BLOOD
TRANSFUSION
REACTIONS
PROF. DR. DARNAL HARI KUMAR MD
FACULTY OF MEDICINE
30 MARCH 2018 MAHSA.
DLO : Students should be able to
• Enumerate 4 major indications for blood transfusion.
• Describe the early and late complications of blood transfusion.
( 2 each)
• Describe the different stages of Acute haemolytic transfusion
reaction.
• State the steps of direct and indirect anti-globulin test.
• Discuss briefly the pathogenesis of Transfusion Related Acute
Lung Injury (TRALI)
• Narrate 4 steps of management of acute haemolysis.
INTRODUCTION
• BLOOD TRANSFUSION INVOLVES THE SAFE TRANSFER OF
BLOOD COMPONENTS FROM A DONOR TO A RECIPIENT.
• MOST COMMONLY THIS IS RED CELLS TRANFER AFTER CAREFUL
MATCHING OF DONOR CELLS AND RECIPIENT PLASMA.
SELECTION AND SCREENING OF DONOR
CAREFUL DONOR SELECTION
17- 70 yrs adults healthy male or female, afebrile, normal BP,
Hb.
MICROBIOLOGICAL TESTING HELP PROTECT BOTH DONOR AND
RECIPIENT.
HIV, HBV, STD, Malaria
RED CELL ANTIGENS
• OVER 400 ANTIGENS ON RED CELL SURFACE -
• ABO AND Rh are MOST IMPORTANT IN TRANSFUSION
• SUBJECTS LACKING ANTIGEN ( A,B) MAY DEVELOP A NATURALLY
OCCURRING ANTIBODY TO IT, USUALLY IgM.
• THESE ANTIBODIES IN RECIPIENT MAY HAEMOLYSE OR
OPSONIZE DONOR RED CELLS IF THESE CONTAIN THE ANTIGEN.
RBC SURFACE BLOOD GROUP ANTIGENS
ABO ANTIGENS AND ANTIBODIES
ABO BLOOD GROUP
O A B AB
---------------------------------------------------------------------------------------------------
Antigens on red cells none A B A+B
Antibody in serum Anti-A + B Anti-B Anti-A none
Frequency (%) 47 42 8 2
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MAJOR INDICATIONS OF RED CELL
TRANSFUSION
• Replace blood loss
• Traumatic injuries, severe burns
• Surgical procedures. GI/ other organ bleed and bleeding
disorders (TTP, HUS, VIII)
• Anaemia correction
• BM FAILURE - aplastic anaemia, leukemia, Myelofibrosis.
• HEAMOGLOBINOPATHIES - thalassemia, sickle cell disease
• CHRONIC LOSS IN MALIGNANCY, renal failure, DIC
• SEVERE HAEMOLYSIS - haemolytic disease of newborn (HDN)
3 IMPORTANT FACTORS FOR BLOOD
TRANSFUSION CONSIDERATION?
• PATIENT’S AGE
• CLINICAL CONDITION
• HAEMOGLOBIN CONCENTRATION
ANTIBODIES IN PLASMA
• MAY ALSO DEVELOP FROM EXPOSURE TO THE FOREIGN
ANTIGEN BY A TRANSFUSION OR PREGNANCY.
• CROSS-MATCHING OF DONOR RED CELLS WITH RECIPIENT
PLASMA IS THEREFORE CARRIED OUT TO ENSURE THEY ARE
COMPATIBLE.
• MISMATCH LEAD TO TRANSFUSION REACTION.
TRANSFUSION REACTIONS/
COMPLICATIONS
• Blood transfusion is basically a save procedure- routinely done
universally
• Rarely serious complications can arise if incompatible blood is
transfused.
• IMMEDIATE LIFE-THREATENING REACTIONS are associated with
Complement activation of IgM or IgG antibodies to ABO
ANTIGENS- LYSIS OF RED CELLS.
• Rh INCOMPATIBILITY -- LESS SERIOUS.
• IgG immune antibody which trigger RE cell - extravascular
hemolysis- so may cause anemia with mild jaundice.
COMPLICATIONS OF BLOOD TRANSFUSION
EARLY COMPLICATIONS LATE
• Hemolytic transfusion reactions- • Transfusion of infection
immediate/ delayed
• Transfusion of iron overload
• Reaction to infected blood
• Immune sensitization- red
• Allergic reaction to HLA antigens
cells, PL, rhD (HDN)
• Pyrogenic reaction to plasma
• Transfusion associated Graft
protein/HLA
Vs Host disease
EARLY COMPLICATIONS OF BLOOD
TRANSFUSION-
• Circulatory overload
• Bacterial contamination
• Air embolism
• Thrombophlebitis
• Citrate toxicity
• Hyperkalaemia
• Clotting/ thrombosis
• TRALI ( TRANSFUSION RELATED ACUTE LUNG INJURY)
• Post-transfusion purpura
HEMOLYTIC TRANSFUSION REACTION
• Potentially fatal reaction due to ABO incompatible blood transfusion.
• Haemolytic shock phase
• Symptoms: Urticaria, Burning skin, chest pain, dyspnea, headache, abdominal and loin
pain
• Signs: Fever, tachycardia, hypotension, Haemoglobinuria, jaundice and DIC
• Lab: Moderate leucocytosis, BT, PT, aPPT, - increased, d-dimers+
• Oliguric phase- Renal tubular necrosis and acute renal failure
• Diuretic phase – Fluid and electrolyte imbalance during recovery phase
INVESTIGATION OF IMMEDIATE TRANSFUSION
REACTION
• CHECK CLERICAL ERRORS - MOST COMMON CAUSE
• REPEAT PRE AND POST TRANSFUSED BLOOD'SAMPLE- ABO AND CROSS- MATCHING
• DO DIRECT ANTI-GLOBULIN (COOMB TEST) ON POST TRANSFUSION SAMPLE
• CHECK FOR HAEMOGLOBINAEMIA AND DIC TESTS - PT, APPT, D-DIMERS +
• SEND FOR BLOOD CULTURE IF INFECTION IS SUSPECTED.
• URINE FOR HAEMOGLOBINURIA ON POST TRANSFUSION URINE SAMPLE
• PATIENT POST TRANSFUSION BLOOD SAMPLE FOR CELL COUNT, BILIRUBIN, FREE
HB, METHAEMOGLOBIN.
• PATIENT'S SERUM TESTED FOR RBC OR WBC ANTIBODIES AFTER 7 DAYS.
DIRECT COOMB TEST (ANTIGLOBULIN
TEST)
• Detect antibody or complement on red cells, sensitized in
vivo
• AHG added to washed red cells
• agglutination indicates positive test :
• Hemolytic transfusion reactions
• Drug-induced immune hemolytic anemia
• Autoimmune hemolytic anemia
• Hemolytic disease of newborn (Rh incompability)
INDIRECT ANTIGLOBULIN TEST ( INDIRECT
COOMB TEST)
• Detect antibodies in plasma coating red cells in vitro
• Incubate TEST RBCS (normal) with patient’s serum
• Wash rbcs with saline to remove free Igs
• Add AHG - agglutination- positive test
• Detect antibody in patient’s serum
• Atypical antibodies in serum of patient
• Detect antibodies in pregnant women
• Detect antibodies in serum in autoimmune hemolytic anemia (specific AHG useful )
• Tube or microplates used
SLIDE METHOD OF BLOOD GROUPING
CROSS MATCHING
PRINCIPLE OF MANAGEMENT OF MAJOR
HAEMOLYSIS
• Maintain BP and Renal Perfusion.
• I.V dextran, plasma or saline and fursemide, hydrocortisone I.V
in shock
• Severe shock may require I.V adrenaline in small doses.
• Acute Renal Failure - Dialysis.
FEBRILE REACTION: WBC ANTIBODIES
• HLA antibodies develop due to previous transfusion or
pregnancy
• Rigor, pyrexia, pulmonary infiltration by inflammatory cells.
• Give leucocyte-depleted Packed red cells.
FEBRILE/ NON-FEBRILE NON-
HAEMOLYTIC ALLERGIC REACTIONS
• Hypersensitivity (type I) to donor plasma proteins.
• May cause severe anaphylactic shock ( C3a)
• Urticaria, pyrexia, dyspnea, facial edema, rigor.
• Treat with antihistamines and hydrocortisone / adrenaline.
• Washed red cell or frozen red cell transfusion may be last
resort.
POST CIRCULATORY OVERLOAD
• May lead to cardiac failure.
• Manage cardiac failure by combination of drugs eg
ACE inhibitors. ARB ( blockers), diuretics, b-
blockers, etc
• Prevented by slow transfusion of Packed red cells
and diuretic therapy.
TRANSFUSION OF BACTERIALLY
CONTAMINATED BLOOD
• VERY RARE BUT SERIOUS.
• CAN PRESENT WITH CIRCULATORY FAILURE.
• ANTIBIOTIC THERAPY.
GRAFT VS HOST DISEASE
• USUALLY OCCUR WHEN LIVE LYMPHOCYTES ARE TRANSFUSED
TO AN IMMUNOCOMPROMISED PATIENT eg BM transplantation.
• APOPTOSIS OF HOST CELLS BY CD8 CELLS VIA CASPASES PATHWAY.
• PREVENTABLE BY IRRADIATION OF BLOOD.
• UNIFORMLY FATAL.
HYPERHAEMOLYSIS SYNDROME
• OVERACTIVITY OF RECIPIENT'S MACROPHAGES /
HYPERSPLENISM.
• PREVENTABLE BY INFUSION OF GAMMA GLOBULIN OR STEROID
THERAPY.
• COMMON IN SICKLE CELL ANAEMIA.
• NO ALLOANTIBODIES TO RED CELLS PRESENT.
TRANSFUSION RELATED ACUTE LUNG
INJURY (TRALI)
• PRESENTS WITHIN 6 HOURS OF INFUSION
• TRANSFUSION OF HLA ANTIBODIES IN DONOR PLASMA
• ENDOTHELIAL AND EPITHELIAL CELL INJURY IN ALVEOLI
• INFLAMMATORY CELL INFILTRATION IN LUNG
• ACUTE AUTOIMMUNE PNEUMONITIS / ALVEOLITIS
• MOST DONORS ARE MULTIPAROUS WOMEN.
• ONLY SUPPORTIVE THERAPY.
POST TRANSFUSION PURPURA
• RARELY SEVERE THROMBOCYTOPENIA CAN OCCUR 7-10 DAYS AFTER
TRANSFUSION OF PLATELETS, USUALLY RED CELL TRANSFUSION.
• ANTIBODIES+ IN PREVIOUSLY TRANSFUSED OR PREGNANT WOMEN
TO PLATELETS
• BOTH TRANSFUSED AND RECIPIENT PLATELTS ARE DESTROYED BY
IMMUNE COMPLEXES ( Eg; TTP)
• USUALLY SELF LIMITED
• PLASMA EXCHANGE OR Ig THERAPY HELPFUL.
VIRAL TRANSMISSION
• POST TRANSFUSION HEPATITIS BY HEPATITIS VIRUSES, CMV,
EBV
• POST TRANSFUSION HEPATITIS AND HIV RARELY SEEN NOW A
DAYS.
• BECAUSE OF ROUTINE SCREENING OF ALL BLOOD DONATIONS.
OTHER INFECTIONS
• TOXOPLASMOSIS
• MALARIA
• SYPHILIS
• TRANSFUSION RELATED CJD (MAD COW DISEASE)
POST- TRANSFUSION IRON OVERLOAD
• REPEATED RED CELL TRANSFUSIONS OVER YEARS
• IN ABSENCE OF BLOOD LOSS- IRON DEPOSITION
• RE CELLS IN LIVER, SPLEEN, HEART, MYOCARDIUM AND
ENDOCRINE
• DAMAGE THESE ORGANS.
• MAJOR PROBLEM IN THALASSEMIA AND CHRONIC REFRACTORY
ANAEMIAS.
HDN (HEMOLYTIC DISEASE OF
NEWBORN)
• Transplacental IgG cross to fetal red cells
• RE system destruction of fetal cells
• Anti-D (Rh –ve) responsible for 94% of Rh HDN
• Usually Rh D - ve women with RhD + fetus
• Anti-Rh D cross placenta in next pregnancy
• IU death due to hemolysis of fetal red cells-- hydrops fetalis in severe case
• Edematous foetus with anemia, jaundice, hepatosplenomegaly.
• Kernicterus (>250umol/L) bile pigment (bilirubin) in
• basal ganglia - spasticity, mental deficiency, deafness, epilepsy
• Prophylactic anti-D Rh vaccine reduces the incidence drastically
SUMMARY
• COMPLICATIONS OF B/T INCLUDE HAEMOLYTIC REACTIONS,
FEBRILE REACTIONS TO WHITE CELLS OR PROTEINS,
CIRCULATORY OVERLOAD, TRANSMISSION OF INFECTIONS
ESPECIALLY VIRAL AND IN LONG TERM, IRON OVERLOAD.
• BLOOD COMPONENTS LIKE PLATELETS AND PROTEIN PRODUCTS
INCLUDING FRESH FROZEN PLASMA, ALBUMIN SOLUTIONS,
COAGULATION FACTOR CONCENTRATES AND IMMUNOGLOBULIN
CAN BE GIVEN. THANKS
