A 40-year-old woman, gravida 4 para 4, comes to the clinic due to anemia. A week ago, the patient was seen in the emergency department due to fatigue, shortness of breath, and increasingly heavy, irregular menses. Laboratory evaluation showed a hemoglobin level of 5.4 g/dL. After a transfusion with packed red blood cells, her follow-up hemoglobin level was 7.8 g/dL prior to discharge. Since then, the patient's energy and breathing have improved, and she has had no further menstrual bleeding. However, yellowing of the eyes and face has developed over the last day. Vital signs are normal. Examination reveals scleral icterus. There is no hepatosplenomegaly. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 5.9 g/dL |
| Reticulocytes | 7% |
| Liver function study | |
| Total bilirubin | 3.8 mg/dL |
This patient's current symptoms are most likely due to which of the following antibody-antigen reactions?
Immunologic blood transfusion reactions | |||
Transfusion | Onset | Cause | Key features |
Allergic | Minutes to hours | Preformed antibodies against blood product component |
|
Acute | Minutes to hours | ABO incompatibility (often clerical error) |
|
Febrile | Hours | Cytokine accumulation during blood storage |
|
Transfusion-related | Hours | Donor antileukocyte antibodies |
|
Delayed hemolytic | Days to weeks | Anamnestic antibody response |
|
DIC = disseminated intravascular coagulation. | |||
This patient has jaundice and hemolytic anemia a week after a transfusion, findings suggestive of a delayed hemolytic transfusion reaction (DHTR). This reaction occurs in patients who were previously exposed to a foreign, minor red blood cell (RBC) antigen (non-ABO) via mechanisms such as pregnancy, prior transfusion, or intravenous drug use. During the first exposure, only a low, typically undetectable, antibody response is initially mounted. On reexposure via transfusion, the patient's memory B cells produced a larger surge of antibodies, resulting in detectable hemolysis. This is known as an anamnestic response.
DHTR is usually mild and develops >24 hours after transfusion, most commonly after 1-2 weeks. Most patients are asymptomatic and diagnosed only after findings of a newly positive direct antibody (+ Coombs) test and antibody screen. Additional laboratory findings include anemia with compensatory reticulocytosis and evidence of hemolysis (eg, ↑ indirect bilirubin, ↑ lactate dehydrogenase).
(Choices A and B) Mild hemolysis can result from the transfusion of plasma products (eg, fresh frozen plasma, platelets), which can contain donor antibodies that target ABO or minor antigens on recipient RBCs. This reaction does not typically occur with the transfusion of packed RBCs, which this patient received, because RBCs are removed from the plasma layer and washed during the blood-separation process.
(Choice C) An acute hemolytic transfusion reaction is caused by ABO incompatibility (eg, due to clerical error). Patients naturally have preformed antibodies against foreign ABO antigens (eg, anti-B antibodies in a type A patient) that will attack antigens on mismatched donor RBCs (eg, type B donor blood). Massive hemolysis occurs within minutes to hours of transfusion, causing fever, flank pain, and hemoglobinuria.
(Choice D) Anaphylactic transfusion reactions occur within minutes of transfusion initiation and present with wheezing, angioedema, and hypotension, findings not seen in this patient. This reaction can occur in patients with IgA deficiency due to the reaction of recipient anti-IgA antibodies against donor IgA.
Educational objective:
Delayed hemolytic transfusion reactions are usually mild, hemolytic reactions that occur >24 hours after blood transfusion. They are a type of anamnestic response (delayed immunologic response) that occurs in patients previously exposed to a minor RBC antigen (eg, previous blood transfusion, pregnancy).