HEMAPHERESIS Thrombotic microangiopathy in a patient with adult-onset Still’s disease Shail Rawal,1 Yael Einbinder,2 Laurence Rubin,1,3,6 Jeff Perl,1,4,6 Martina Trinkaus,1,5,6 Jerome Teitel,1,5,6 and Katerina Pavenski7,8
BACKGROUND: Since there are many disorders that can present with thrombotic microangiopathy (TMA), establishing a correct diagnosis is important to offer the most appropriate therapy. CASE REPORT: A 26-year-old woman was transferred to our hospital with fragmentation hemolytic anemia, thrombocytopenia, and acute kidney failure. History revealed that she was recently diagnosed with adultonset Still’s disease (AOSD) and received intraocular injections of bevacizumab to treat acute retinal artery occlusion. At our hospital, she underwent extensive investigations and was treated with high-dose steroids, hemodialysis, and therapeutic plasma exchange. For recurrent disease, she received a single dose of eculizumab. RESULTS: The patient’s ADAMTS13 activity was normal and she had evidence of complement activation. Genetic testing identified a benign polymorphism in the C3 gene. Pathophysiology of TMA in AOSD is briefly discussed and an overview of the literature is presented. CONCLUSION: Work-up of a new fragmentation hemolytic anemia and thrombocytopenia should include careful review of past history, including medications, as well as relevant laboratory investigations with aim to establish a correct diagnosis. Occasionally, the correct diagnosis is not the obvious one and there could be multiple contributors to the pathogenesis. Establishing diagnosis is important for counseling patient on disease prognosis and to guide treatment.
A
26-year-old woman was transferred to our hospital with a presumed diagnosis of thrombotic thrombocytopenic purpura (TTP). Her past medical history was remarkable for a recent diagnosis of adult-onset Still’s disease (AOSD). A few months earlier she presented with evanescent rash, myalgias, recurrent fevers, and abdominal pain. The patient subsequently developed peritonitis and underwent urgent laparotomy that did not reveal any pathology. While in the hospital, she suffered left-sided vision loss and fundoscopy showed an acute retinal artery occlusion. Based on the presence of rash, serositis, fever, granulocytosis, and a ferritin of more than 1500 nmol/L, a diagnosis of AOSD was made. Therapy with oral prednisone was initiated. The patient also received intraocular injections of bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, to treat complications of retinal artery occlusion. A few weeks later, laboratory investigations revealed anemia, thrombocytopenia, and increased
ABBREVIATIONS: aHUS = atypical hemolytic uremic syndrome; AOSD = adult-onset Still’s disease; TMA = thrombotic microangiopathy; TPE = therapeutic plasma exchange; TTP = thrombotic thrombocytopenic purpura; VEGF = vascular endothelial growth factor. From the Divisions of 5Hematology, 4Nephrology, and 3 Rheumatology, the 6Department of Medicine, and the 7Division of Transfusion Medicine, Department of Laboratory Medicine, St Michael’s Hospital, Toronto, Ontario, Canada; the 1 Department of Medicine and the 8Department of Laboratory Medicine and Pathobiology of Disease, University of Toronto, Toronto, Ontario, Canada; and the 2Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel. Address reprint requests to: Katerina Pavenski, Transfusion Medicine, St Michael’s Hospital, 30 Bond Street, Toronto, ON, Canada M5B 1W8; e-mail: [email protected]. Received for publication January 15, 2014; revision received March 31, 2014, and accepted March 31, 2014. doi: 10.1111/trf.12708 © 2014 AABB TRANSFUSION 2014;54:2983-2987. Volume 54, November 2014 TRANSFUSION
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TABLE 1. Patient’s laboratory test results at presentation Laboratory test Hb PLTs WBCs LDH Total bilirubin Haptoglobin Creatinine Urinalysis
Troponin I Beta HCG
Patient’s result 64 g/L 63 × 109/L 6.36 × 109/L 734 15 3 g/L, blood large Microscopy: no casts 0.007 μg/L Negative
Reference range 115-155 g/L 140 × 109-400 × 109/L 4.0 × 109-11.0 × 109/L 100-195 u/L 0-23 μmol/L 0.36-1.95 g/L 42-102 μmol/L
1500 nmol/L and C-reactive protein 8.2 [0.0-5.0 mg/L]). Direct antiglobulin test was negative. Her ADAMTS13 activity was normal at 68% by enzyme-linked immunosorbent assay (Technozym, Technoclone GmbH, Vienna, Austria). Complement studies conducted at our hospital were consistent with complement activation and consumption, revealing depressed C3 at 0.58 (range, 0.791.52 g/L) and C4 at 0.11 (range, 0.16-0.38 g/L). Complement studies conducted at a reference laboratory showed normal classical pathway function 72% (range, 65%135%) and alternative pathway function 123% (range, 60%-140%), normal C3d 30 (
BACKGROUND: Since there are many disorders that can present with thrombotic microangiopathy (TMA), establishing a correct diagnosis is important to offer the most appropriate therapy. CASE REPORT: A 26-year-old woman was transferred to our hospital with fragmentation hemolytic anemia, thrombocytopenia, and acute kidney failure. History revealed that she was recently diagnosed with adultonset Still’s disease (AOSD) and received intraocular injections of bevacizumab to treat acute retinal artery occlusion. At our hospital, she underwent extensive investigations and was treated with high-dose steroids, hemodialysis, and therapeutic plasma exchange. For recurrent disease, she received a single dose of eculizumab. RESULTS: The patient’s ADAMTS13 activity was normal and she had evidence of complement activation. Genetic testing identified a benign polymorphism in the C3 gene. Pathophysiology of TMA in AOSD is briefly discussed and an overview of the literature is presented. CONCLUSION: Work-up of a new fragmentation hemolytic anemia and thrombocytopenia should include careful review of past history, including medications, as well as relevant laboratory investigations with aim to establish a correct diagnosis. Occasionally, the correct diagnosis is not the obvious one and there could be multiple contributors to the pathogenesis. Establishing diagnosis is important for counseling patient on disease prognosis and to guide treatment.
A
26-year-old woman was transferred to our hospital with a presumed diagnosis of thrombotic thrombocytopenic purpura (TTP). Her past medical history was remarkable for a recent diagnosis of adult-onset Still’s disease (AOSD). A few months earlier she presented with evanescent rash, myalgias, recurrent fevers, and abdominal pain. The patient subsequently developed peritonitis and underwent urgent laparotomy that did not reveal any pathology. While in the hospital, she suffered left-sided vision loss and fundoscopy showed an acute retinal artery occlusion. Based on the presence of rash, serositis, fever, granulocytosis, and a ferritin of more than 1500 nmol/L, a diagnosis of AOSD was made. Therapy with oral prednisone was initiated. The patient also received intraocular injections of bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, to treat complications of retinal artery occlusion. A few weeks later, laboratory investigations revealed anemia, thrombocytopenia, and increased
ABBREVIATIONS: aHUS = atypical hemolytic uremic syndrome; AOSD = adult-onset Still’s disease; TMA = thrombotic microangiopathy; TPE = therapeutic plasma exchange; TTP = thrombotic thrombocytopenic purpura; VEGF = vascular endothelial growth factor. From the Divisions of 5Hematology, 4Nephrology, and 3 Rheumatology, the 6Department of Medicine, and the 7Division of Transfusion Medicine, Department of Laboratory Medicine, St Michael’s Hospital, Toronto, Ontario, Canada; the 1 Department of Medicine and the 8Department of Laboratory Medicine and Pathobiology of Disease, University of Toronto, Toronto, Ontario, Canada; and the 2Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel. Address reprint requests to: Katerina Pavenski, Transfusion Medicine, St Michael’s Hospital, 30 Bond Street, Toronto, ON, Canada M5B 1W8; e-mail: [email protected]. Received for publication January 15, 2014; revision received March 31, 2014, and accepted March 31, 2014. doi: 10.1111/trf.12708 © 2014 AABB TRANSFUSION 2014;54:2983-2987. Volume 54, November 2014 TRANSFUSION
2983
RAWAL ET AL.
TABLE 1. Patient’s laboratory test results at presentation Laboratory test Hb PLTs WBCs LDH Total bilirubin Haptoglobin Creatinine Urinalysis
Troponin I Beta HCG
Patient’s result 64 g/L 63 × 109/L 6.36 × 109/L 734 15 3 g/L, blood large Microscopy: no casts 0.007 μg/L Negative
Reference range 115-155 g/L 140 × 109-400 × 109/L 4.0 × 109-11.0 × 109/L 100-195 u/L 0-23 μmol/L 0.36-1.95 g/L 42-102 μmol/L
1500 nmol/L and C-reactive protein 8.2 [0.0-5.0 mg/L]). Direct antiglobulin test was negative. Her ADAMTS13 activity was normal at 68% by enzyme-linked immunosorbent assay (Technozym, Technoclone GmbH, Vienna, Austria). Complement studies conducted at our hospital were consistent with complement activation and consumption, revealing depressed C3 at 0.58 (range, 0.791.52 g/L) and C4 at 0.11 (range, 0.16-0.38 g/L). Complement studies conducted at a reference laboratory showed normal classical pathway function 72% (range, 65%135%) and alternative pathway function 123% (range, 60%-140%), normal C3d 30 (
