This patient has delayed hyperhemolytic transfusion reaction (DHTR). Chronic transfusion in patients with sickle cell disease (SCD) can lead to iron overload, alloimmunization, and an increased risk for DHTR. DHTR is caused by an amnestic response of a preformed erythrocyte alloantibody after re-exposure to an erythrocyte antigen outside the ABO system. Additionally, an autoimmune component could be worsening the hemolysis. Following transfusion, a 1% to 1.6% chance exists of developing these antibodies. DHTR may then occur after re-exposure with subsequent transfusion. Clinical findings, which typically develop approximately 2 to 19 days after erythrocyte transfusion, include anemia, reticulocytosis, jaundice, a significant decrease in hemoglobin level, and increases in hemolytic markers such as lactate dehydrogenase and bilirubin levels, although many patients will be asymptomatic. Patients with SCD may present with a worsening pain crisis. Hemolysis is typically extravascular, and life-threatening complications are rare. Treatment is supportive. Subsequent transfusions should be minimized but not withheld when indicated, such as in situations of severely symptomatic anemia and multiorgan failure.

Transient aplastic crisis can occur when patients with chronic hemolytic anemia and shortened erythrocyte survival are infected with parvovirus B19, which leads to suppression of erythrocyte production identified by anemia and lack of reticulocytosis. Parvovirus B19 infection is a viral syndrome characterized by malaise, fever, and arthralgia; 25% of patients are asymptomatic.

A rare complication of SCD is hepatic sequestration crisis, characterized by large numbers of erythrocytes becoming trapped in the liver. Patients may develop acute anemia, reticulocytosis, hypovolemia, and distributive shock. Prominent symptoms include right upper quadrant pain, hepatomegaly, and anemia. The patient has none of these manifestations.

Splenic sequestration crisis occurs when splenic pooling of erythrocytes causes an acute anemia with reticulocytosis and a rapidly enlarging spleen. Patients may develop hypotension and shock. This condition is found primarily in children who have functional spleens that have not been subjected to multiple infarctions and subsequent development of fibrotic atrophy. This adult patient does not have splenomegaly. Splenic sequestration crisis is not the most likely diagnosis for anemia following a transfusion.