Download Transfusion Reaction

Ahmad Sh. Silmi
Msc , FIBMS
Staff Specialist in Hematology
Head of Medical Laboratory sciences Dept
Islamic University of Gaza
“Blood is the
most
dangerous
medication that a
physician ever
prescribes”
Blood Transfusion Reactions
(BTR’s)

may be life-threatening and even fatal

require immediate recognition and
management

must be treated if indicated and prevented
in transfusion practice
Transfusion Reaction

any unfavorable transfusion-related
event occurring in a patient during or
after transfusion of blood components
Blood Transfusion Reactions
Haemovigilance
Serious Hazards of Transfusion ( SHOT )
65% Incorrect Blood Component
10% Acute Transfusion Reaction
10% Delayed Transfusion Reaction
5% Transfusion Lung Injury
3% Post-transfusion purpura
3% Transfusion Transmitted Infection
1% Transfusion-GVHD
Blood Transfusion:
Immediate
Reactions
1.
2.
3.
4.
5.
6.
7.
Acute Haemolytic Transfusion Reactions
Febrile Non-Haemolytic Transfusion Reactions
Allergic Reactions:
1. Anaphylaxis
2. Skin Reaction
Transfusion-related Acute Lung Injury
Bacterial Contamination
Circulatory Overload
Physically or Chemically Induced Transfusion
Reactions (PCITR’s)
Blood Transfusion:
Delayed
Reactions
1.
2.
3.
4.
5.
6.
Delayed Haemolytic Transfusion
Reactions
Post- transfusion Purpura
Infection Transmission
Transfusion-related Graft-versus-Host
Disease
Immune Modulation
Iron Overload
Immediate Blood Transfusion Reactions:
Acute Haemolytic Transfusion
Reactions

Intra-vascular

Extra-vascular
Immediate Blood Transfusion Reactions:
Acute Intra-vascular Haemolytic
Transfusion Reactions


Trigger: ABO antigens on transfused red
cells Not shared by the Recipient
Reactor: Anti-A or Anti-B of Ig M type
Immediate Blood Transfusion Reactions:
Acute Intra-vascular Haemolytic
Transfusion Reactions
Pathophysiology
Full Complement Cascade Activation
1.
Complement Components C3a,C5a
2. Cytokines: IL-1, IL-6,IL-8, TNF
3. Free Haemoglobin.
4. DIC
Immediate Blood Transfusion Reactions:
Acute Intra-vascular Haemolytic Transfusion
Reactions
Clinical Picture










Fever, Flushing, Rigors
Headache
Heat or pain at cannulated vein
Restlessness
Bronchospasm
Hypotension
Back or loin pain
Oozing in the surgical field
Red urine ( haemoglobinuria )
Oliguria or anuria
Immediate Blood Transfusion Reactions:
Acute Intra-vascular Haemolytic Transfusion
Reactions
Diagnosis





Clinical picture
Transfusion Mistake
Red urine
Red plasma
Lab Confirmation
Immediate Blood Transfusion Reactions:
Acute Intra-vascular Haemolytic Transfusion
Reactions
Laboratory Workup









Obtain Blood and urine samples, inspect color
Check paper work
Repeat cross Match
CBC
Direct Coombs’ test
DIC screen: PT,PTT, Fibrinogen
BUN, Cr, electrolytes
Haemolysis screen: LDH, Haptoglobin
Blood culture if sepsis is suspected
Immediate Blood Transfusion Reactions:
Acute Intra-vascular Haemolytic Transfusion
Reactions
Management





Stop transfusion Immediately
Replace giving set, keep IV line with Normal
saline
Check patient ID against donor unit
Cardio-pulmonary support
Insert urine cath. And start Forced Diuresis
( ensure 100 ml/h for 24 h to get rid of free Hb)
Immediate Blood Transfusion Reactions:
Acute Intra-vascular Haemolytic Transfusion
Reactions
Outcome
Mortality ~ 10 %
Immediate Blood Transfusion Reactions:
Acute Extra-vascular Haemolytic
Transfusion Reactions
Trigger: Rh antigens not shared by the
patient
Reactor: Anti-Rh antibodies of Ig G type
Immediate Blood Transfusion Reactions:
Acute Extra-vascular Haemolytic
Transfusion Reactions
Response: Pathophysiology
 Incomplete complement activation
Coating of transfused red cells with C3b
 Extravascular phagocytosis by RES
 Cytokines from activated RES
Immediate Blood Transfusion Reactions:
Acute Extra-vascular Haemolytic
Transfusion Reactions
Clinical Features





Less severe, may be no signs
Onset > I hour
Fever
+ Jaundice
Rarely Haemoglobinuria or renal dysfunction
Immediate Blood Transfusion Reactions:
Acute Extra-vascular Haemolytic
Transfusion Reactions

Laboratory
Anti-complementary Coombs positive
Immediate Blood Transfusion Reactions:
Acute Extra-vascular Haemolytic
Transfusion Reactions



Managment
Stop Transfusion
Supportive
Mortality very rare
Immediate Blood Transfusion Reactions:
Febrile Non-Haemolytic Transfusion
Reaction ( FNHTR)
Trigger: Leucocyte antigens on infused blood
not shared by the patient
Reactors: Leuco-agglutinins in the patient
from previous exposure
Immediate Blood Transfusion Reactions:
Febrile Non-Haemolytic Transfusion
Reaction ( FNHTR)
Pathophysiology

Cytokine released from the transfused activated
leucocytes
Immediate Blood Transfusion Reactions:
Febrile Non-Haemolytic Transfusion
Reaction ( FNHTR)
Clinical Features








Fever after 30-90 min
+ Rigors
+ Headache
No Hypotension
No Bronchospasm
No flank pain
No haemoglobinaemia
No Haemoglobinuria
Immediate Blood Transfusion Reactions:
Febrile Non-Haemolytic Transfusion
Reaction ( FNHTR)

Management
If Temp < 40 + Stable patient:






Stop transfusion
Antipyretics ( No rule of Anti-histamines )
Check the bag and cross match
Exclude red urine or red plasma
Resume transfusion at a slower rate
If recurrent: Leucodepleted transfusion in the future
Immediate Blood Transfusion Reactions:
Febrile Non-Haemolytic Transfusion
Reaction ( FNHTR)

Management
If Temp 40 or more + Unstable patient:


Stop transfusion
Manage as possible acute haemolytic
reaction till lab. Confirmation or
exclusion.
Immediate Blood Transfusion Reactions:
Febrile Non-Haemolytic Transfusion
Reaction ( FNHTR)

Prevention/ Recurrence of FNHTR’s:

pre-transfusion administration of antidotes


use leukocyte-depleted blood




documented BTR, warrants pre-transfusion medications
30 minutes before blood transfusion
removal of buffy coat
sedimentation
red cell washing
use of micro-aggregate filtration (leukoreduction)
Immediate Blood Transfusion Reactions:
Transfusion- Related Acute Lung Injury
( TRALI)
Sudden onset of acute respiratory distress
within 6 hours( u. 1-2h) of transfusion
Immediate Blood Transfusion Reactions:
Transfusion- Related Acute Lung Injury
(TRALI)
Rare: 1/5000 transfusions
Immediate Blood Transfusion Reactions:
Transfusion- Related Acute Lung Injury
( TRALI)



Pathophysiology
Trigger: Leucoagglutinins in the bag
against patient’s leucocytes
Reactors: Patient leucocytes
Result: massive Leucocyte activation
 Cytokine storm
 Pulmonary Endothelial and
Epithelial Injury  ARDS
Pathophysiology of (TRALI)
Leukocyte Ab in donor react with pt. leukocytes
Activate complements
Adherence of granulocytes to pulmonary endothelium with release
of proteolytic enz.& toxic O2 metabolites
Endothelial damage
Interstitial edema and fluid in alveoli
Immediate Blood Transfusion Reactions:
Transfusion- Related Acute Lung Injury
( TRALI)
Clinical Features




Fever, chills
Acute Respiratory Distress
Normal CVP (Central Venous Pressure)
CXR: Pulmonary Infiltrate
Immediate Blood Transfusion Reactions:
Transfusion- Related Acute Lung Injury
( TRALI)
Management



Cardio-Pulmonary Support
Steroids
Diuretics of No value
Mortality
High
Immediate Blood Transfusion Reactions:
Allergic Acute Transfusion Reactions
Pathophysiology



Trigger: Plasma proteins in the transfused blood
Reactors: Patient antibodies of IgE type
Response:

Mast cell degranulation

+ Complement Activation

+ Cytokines
Immediate Blood Transfusion Reactions:
Allergic Acute Transfusion Reactions
Clinical Features


Mild / Skin-restricted ( common: 1%):

Pruritus, Uerticaria, No fever or Hypotension
Severe / Systemic ( Anaphylaxis):

As above +

Fever

Hypotension

Bronchospasm, Angio-edema
Immediate Blood Transfusion Reactions:
Allergic Acute Transfusion Reactions
Management

Mild / Skin-restricted :

Stop transfusion temporary
 Anti-histamines
 Resume Transfusion
Immediate Blood Transfusion Reactions:
Allergic Acute Transfusion Reactions
Management

Severe / Systemic ( Anaphylaxis):

Stop transfusion
 Anti-histamines ( H1+H2 blockers)
 Epinephrine: 1 ml of 1/1000 IM
 Hydrocortisone 100 mg IV
 Cardio-pulmonary support
Immediate Blood Transfusion Reactions:
Acute Pyrogenic Transfusion Reactions
Pathophysiology

Trigger: Bacterial Pyrogens/Endotoxins in the
transfused blood contaminated with cold-growing
organisms as:

Pseudomonas

Yersinia

Some Staph

Reactors: Patient Mono-nuclear cells

Response:

Cytokine Storm
Immediate Blood Transfusion Reactions:
Acute Pyrogenic Transfusion Reactions
Clinical Features


Like :
Acute Haemolytic reaction BUT:
 No Hemoglobinuria
 No Hemoglobinaemia
FNHTR BUT More Severe
Immediate Blood Transfusion Reactions:
Acute Pyrogenic Transfusion Reactions
Management

As Acute Haemolytic reaction
BUT
Add Broad- spectrum Antibiotics
Immediate Blood Transfusion Reactions:
Acute Circulatory Overload



Acute cardiogenic pulmonary edema
In rapidly transfused, non-bleeding
(euovolemic) patients
More in infants, elderly or cardiac patients
Immediate Blood Transfusion Reactions:
Acute Circulatory Overload


D.D. from other Acute transfusion reactions:
No Fever ( DD from TRALI, FNHTR)
No red urine or plasma and Negative Coombs
( DD from Acute haemolytic reaction)
Immediate Blood Transfusion Reactions:
Acute Circulatory Overload
Prevention


Never exceed 2-3 ml/kg/hour Unless Bleeding
Pre-medicate with Diuretics in Cardiac or
severely anemic patients
Management



Diuretics
Consider Haemodialysis
Supportive
Immediate Blood Transfusion Reactions:
Physically or Chemically Induced Transfusion
Reactions (PCITR’s)

heterogenous group of conditions including:
 physical RBC damage
 depletion and dilution of coagulation factors
and platelets
 hypothermia
 citrate toxicity
 hypokalemia / hyperkalemia
Immediate Blood Transfusion Reactions:
Physically or Chemically Induced Transfusion
Reactions (PCITR’s)

Physical Damage to RBC’s
intravascular lysis due to hypertonic or hypotonic
solutions
 heat damage from blood warmers, during shipping,
in hot rooms
 freeze damage in absence of cryoprotective agent
during shipping

Immediate Blood Transfusion Reactions:
Physically or Chemically Induced Transfusion
Reactions (PCITR’s)

Mechanical Damage


blood pumps, roller pumps
infusion under pressure through small bore needles
Immediate Blood Transfusion Reactions:
Physically or Chemically Induced Transfusion
Reactions (PCITR’s)

Citrate toxicity



ACD/ CPD has 1.4-1.6 g of citrate - no toxicity
citrate > 100 mg/ dl - citrate toxicity
Causes
 ADULTS
 rate of BT > 1 liter/ 10 min or BT volume
exceeds 6 L administered in < 2 hours
 CHILDREN
 exchange transfusion - hypocalcemia
Immediate Blood Transfusion Reactions:
Physically or Chemically Induced Transfusion
Reactions (PCITR’s)

Potassium toxicity:
Mechanism: high potassium load with prolonged
blood storage - hyperkalemia
 Clinical manifestations: cardiac excitability
 ECG findings: peak T waves
 Laboratory findings: hyperkalemia
 Management: calcium gluconate

Delayed Blood Transfusion
Reactions
1. Delayed Haemolytic transfusion reactions
2. Post-transfusion Purpura
3. Infection transmission
4. Transfusion GVHD
5. Iron Overload
6. Immune Modulation
Delayed Blood Transfusion Reactions
Post-Transfusion Purpura (PTP)

Consists of profound thrombocytopenia
occurring 1-2 weeks after transfusion

Pathophysiology:
 Effect of antibody directed against donor
platelet antigens that the recipient lacks
 Commonly associated with human plateletspecific alloantigen 1a (HPA-1a)
Delayed Blood Transfusion Reactions
Post-Transfusion Purpura (PTP)

Treatment and Prevention of PTP:
 IVIG
 plasmapheresis
 steroids
 avoidance of antigen-positive platelet
transfusion with previous PTP
Delayed Blood Transfusion Reaction
Transfusion-associated Graft-versus-Host
Disease ( TA-GVHD)
Pathophysiology
Infusion of Immunocompetent Cells
(Lymphocyte)
Patient at risk
proliferation of donor T lymphocytes
attack against patient tissue
Delayed Blood Transfusion Reaction
Transfusion Associated Graft versus Host
Disease (TA-GVHD)

Clinical Manifestations of GVHD:
 onset: 7-10 days from transfusion
 fever
 reddish, raised rash spreading from trunk or face to
extremities - bullous lesions -- erythroderma
 hepatitis
 watery diarrhea
 non-specific signs: anorexia, nausea and vomiting
Delayed Blood Transfusion Reaction
Iron Overload





common in patients with chronic diseases
requiring multiple and prolonged transfusions
(thalassemia)
on the average, 1 unit PRBC = 200 mg iron
also “transfusion hemosiderosis”
chronic iron overload leads to hepatic, cardiac
and pancreatic disease.
prevention:
 iron chelation therapy (desferoxamine)
Delayed Blood Transfusion Reaction
Alloimmunization

Pathophysiology:
after first exposure to donor antigen - recipient
memory lymphocytes are invoked -- moderate
production of IgG and IgM
 on second exposure to donor antigen -- rapid and
large production of IgG within the first 2 days

Delayed Blood Transfusion Reaction
Alloimmunization

Clinical manifestations:


Laboratory tests:


mild to severe
antibody screening
Treatment of Alloimmunization:

Accurate matching of donor and recipient RBC
phenotypes
Delayed Blood Transfusion Reaction
Immunosuppression


generalized non-specific effect diminishing the activity
of the recipient’s immune system soon after blood
transfusion
pathophysiology:
 unknown
 rapid uptake of blood component cellular matter
into the RES
Massive Blood Transfusion
Massive Blood Transfusion
Definition
Transfusion of Blood ~ Blood Volume within
24 hours
•20 units whole blood
•10 units packed cells
Massive Blood Transfusion
Complications
• Dilutional Thrombocytopenia
•Dilutional Coagulopathy
•Metabolic
•Hypothermia
Massive Blood Transfusion
Complications
• Dilutional Thrombocytopenia
•Common after 10 units
•Severe after 20 units
•Give platelet transfusion if < 80,000 +
bleeding
Massive Blood Transfusion
Complications
•Dilutional Coagulopathy
•Particularily if blood stored > 2 weeks
•Monitor Coagulation profile
•FFP if Abnormal lab
•DIC is Rare
Massive Blood Transfusion
Complications
•Metabolic: Citrate Intoxication
•Acidosis, Hypocalacemia, Hyperkalaemia
•Rare Except in Infants or Hepatic
patients