Patient 2
A 16-year-old boy with HbSC disease, who had undergone splenectomy splenectomy at age 4 years after splenic sequestration, presented with fever, sore throat, fatigue, headache, and chest pain. There was no lymphadenopathy. WBC count was 13 x 103/µL, with increased atypical lymphocytes (1.1 x 103/µL), Hb was 12.9 g/dL, and platelet count was 409 x 109/L. Creatinine was elevated at 1.4 mg/dL, possibly reflecting dehydration, but electrolytes were within normal limits. Liver function tests were not performed at that time. Nasopharyngeal viral nucleic acid swab and blood culture were negative, and chest x-ray showed clear lungs. He received ceftriaxone and intravenous fluids. His pain was controlled with oral analgesics, so he was discharged home.
He returned 2 days later with persistent fever and progressive lower back, chest, and upper abdominal pain. His WBC had increased to 26.3 x 103/µL with a persistent atypical lymphocytosis. Hb was 10.8 g/dL and platelet count was 297 x 109/L. Serum chemistries were notable for elevated bilirubin (4.5 mg/dL), ALT (366 U/L), AST (375 U/L), and γGT (74 U/L). Creatinine was slightly lower than his previous visit at 1.04 mg/dL. Plasma lipase and amylase were normal. His chest x-ray remained clear, and abdominal ultrasound showed a normal gallbladder. He was admitted for intravenous analgesia and monitoring.
Over the next 12 hours, his pain intensified and his abdomen became distended. Hepatic ultrasound demonstrated hepatomegaly with low hepatic arterial velocity and resistive index, suggestive of sequestration. He developed hypoxemic respiratory failure and was intubated. Chest x-ray showed interval development of right hilar consolidation and basilar opacities. Serial laboratory tests demonstrated a progressive leukocytosis and marked increase in ALT and total bilirubin (Fig 1) consistent with acute hepatitis. Plasma ammonia was normal.
He underwent an automated red cell exchange on the first hospital day with goal Hb 10 g/dl and Hb S <30%. Shortly thereafter, he developed hypotension requiring vasopressors. He had hypocalcemia likely caused by inability to hepatically metabolize the citrate anticoagulation utilized in the erythrocytapheresis procedure. He developed laboratory evidence of coagulopathy (aPTT = 52 s, INR = 2.3) on day 3, without clinical bleeding, that resolved over the ensuing week. He required continuous renal replacement therapy for acute kidney injury with creatinine > 5 mg/dL and circulatory overload. He received additional erythrocyte transfusions to maintain his Hb >8 g/dL.
His clinical course was consistent with intrahepatic cholestasis, a severe form of hepatopathy marked by liver synthetic dysfunction, coagulopathy and often multi-organ failure.1, 5 He gradually improved and was extubated on day 9 but was persistently febrile, so he underwent an evaluation for infection. Cytomegalovirus IgM and IgG were negative. EBV viral capsid antigen (VCA) IgM and IgG were positive on day 10, suggesting that acute EBV infection incited his critical illness. Reinforcing this premise, a convalescent EBV VCA IgM drawn 5 months later was negative. A 6-month regimen of chronic transfusion therapy was administered to facilitate organ healing.