1. Clinical Aspects of Transfusion Reactions.
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2. This lecture is designed to give an overview of:
Acute haemolytic transfusion reaction.
Signs and symptoms.
Investigation of serious reactions.
Example.
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3. This lecture is designed to give an overview of:
Renal failure.
Management of an ABO incompatible transfusion.
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4. This lecture is designed to give an overview of:
Delayed haemolytic transfusion reaction.
Definition.
Clinical features.
Haematological and serological features.
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5. This lecture is designed to give an overview of:
Bacterial contamination.
Symptoms.
Implicated components/organisms.
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6. This lecture is designed to give an overview of:
Transfusion-associated graft- versus-host disease (TAGvHD).
Causes.
Clinical features.
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7. This lecture is designed to give an overview of:
Investigations.
Indications for gamma irradiation.
Components requiring irradiation.
Shelf-life post-irradiation.
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8. This lecture is designed to give an overview of:
IgA deficiency with anti-IgA.
Signs and symptoms.
Treatment of anaphylactic reaction.
Antibody-antigen reactions.
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9. This lecture is designed to give an overview of:
Febrile non-haemolytic transfusion reaction (FNHTR).
Signs and symptoms.
Causes.
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10. This lecture is designed to give an overview of:
Cytokine generation.
The role of cytokines in the pathogenesis of fever.
Hypotensive reactions.
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11. This lecture is designed to give an overview of:
Post-transfusion purpura (PTP).
Mechanism of autologous platelet destruction.
Differential diagnosis.
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12. This lecture is designed to give an overview of:
Course of the disease.
Management.
Prevention.
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13. Acute Haemolytic Transfusion Reaction.
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14. Symptoms: Apprehension. Flushing. Pain at VP site.
Pain in chest, abdomen, loin.
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15. Signs: Fever. Hypotension. Generalised bleeding. Haemoglobinaemia.
Haemoglobinuria.
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16. Investigation of Serious Reactions.
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17. Re-check patient identity and ABO group.
Expiry date.
Urine output.
Volume, haemoglobinuria, etc.
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18. Blood samples from patient.
ABO group, antibody screen and cross- match.
DAT and eluate, even if the DAT is negative.
FBC and platelets.
Coagulation screen.
Blood culture.
Biochemistry.
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19. Example.
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20. Anti-A reacts with the A antigen.
This activates the complement cascade from C1q to C9a.
This causes membrane damage.
Resulting in intravascular haemolysis.
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21. Activates clotting factors
Neutrophils
Complement
Cytokines
Macrophages
Activates clotting factors
Thrombosis
Consumption of
clotting factors
Organ failure
Bleeding
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22. Renal Failure.
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23. Free haemoglobin binds nitric oxide.
Hypotension, Shock.
DIC.
Free haemoglobin binds nitric oxide.
Causes excessive vasoconstriction.
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24. Management of an ABO Incompatible Transfusion.
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25. Maintain urine output >100mL per hour.
IV saline infusion.
Treat shock.
Monitor urine output.
Maintain urine output >100mL per hour.
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26. Frusemide if urine output <100mL per hour.
Dialysis for renal failure.
Blood components for DIC with bleeding.
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27. Delayed Haemolytic Transfusion Reaction.
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28. Occurs 24 hours or more after the transfusion.
Usually >7-10 days due to anamnestic response of red cell alloantigens to which the patient has been previously sensitised.
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29. Clinical features. Fever. Fall in haemoglobin. Jaundice.
Haemoglobinuria.
Renal failure (very rarely).
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30. Haematological and Serological Features.
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31. Antibody in serum (usually). Antibody eluted from red cells.
Spherocytosis.
Positive DAT.
Antibody in serum (usually).
Antibody eluted from red cells.
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32. Bacterial Contamination.
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33. Bacterial Contamination of Blood Components.
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34. Feeling unwell.
Fever.
Chills.
Hypotension.
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35. Nausea.
Vomiting.
Dyspnoea.
Shock.
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36. Renal failure.
DIC.
Death.
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37. Implicated Components/Organisms.
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38. Implicated units; RBC/platelets.
Organism depends upon type and storage of components.
Blood culture, culture of bag.
Contact donor; arm swab culture.
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39. Transfusion-associated Acute Lung Injury (TRALI).
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40. See separate lecture on TRALI.
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41. Transfusion-associated Graft-versus-host Disease (TAGvHD).
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42. Caused by engraftment and proliferation of donor T lymphocytes in the recipient.
Activated donor T lymphocytes produce cytokines, causing inflammation and tissue damage.
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43. Sharing of HLA haplotypes. Defective recipient cell-mediated immunity.
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44. Clinical Features.
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45. Onset 1 to 2 weeks post-transfusion.
Fever, skin rash.
Diarrhoea.
Hepatitis.
Pancytopenia.
>90% mortality.
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46. Diagnosis. Skin biopsy. DNA analysis. Bone marrow.
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47. Investigations.
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48. Donor samples. Recipient sample. Fresh sample – 10-20mL EDTA.
Pre-transfusion (whatever is available).
Post-transfusion – 10-20mL EDTA.
Hair follicles, nail clippings, etc, as an alternative source of pre-transfusion DNA.
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49. Skin, affected and unaffected areas.
Bone marrow.
Spleen (post-mortem).
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50. Gamma Irradiation; Indications.
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51. Donations from first or second degree relatives.
All HLA selected platelets.
Foetus IUT and subsequent exchange/top-up transfusions.
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52. Infants receiving exchange transfusion.
Granulocyte transfusion (Buffy coat).
Patients with evidence of an underlying state (except chronic muco-cutaneous candidiasis and HIV).
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53. Allogeneic BMT from conditioning therapy until GvHD prophylaxis is completed (usually 6 months) or until the lymphocyte count is >1x109L-1.
Chronic GvHD can be immunosuppressive.
Active chronic GvHD; continue irradiation.
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54. Patients on purine analogues.
Bone marrow donors.
Blood transfused to bone marrow donors prior to, or during the harvest.
Patients on purine analogues.
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55. Components Needing Irradiation for Patients at Risk.
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56. Any other cellular components.
Red cells.
Platelets.
Any other cellular components.
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57. Shelf-life Post-irradiation.
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58. Exchange and IUT RBCs = 24 hours. Top-up and other RBCs = 14 days.
Platelets = 5 days.
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59. Not Necessary to Irradiate.
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60. Fractionated blood products.
Fresh frozen plasma.
Cryoprecipitate.
Frozen red cells.
Fractionated blood products.
Albumin.
Clotting factors.
Anti-D immunoglobulin.
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61. IgA Deficiency with Anti-IgA.
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62. Signs and Symptoms.
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63. Immediate reaction. Hypotension. Dyspnoea. Wheeze.
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64. Stridor.
Rash.
Angioedema.
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65. Treatment of Anaphylactic Reaction.
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66. Maintain venous access. Adrenaline. Piriton.
Stop transfusion.
Maintain venous access.
Adrenaline.
Piriton.
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67. IgA Deficiency with Antibodies. Anaphylactic Reactions.
1 in 700.
IgA Deficiency with Antibodies.
1 in 2, 300.
Anaphylactic Reactions.
1 in 20x103 to 1 in 50x103.
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68. Antigen-antibody Reactions.
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69. Anti-IgA bound to mast cells reacts with IgA. Mast cells degranulate.
Histamines.
Leucotrines.
Cytokines.
Brochospasm.
Endothelium.
Vasodilation.
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70. IgA Deficient Patient with a History of Severe Anaphylactic Reaction.
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71. Use IgA-deficient components irrespective of IgA antibody status.
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72. IgA Deficient Patients With Anti-IgA.
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73. Red cells - IgA deficient or washed. FFP - IgA deficient.
Platelets - IgA deficient or PSM.
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74. IgA Deficient Patients Without Anti-IgA.
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75. Occasional transfusions.
Regular transfusions.
Occasional transfusions.
Urgent.
Elective.
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76. Febrile Non-haemolytic Transfusion Reaction (FNHTR).
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77. Patient experiences chills.
The fever may develop between ½ hour to several hours after the start of the transfusion.
It is usually self-limiting.
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78. Differential diagnosis.
Haemolysis of transfused red cells.
Bacterial contamination of blood components.
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79. Causes of FNHTR.
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80. 30% of patients have no detectable antibody in their plasma.
Antibodies directed towards granulocyte and HLA antigens have been implicated as major causes of this immune-mediated event.
30% of patients have no detectable antibody in their plasma.
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81. This is inconsistent with an immune-mediated response.
It is not uncommon for patients who have had no previous transfusions or pregnancies to have an FNHTR during their first platelet transfusion.
This is inconsistent with an immune-mediated response.
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82. Cytokine Generation.
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83. RBCs stored at 4oC (+/-2oC). Platelets stored at 22oC (+/-2oC).
The levels of cytokines measured in stored blood were lower, compared with cytokines measured in stored platelet concentrates.
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84. The Role of Cytokines in the Pathogenesis of Fever.
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85. Circulatory pyrogenic cytokines IL-1β, IL-6 and TNF-α stimulate prostoglandin (PG) E2 production in the anterior hypothalamus.
PG reach the thermoregulatory neurons in the preoptic area of the anterior hypothalamus by diffusion.
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86. Aspirin/indomethacin block the generation of fever (PG inhibitors).
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87. Most reactions occur during, or immediately after transfusion.
The frequency of NHFTR with platelet transfusions is up to 30%.
The incidence is higher with pooled platelet products than with apheresis units.
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88. Frequency of NHFTR with RBC transfusion:
General hospital population = 0.5%.
Patients with haematological malignancies = 0.6%.
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89. Hypotensive Reactions.
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90. Recently described. Blood pressure <10mmHg baseline
Recently described. Blood pressure <10mmHg baseline. Resolved quickly when transfusion discontinued.
Causes:
Associated with ACE drugs (breakdown bradykinin).
Filters with net negative charge (activates kallikrein, causing bradykinin release).
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91. Treatment:
Positioning.
Normal saline.
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92. Post-transfusion Purpura (PTP).
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93. PTP is an acute episode of severe thrombocytopenia occurring about a week after a blood transfusion. It usually effects HPA-1a negative women who have previously been alloimmunised by pregnancy.
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94. The transfusion precipitating PTP cause a secondary immune response, boosting the HPA-1a antibodies.
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95. PTP typically occurs in middle-aged or elderly women (average 57 years, range 21 to 80 years).
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96. Mechanism of Autologous Platelet Destruction.
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97. Bystander mechanism (immune destruction).
Adsorption of soluble platelet antigens from donor plasma.
Immune complexes bind to autologous platelets.
Transient auto-antibody formation.
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98. Differential Diagnosis.
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99. ITP, TTP.
DIC.
Marrow failure.
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100. Heparin-induced thrombocytopenia (HIT).
Drug-related thrombocytopenia.
Blood components implicating PTP: Most reported cases involve RBCs.
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101. Course of the Disease.
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102. Usually self-limiting. Mortality 7-10% (early in the course).
If not treated, lasts, on average 2 weeks (range 1 to 4 weeks).
Remission (platelet count >100x109L-1) is, on average, 24 days (range 6 to 70 days).
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103. Management.
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104. IV steroids/plasma exchange.
IVIgG (2gdL-1 over 2 days).
85% respond.
IV steroids/plasma exchange.
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105. Prevention.
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106. HPA-compatible blood.
Leukodepleted blood.
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