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Epidemiologic Notes and Reports Thrombotic Thrombocytopenic Purpura Associated with Escherichia coli O157: H7 -- Washington

Since Escherichia coli was first associated with bloody diarrhea in 1982 (1), several well-documented cases of hemolytic-uremic syndrome (HUS) related to E. coli O157:H7 have been described among children and adults (2,3). Patients with thrombotic thrombocytopenic purpura (TTP) have clinical and pathologic features similar to patients with HUS. In contrast to HUS, however, gastrointestinal infections have not been strongly implicated in the pathogenesis of TTP (4,5). A patient who recently died in Seattle with a clinical and pathologic diagnosis of TTP had bloody diarrhea associated with E. coli O157:H7 infection for 1 week before the onset of her other symptoms. This patient's clinical course suggested that E. coli O157:H7 infection may have been related to the development of TTP.

In February 1986, a 53-year-old, previously healthy woman was admitted to a Seattle hospital with severe neurologic abnormalities, microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. One week before admission, she had developed bloody diarrhea. There was no past history of bowel disease or travel. The patient had not eaten hamburger or shellfish within the preceding 2 weeks, and in the several days before onset of diarrhea, she had eaten the same foods as her husband who did not become ill. Three days after onset of diarrhea, a hematocrit was normal, and a stool examination for ova or parasites was negative. Cephalexin and metronidazole were prescribed. Her diarrhea continued, and hematuria developed. The day before admission, she became extremely lethargic. Following a generalized seizure while being evaluated in an emergency room, she was admitted.

On admission, the patient was intubated and comatose. Rectal temperature was 35.6 C (96.1 F); blood pressure, 180/100 mm Hg supine; heart rate, 66 beats per minute; and respiratory rate, 10/minute on the ventilator. Pupils were pinpoint and minimally reactive. Cranial nerve functions were intact, and the patient withdrew her extremities to noxious stimuli. The abdomen was soft without guarding and bowel sounds were hypoactive. Stool was guaiac positive. Laboratory data included a hematocrit of 41%, a leukocyte count of 29,200/mm((3)) with a left shift, and a platelet count of 38,000/mm((3)). A blood smear showed schistocytes, helmet cells, burr cells, and target cells consistent with a microangiopathic hemolytic anemia. The serum urea nitrogen was 48 mg/dl, and creatinine was 3.3 mg/dl. PT and PTT were normal, and the thrombin time was 22 seconds. Fibrinogen was 454 mg/dl, and fibrin degradation products were less than 40 ug/ml but greater than 10 ug/ml. A culture from a rectal swab obtained the day of admission yielded E. coli O157:H7.

TTP was diagnosed; plasmapheresis was begun after treatment with fresh frozen plasma, and she received corticosteroids, dipyridamole, and aspirin. Her neurologic status deteriorated rapidly during the first 24 hours after admission, and a computerized tomographic scan of her head showed diffuse cerebral edema. Despite aggressive therapy for increased intracranial pressure, she lost all cranial nerve and motor function and died 48 hours after admission. An autopsy revealed diffuse fibrin microthrombi in multiple organs, including kidneys, pituitary, and myocardium. Transtentorial herniation appeared to be the cause of death. Cultures of food samples from the patient's refrigerator yielded no pathogens. Reported by PG Ramsey, MD, MA Neill, MD, Dept of Medicine, Dept of Microbiology, University of Washington, Dept of Microbiology, Children's Hospital and Medical Center, Seattle; Enteric Diseases Br, Div of Bacterial Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: The syndromes of TTP and HUS share many features, including thrombocytopenia, microangiopathic hemolytic anemia, and renal disease (4,6). Neurologic manifestations and fever complete the pentad of symptoms characteristic of TTP; these symptoms can also be present in HUS. Diarrhea, frequently bloody, is usually present a few days before the onset of HUS. Although diarrhea is not often described before onset of TTP, abdominal pain has been noted in 13%-14% of patients (4,7), and major gastrointestinal hemorrhage can occur (7).

Verotoxin-producing E. coli, including E. coli O157:H7, has been associated with HUS (2,3,8). It has been postulated that one or more verotoxins may be involved in HUS, but the mechanism remains unknown. A rise in verotoxin-neutralizing antibody has been detected in paired sera from patients with HUS (2). Drugs, toxins, infectious agents, immunologic disease, and pregnancy have all been proposed as etiologic agents for TTP (4). The isolation of E. coli O157:H7 from stool of the patient described here with bloody diarrhea and TTP suggest infection with this agent may represent another feature common to both TTP and HUS. E. coli O157:H7 can cause nonbloody diarrhea and asymptomatic infection (8,9). It is not known whether E. coli O157:H7 may be associated with HUS or TTP without antecedent bloody diarrhea.

Recovery of E. coli O157:H7 is optimal when specimens are obtained within 6 days after onset of diarrhea (10). Laboratories can screen for E. coli O157:H7 using media containing sorbitol, since E. coli O157:H7 does not ferment sorbitol rapidly, whereas 93% of other E. coli do (11). Isolates that do not ferment sorbitol within 24 hours can be sent to an appropriate reference laboratory for serotyping. However, since E. coli other than serotype O157:H7 have also been associated with HUS (2), and these E. coli may ferment sorbitol, a thorough investigation requires screening of stool specimens by a reference laboratory. An aliquot of stool can be frozen at -70 C (-94 F) as soon as the diagnosis of HUS or TTP is considered, pending the investigation of other causes. CDC's Enteric Diseases Branch is interested in obtaining frozen stool specimens from patients with HUS or TTP to analyze for verotoxin-producing E. coli; arrangements can be made through state epidemiologists or laboratory directors.

References

  1. Riley LW, Remis RS, Helgerson SD, et al. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med 1983;308:681-5.

  2. Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, Lior H. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. J Infect Dis 1985;151:775-82.

  3. Neill MA, Agosti J, Rosen H. Hemorrhagic colitis with Escherichia coli O157:H7 preceding adult hemolytic uremic syndrome. Arch Int Med 1985;145:2215-7.

  4. Ridolfi RL, Bell WR. Thrombotic thrombocytopenic purpura. Report of 25 cases and review of the literature. Medicine 1981;60:413-28.

  5. Lichtin AE, Silberstein LE, Schreiber AD. Thrombotic thrombocytopenic purpura with colitis in an elderly woman (Letter). JAMA 1986;255:1435-6.

  6. Fong JS, deChadarevian JP, Kaplan BS. Hemolytic-uremic syndrome. Current concepts and management. Ped Clin NA 1982;29:835-56.

  7. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine 1966;45:139-59.

  8. Spika JS, Parsons JE, Nordenberg D, Wells JG, Gunn RA, Blake PA. Hemolytic uremic syndrome and diarrhea associated with Escherichia coli O157:H7 in a day care center. J Peds 1986;109:287-91.

  9. Ryan CA, Tauxe RV, Hosek GW, et al. Outbreak of Escherichia coli O157:H7 diarrheal illness in a nursing home: clinical, epidemiologic and pathologic findings. J Infect Dis (in press).

  10. Wells JG, Davis BR, Wachsmuth IK, et al. Laboratory investigation of hemorrhagic colitis outbreaks associated with a rare Escherichia coli serotype. J Clin Microbiol 1983;18:512-20.

  11. Farmer JJ III, Davis BR. H7 antiserum-sorbitol fermentation medium: a single tube screening medium for detecting Escherichia coli O157:H7 associated with hemorrhagic colitis. J Clin Microbiol 1985;22:620-5.



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