Hemoglobinopathies

Johnny is a 29-year-old male with beta-thalassemia major, for which he has received chronic transfusions since infancy. He had undergone splenectomy in childhood. He has a history of allergic reaction to deferoxamine and was not treated with chelation therapy for many years during his childhood. He is now on full-dose combination therapy with deferiprone and deferasirox for management of severe iron overload. His most recent magnetic resonance imaging (MRI) results indicate severe hepatic and pancreatic and cardiac iron overload, with a normal ejection fraction. He has a high transfusion burden every 2 weeks, due to issues with multiple types of red cell antibodies. He has a port-a-cath in place for IV access, and treatment with luspatercept was recently initiated in an attempt to reduce his transfusion burden. Johnny is being followed by endocrinology specialists to monitor for hypogonadism and glucose intolerance secondary to iron overload.

Johnny is scheduled in the infusion center (IC) for laboratory testing and treatment with a dose of luspatercept. Before coming in, he calls to report that he has had a cough and headache for the past 2 to 3 days and has been in contact with several ill individuals. He has received 2 doses of the Pfizer SARS-CoV-2 vaccine against Covid-19, finishing his series in September 2021. You are covering the IC and let the nurses know that this patient will need isolation. You have also added Covid-19 PCR testing to his laboratory test order.

The nurse calls you after giving the patient his luspatercept dose to report the following vital signs: temperature, 37.5 degrees C [99.5 degrees Fahrenheit]; heart rate, 95 bpm [normal range, 60-100]; respiratory rate [RR], 18 breaths per minute [BPM; normal RR, 12-20 BPM]; and blood pressure, 78/41 [BP; a reading <90 mm Hg for systolic BP or <60 mm Hg for diastolic BP generally indicates hypotension]. Johnny reports that he has been taking all of his medications but has eaten and drunk very little over the past few days. When you go in to see him in the IC, he has normal mentation and is alert and cooperative. He states that he is very tired and does not feel well. You reassure the nurse that hypotension is not a side effect of luspatercept.

Johnny's hypotension needs to be addressed. Your first response is to draw blood for a complete blood count (CBC), CBC with differential, a comprehensive metabolic panel (chem 14), and blood cultures. You administer a bolus of normal saline. Because of his severely elevated cardiac iron levels and your concerns about fluid management, you administer IV fluids at 10 cc/kg over a period of 1 hour times 2, with frequent reassessments. His BP improves only slightly, to 81/43. His oxygen saturation is at 95% on room air. Blood chemistry results confirm that he is dehydrated. His creatinine levels have tripled from 0.5 to 1.5, with a BUN [blood urea nitrogen] of 51 mg/dL [normal range, 7-21 mg/dL]. His CBC shows a hemoglobin level of 10.1 g/dL, with an increased WBC [white blood cell] count of 9.32 k/µL and 80% neutrophils. You encourage increased PO fluids while you call his primary care team to touch base since Johnny is not responding to fluid resuscitation.

Considerations for Management

Any patient receiving chronic blood transfusions will accumulate excess iron and require chelation therapy. Many patients may have varying degrees of iron overload as a consequence of nonadherence with chelation treatment or chelation difficulties due to allergies or an excessive transfusion burden. The endocrine system is very sensitive to iron overload, which can cause glucose intolerance, diabetes, hypogonadism, and adrenal insufficiency.

Adrenal insufficiency resulting from iron overload is a common but often undiagnosed and overlooked problem in patients with thalassemia major. Johnny's primary team advised that he is likely adrenal-insufficient and therefore his response to infection is severely hampered — a condition that could become life-threatening if not addressed.

Stress dosing of hydrocortisone was ordered, and Johnny was transferred to the hospital's emergency department for further monitoring and care. His BP improved after treatment with steroids, but he did require admission for continued care. His blood cultures were negative, but he was PCR [polymerase chain reaction]-positive for Covid-19, requiring therapy including steroids, remdesivir, and anticoagulation therapy. He continued on treatment with steroids during his care and was discharged home after recovering.

Suggested Reading

1. Huang KE, Mittelman SD, Coates TD, et al. A significant proportion of thalassemia major patients have adrenal insufficiency detectable on provocative testing. J Pediatr Hematol Oncol. 2015;37(1):54-59.
2. Baldini M, Mancarella M, Cassineiro E, et al. Adrenal insufficiency: An emerging challenge in thalassemia? Am J Hematol. 2017;92(6):E119-E121.
3. Nieman LK, Lacroix A, Martin KA. Clinical manifestations of adrenal insufficiency in adults. UpToDate.