A 56-year-old, Jamaica-born woman of Afro-Caribbean ethnicity presented to our emergency department with a 3-day history of abdominal pain, jaundice, subjective fever, dark urine and persistent dysuria after nitrofurantoin treatment for possible urinary tract infection. She reported that she had the sickle cell trait, and had had unprovoked pulmonary emboli in 2002 and 2010 and pneumococcal meningitis in her twenties.
In the emergency department, the patient's temperature was 36.7[degrees]C, her heart rate was 107 beats/min, blood pressure was 128/87 mm Hg and oxygen saturation on room air was 100%. She was jaundiced with epigastric tenderness. She had conjugated hyperbilirubinemia, elevated serum creatinine, leukocytosis, normocytic anemia and thrombocytopenia (Table 1). The emergency department team ordered abdominal ultrasonography to investigate the hyperbilirubinemia; there was no biliary duct dilatation or thickening. They drew blood and urine samples for bacterial culture and started broad spectrum antibiotics.
On day 2, the patient became hemodynamically unstable and was transferred to the intensive care unit (ICU), where she received vasopressors and renal replacement therapy. Nine units of packed red blood cells were administered over 5 days for persistent anemia. Escherichia coli grew in urine and blood samples. The nephrology consultant identified bile casts on urine microscopy and ascribed the renal failure to sepsis and bile cast nephropathy. To investigate the conjugated hyperbilirubinemia, the ICU team ordered autoimmune, viral and toxicological screens, which were all normal. Doppler studies showed no portal vein thrombosis. Computed tomography (CT) and magnetic resonance cholangio-pancreatography showed no intrahepatic or biliary tract obstruction but suggested bilateral pyelonephritis and splenectomy, although the patient had no surgical scar. The working differential diagnosis was nitrofurantoin-induced liver injury, intrahepatic cholestasis of sepsis and ischemic hepatopathy.
A liver biopsy showed sickle-shaped red blood cells within the hepatic sinusoids (Figure 1), sinusoidal Kupffer cell hyperplasia with erythrophagocytosis (Figure 2) and mild-to-moderate iron deposition (Figure 3). Because of the patient's self-reported sickle cell trait, the emergency department team had ordered a blood smear and hemoglobin (Hb) fractionation. The automated smear showed both target cells and sickle cells. A normal fractionation consists primarily of HbA with small proportions of fetal HbF (< 1%) and HbA2 (normal variant of HbA, < 3.5%). Our patient's sample had 2 Hb variants in similar amounts (HbS 46.6%, HbC 47.3%; Figure 4), some HbA2 (3.9%) and small amounts of other Hb types (HbF 1.2%, HbA 1.2%). The laboratory report stated that these results were compatible with hemoglobin SC disease (HbSC), a form of sickle cell disease. Repeat fractionation, ordered in the ICU for our patient after she had received 3 units of packed red blood cells, showed HbS (24.6%), HbC (24.8%), HbF (1.1%), HbA (40%) and HbA2 (3.3%).
The patient improved and was transferred to the medical floor to our care. We reviewed the fractionation and liver biopsy results with pathology and hematology consultants. We agreed that the patient's clinical course was likely related to previously unrecognized HbSC disease. This placed her at risk for urosepsis, which triggered intrahepatic sickling and microscopic biliary obstruction. Together, these caused...