2. Acute Transfusion Reactions
Clinical Symptoms and Laboratory Investigation

3. Acute Transfusion Reactions

4. Types of Transfusion Reactions
Acute
Hemolytic
Febrile
Allergic
Anaphylactic
Transfusion Related Acute Lung Injury (TRALI)
Bacterial Contamination (Sepsis)
Circulatory Overload

5. Acute Hemolytic Transfusion Reactions (AHTR)
Pathophysiology:
-Transfusion of ABO incompatible RBC
-Other antibodies
-Transfusion of ABO incompatible Plasma
Incidence:
Acute Hemolytic: 1/6000-1/20,000
Fatal: 1/100,000-1/600,000 5 5

6. Acute Hemolytic Transfusion Reactions (AHTR)
Pathophsiology:
When incompatible blood is given, antibodies and complement in the recipient plasma attack the antigens on the donor RBC.
Hemolysis ensues
The antigen-antibody complex activate the Hageman factor (factor XII), which acts on the kinin system to produce bradykinin
Bradykinin increases capillary permeability and dilates arterioles, both which cause hypotension 6 6

7. Acute Hemolytic Transfusion Reactions (AHTR)
Activation of the complement system results in the release of histamine and serotonin from mast cells resulting in bronchospasm.
DIC
Renal damage occurs for several reasons, blood flow is reduced because of hypotension and renal vasoconstriction, free hemoglobin can cause a mechanical obstruction, and if DIC occurs fibrin thrombi can be deposited in the renal vascular 7 7

8. Signs and Symptoms of AHTR
Fever
Chills
Nausea and Vomiting
Diarrhea
Hypotension
Flushed appearance and Dyspnea
Chest pain and back pain
Pt is restless, and has a headache
Hemoglubinuria, and possible diffuse bleeding 8 8

9. Symptoms under GA
Many signs and symptoms will be masked by general anesthesia.
Hypotension, hemoglobinuria, and diffuse bleeding may be the only clues that a transfusion reaction has occurred. 9 9

10. Management of AHTR Management has 3 main objectives:
1-Maintenance of systemic blood pressure
2-Preservation of renal function
3-Prevention of DIC 10 10

11. Therapeutic Approach
*Keep urine output >1/ml/kg/hr with fluid & IV diuretic (furosemide)
*Analgesic( may need morphine)
*Low dose dopamine
*Haemostatic components (PlT,Cryo,FFP) for bleeding 11 11

12. The Most Common Cause of Acute Immediate Intravascular Hemolysis
Failure to identify the patient with the donor unit at the time of administration
Collecting pre-transfusion specimen from the wrong patient
Incorrectly labelled specimens
Unlabelled specimens that are labelled after leaving the bedside (in the lab or at the nursing station)

13. Non immune Hemolysis *Improper shipping or storage temp.
* Using small needle size
* Improper use of blood warmer
* Bacterial contamination 13 13

14. Febrile Reactions (FNHTR)
Definition:
*Temperature increase of greater than 1 degree centigrade within 1-2 hours for which no other cause is identifiable.
*The response occurs in
0.5-6% of RBCs transfused
*Up to30% of PLT transfused 14 14

15. Symptoms Raises temperature >1°C (fever) Chills with fever Shaking:
Raises temperature >1°C (fever)
Chills with fever
Shaking
Antipyretics are drugs that reduce fever (i.e., acetaminophen)

16. Febrile Reactions (FNHTR)
Pathophysiology:
1-Patients who receive multiple transfusions often develop antibodies to the HLA antigens on the passenger leukocytes
During subsequent RBC transfusions, febrile reactions may occur as a result of antibody attack on donor leukocytes
2-Generation of leukocyte-derived cytokines during storage 16 16

17. Febrile Reactions (FNHTR)
TREATMENT:
*Antipyretic
(Acetaminophen, no aspirin)
Prevention: 17 17

18. Minor Allergic Reactions
*Soluble antigens in the donor plasma react with IgE bound to mast cells causing histamine release.
*Allergic reactions can cause urticarial reactions in 1-3% of all transfusions
*The pt. may have itching, swelling, and a rash as a result of histamine release 18 18

19. Therapeutic/Prophylactic Approach
*Antihistamine,treatment or premedication(PO or IV)
*Transfusion restart slowly after Antihistamine if symptom resolve
Prevention: 19 19

20. Anaphylactic Reactions
This occurs in :
*Pts with hereditary IgA deficiency
*Ab against C4-Haptoglobin-Ethylene Oxide
Incidence: 1/20,000-1/50,000 of transfusions
Symptoms:
NO fever Hypotension
Skin flushing Cardiac arrhythmia
Nausea Cardiac arrest
Diarrhea Laryngeal edema 20 20

21. Laboratory evaluation in Anaphylaxis
*-Perform quantitative IgA test
*-Perform Anti IgA 21 21

22. Therapeutic/Prophylactic Approach
*Trendelenberg position
*Epinephrine(Adult dose : ml of 1/1000 solution SC IM , in sever cases 1/10000 IV
*Antihistamines,corticosteroids,
beta-2 agonists
Prevention:
*transfusion of IgA –deficient
components or Washed cellular
components 22 22

23. Transfusion-related acute lung injury (TRALI)
Definition :
* Acute Onset
* Hypoxemia
O2 saturation<90%
*The onset of signs and symptoms occur during or within 6 h of transfusion
* No pre-existing ALI before transfusion
*No temporal relationship to an alternative risk factor for ALI
*Bilateral lung infiltration on the
Chest-XRAY 23 23

24. Transfusion-related acute lung injury (TRALI)
Incidence :1/5000-1/190,000 blood and blood components transfused
*Packed red cells and -Cryo-FFP can cause TRALI
* 15ml of blood component are sufficient to cause TRALI 24 24

25. Transfusion-related acute lung injury(TRALI)
Etiology:
The antibody-mediated model
(Ab to HLA Class-HNA) 25 25

26. Transfusion-related acute lung injury (TRALI)
Common symptoms and signs:
Fever
Progressive dyspnea
Cyanosis
Hypoxemia
Hypotension or
Hypertension (rarely) 26 26

27. Transfusion-related acute lung injury (TRALI)
Management :
*Supportive
*Transfusion of the suspected blood product should cease immediately
* Oxygen therapy
*Mechanical ventilation in severe TRALI
* No diuretics
* Corticosteroids in TRALI: unproven 27 27

28. Transfusion-related acute lung injury (TRALI)
Prognosis :
*Most patients recover within
48–96hr h
*Hypoxemia and radiological evidence of pulmonary infiltration can persist for 7 days in 20% of patients
*70% patients require mechanical ventilation
*In-hospital mortality: 5–10% 28 28

29. Transfusion-related acute lung injury (TRALI)
Prevention :
No universally agreed approach to donor management
1-It is suggested that donors implicated in TRALI and who have demonstrable antibodies should be permanently disqualified from the donor pool
2-Deferring multiparous female
3-Using male donor plasma
4-Washed blood products 29 29

30. Bacterial Contamination
*The source of the bacteria can be donor blood, donor skin flora, or contaminants introduced during collection, processing, and storage.
*Numerous gram-positive and gram-negative organisms can occur: Staphyloccus aureus, Klebsiella pneumoniae, Serratia marcescens,Pseudomonas and Staphyloccus epidermidis. 30 30

31. Bacterial Contamination
Bacterial sepsis;
Incidence :Pooled RDP :1/ Unit of RBC:1/31,000
Rate of bacterial infection/contamination
is higher with platelets is because they are stored at room temperature and the units are generally pooled between 6 and 10 donor units. 31 31

32. Bacterial Contamination
Presentations:
Fever
Chills
Tachycardia
Hypotension
Shock
* The patient may also develop DIC and acute renal failure. 32 32

33. Bacterial Contamination MANAGEMENT
Other products from the same donor can be quarantined
*Return clamped blood unit& tubing attached for culture
Collect blood samples for blood culture
Broad spectrum antibiotic therapy 33 33

34. Bacterial Contamination
PREVENTION :
*Inspect all blood products for visual evidence of contamination
*The first 40 ml of blood collected is diverted in a pouch to reduce risk of transmitting organisms from skin 34 34

35. Circulatory Overload High risk patients are: Adults >60y & infants
Incidence : <1% of transfusions
Symptoms :
Dyspnea, Orthopnea, Cyanosis,
Tachycardia & Hypertension
D.D: TRALI 35 35

36. Circulatory Overload Treatment: Stop transfusion Upright posture
Oxygen therapy
IV diuretic (furosmide)
Phlebotomy
Prevention:
* Administer transfusion slowly
(1ml/kg/hr)
* Use of diuretics 36 36

37. When a Reaction is Suspected…

38. Signs & Symptoms GENERAL Nervous System Respiratory Fever
Chills
Muscle ache,pain
Back pain
Chest pain
Headache
Heat at the site of infusion or along vein
Nervous System
Apprehension, impending sense of doom
Tingling, numbness
Respiratory
Tachypnea
Apnea
Dyspnea
Cough
wheezing

39. Signs & Symptoms Gastrointestinal Renal Cardiovascular Cutaneous
Nausea
Vomiting
Pain, abdominal cramping
Diarrhea (may be bloody)
Renal
Changes in urine volume
Changes in urine color
Cardiovascular
Heart rate
Blood Pressure
Circulatory
Bleeding
Cutaneous
Rashes, Hives(urticaria)
Itching

40. Signs in an Unconscious Patient
Weak Pulse
Fever
Hypotension
Visible hemoglobinuria
Increased operative bleeding
Vasomotor instability
Tachycardia, brachycardia, hypotension
Oliguria/anuria

41. Remember
Reactions from different causes can exhibit similar manifestations; therefore, every symptom should be considered potentially serious and transfusion should be discontinued until the cause is determined

42. Immediate Actions to Take
Stop TX immediately and keep an IV open with 0.9 Saline
Check vital signs every 15 minutes
Do clerical check at bedside of identifying tags and numbers, Check labels,forms,and Ids
Notify the attending physician and the laboratory immediately
Send bags &patient’s blood to BB
Collect blood specimen and first voided urine

43. Post Transfusion Reaction blood samples to be collected from the recipient:
Repeat ABO, Rh, IAT and Crossmatch. Visual check for hemolysis and compare with pre transfusion sample.
DAT (Direct Antiglobulin Test)
Collect 5-7 hours post transfusion to check for bilirubin
Free hemoglobin determination
Clotted specimen
EDTA specimen
1st voided urine specimen post-tx’n

44. Immediate Actions to Take
Treat patient symptoms
as per physician instructions
Take vitals
Pulse
Temperature
Blood Pressure
Document thoroughly
Complete reaction form
Send form, bag, tubing and set to laboratory

45. Did the patient develop fever?
Yes
Acute hemolytic
FNHTR
TRALI
Bacterial contamination (Sepsis) No
Allergic
Anaphylactic
Hemolytic,
FNHTR or TRALI
How high did the temperature rise?
<2°C >2°C
Consider:
Acute hemolytic FNHTR
TRALI
Bacterial contamination
Concomitant clinical factors
Typically seen in
Bacterial contamination (Sepsis)

46. When did the fever present?
Immediately/at start of transfusion:
Bacterial contamination
Acute hemolytic
Concomitant clinical factors
During or at the end of the transfusion:
•FNHTR
Bacterial contamination
Acute hemolytic
TRALI
Concomitant clinical
Several hours after transfusion:
FNHTR
Bacterial contamination
TRALI
Concomitant clinical factors

47. اسلايدهاي سيستم هموويژلانس- ويژه پزشكان
تنگي نفس
علل :
TRALI
TACO
Anaphylaxis
Other Causes
Clinical Guide To Transfusion ; Canadian Blood Service ;Chapter10;p:82-111;July2006
اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

48. Minor Allergic Reactions
كهير
علل :
Minor Allergic Reactions
Anaphylaxis
TRALI
Other Causes
اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

49. Bradykinin mediatedHypotension -
افت فشار خون
علل :
Bradykinin mediatedHypotension -
-Sepsis
-AHTR
-TRALI
-Other Causes

50. GOOD LUCK

51. Investigation of transfusion reactions.

52. Investigations of transfusion reaction are necessary for :
Diagnosis
Selection of appropriate therapy
Transfusion management
Prevention of future transfusion reaction
اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

53. Investigations should include correlations of clinical data with laboratory result

54. Important clinical data :
Diagnosis
Medical history of pregnancies, transplant, and previous transfusion.
Current medication
Clinical signs and symptoms of the reaction.
اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

55. Important clinical data :
5. Question related to the transfusion:
Amount of blood transfused to cause the reaction.
How fast , how long ?
The use of blood warmer.
Any filter used ? Other solutions.
Any drugs given at the time of transfusion
اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

56. Laboratory investigation outline of transfusion reaction.
Immediate procedures
Clerical checks.
Visual inspection of serum and plasma for free hemoglobin ( pre and post transfusion )
Direct anti – globulin test. ( post transfusion EDTA sample )
اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

57. 2. As required procedures
ABO grouping and RH typing, pre and post transfusion
Major compatibility testing , pre and post transfusion
Antibody screening test , pre and post transfusion
Alloantibody identification
Antigen typings
Free hemoglobin in first voidedurine post transfusion
Unconjugated bilirubin 5 – 7 hours post transfusion.
اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

58. اسلايدهاي سيستم هموويژلانس- ويژه پزشكان
3. Extended procedures
Gram stain and bacterial culture of unit
Quantitative serum Hemoglobin.
Serum Haptoglobin , pre and post transfusion
Peripheral blood film.
Coagulation and renal output study
Urine hemosiderin
اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

60. What Happens in the Lab…

61. Laboratory Actions when Notified of Suspected Reaction
Quarantine all other crossmatched units
When Reaction form, unit, set, tubing, urine received
Centrifuge specimen
Clerical Check
Review Symptoms
To determine extent of investigation required

62. Clerical Check Check test results vs. interpretation
Check tag information with bag information (unit number, ABO/Rh)
Check Pre-transfusion specimen information with tag information (name, number)
Check that information on pre-transfusion specimen is identical to post-transfusion

63. Visual Inspection
Compare plasma color of pre-transfusion and post-transfusion specimens
Is post-transfusion specimen hemolyzed?
If yes, ensure that hemolysis is not due to difficult collection (recollect if necessary)
If still yes, notify physician immediately
Check contents of unit for hemolysis
Check blood in tubing for hemolysis

64. Direct Antiglobulin Test (DAT)
To determine if there is in vivo sensitization
May be negative if intravascular hemolysis has occurred
If positive, perform monospecific DAT to determine if it is IgG, C3 or both

65. Extended Testing ABO/Rh on pre and post transfusion specimens
ABO/Rh on donor unit
Antibody screen on pre and post transfusion specimens
Antibody Investigation, positive
DAT on pre transfusion specimen and donor unit

66. Reporting
Classified as to type of reaction given symptoms and investigation outcome
Should be signed off by laboratory physician or designate
Reference for follow up for any attending physician questions regarding future transfusions given the patient’s clinical need
Patient should be informed of reaction and outcome

67. Reporting
Should include future pre medication or special requirements, if applicable
Examples
Antihistamines
Anti pyretics
Washed blood (when anaphylactic reactions are under investigation and results are not back yet)
Antigen negative blood if a clinically significant antibody is identified

68. Reporting
Hospitals should report all severe and fatal reactions to the blood supplier