections
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

62. Hoffbrand A. V., Moss P. A. H. (2016), Hoffbrand’s Essential Haematology, John Wiley & Sons, pp. 333-345

63. Hoffbrand A. V., Moss P. A. H. (2016), Hoffbrand’s Essential Haematology, John Wiley & Sons, pp. 333-345

64. •Allbloodproducts:screenedforhepatitisB,hepatitisC,humanimmunodeficiencyvirus
1and2,andhumanT-lymphotropicvirusIandII.
•Otherinfectiousrisks:virusesthatarenotscreenedfor(CMV,parvovirusB19,prion
transmittedCreutzfeldt–Jacobdisease)

65. Marino P. L. (2014), Marino's the ICU Book, Wolters Kluwer, pp. 349-368

66. Goodnough L. T. (2016), Goldman-Cecil Medicine, Lee Goldman , Andrew I. Schafer, Editors, Elsevier Saunders, pp. 1191-1198

67. Galel S. A., fontaine M. J., Viele M. K., et al. (2014), Wintrobe's Clinical Hematology, John P. Greer, Daniel A. Arber, Bertil Glader, Editors, Wolster Kluwer, pp. 547-586.

68. Galel S. A., fontaine M. J., Viele M. K., et al. (2014), Wintrobe's Clinical Hematology, John P. Greer, Daniel A. Arber, Bertil Glader, Editors, Wolster Kluwer, pp. 547-586.

69. Iron Overload
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

70. •Longtermredcelltransfusionsupportfor
chronicanemias(e.gbonemarrowfailure,
Thalassemia)
•Eachunitofredcells=0.2-0.25gofiron
depositionofironinitiallyin
reticuloendothelialtissueattherateof
200–250mg/unitofredcells
OVERVIEW
•Stigmataoftransfusionsiderosis:impairedgrowth,failureofsexualmaturation,myocardial
andhepaticdysfunction,hyperpigmentation,and,often,diabetes
•Endocrine,hapatic,cardiac

71. APPROACH

72. Goal:serumferritinlevelbetween1000and1500μg/L
•Deferasirox
•Deferiprone
•Deferoxamine
IRON CHELATION THERAPY

73. Massive transfusion
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

74. •Replacementofthecirculatingvolumein24hours
•>4unitsofbloodin1hourwithcontinuingbloodloss
•Transfusionof10unitsofredcellsin24hours
•lossof50%ofcirculatingbloodvolumewithin3–4hours.
DEFINITION

75. Pham H. P., Shaz B. H. (2013), Br J Anaesth, 111 Suppl 1,
pp. i71-82.

76. PATHOPHYSIOLOGY
Pham H. P., Shaz B. H. (2013), Br J Anaesth, 111 Suppl 1, pp. i71-82.

77. •Citratetoxicity
•Acid-basedisturbance
•Electrolytedisturbance(Ca,K,Na)
•Hypothermia
•Coagulopathy
•Hyperbilirubinaemia
coagulationparameters,plateletcount,andmetabolicstatus(acid-base,electrolyte)
ADVERSE EFFECTS

78. •Citratebindsfreeionizedcalcium
•Citrate:metabolisedbytheKrebscycleinALLnucleatedcells(espliver)bicarbonate
•Citratemetabolismimpaired:hypotension,hypovolaemia,hypothermiaandliverdisease
•Toxicitypotentiatedbyalkalosis,hyperkalaemia,hypothermiaandcardiacdisease
•freecalciumconcentration±metabolicalkalemia(hypokalemia)
•Awarm,well-perfusedadultpatientwithnormalliverfunctioncantolerateaunitofbloodeach
5minuteswithoutrequiringcalcium
•Rateoftransfusion:moresignifcantthantotalvolumetransfused
•Perioralanddigitalparesthesiasandnausea;rarely:tetanyandcardiacarrhythmias
ADVERSE EFFECTS Citrate toxicity (1)

79. •Maximumcitrateinfusionrate(mmol/kgpermin)=(mmolcitratepermLofbloodxmLof
bloodinfusedpermin)÷wt(kg)
•mLofbloodinfusedpermin=(0.02÷0.015)xwt(kg)=1.33xwt(kg)
•Maximumcitrateinfusionrateshouldbe0.02mmol/kgperminute(maximumrateofcitrate
metabolism)
•Citrateconcentrationinwholebloodis15mmol/L(0.015mmol/mL),~450ml/unit
ADVERSE EFFECTS Citrate toxicity (2)

80. •Management:Perioralanddigitalparesthesiasandnausea;rarely:tetanyandcardiac
arrhythmias
•If10percentcalciumgluconateisused,10to20mLshouldbegivenintravenously(into
anothervein)foreach500mLofbloodinfused.
•If10percentcalciumchlorideisused,only2to5mLper500mLofbloodshouldbegiven
•Calciumchloridemaybepreferabletocalciumgluconate(inthepresenceofabnormalliver
function:citratemetabolismslowerreleaseofionizedcalcium)
ADVERSE EFFECTS

81. •Storedbankbloodcontainsanappreciableacidload(citricacidoftheanticoagulantand
lacticacidgeneratedduringstorage)
•Routineuseofsodiumbicarbonate:unnecessary,generallycontraindicated!(Alkali:
furthershiftstheoxygendissociationcurvetotheleft,providesalargeadditionalsodium
load,depressesthereturnofionisedcalciumtonormalfollowingcitrateinfusion)
•Citratebicarbonatealkali
ADVERSE EFFECTS Acid-base disturbance

82. •K+contentofstoredredcells(RBCleakageduringstorage)hyperkalemia:rarely
(Risk:renalfailure,shockwithacidosis,hemolysis)
•Citrateexcessbicarbonategeneratedalkalemiadrivingpotassiumintothecells
hypokalemia
ADVERSE EFFECTS Potassium
McEvoy C., Murray P. T. (2015), Principles of Critical Care, Jesse B. Hall, Gregory A. Schmidt, John P. Kress, Editors, McGraw Hill, pp. 943-974

83. •Sodiumcontentofwholebloodandfreshfrozenplasma:higherthanthenormalbloodlevel
(duetothesodiumcitrate)
•Caution:largevolumesofplasmainfusedintopatientswithdisorderedsaltandwater
handling(e.g.renal,liver,cardiacdisease)
ADVERSE EFFECTS Sodium

84. •Oneofthemostcommon
•Largevolumeofcoldbloodisinfusedrapidly
•Neonatesandtheelderlyareparticularlysensitive
•Effect:
•Affectsthewaythelivermetabolizescitrate
•Contributestotheassociatedcoagulopathy,interfereswithplateletfunctionandclotting
•Cardiacdysrhythmiasexposingthesinoatrialnodetocoldfluid
•Blood-warmingdevices:recommended>3unitsaretransfused(careful:overheated
hemolysis)
ADVERSE EFFECTS Hypothermia

85. •Dilutionalcoagulopathy
•Citratetoxicities,hypothermia
•AbnormalitiesofPT,aPTT,thrombocytopenia
•FactorVIIIactivitymayrise:responsetostress
•FactorV:falls,butrarelytodangerouslevels
•Shouldincludeplasmatocorrectthelevelsofcoagulationfactors,followedbyplatelet
products(1URBC/1Uplasma/1randomdonorunitofPLTs:controversial)
•THRESHOLD:PT,aPTT1.5x;PLT<50x10
9
.
ADVERSE EFFECTS Coagulopathy

86. Pham H. P., Shaz B. H. (2013), Br J Anaesth, 111 Suppl 1, pp. i71-82.

87. Hypotensive reaction
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

88. •Transienthypotension:notedamongtransfusedpatientswhotakeangiotensin-converting
enzyme(ACE)inhibitors
•Bloodproductscontainbradykinin(degradedbyACE)ACEinhibitorsmayhaveincreased
•bradykininlevelshypotension
•Bloodpressuretypicallyreturnstonormalwithoutintervention

89. Pandey S., Nambiar A. (2014), Irwin & Rippe’s Manual of Intensive Care Medicine, Richard S. Irwin, Craig M. Lilly, James M. Rippe, Editors, Lippincott Williams & Wilkins, pp. 724-731

90. Pandey S., Nambiar A. (2014), Irwin & Rippe’s Manual of Intensive Care Medicine, Richard S. Irwin, Craig M. Lilly, James M. Rippe, Editors, Lippincott Williams & Wilkins, pp. 724-731

91. Blood products SUMMARY
PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE

92. Hoffbrand A. V., Moss P. A. H. (2016), Hoffbrand’s Essential Haematology, John Wiley & Sons, pp. 333-345

93. SAFE TRANSFUSION
Isbister J. P. (2014), Oh’s Intensive Care Manual, Andrew D Bersten , Neil Soni, Editors,
Elsevier, pp. 973-986.

94. Hoffbrand A. V., Moss P. A. H. (2016), Hoffbrand’s Essential Haematology, John Wiley &
Sons, pp. 333-345

95. Watson H. G., Craig J. I. O., Manson L. M. (2014), Davidson’s Principles and Practice of Medicine, Brian R. Walker, Nicki R. Colledge, Stuart H. Ralston, Editors, Churchill Livingstone
Elsevier, pp. 989-1056

96. Watson H. G., Craig J. I. O., Manson L. M. (2014), Davidson’s Principles and Practice of Medicine, Brian R. Walker, Nicki R. Colledge, Stuart H. Ralston, Editors, Churchill Livingstone
Elsevier, pp. 989-1056

97. Coil C. J., Santen S. A. (2016), Tintinalli’s Emergency Medicine -A Comprehensive Study Guide, Judith E. TintinalliJ, Stephan Stapczynski, O. John Ma, Editors, McGraw Hill, pp. 1518-1523.

98. Dzieczkowski J. S., Anderson K. C. (2016), Harrison's Principles of Internal Medicine, Anthony S. Fauci Dennis L. Kasper, Stephen L. Hauser, Editor, McGraw Hill Education, pp. 138e1-6

99. •Plateletcount<5000/mm
3
(<5×10
9
/L)
•Plateletcount<20,000/mm
3
(<20×10
9
/L)withacoagulationdisorder,low-riskprocedure,or
duringoutpatienttreatment
•Plateletcount<50,000/mm
3
(<50×10
9
/L)withactivebleedingorinvasiveprocedurewithin
4h
•Plateletcount<100,000/mm
3
(<100×10
9
/L)withneurologicorcardiacsurgery
•Aspartofamassivetransfusionprotocol
PLATELETS TRANSFUSION: General indications

100. •Reversalofwarfarinoveranticoagulation(nottheprimaryagent)
•Bleedingwithmultiplecoagulationdefects
•Correctionofcoagulationdefectsforwhichnospecificfactorisavailable
•Asacomponentofamassivetransfusionprotocol
•Aspartofplasmaexchangewhentreatingthromboticmicroangiopathiesorneurologic
•disorders
FFP TRANSFUSION: General indications

101. •Bleedingwithafibrinogenlevelof<100milligrams/dL(<1g/L)
•Dysfibrinogenemia
•BleedinginsomesubtypesofvonWillebrand’sdiseasethatareunresponsiveto
desmopressin,andfactorVIIIconcentratesareunavailable
CRYOPRECIPITATE TRANSFUSION: General indications

102. PHUNG HUY HOANG
RESIDENT IN INTERNAL MEDICINE
PHAM NGOC THACH UNIVERSITY OF MEDICINE
July 2017
BLOOD TRANSFUSION
COMPLICATIONS

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TintinalliJ,StephanStapczynski,O.JohnMa,Editors,McGrawHill,pp.1518-1523.
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CareMedicine,RichardS.Irwin,JamesM.Rippe,Editors,LippincottWilliams&Wilkins,pp.1276-1283.
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8.HessJ.R.(2016),"Massivebloodtransfusion",UpToDate.
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345.
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986.
11.KaushanskyK.,LichtmanM.A.,PrchalJ.T.(2016),"WilliamsHematology",McGrawHill.
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ofaconsensuspanel",Transfusion,44(12),pp.1774-89.
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