Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) in Adults Following a Prodrome of Bloody Diarrhea.
Authors: Lewis Qurana F. , Terrell Deirdra R. , Lammle Bernhard , Kremer-Hovinga Johanna , George James N. , Vesely Sara K. 
Published: October 2019

Diarrhea, often bloody diarrhea caused by infection with E. coli 0157:H7, is the prodrome for typical HUS in children. In adults, HUS has been reported following epidemics of enteric infections, however the frequency and clinical features of sporadic HUS or TTP in adults following a prodrome of bloody diarrhea have not been characterized. In the Oklahoma TTP-HUS Registry, January 1, 1989 to December 31, 2003, 19 (6%) of 301 consecutive patients had a prodrome of bloody diarrhea. The 19 cases were separated by time and location, indicating no common source outbreak. 5/10 patients who were appropriately tested had positive stool cultures for E. coli O157:H7. Although more cases (12/19, 63%) occurred in warm months, April–September, a seasonal difference was not significant (p= 0.25). We compared the clinical features of these 19 patients to the 119 patients who had no apparent etiologies or associated conditions and were therefore defined as idiopathic TTP-HUS.

Bloody Diarrhea Idiopathic p-value (n=19) (n=119) Median values are presented for continuous data. Laboratory data: most abnormal value at diagnosis of TTP-HUS ± 7 days Age (years) 59 48 0.109 Race (% Black) 5% 25% 0.073 Gender (% female) 79% 74% 0.781 Obesity (BMI≥30 kg/m2) 21% 40% 0.120 Severe neurologic abnormalities 63% 49% 0.243 Platelet count 26 13 0.010 Hematocrit 22 22 0.931 LDH 1410 1305 0.115 Acute renal failure 68% 29% <0.001 Response to PE 84% 82% 1.000 ADAMTS13 deficiency (<5%) 0% (0/13) 30% (20/67) 0.031 Death 32% 19% 0.233 Relapse in 30 day survivors 0% 20% 0.119

Although women predominated in both groups, 18/19 patients with a prodrome of bloody diarrhea were White, consistent with the predominance of White subjects among children with diarrhea-associated HUS, but distinct from the significantly higher incidence of Blacks among adult patients with idiopathic TTP-HUS (compared to the incidence among other races, p<0.0001). 3 patients with a prodrome of bloody diarrhea never had an abnormal serum creatinine, therefore the term TTP-HUS, rather than HUS, may better describe these patients. The only significant differences in presenting features and outcomes were the severity of thrombocytopenia, the relative frequency of acute renal failure, and the relative frequency of severe ADAMTS13 deficiency (<5% activity). ADAMTS13 activity was measured in 13 of the 19 patients with a prodrome of bloody diarrhea (median 50%, range 5–100%). We conclude that there is a continuous occurrence of TTP-HUS in adults preceded by a prodrome of bloody diarrhea, presumably related to Shiga toxin-producing enteric infections, even in the absence of recognized outbreaks. Plasma exchange is an appropriate treatment for adult patients with a prodrome of bloody diarrhea since they cannot be accurately distinguished from patients with idiopathic TTP, they have a high mortality rate, and they apparently respond to plasma exchange treatment.