Thrombotic thrombocytopenic purpura: A treatable cause of childhood encephalopathy E. R. Lawlor, MD, D. W. M. Webb, MD, A. Hill, MD, PhD, and L. D. Wadsworth, MBChB From the Departments of Pediatrics and Pathology, University of British Columbia, British Columbia's Children's Hospital, Vancouver, Canada We describe two patients less than 13 years of age with thrombotic thrombocy- topenic purpura, a rare disorder in childhood. Both children were treated with plasma exchange therapy, which resulted in a rapid resolution of symptoms. This disorder is a cause of childhood encephalopathy, which can be treated effec- tively with plasma exchange. (J Pediatr 1997; 130:313-6) Thrombotic thrombocytopenic purpura is a rare disorder in childhood that, if untreated, is associated with a high mor- tality rate. It is characterized by intravascular platelet-rich thrombi, which result in thi'ombocytopenia and microangio- pathic hemolytic anemia. MAHA can be defined as any hemolytic anemia related to erythrocyte fragmentation oc- curring in association with small vessel disease, t The thrombi are presumed to be responsible for ischemic events that lead to cerebral and renal dysfunction. Recent studies of adults with TTP have demonstrated a substantial benefit from plasma exchange therapy. 25 However, experience with this treatment in children is limited. We describe two chil- dren with TTP who responded promptly to plasma exchange. CASE REPORTS Patient 1. A 12-year-old boy was admitted with fever, malaise, arthralgia, and myalgia of 1 week's duration. There was a 2-month history of intermittent pruritic rash. The medical and family history were uuremarkable. On admission the temperature was 37.9 ° C, respiratory rate 24 breaths/rain, heart rate 96 beats/min, and blood pressure 125/75 mm Hg. He had a maculopapular eruption on his trunk and limbs, generalized tender lymphadenopathy, and hepatomegaly. There was a painful effusion of his right knee, and movement at most large joints was limited by pain. Investigations showed mild neutrophilia (leukocyte count, 17.6 x 109/L; neutro- phil count, 14.3 x 109/L), elevated erythrocyte sedimentation rate (46 mm/hr), liver enzymes (aspartate transaminase, 213 U/L; ala- nine transaminase, 335 U/L; lactate dehydrogenase, 1796 U/L), Submitted for publication March 26, 1996; accepted Aug. 23, 1996. Reprint requests: L. D. Wadsworth, MBChB, Program Director, Department of Hematopathology, British Columbia's Children's Hospital, 4480 Oak St., Vancouver, BC V6H 3V4, Canada. Copyright © 1997 by Mosby-Year Book, Inc. 0022-3476/97/$5.00 + 0 9/22/77544 with a normal prothrombin time and a normal activated partial thromboplastin time. The patient's fever persisted with temperature spikes to greater than 39 ° C. On day 16 of admission to the hospital, generalized edema, and pleural, pericardial, and abdominal effusions developed in association with a protein-losing enteropathy. There was evi- dence of a new purpuric rash, which was diagnosed, on biopsy, as a leukocytoclastic vasculitis of superficial and deep blood vessels. Treatment with albumin infusions, diuretics, and intravenously ad- ministered methylprednisone resulted in a rapid resolution of fever, normalization of liver enzyme values and erythrocyte sedimentation rate, and improvement in the rash and edema. Investigations revealed no evidence of infection nor of an underlying collagen vascular disorder. All results of autoantibody screens were negative (antinuclear antibody; anti-double-stranded DNA; anti-neutro- philic-cytoplasmic antibody; antibodies to extractable nuclear anti- HUS MAHA TTP vWF Hemolytic-uremic syndrome Microangiopathic hemolytic anemia Thrombotic thrombocytopenic purpura von Willehrand factor gens SS-A, SS-B, and ribonucleoprotein; rheumatoid factor; anti- smooth-muscle antibody), and complement levels were normal. Though the patient' s symptoms abated after the initiation of ste- roid therapy, there was evidence of progressive renal failure with an increasing serum creatinine concentration (Table I). On day 25, he had hypovolemia and oliguria, and fulminant renal failure requiring hemodialysis developed. The blood cell count became abnormal with morphologic evidence of MAHA. On day 37 the patient had a partial seizure with secondary generalization lasting 5 minutes. He had altered consciousness for a period of 24 hours, with response only to deep pain, which was followed by a period of confusion and halhicinations for 7 days. The electroencephalo- gram demonstrated a markedly abnormal background with contin- 313