A Case of Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab
A 51-year-old Caucasian man was brought into the Emergency Department following a mechanical fall. His past medical history was significant for rheumatic heart disease, mechanical mitral valve replacement at the age of 29 years, repeat replacement at the age of 33 years, and left-sided stroke. He was on warfarin for anticoagulation (mechanical valve). His social history was significant for smoking (2–3 cigarettes/day) and occasional use of alcohol, while family history was significant only for diabetes mellitus.\nOn physical examination, his vitals were stable with a temperature 98° F, blood pressure 113/79 mm Hg, pulse rate 88 beats/min, and respiratory rate 18 breaths/min. There was no rash except for mild ecchymosis over the right eye and helix of the right ear. His conjunctiva was pale but anicteric. There was mild pedal edema. A cardiac examination demonstrated a mechanical heart valve click, normal second heart sound, absent murmur, and no pericardial rub. His neurological exam revealed mild confusion and right-sided weakness. The rest of the examination was unremarkable.\nA computed tomography of the head without contrast, performed in the Emergency Department, showed a right subdural hematoma. He was subsequently transferred to the Intensive Care Unit for observation and neurological monitoring. Laboratory tests showed a very high prothrombin time. Serum creatinine on the day of admission (day 1) was 70.72 μmol/l (normal range: 53.04–97.24 μmol/l). He received 4-factor (II, VII, IX, and X) prothrombin complex concentrate for reversal of the high international normalized ratio in view of his subdural hematoma. By the next morning (day 2), he had become oliguric, and serum creatinine increased to 247.52 μmol/l. Other laboratory results on day 2 are shown in table . Urine sediment showed granular casts. There were no dysmorphic red blood cells or cellular casts.\nIn view of the drop in hemoglobin and platelets, elevated lactate dehydrogenase (LDH), indirect hyperbilirubinemia, and acute kidney injury, the possibility of TMA secondary to hemolytic uremic syndrome/thrombotic thrombocytopenic purpura was considered. Complement studies showed C3 0.70 g/l (normal range: 0.82–1.85 g/l) and C4 0.19 g/l (normal range: 0.15–0.53 g/l). ANA, anti-dsDNA, hepatitis panel, HIV, anti-scl-70, ANCA and anticardiolipin antibody were all negative.\nA peripheral smear demonstrated the presence of schistocytes consistent with microangiopathic hemolytic anemia. A renal ultrasound was unremarkable. A Tc-99m MAG3 scan demonstrated decreased perfusion to both kidneys and severely decreased cortical uptake. Renal Doppler study of the right kidney showed a resistive index of 0.69. Blood flow to the left kidney could not be assessed completely due to abdominal gas.\nOn day 4, a renal biopsy was performed which conformed TMA. The findings are outlined below (fig. , fig. , fig. ).\nA diagnosis of aHUS was made based on biopsy findings, serological data, and clinical history. A normal ADAMTS 13 and an equivocal antibody test to ADAMTS 13 ruled out thrombotic thrombocytopenic purpura. On day 3, hemodialysis was initiated due to anuria and hyperkalemia. Plasma exchange with fresh frozen plasma was initiated on day 5 for treatment of aHUS (60 ml/kg of fresh frozen plasma for restitution). Fresh frozen plasma was selected as the restitution fluid in view of the initial concern about genetic or inherited complement defects. Subsequent quantitative assays looking for genetic or inherited complement defects [factor B 239.7 μg/ml (127.6–278 μg/ml), MCP CD46 positive, factor H 253 μg/ml (160–412 μg/ml) and factor I 33.5 μg/ml (29.3–58.5 μg/ml)] were within normal limits. Factor H antibody was negative. A genetic mutational analysis for the above described complement factors was unable to be performed due to denial from the patient's insurance company. Plasma exchange was discontinued after 2 days, and eculizumab was started after administration of a meningococcal vaccine (day 7). By day 8, the patient's platelets improved to 142 × 10/l and LDH decreased to 945 U/l. Hemoglobin also stabilized. Eculizumab was continued at 900 mg every week for a total of 5 weeks and then transitioned to 1,200 mg every 2 weeks. Urine output gradually improved and hemodialysis was terminated after 2.5 months. His estimated glomerular filtration rate at 6 months was 41 ml/min/1.73 m2 as determined by the MDRD formula. The trends in LDH and platelets over time are represented in fig. . A computed tomography scan of the chest/abdomen/pelvis was also done to rule out infection or malignancy as precipitants for aHUS.\nInformed consent was obtained from the patient for the publishing of this work.