Blood transfusion involves transferring blood or blood components from a donor to a recipient. There are several types of blood transfusions including whole blood transfusion and transfusion of individual blood components like red blood cells, platelets, and plasma. Blood transfusions can cause various complications such as transfusion-related acute lung injury (TRALI), febrile nonhemolytic reactions, allergic reactions, hemolytic reactions if there is an ABO incompatibility, infections transmitted through the blood, and transfusion-associated circulatory overload (TACO). It is important to carefully screen and type donor blood and properly match it to the recipient to reduce risks of complications from blood transfusions.

1. Blood TransfusionDiana GirnitaMD, PhDThe Christ Hospital, CincinnatiNovember 10th, 2010

2. Transfusion of Blood CellsThe transfer of blood or blood components from one person (the donor) into the bloodstream of another person (the recipient).

3. Transfusion is the first form of transplantationDonor – recipient from the same species = Allogeneic transfusions Autologoustransfusions using the patient's own stored blood.

4. Types of Blood TransfusionWhole Blood

5. Blood Components

6. Red Blood cells

7. Platelets

8. Fresh Frozen Plasma

9. Leukocyte concentrate(granulocytes)

10. Plasma Substitutes (dextran, hydroxyethyl starch formulation - HES)!! Use of whole blood is considered to be a waste of resources !!

11. Red Blood CellsSymptomatic anemia or tissue hypoxia (providing oxygen-carrying capacity)

12. Transfusion trigger (HCT<30% ; HB<10g/dl)

13. 1 Unit increases 3% HCT or 1g/dl

14. Shelf life =42 d (1-6 ℃)PlateletsBleeding due to critically decreased platelets < 10000/mm3

15. Functionally abnormal platelets.

16. Each unit increase 5,000 PLTs after 1 HGranulocytesProfoundly granulocytopenia (<500/mm3)

17. Serious infection not responsive to antibiotic therapyFresh Frozen Plasma (FFP)Active / risk of bleeding due to deficiency of multiple coagulation factors, or due to a single coagulation factor deficiency

18. Severe bleeding due to warfarin therapy

19. Massive transfusion with coagulopathic bleeding.

20. Thrombotic thrombocytopenic purpuraPlasma Substitutes (Volume Expanders)DextranMost widely used

21. Low/Middle M.W. (40,000-70,000)Hydroxyethyl Starch Formulation (HES)More stable

22. Containing essential electrolytes

23. No allergic reactionNo risk of infectious disease transmission

24. No transfusion reactions

25. No compatibility testing

26. An immediate source of autologousblood

27. Sportive medicine Autotransfusion

28. Alloantigens represents the blood groups major barriers for transfusionOn RBCs - 30 major blood group systems and over 200 minor group systemsABO molecules are glyco-sphingolipids (major histocompatibility antigens)A and B = terminal sugars (A = N-Acetyl-Dgalactosamine; B = alpha-D-galactose)Availability of blood donors – major limitationABO matching is also important in solid organ transplantation.

29. Pre-Transfusion compatibility testingCross-matching = donor cells with recipient serum/ plasmadetermines the blood group (ABO compatibility)AlloantibodiesNew methods: PCR with specific probes (DNA typing)Serological TypingCDC- Method or Hemmaglutination

30. ABO Blood TypesThe A Blood Type contains aprox. 20 subgroups (A1 =80% , A2 = 20%) are the most common (over 99%).

31. 30 major blood group systems and over 200 minor group systemsLewisI P MNSs KellKiddDuffyThe cell surface is a jungle!

32. HLA -A and B are important in platelet transfusion; HLA class I and II in neutrophil transfusionN > 2400

33. Transfusion ReactionsInfectious or Non-infectiousAcute or Chronic

34. FDA report on fatalities following transfusions (2005-2008)

35. Transfusion transmitted infectionsHIV-1 and HIV-2

36. Human T-lymphotropic virus (HTLV-1 and HTLV-2)

37. Hepatitis B and C virus (responsible for >90% of post-transfusion hepatitis)

38. Treponemapallidum

39. Malaria

40. Chagas Disease

41. Creutzfeldt-Jakob Disease or "Mad Cow Disease"Over the past decade, the risk of transfusion-transmitted infectious decreased approx. 10,000- fold

42. August, 2010 - New virus Linked to Chronic Fatigue Syndrome

43. Noninfectious Serious Hazards of Transfusion

44. Hemolytic transfusion reactions Transfusion of RBCs to a patient with a preexisting antibody may cause a hemolytic reaction. Acute hemolytic transfusion (within 24h): fever, chills, chest/back/abdominal pain, pain at the infusion site, dyspnea, hypotension, Hb-nuria, renal failure and DICAlloantibodies: IgM (anti-A and -B) or IgG

45. Transfusion of O plasma products with high titer anti-A or -B to nongroup O patients

46. Nonimmune-mediated: in vitro hemolysis(unit shipped or stored improperly)Hemolytic transfusion reactions Delayed hemolytic transfusion (days to weeks)the recipient has previously been alloimmunized to minor RBC antigens (pregnancy or transfusion)

47. alloantibodies (anti-Rh and Kidd antigens) are present in low levels; they are undetectable in the pretransfusion antibody screen.

48. there is a rapid anamnestic response after transfusion leading to hemolysis. Hemolytic transfusion reactions -treatment Stop transfusion as soon as reaction is suspected, and replace the donor blood with normal saline.

49. Check the name, type and crossmatch

50. Renal protection - maintain urine output at 30-100 mL/h(aggressive fluid resuscitation, furosemide , low-dose dopamine - to improve renal blood flow.)DIC MonitorFebrile Nonhemolytic Transfusion Reaction >1°C increase in T° during/ soon after transfusion

51. Frequent with platelet transfusions, but declined with prestorageleukoreduction

52. Recipient alloantibodies(that react with antigens from the donor blood) and leukocyte-derived cytokines (released during storage) have been implicatedTreatment:Stop transfusion

53. Evaluate for hemolysis

54. Fever: acetaminophenUncommon, but deadly

55. Due to bacterial contamination

56. Platelets transfusion- more susceptible due to RT storage (Staphylococcus aureus, coagulase-negative staphylococci, diphtheroid bacilli, streptococci, and other skin flora)

57. RBCs transfusion (Yersiniaenterocolitica replicate at cold temperatures) Septic transfusion reaction

58. Allergic ReactionsMinor allergic reactionHives /“urticaria”

59. Edema

60. Pruritis

61. AngioedemaTreatment: antihistamines

62. +/- stop the transfusionAnaphylactic reaction(hypotension, bronchospasm, stridor, GI) Causes: IgA deficiency

63. anti-HLA antibodies

64. anticomplement antibodiesTreatment:Stop the transfusion immediately.

65. Support the airway and circulation

66. Administer epinephrine, diphenhydramine, and corticosteroids.

67. Maintain intravascular volume.Transfusion-related acute lung injury (TRALI)Acute lung injury that develops due to the presence of anti-HLA antibodies and anti- Neutrophil Antigens (HNA) with a clear temporal relationship to transfusion

68. in patients without alternate risk factors for acute lung injuryIn 2006, TRALI was the leading cause of transfusion-related death reported to the FDAUnderrecognition and underreportingAll plasma-containing blood and blood compartments may induce TRALI

69. Sensitization mechanismsMultiparous women (10-15% anti -HLA antibodies / pregnancy)

70. Previous transfusion

71. TransplantationTRALI- immune mechanism

72. The antibody –dependent hypothesisAnti-HLA or human neutrophil antigen (HNA) antibodies in the transfused component reacts with neutrophil antigens in the recipient (ie, when antileukocyte antibodies are transfused passively in a plasma-containing blood component) The recipient's neutrophils lodge in the pulmonary capillaries and release mediators that cause pulmonary capillary leakage.As a consequence, many patients with TRALI will develop transient leukopenia.TRALI- pulmonary edema with neutrophilic aggregates in the pulmonary vasculatureCherry et al, Am J ClinPathol 2008;129:287-297

73. The antibody –independent hypothesisOccurs in patients with clinical conditions that predispose to neutrophil priming and endothelial activation: infection, surgery, or inflammation.Bioactive substances (lipids) in the transfused component activate the primed, sequestered neutrophils and pulmonary endothelial damage occurs.

74. TRALI-Clinical PresentationSudden onset, within 6 hours (usually within 1~2 hours) of respiratory distress after transfusion

75. TRALI - Clinical PresentationCXR: bilateral patchy alveolar infiltrates, normal cardiac silhouette and w/out effusions, consistent with ARDSLabs: transient, acute neutropeniaRapid Resolution , even when initial hypoxemia is severeMost can be extubated within 48 hours

76. CXR return to normal within 4 days, although hypoxemia and pulmonary infiltrates may persist up to 7 days TRALI – Current Criteria of DiagnosisCherry et al, Am J ClinPathol 2008;129:287-297

77. D/D: think more before TRALIUnderlying pulmonary diseaseUnderlying cardiac disease (CHF)Transfusion- associated cardiac overload (TACO)Severe allergic or anaphylactic reactions

78. TRALI -TreatmentSupportive: oxygen, ventilator

79. Diuretic: conflicting reports!

80. Steroid?? – not randomized trials available

81. Fluid replacement (5% albumin) – improved oxygenation and hemodynamicsTRALI -Prevention Producing FFP only from male donors

82. Screening previously-pregnant and previously-transfused apheresis donors for HLA antibodies

83. Improving tests for the detection of leukokytesantibodies Transfusion associated circulatory overload (TACO)TACO is due to circulatory overload

84. Incidence: aprox. 1% of transfusions

85. It is not an antibody-mediated phenomenon

86. Symptoms

87. Dyspnea

88. Tachycardia

89. Hypertension (Hypotension in TRALI)

90. Widened pulse pressure

91. Evidence of cardiac decompensationTACO -DiagnosisCXR- presence of fluid, but cannot be distinguish of TRALIPulmonary edema protein content/ plasma protein content >0.75BNP/ ANP pre- and post -transfusion values are increased; not in TRALI!!

92. TACO- Risk Factors and PreventionIncreased risk in pts with cardiopulmonary compromise renal failureinfants or >60 yoPrevention measuresTransfuse slowly (1 ml/min) or space units over time

93. Consider pre-transfusion diuretics

94. Watch fluid balance and monitor for at least 24HTACO - TreatmentStop transfusion

95. Diuretics

96. Oxygen

97. Cardiac support

98. Assisted ventilationTransfusion Associated Graft versus Host Disease (TA-GVHD) Uncommon, TA-GVHD is often fatal (mortality over 90%). The pathophysiology of TA-GVHD involves the proliferation and engraftment of immunocompetent donor T-lymphocytes, typically in an immunocompromised host incapable of clearing them. Alternatively, TA-GVHD can occur in immunocompetent recipients whose HLA closely matches that of the donor (a so-called “one-way” HLA match), with donor cells being homozygous for a HLA type for which the recipient is heterozygous.

99. EXAMPLEDonor HLA-A1,-; B8,-; Cw7,-.(homozygosity)Recipient HLA A1, A2; B8, B27; Cw7, Cw9.No mismatched HLA in Host versus Graft Direction (A1, B8 and Cw7 are self HLA)A2, B27 and Cw9 mismatches in GVH direction.

100. Roles of CD4+ and CD8+ T cells in graft rejectionCD8 cellsRecognition of class I MHC molecules expressed on all donor tissue cellsDirect cytotoxic effectsRelease of TNF+IFN augments macrophage activation and non-specific destructionCD4 cellsRecognition of class II MHC molecules on passenger leukocytes (direct allorecognition) or infiltrating host DC (indirect allorecognition)Help the activation of CD8 T cellsRelease of TNF+IFN induces macrophage activation and non-specific destruction

101. Types of AllorecognitionDirect – activation of recipient T cells by donor-derived professional APCs (dendritic cells) Indirect – activation of recipient T cells by recipient-derived professional APCs.The professional APCs that present the alloantigens also provide co-stimulatory signals that activate helper T cells and cytotoxic T cells.

102. Two forms of TA -GVHDAcute GVHDDuring first 3 months post-transplant

103. Skin, GI tract, hepatosplenomegalyChronic GVHDAfter 3 months

104. Skin, Liver, GI tract

105. Similarities to connective tissue diseases (e.g. scleroderma)TA- GVHD- No treatment, just prevention!!!High- risk individuals intensive chemotherapyimmunodeficiencyHodgkin’s diseasestem cell transplantintrauterine transfusionerythroblastosisfetalispremature infantsMethods: Gamma- or UV-irradiation of cellular blood products (RBCs, platelets, and granulocytes), which renders donor lymphocytes incapable of proliferating.

106. MICROCHIMERISMOccurs when a small percentage of donor lymphocytes (typically <5%) persist in a recipient

107. The long-term consequences are unclearMetabolic ReactionsSodium Citrate toxicityused to prevent blood coagulation metabolized by liver ; the metabolic capacity can be exceeded with large volumes of blood transfused. increased levels of citrate hypocalcemia and hypomagnesemia (paresthesia, tetany, and arrhytmia), metabolic alkalosis (accumulation of bicarbonate - the metabolic derivative of citrate) Hypothermiaassociated with rapid transfusion of large amounts of cold bloodresult in cardiac arrhythmiasHyperkalemia– K level in the plasma increases during blood storage in a massive or rapid transfusion, particularly among premature infants and acidotic patients

108. Rare complicationsTransfusion Associated Air EmbolismTransfusion of blood under pressure using an open system

109. Symptoms : cough, dyspnea, chest pain , shock , deathPosttransfusionPurpura (PTP)5-10 days after; associated with platelets / packed RBCs/ plasma transfusion; a sudden decrease of the platelet s < 10,000/µL

110. Symptoms: hemorrhage (skin, epistaxis, GI, UT, most severe intracranial)

111. Increased risk in individuals with h/o transfusion or pregnancyIron Overloadrepeated RBCs transfusions over a long period induce liver, heart, and kidneys damage.

112. Increased risk in thalassemia, SSD and myelodysplasia

113. Prevention:

114. minimization of RBCs transfusions

115. iron-chelating agents Thank you!