Hemoglobinopathies

Presentation

Andrea is a 22-year-old woman with sickle cell disease type SS (SCD SS). She was previously receiving chronic blood transfusions due to a history of elevated blood flow velocity by transcranial Doppler (TCD) ultrasonography but was weaned and started on treatment with hydroxyurea last year. At that time, treatment with voxelotor (an orally available stabilizer of sickle cell hemoglobin, or HbS) was also initiated. Her other medications include deferiprone (for chelation of her transfusional iron overload) and folic acid. She has responded well to hydroxyurea, with a fetal Hb level of 31% of total hemoglobin and elevated mean corpuscular volume (MCV). Over the past few months of treatment with hydroxyurea, her Hb levels have typically been 7–8 g/dL.

At routine clinical follow-up, Andrea arrives in a wheelchair, which she normally does not use. She is pale and complains of severe fatigue. She has had labs done before her visit: CBC, CBC with differential, and reticulocyte:CBC. The results are: WBC, 11.8 k/µL; RBC, 1.08; Hb, 4.1 g/dL; HCT, 14; MCV, 129.6; platelet count, 127 k/µL; NRBC %, 12.6; retic %, 63.72; ARC, 796.5; and ANC, 7.84.

Differential Diagnosis

Andrea has acute anemia with a high reticulocyte count and low platelet count. Based only on her laboratory results, the differential diagnoses include acute hemolytic crisis, acute blood loss, and splenic sequestration. Normally patients with SCD-SS have autoinfarcted their spleens by the age of 5 years and stop being at risk for splenic sequestration. Patients who have been  chronically transfused are the exception, however; Andrea’s history indicates she underwent transfusions a few years ago and now has chronic hypersplenism. A low platelet count can indicate splenic sequestration, but Andrea’s current count is a bit higher than her last level. She is obese and it is difficult to accurately palpate her spleen. A careful history and physical are required to accurately diagnose and treat this patient.

History

Andrea’s physical examination is significant for pallor, icteric sclera, and increased heart rate. Her abdomen is soft and nontender, with her spleen palpable 2–3 cm below the costal margin, which is baseline for her. Andrea denies any recent infections or fevers (which could precipitate a hemolytic crisis). She reports good adherence with her medications. She denies easy bruising or nosebleeds but does endorse a new complaint of heavier menses over the past few months, and more recently a prolonged menstrual period lasting about 3 weeks with variable severity of flow. She reports some days with frequent pad changes, clots, and episodes of a “gushing or whooshing” sensation. She states that she did not report this condition at earlier follow-up visits because she experienced several light days when her menstrual flow seemed to be tapering.  

Diagnosis and Treatment

Based on her laboratory results and remarkable history, Andrea was diagnosed with acute anemia secondary to blood loss from menorrhagia. Her elevated reticulocyte count was consistent with inadequate compensation. Andrea was admitted for a blood transfusion for symptomatic severe anemia, and started on treatment with oral contraceptives to stop her menses. Once stable, she was discharged and urgently referred to the Hem-Adolescent clinic for interventions to regulate her menses and further evaluation of the cause of her menorrhagia. 

Final Thoughts

SCD is complicated disease, with multiple causes of acute anemia below baseline. Transfusions are reserved for patients who meet certain criteria, including symptomatic acute anemia.¹ It is important for patients and providers to know patients’ baseline hemoglobin and reticulocyte levels. We also need to be mindful of non–sickle-related events that can exacerbate anemia and which should be treated. Andrea’s menses are now well regulated. Her baseline Hb has improved to 9–10 g/dL and she is feeling much better.

Reference

1. National Heart, Lung, and Blood Institute. Evidence-based management of sickle cell disease: Expert panel report, 2014. Published September 2014. Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014 | NHLBI, NIH.