A 27-year-old man with sickle cell anemia comes to the emergency department due to increasing dyspnea that started 3 hours ago. The patient was seen in the emergency department 5 days ago for symptomatic anemia, and his hemoglobin level was 6.2 g/dL. He received a blood transfusion, after which his hemoglobin level improved to 8 g/dL, and he was sent home. Temperature is 38.1 C (100.6 F), blood pressure is 105/66 mm Hg, pulse is 112/min, and respirations are 28/min. Oxygen saturation is 97%. The patient appears pale; scleral icterus is present. Lungs are clear. Abdomen is soft and nontender with no hepatosplenomegaly. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 4.5 g/dL |
| Reticulocytes | 7% |
| Platelets | 327,000/mm3 |
| Liver function studies | |
| Bilirubin, indirect | 4.5 mg/dL |
Which of the following is the most likely cause of his current symptoms?
Delayed hemolytic transfusion reaction | |
Pathogenesis |
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Clinical |
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Laboratory |
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Management |
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Prevention |
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*Prior transfusion (eg, sickle cell disease), pregnancy, or transplant. LDH = lactate dehydrogenase; RBC = red blood cell. | |
This patient with sickle cell disease has symptomatic anemia, indirect hyperbilirubinemia, and low-grade fever days after receiving a blood transfusion. These findings are concerning for a delayed hemolytic transfusion reaction (DHTR).
DHTRs occur in patients who have been previously exposed to a foreign red blood cell (RBC) antigen (eg, prior transfusion, pregnancy). The antigen is minor (non-ABO) and typically causes a low, often undetectable antibody response after initial exposure (ie, alloimmunization, similar to that seen in a Rhesus-negative primigravida with a Rhesus-positive fetus). However, on subsequent exposure via repeat transfusion, an anamnestic antibody response occurs in which memory B cells rapidly produce more antibodies; these antibodies bind to donor RBCs, causing extravascular hemolysis.
Sickle cell disease patients are at high risk of DHTRs due to frequent exposure to minor antigens via repeated transfusions. Onset of DHTR is >24 hours up to a month after transfusion. Most patients are asymptomatic. However, sickle cell disease patients are more likely to have symptomatic, severe anemia due to sickle cell-related intravascular hemolysis in addition to DHTR-related extravascular hemolysis. Symptomatic DHTR causes fatigue, dyspnea, jaundice, and low-grade fever, with laboratory evidence of hemolysis, including elevated indirect bilirubin, lactate dehydrogenase, and reticulocyte count as well as decreased haptoglobin. Because these results may be present at baseline in sickle cell disease patients, a new positive direct antiglobulin (Coombs) test is important for diagnosing DHTR.
Management is supportive. Prevention includes thorough review of prior antibody screens and use of extended-antigen cross-matched blood when transfusion is required.
(Choice B) Patients with sickle cell disease often have iron overload, not deficiency, due to frequent transfusions. In addition, iron deficiency anemia is associated with a low reticulocyte count.
(Choice C) Splenic sequestration in young children with sickle cell disease causes splenomegaly and a rapid drop in hemoglobin with compensatory reticulocytosis. This patient's age is inconsistent with this diagnosis.
(Choices D and E) Transfusion-transmitted parvovirus infection in sickle cell disease can cause a transient aplastic crisis with severe, acute anemia. However, reticulocyte count is low due to decreased erythropoiesis. Transfusion-transmitted viral hepatitis causing jaundice and hepatomegaly is rare due to blood donor screening, and it does not cause anemia.
Educational objective:
Sickle cell disease patients are at high risk of delayed hemolytic transfusion reactions due to alloimmunization from frequent transfusions. Reactions develop >24 hours after transfusion and can cause hemolytic anemia. Diagnosis is confirmed with a newly positive Coombs test.