12 Adverse Reactions in Blood Transfusion

• Transfusion reactions are any unfavorable transfusion related event occurring in a patient during or after transfusion of blood components.
• Immediate transfusion reactions are onset of signs of symptoms appears very rapidly, usually from few minutes to hours during the blood transfusion
• Delayed transfusion reactions usually occurs three to seven days post completion of the transfusion.
• Febrile Non-hemolytic Transfusion Reaction is the most common transfusion reaction that we encounter
• Transfusion-related Acute Lung Injury is one of the common causes of transfusion related fatalities
• Alloimmmunization is the development of antibodies to antigen that she/he lacks
• Post-transfusion Purpura is when antibodies of patient attacks the platelets product therefore the patient becomes extremely thrombocytopenic despite the transfusion of platelets product
• Transfusion-associated Graft vs Host Disease is when the immunocompetent donor's T-cells mounts an immune attack against your immunocompromised host tissues
• Hemolytic transfusion reaction occurs during transfusion (immediate) or 3-7 days post-transfusion (delayed)

  • Often occur with transfusion of incompatible RBCs
• Immediate HTR occurs very soon after transfusion of incompatible RBCs

  • 1-2 hours (but can occur within minutes)
  • Anti-A, anti-K, anti-Jka , anti-Fya (C’ binders)
  • Can be intravascular or extravascular means
• Back pain is a classic sign of Immediate HTR because it involves the kidney.

  • Hemoglobin in higher concentration (free hemoglobin), it is toxic to kidney and can lead to renal failure
• Intravascular Hemolysis pathway

  
• Delayed HTR is caused by antibodies and has a manifestation occurs 3- 7 after transfusion

  • Most often a result of an anamnestic response in a patient who have been previously sensitized by pregnancy, transfusion, transplantation, and in whom antibody is not detectable by standard pre-transfusion methods
• Extravascular Hemolysis pathway

  
• Febrile Non-Hemolytic TR is the most commonly encountered type of transfusion reaction

  • Defined as a 1°C temperature rise associated with transfusion and having no medical explanation other than blood component transfusion
  • Caused by anti-leukocyte antibodies present in the patient’s plasma
• Febrile Non-hemolytic TR

  • Prior alloimmunization is the causative stimulus
  • Febrile mechanism still not fully explained
  • Febrile reaction may follow complement activation and production of IL-1 and prostaglandin
  • Leukoreduced blood components are indicated
  • Diagnosis is by exclusion
• Allergic (Urticarial) TR commonly reported as FNHTR, is one of the 2 most common reactions yet definitive causes are not yet known but similar with type 1 hypersensitivity mechanism

  • Two possible etiologies:
  • Donor plasma has allergen with IgE/IgG antibodies in patient’s plasma
  • Donor plasma has IgE/IgG that combine with allergens in patient’s plasma
• Histamine is the primary mediator of the allergic response in Allergic TR
• Anaphylactic/Anaphylactoid TR ranges from mild urticaria and pruritus to severe shock and death

  • Two distinguishing features:
  • Absence of fever
  • Signs and symptoms occur after transfusion of just a few mL of plasma or plasma-containing blood components
  • Mediated by histamine and leukotriene
• Anaphylactic/Anaphylactoid TR is attributed to IgA-deficient patients who have developed anti-IgA by sensitization or pregnancy
• Anaphylactic IgA happens to persons deficient with anti-IgA
• Anaphylactoid has normal levels of IgA but a limited type-specific anti-IgA reacts with light chains of the donor IgA
• Transfusion-related Acute Lung Injury is similar to adult respiratory distress syndrome (ARDS)

  • Pathophysiology is not well understood
  • Consistent finding is leukocyte antibody in donor or patient plasma
  • Postulated mechanisms include:
  • Anti-leukocyte antibodies could initiate C-mediated pulmonary capillary endothelial injury
  • Anti-leukocyte antibodies could react with leukocytes to trigger complement system to produce C3a and C5a
• Transfusion-associated Circulatory overload is an iatrogenic transfusion reaction

  • Individuals at risk:
  • Pediatric & geriatric patients
  • Patients with chronic normovolemic conditions (anemia, leukemia etc.)
  • Patients with cardiac disease
  • Patients with thalassemia major disease
  • Caused by transfusion of a blood unit too fast (> 200 mL/hr)
  • Leads to congestive heart failure and pulmonary edema

  
• Bacterial contamination, a non-immune TR, is a type of septic reaction that can have a rapid onset and lead to death

  • Yersinia enterocolitica → most common cause
  • Caused by endotoxin produced by psychrophilic bacteria (Pseudomonas spp., Escherichia coli, Yersinia enterocolitica)
• Physically/Chemically Induced TR are caused by broad range of physical or chemical factors that either affect a blood component or are a consequence of the transfusion event

  • RBC damage, dilution/depletion of clotting factors and platelets, hypokalemia, hyperkalemia, air embolism
• Primer for blood transfusion used is always NSS
• Post-transfusion purpura is rare complication of blood transfusion involving platelets

  • Rapid onset of thrombocytopenia due to production of platelet alloantibodies
  • Patient has antibodies against platelets
  • Attaches to platelet surface and allow extravascular destruction by the RES
  • Management: Corticosteroids, Exchange transfusions, plasmapheresis
• Anti-PLA1 is the most frequently identified platelet alloantibody in Post-transfusion purpura
• Transfusion-associated Graft vs Host disease is a complication of blood transfusion or BM transplantation

  • Individuals at risk:
  • Immunocompromised patients
  • Patients w/ lymphopenia/BM suppression
  • Patients receiving blood components from blood relatives
  • Fetuses receiving intrauterine transfusion
  • Newborns receiving exchange transfusions
  • Death due to infection or hemorrhage secondary to BM aplasia
• Blood component irradiation is the best current technology to reduce risk of TA-GVHD

  • It inactivates lymphocytes
  • 25-35 Gy
• Iron overload is a long term complication of RBC transfusion.

  • AKA Transfusion Hemosiderosis
  • 225 mg Fe/RBC unit
  • Iron accumulation affects:
  • Heart
  • Liver
  • Endocrine organs
  • Interference of mitochondrial function by excess iron
• Desferrioxamine/Deferoxamine is a chelating agent to avoid Iron Overload; subcutaneous infusion
• Hypertransfusion of neocytes (young RBCs) is a chelating agent to avoid Iron Overload; to reduce frequency of transfusion
• Transfusion Reaction Investigation

  • Necessary for:
  • Diagnosis
  • Selection of appropriate therapy
  • Transfusion management
  • Prevention of future transfusion reactions
  • Should include correlation of clinical data with laboratory results
  • Absence of evidence is not evidence of the absence of a transfusion reaction

  
• Specimen that may be required during TRI:

  • Clotted blood drawn 5-7 hours post transfusion
  • First voided post-transfusion urine in order to determine whether hemoglobinuria is present
  • Other specimens collected at various times that are considered appropriate to TRI
  • Pre-transfusion samples
• Clerical checks should identify any possible error or discrepancies in patient or donor identification

  • mislabeling, misidentification
• Immediate Laboratory Investigation: Visual inspection

  
• Direct AHG is immune in nature

  • Immediate Laboratory Investigation is done using post-transfusion specimen
  • Test may yield negative result if incompatible transfused cells have been immediately destroyed
  • MF agglutinated donor RBCs
  • Unagglutinated patient RBCs
• Compatibility testing

  • Patient pre/post transfusion specimen + donor unit involved (PSDR)
  • Pre transfusion Spx and post transfusion Spx
  • Incompatible crossmatch (pre trans spx) → original error
  • Incompatible crossmatch (post trans spx) → possible anamnestic response