Sporadic Bloody Diarrhea-Associated Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) in Adults in Oklahoma: Comparison to Adults with Severe Adamts13 Deficiency and to Children with Typical HUS.

Abstract

The frequency, presenting features and clinical outcomes of sporadic TTP-HUS following a prodrome of bloody diarrhea in adults are not described. The Oklahoma TTP-HUS Registry enrolled 237 consecutive patients over age 18 years with their first episode of clinically diagnosed TTP from 11-13-1995 (the date of our initial ADAMTS13 measurement) to 12-31-2006 for whom plasma exchange treatment (PEX) was requested. ADAMTS13 activity was measured on 218 (92%) patients immediately before their first PEX. 16 (7%) of these 218 patients presented with a prodrome of acute bloody diarrhea. 42 (19%) patients had ADAMTS13 activity <10%. 2 patients who presented with acute bloody diarrhea had ADAMTS13 activity <10%; they are analyzed with the bloody diarrhea patients; ADAMTS13 activity in the remaining 14 patients was 40–100%. Children with typical HUS are not usually treated with PEX and therefore are not all included in the Registry. Data on children were retrieved from the Children's Hospital of Oklahoma for 2002–2006 to identify all children with typical HUS; 28 children were identified. E. coli O157:H7 infection was identified in 5 adults (of 12 tested) and 19 children (of 25 tested). No source for E. coli O157:H7 infection was identified. There were no case clusters except for one family with 2 affected children. In 2 of the adults with bloody diarrhea, a colectomy was performed before the correct diagnosis was made.Patient characteristicsAdults, bloody diarrhea prodrome (n=16)Adults, ADAMTS13 deficiency (n=40)Children, diarrhea prodrome (n=28)Age (years, median)5840*3.8**Female (%)80%81%64%Race (% white)94%53%*75%Severe neurologic abnormalities†63%45%7%**Platelet count (/μL)‡24,00010,000*34,000Hematocrit (%)‡222118**LDH (/UL) ‡141014311161Creatinine (mg/dL)‡2.71.0*3.7Acute renal failure§50%8%*57%Response to PEX (%)81%85%NADialysis (%)31%3%*57%Death (30 days)31%15%0%**Relapse (%)0% (0/10)38% (13/34)*NA* p≤0.05 for adult bloody diarrhea prodrome compared to adult ADAMTS13 deficient patients; ** p≤0.05 for adult bloody diarrhea prodrome compared to children bloody diarrhea prodrome patients; †seizure, stroke, coma, focal abnormalities anytime during the course; ‡most abnormal values on the day of diagnosis ± 7 days; median §defined by ↑ Cr ≥ 0.5 mg/dL x 2 days or Cr ≥4.0 and dialysis.Conclusions:1.TTP-HUS following bloody diarrhea is an endemic, sporadic disorder among adults that is less common and less familiar than in children.2.Distinct from children, adults with bloody diarrhea have a higher frequency of severe neurologic abnormalities and death; distinct from adults with severe ADAMTS13 deficiency, adults with bloody diarrhea are primarily white, have a higher frequency of acute renal failure, and have not relapsed.3.Although the role of PEX in the recovery of adult patients presenting with bloody diarrhea is unclear, PEX may be appropriate initial treatment since the mortality is high, many patients appear to respond, and patients with severe ADAMTS13 deficiency may also present with bloody diarrhea apparently caused by intestinal ischemia.