Investigating transfusion reactions:

All adverse reactions to blood products should be reported to the blood bank, including non-immune-mediated reactions such as circulatory overload or thrombosis. Depending upon the results of the investigation, reporting may be required to the manufacturer and hemovigilance systems such as those maintained by the provincial Ministries of Health or the Public Health Agency of Canada.

The appropriate assessment of adverse transfusion reactions is an important skill for all clinicians to possess and is summarized in Table 1. The blood transfusion laboratory’s specific role is to assess whether the reaction was evidence of serologic incompatibility. This assessment is performed through the following:

1. A clerical check to confirm the correct product was transfused to the correct patient. This involves ensuring that the compatibility label was placed on the correct product, and that the compatibility label matches the patient’s identifiers.
2. Repeating the ABO group on both the patient and the blood product to confirm that the original result was correct. Checking the patient’s ABO group post-transfusion also allows for the detection of mixed field reactions in the forward group, which may be evidence that incompatible RBCs have been transfused.
3. Repeating the antibody screen to confirm the original result. A change in reaction strength may indicate the presence of an antibody which was not initially detected, and an antibody investigation will be required.
4. Performing a direct antiglobulin test. If reaction is newly positive or stronger than it was pre-transfusion, an eluate should be performed to help identify it.

If all of the above investigations are normal, it is unlikely that the transfusion reaction was due to serologic incompatibility. Further confirmation may be sought by performing the following:

1. Performing a serologic crossmatch against any transfused RBCs, using a post-transfusion sample.
2. Checking the titre of isoagglutinins in any transfused components containing plasma (e.g., in group O platelets with anti-A and anti-B given to a non-O recipient).

Note that even if serologic incompatibility is detected, that does not mean that the patient has experienced a hemolytic transfusion reaction: this assessment relies on the presence of positive hemolytic markers such as an increase in reticulocyte count, LDH or bilirubin level. Conversely, failing to demonstrate serologic incompatibility does not rule out acute hemolysis due to non-immune causes such as osmotic stress (e.g., coadministration of RBCs with D5W), physical trauma (e.g., rapid infusion through a small catheter) or heat stress (e.g., use of a non-calibrated blood warmer).

More detailed guidance on the clinical management of transfusion reactions is also available through on-line resources. (https://ttiss.mcmaster.ca/)

Table 1

Reaction	Clinical Features	Investigations
Febrile non-hemolytic: 1 in 20 with platelets 1 in 300 with RBCs	Temp > 38C with a > 1C increase ± rigors, chills	In severe cases (>39C) or presence of chills/rigors, rule out other causes of fever. Compatibility testing to exclude acute hemolytic transfusion reaction Bacterial culture to exclude bacterial contamination
Minor allergic: 1 in 100	Urticaria < 2/3 of the body, flushing, pruritus	None
TACO: 1 in 700 to 8 in 100	Dyspnea, hypertension, features of volume overload, excessively rapid rate of transfusion, history of renal impairment or heart failure.	Differentiate from TRALI: CXR ± Echo Response to diuretics BNP and troponin
TRALI: 1 in 1 200 to 1 in 5 000 in plasma-containing transfusions (rates from studies performed before TRALI reduction measures; therefore, probably rarer now)	Acute hypoxia within 6 hours with new bilateral infiltrates and absence of volume overload	Differentiate from TACO: TACO investigations Donor HLA antibody testing Recipient HLA typing
Delayed hemolysis: 1 in 7 000	Jaundice, dark urine, biochemical evidence of hemolysis	Identify an alloantibody: Group & screen DAT Phenotype of transfused units Identify hemolysis (hemolytic makers workup) Assess for clinical complications: Renal failure (creatinine) Disseminated intravascular coagulation (INR, APTT, fibrinogen)
Severe allergic/anaphylaxis: 1 in 40 000	Dyspnea, urticaria, angioedema, hypotension	Assess allergy history Assess for uncommon causes: IgA deficiency + anti-IgA Haptoglobin deficiency
Bacterial contamination: 1 in 1000 (in buffy coat platelet pool) to 1 in 50 000 (in RBC) Symptomatic septic reaction 1 in 10 000 (in buffy coat platelet pool) to 1 in 250 000 (in RBC)	Fever, features of sepsis	Aerobic & anaerobic cultures of the patient and unit
Post-transfusion purpura: 1 in 100 000	Severe thrombocytopenia 10-14 days following RBC/platelet transfusion due to autologous platelet destruction	Assess for HPA antibodies
Graft-versus-host-disease: Rare	Fever, rash, pancytopenia, liver dysfunction, diarrhea 1-2 weeks following transfusion of fresh non-irradiated unit into at-risk patient	Assess for evidence of donor engraftment: HLA studies Chimerism studies
Acute hypotension: Unknown	Isolated hypotension with a drop in systolic of 30 mmHg and a systolic pressure < 80 mmHg	Differentiate from acute hemolysis, sepsis and anaphylaxis.

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