Hemoglobinopathies

Presentation

Michael is a 20-year-old man with beta-thalassemia major. He has been receiving chronic blood transfusions since the age of 1 year. He was diagnosed via newborn screening, and DNA analysis confirmed him to be compound heterozygous for beta zero/beta plus thalassemia. He was recently transitioned to the adult oncology practice from the thalassemia program at the children’s hospital where he has always received his care.

Michael has been undergoing blood transfusions every 3 weeks. He does not have any antibodies and receives blood matched for C, E, and Kell antigens. He is premedicated with acetaminophen and diphenhydramine due to a history of hives.

He has mild hepatic iron overload as diagnosed and confirmed by MRI. He does not have cardiac iron. He is receiving deferasirox and is adherent with therapy. He was originally seen by Hematology, and orders were written for transfusions and labs. Upon presenting for a follow-up appointment about 4 months later, he reported to the medical assistant that he was experiencing recurring back pain.

During the patient history and physical, it emerges that Michael’s back pain—which he says started a few months ago—usually occurs in the week prior to his transfusion and resolves the day after transfusion. Michael describes the pain as throbbing and says it sometimes radiates down his legs. He grades it at 7 on a scale of 1 to 10 at its worst, stating that the pain interferes with his daily activities and sleep but noting that ibuprofen helps. He denies any recent trauma, new activities, paresthesia, or peripheral tingling.

Differential Diagnosis and Evaluation

The differential diagnosis includes arthritis, muscle spasm, spinal cord compression, osteoporosis, kidney stones, and low hemoglobin levels.

Spine films are negative for any fractures or compression. The radiologist mentions low bone density and changes consistent with chronic anemia. Review of Michael’s chart shows his transfusions to be 2 units of packed RBCs every 3 weeks. He was previously receiving 3–4 units at the children’s hospital. His pretransfusion hemoglobin levels have been 8–9 g/dL. His chemistry and urine results are within normal range. His ferritin level is 898 ng/dL.

Diagnosis

Michael’s back pain is secondary to increased bone marrow activity due to low hemoglobin levels. The goal of transfusions in thalassemia is to suppress ineffective erythropoiesis. He has been receiving less blood since transitioning to adult care, and his baseline hemoglobin is now below optimal levels. Many patients are fine with baseline Hb of 9.5–10 g/dL, but some require baseline Hb > 10.5 g/dL to effectively suppress their bone marrow. Undertransfusing thalassemia patients can lead to thalassemic facies, growth failure, back and bone pain, splenomegaly, osteoporosis, pulmonary hypertension, and spinal pseudotumors caused by ineffective erythropoiesis.

Treatment

Michael needs to receive either more blood during each transfusion (can be titrated based on Hb level) or a transfusion every 2 weeks to raise his baseline hemoglobin level. He should be reassessed after 3 or 4 transfusion cycles to determine whether his symptoms have improved. Any increase in iron levels caused by increased RBC levels can be treated with chelation therapy.