1. MANAGEMENT OF ACUTE TRANSFUSION REACTIONS
DR SHABNEEZ HUSSAIN
F.C.P. S HAEMATOLOGY (AKUH)
CONSULTANT HAEMATOLOGIST
FATIMID FOUNDATION

2. OUTLINE Definition Types of transfusion reactions Hemolytic
Febrile non hemolytic
Allergic
Anaphylactic/ anaphylactoid
Pulmonary transfusion reactions
Bacterial contamination
Clinical and laboratory management of transfusion reactions

3. What is a transfusion reaction?
Any unfavorable transfusion related event, occurring in a recipient during or after transfusion.

4. Types of transfusion reactions
Immediate
Delayed
HEMOLYTIC
FEBRILE NON HEMOLYTIC
ALLERGIC
ANAPHYLACTIC
TRALI
BACTERIAL CONTAMINATION
TACO
PHYSICAL OR CHEMICAL RBC DAMAGE
DEPLETION OR DILUTION OF COAGULATION FACTORS/ PLATELETS
DELAYED HEMOLYTIC
ALLOIMMUNIZATION
POST TRANSFUSION PURPURA
TA-GVHD
IMMUNOSUPPRESSION
IRON OVERLOAD
AIR EMBOLISM

5. Typical causes of transfusion associated deaths
Acute hemolysis (ABO incompatible)
Acute pulmonary edema
Bacterial contamination
Delayed
Anaphylaxis
External hemolysis (>40C)
Damaged red cell component
Ta-GVHD

6. IMMEDIATE HEMOLYTIC TRANSFUSION REACTION

7. Definition Occurs soon after transfusion of incompatible RBC
Reaction period: 1-2 hours
Surgery: hypotension/haemoglobinuria/
abnormal bleeding

8. SIGNS/SYMPTOMS Fever Chills Facial flushing Chest pain
Back or flank pain
Hypotension
Abdominal pain
Nausea
Dyspnea
Haemoglobinemia
Haemoglobinuria
Shock
Anemia
Oligouria/anuria
Pain at transfusion site
Generalized bleeding
Urticaria
Diarrhea
DIC

9. Treatment Perform immediate bedside procedure
Mannitol / furosemide to induce renal diuresis and to prevent failure
Hypotension: IV fluids and dopamine
FFP/cryoprecipitate and platelet for bleeding diastheis
Vital signs/coagulation status and renal output

10. Prevention Storage Do not warm RBC >37 C
Ensure correct identification
Do not add medications to blood
Specimen collection labeling and testing
Never sign out blood by name only

11. Febrile non hemolytic

12. Definition 1% of all transfusions
1C rise in temperature above patient’s baseline temperature during or within 24 hours after transfusion with a minimum recorded temperature being 38C

13. Pathophysiology Leukocyte antibodies (HLA) in patient’s plasma
Stimulus: prior transfusion/tissue transplant/ pregnancy
Release of pyrogens from transfused WBC

14. Signs and symptoms Fever ± chills Rarely hypotension
Severe: cyanosis/tachycardia/ tachypnea/ dysnea / cough/transient leukopenia

15. Differentials
IHTR
Bacteremia
Drugs

16. Prevention Leukoreduction: pre-storage or bedside (≤ 5 × 106)
Washed red cell concentrate — 107 WBCs (1-2 log leukodepletion)
Frozen deglycerolized red cells —  (2-3 log leukodepletion)
Centrifugation and buffy coat removal — 108 WBCs (1 log leukodepletion)
Premedication: paracetamol

17. Leukoreduction To minimize: Febrile nonhemolytic transfusion reactions
HLA alloimmunization
platelet refractoriness in multitransfused patients
Prevention of transmission of leukotropic viruses such as EBV and CMV. 

18. Pre storage over post storage
It eliminates the accumulation of inflammatory cytokine
It removes the intact leukocytes as against filtration, at the bedside, where leukocyte fragments after storage can pass through filters
Minimize the risk of leukotropic virus transmission as leukocytes disintegrate and release the intracellular organisms after 72 hours of storage in blood components.

19. Allergic / urticarial transfusion reaction

20. Definition Common Donor plasma has an allergen
Patient plasma has IgG/IgE
Or vice versa
Release of histamine and leukotrienes
Vasodilation
Swelling/welts: itching

21. Signs/symptoms Erythema (redness) Pruritis (itching)
Hives (raised firm red welts)
± fever
Severe : angioneurotic edema/laryngeal edema/bronchial asthma

22. Treatment Mild: Diphenhydramine, can stop transfusion then resume
Severe: aminophylline/epinephrine /corticosteroids

23. Prevention Repeated allergic reactions: washed
Premedication with antihistamine

24. Anaphylactic/anaphylactoid

25. Definition Immediate hypersensitivity Spectrum :
Hives …..pruritis….shock …. Death
Any organ : lung, vessels, nerves, skin, GIT
Differentiating feature :
Fever is absent
Signs and symptoms occur after transfusion of a few ml of plasma containing component

26. Pathophysiology
IgA deficiency who develop anti IgA by sensitization from transfusion or pregnancy
Histamine and leukotrienes
Anaphylactic: Ig A deficient
Anaphylactoid: normal levels of IgA but have limited type specific anti IgA that reacts with light chain of donor IgA

27. Signs and symptoms

28. Treatment Stop transfusion IV line open with saline
Epinephrine immediately
Corticosteroids or aminophylline
Airway patency
Vital signs

29. Prevention Washed PRBC
Transfuse blood components from donors lacking IgA

30. Pulmonary transfusion reactionS
TRALI
TACO
TAD
Pulmonary transfusion reactionS

31. Pulmonary transfusion reactions
PRIMARY
SECONDARY
Reactions occur in the wake of another transfusion reaction in
which the lung is not the mainly affected tissue.
Reactions with predominant
pulmonary injury and respiratory distress
Haemolytic transfusion reactions
Hypotensive/anaphylactic reactions
Transfusion transmitted bacterial infections
Transfusion-related acute lung injury (TRALI)
Transfusion-associated circulatory overload (TACO)
Transfusion associated dyspnea (TAD)

32. Transfusion-related acute lung injury

33. Pathophysiology
Immune: Occurs due to passive transfer of leukocyte antibodies or neutrophil priming substances accumulated in stored blood
Antibodies bind to neutrophil, actin polymerizes  entrapment  release of reactive oxygen species and toxic enzymes  leakage of protein rich fluid and neutrophil emigration
Non-immune: TRALI occurs after transfusion of stored platelet and erythrocyte concentrates 

34. Risk factors HNA and HLA antibodies in multiparous female donors
Anti HNA3a :severe and fatal TRALI

35. Signs and symptoms
Non cardiogenic pulmonary edema, Hypoxemia, Respiratory distress, Fever, Cyanosis, hypotension
In ventilated patients, sudden drop in arterial oxygen tension, copious frothy ooze from endotracheal tube
TRALI improves within 48 hours
Pulmonary infiltrates remain till 7 days

36. Diagnostic tests
X ray: bilateral generalized lung infiltrates (white lung)
Pao2/Fio2 : < 300 mmHg, Pulse oximetry <90%

37. Treatment
Stop transfusion
Respiratory and hemodynamic support

38. Prevention
If caused by patient anti leukocyte antibodies: leukoreduction
If caused by donor anti leukocyte antibodies: defer donor (controversial)

39. Transfusion-associated circulatory overload

40. TACO
Transfusion can cause rise in central venous pressure and heart failure
Elevated transvascular fluid filtration and lung edema

41. Risk factors Advanced age or very young age
Congestive cardiac or renal failure patients

42. Clinical features
Mostly within 1 to 2 hours after beginning transfusion
chest tightness, headache, dry cough, tachycardia, tachypnea, elevated blood pressure
Engorgement of neck vessels
S3 on auscultation
Positive fluid balance

43. Diagnostic tests X ray: Pulmonary edema ± cardiomegaly
Pulmonary artery occlusion pressure >18mmHg

44. Treatment Rapid reduction of hypervolemia
Respiratory and cardiac support
Oxygen therapy
Intravenous diuretics
Correction of cardiac arrhythmias and decreased myocardial function

45. Prevention Usual transfusion rate : 200ml/hr
With TACO : 100 ml/hr or less
Aliquots of donor units
RBC instead of whole blood

47. Transfusion associated dyspnea
Respiratory distress associated with transfusion
Those reactions that are not assigned to other pulmonary transfusion reactions

48. Bacterial contamination

49. Definition Yersinia enterocolitica Endotoxin
Bacteria in cold temperature (peudomonas , E coli)

50. Signs and symptoms Rapidly or within 30 mins after transfusion
Dryness, flushing of skin
Fever
Hypotension
Shaking
Chills
Muscle pain
Vomiting
Abdominal cramps
Bloody diarrhea
Haemoglobinuria
Shock
Renal failure
DIC

51. Treatment Stop transfusion IV line: fluid support
Send bag and patient’s blood sample for Cultures
Broad spectrum antibiotics
Dopamine
Respiratory ventilation
Maintenance of renal function

52. Prevention Occurs at the time of phlebotomy
During component preparation or processing
Thawing of blood in waterbath
Visual inspection for colour change before release (brown/purple discolouration /clots/ hemolysis)
Infused within 4 hours

53. Transfusion reaction …… what will you do ???

54. Immediate bedside procedure
STOP TRANSFUSION
Keep IV line open with saline
Notify physician
Perform bedside clerical checks
Return unit /set/attached solution to the blood bank
Collect appropriate blood specimen
Document reaction

55. Laboratory investigation outline
Immediate:
Visual inspection of serum and plasma for free hb (pre and post transfusion)
Direct coombs’ test (post transfusion)
As required:
ABO and rh (pre and post)
Major compatibility test (pre and post)
Antibody screening (pre and post) and identification
Antigen typing
Free hb in the first voided urine post transfusion
Indirect bilirubin 5 to 7 hours post transfusion

56. Laboratory investigation outline
Extended procedure:
Gram stain and culture of unit and patient
Quantitative serum Hb
Serum haptoglobin (pre and post)
Serial Hb , haematocrit and platelet count
Peripheral blood smear
Coagulation and renal output studies
Urine for haemosiderin