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
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Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, Lior H. The
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Neill MA, Agosti J, Rosen H. Hemorrhagic colitis with
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coli O157:H7 preceding adult hemolytic uremic syndrome. Arch
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Ridolfi RL, Bell WR. Thrombotic thrombocytopenic purpura.
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of 25 cases and review of the literature. Medicine
1981;60:413-28.
Lichtin AE, Silberstein LE, Schreiber AD. Thrombotic
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coli O157:H7 in a day care center. J Peds 1986;109:287-91.
Ryan CA, Tauxe RV, Hosek GW, et al. Outbreak of Escherichia
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O157:H7 diarrheal illness in a nursing home: clinical,
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Wells JG, Davis BR, Wachsmuth IK, et al. Laboratory
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