A boy was diagnosed with SS on newborn screening. By 5 years of age, he had 6 hospital admissions for presumptive reactive airway disease and 3 for acute chest syndrome. At 6 years of age, his pulmonary function tests revealed mild restrictive disease (forced vital capacity, 76% predicted) with early obstructive impairment (forced expiratory flow, 25% to 75%, 43% predicted) and responsiveness to a bronchodilator. Room air pulse oximetry was 99%. Therapy for reactive airway disease was prescribed.
The child had a presumed fourth episode of acute chest syndrome at 7 years of age. At 7½ years, he presented with fatigue, tachypnea, chest pain, retractions, wheezing, hepatomegaly (4 cm), and pulse oximetry of 71% to 79%. Hemoglobin and reticulocyte counts were baseline: 6.9 g/dL and 39 %, respectively. Chest radiography revealed severe cardiomegaly and biventricular hypertrophy on the ECG. An echocardiogram showed mild biatrial, biventricular, and pulmonary artery dilation with a TRJV of 3.4 m/s and estimated right ventricular systolic pressure of 50 mm Hg on room air, reducing to 45 mm Hg with oxygen. Oxygen, red cell transfusion, furosemide, bronchodilators, and nasal steroids were administered and at discharge, he was receiving 0.75 L oxygen continuously to maintain pulse oximetry >90%. Subsequent TRJVs, hemoglobin, reticulocyte counts, and treatment are shown in the .
Figure Month and treatment are as follow: 0, red cell transfusion/continuous oxygen/bronchodilators/Lasix/nasal steroids; 0.5, begin arginine/continuous oxygen/stop bronchodilator and Lasix; 2.5, arginine/continuous oxygen; 4.5, arginine/begin red cell transfusion (more ...)
Two weeks after presentation, the TRJV remained elevated and pulmonary function tests showed forced vital capacity and forced expiratory flow 25% to 75%, both 58% predicted, without response to albuterol. An evaluation to exclude thrombophilia revealed a normal protein C activity, free protein S, antithrombin III, vonWillebrand antigen and activity, and negative D-dimer. Prothrombin G20210A and Factor V Leiden mutations and antiphospholipid antibodies were absent. L-Arginine was prescribed at 4.5 g/d (0.18 g/kg per day) delivered as Arginaid (Novartis Oncology; East Hanover, NJ), and oxygen was continued.
Four and one-half months from presentation, the TRJV remained elevated and a transcranial Doppler ultrasound showed a mean flow of 178 m/s in the left middle cerebral artery. Therapy was commenced with monthly minor antigen–matched, red cell transfusions; hydroxyurea therapy was refused by the family.
One month after his first transfusion, the room air pulse oximetry was 91% and our patient was as active as his classmates, so only nocturnal oxygen was continued. The adenoids were removed for obstructive sleep apnea diagnosed by sleep study. The abdominal ultrasound showed a few gallstones, but, because he was asymptomatic, the family refused concurrent cholecystectomy.
Ten months from presentation, a TRJV could not be detected and arginine was discontinued. Due to difficulty suppressing hematopoiesis, transfusion therapy was intensified 1 month later, from 15 cc/kg of red cells every 4 weeks to every 3 weeks. He continued to present with low hemoglobin level, high reticulocyte count, and approximately 40% sickle hemoglobin. An evaluation for red cell antibodies was negative.
Sixteen and one-half months from presentation, the TRJV was again undetectable, our patient appeared well, and his mother ended transfusion therapy. About 2 months later, he presented with fatigue, chest pain, hepatomegaly, and a room air pulse oximetry of 80%.
There was a brisk hemolytic anemia with a markedly elevated TRJV (). Mild biatrial and left ventricular dilation (5.43 cm) were present. He was again treated with oxygen, red cell transfusion, diuretics, and steroids.
Results of right heart catheterization performed 1 month later and simultaneously obtained laboratory data are shown (). After catheterization, sildenafil (20 mg 3 times daily) was added to the treatment regimen. Because of persistent elevation in TRJV and an ECG showing left ventricular hypertrophy with mild biatrial and left ventricular dilation, sildenafil was subsequently increased to 30 mg 3 times daily.
Results of right heart catheterization and simultaneously obtained laboratory data
Twenty-nine months from presentation, 10 months from relapse, our patient appeared clinically well, but he had persistent mild biatrial dilation, left ventricular end-diastolic dilation (6.13 cm), and a TRJV unchanged from the time of right heart catheterization with a persistently elevated N-terminal pro–brain natriuretic peptide. He had development of a red cell autoantibody (e) but continued with transfusions every 3 weeks.