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CASE REPORT
A CASE REPORT OF EVANS SYNDROME
R. V. DOSI, A. P. AMBALIYA, R. D. PATELL, R. S. PATIL, P. J. SHAH

ABSTRACT
Evans Syndrome(ES) is the rare simultaneous or subsequent development of immune
thrombocytopenia purpura(ITP) and autoimmune hemolytic anemia(AIHA). It portends
a poorer prognosis and a more aggressive line of management than either condition
presenting alone. Here we report a case of a young female who presented with both
bleeding and acute decompensated anemia. Although she was successfully treated,
mystery still shrouds the etiology, pathophysiology, as well as line of management of
this rare and enigmatic disease.
Key words: Autoimmune hemolytic anemia, Evans syndrome, immune thrombocytopenic
purpura

INTRODUCTION

CASE REPORT

Evans syndrome, the simultaneous


development of ITP and AIHA is a rare
diagnosis and has significant impact on the
investigations, management and prognosis
as compared to either condition when
diagnosed alone. We report a case of a
young woman diagnosed with ES who
presented with epistaxsis and prostration
and detail the management and outcome in
this particular case. Abrief discussion of the
case and a review of recent changes in the
understanding of this uncommon condition
as well as some recent recommendations
are included.

A 22yearold female presented to us with a


history of sudden onset of severe prostration,
palpitations, dyspnea on minimal exertion,
and jaundice of seven days duration. The
above symptoms were associated with a
history of marked pallor. There were also
two episodes of epistaxsis on the third day
of her illness. Bleeding continued for 10 to
15minutes, but stopped spontaneously.
Lowgrade fever was also reported since three
days prior to admission. The patient denied any
history of passage of dark/red urine, ingestion
of any drugs or toxin exposure, or further
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Department of Medicine, Government Medical College


and S. S. G. Hospital, Vadodara, Gujarat, India
Address for correspondence:
Dr.Rupal Dosi,
74B, Kunj Society, Alkapuri,
Vadodara390007, Gujarat, India.
Email:rupal265@yahoo.com

Indian Journal of Medical Sciences, Vol. 66, No. 3 and 4, March and April 2012

Website:
www.indianjmedsci.org
DOI:
10.4103/0019-5359.110920
PMID:
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EVANS SYNDROME

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bleeding episodes. She reported a normal


menstrual history, and currently had lactational
amenorrhea following an uncomplicated vaginal
birth nine months before presentation.
On examination, the patient was severely pale,
and an icteric scleral tinge was noted. The
patients heart rate was 120/min and blood
pressure was 110/70 mmHg. No palpable
peripheral lymph nodes were found. Acareful
examination of the abdomen did not reveal any
palpable organomegaly. No sternal tenderness
or hypertrophied gums were present.
The patient was urgently admitted, investigated,
and subsequently transfused. Although the
patients general condition improved, on the
third day of admission, the patient developed
severe malaise palpitations and dyspnea.
This was associated with a return of pallor
and tachycardia. She was retransfused
and stabilized. Two days later, she required
transfusions again. These catastrophic declines
were not associated with any external bleeding
or signs of internal bleeding, nor followed by
passage of dark/red urine.
Initial investigations revealed hemoglobin
3gm/dl(normal range 12.0-16.0gm/dl), total
leukocyte count of 22,000(450011,000)
with a differential of 68% neutrophils, 30%
lymphocytes, and 2% eosinophils. Platelet
count was 60,000/cu.mm. Indices revealed
HCT 9.2%(3636%), MCV 73.8 cumm(7696),
MCH 23.2pg(2732), and MCHC
31.5gm/dl(3035). Peripheral smear revealed
a predominantly microcytic hypochromic
picture with marked anisopoikilocytosis
[Figure 1]. Polychromatophilic cells and
occasional normoblasts were also noted. No

Figure 1: Peripheral smear shows severe


thrombocytopenia, occasional spherocytes, fragmented
RBCs and teardrop cells

other abnormal precursors were seen. Malarial


parasite was also not identified. Bone marrow
aspiration was sent. Erythrocyte sedimentation
rate was 52/mm at the end of the first hour.
Reticulocyte count was 6% when adjusted for
her hematologic profile was 0.6% (0.51.5%).
Serum lactate dehydrogenase was 1062
U/L(80285). Serum bilirubin was 5.0gm/dl
with a direct level of 3.5gm/dl. Other liver
function tests were normal. An examination
of the urine(including hemosiderin) and
stool did not reveal any abnormality or
evidence of bleeding. Sickling and hemoglobin
electrophoresis was normal. Viral markers
including human immunodeficiency virus and
hepatitis B and C were normal.
Each time the patient deteriorated, a marked
fall in the patients hematocrit was noted.
Thrombocytopenia was also consistently noted.
Direct antiglobin(Coombs) test was positive. The
bone marrow aspiration revealed hypercellular
marrow(7080%) with erythroid hyperplasia
with normoblastic maturation. Myeloid:Erythroid
ratio was 1:4. Megakaryocytes were adequate.
An abdominal sonogram and chest xray

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INDIAN JOURNAL OF MEDICAL SCIENCES
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did not reveal any abnormality. Antinuclear


antibody (ANA) study by immunofluorescence
was positive with a speckled pattern and titer of
1:200. Ascreen for ANA antigens did not reveal
any specific markers.
Thus, the patient was diagnosed with
simultaneous development of autoimmune
hemolytic anemia and immune thrombocytopenic
purpura or Evans syndrome (ES). The patient
was started on a course of corticosteroids and
other supportive management. Ten days after
admission, the patient began to stabilize, and her
hematocrit was on the rise. She was discharged
with hemoglobin of 7gm/dl and platelet count of
72,000cu/mm on prednisolone, which was then
tapered and finally withdrawn over three months.
After three months of followup, the patient was
asymptomatic; her hemogram revealed Hb of
11.6gm/dl, total count 5300cu/mm, reticulocyte
count 0.5%. Platelet count was 33,000; however,
there were no stigmata of abnormal bleeding.

DISCUSSION
Since its first recognition in the 1950s, Evans
Syndrome has been identified as an extremely
rare occurrence, seen in less than 0.8-3.7% of
all patients with ITP or AIHA at onset. ES has
long been considered as a rather incidental and
anecdotal combination of simultaneous and
sequential ITP and AIHA and/or autoimmune
neutropenia in the absence of any underlying
cause.[1] More recently, the spectrum of the
disease has broadened, especially in children,
and there is increasing evidence to suggest
that ES may be associated with or show other
diseases or conditions such as systemic lupus
erythematous(SLE), [2] lymphoproliferative
disorders.[3,4]

The diagnosis of ES requires the simultaneous


presence of coombs positive hemolytic
anemia and thrombocytopenia without
any other obvious cause. An upper limit
of 10years has been proposed by some
to prevent a diagnostic bias. The role of
antiplatelet antibodies is yet under review.
Other causes of bicytopenia including
thrombotic thrombocytopenic anemia or a
lymphoproliferative disorders need to be
excluded carefully. With the recognition of
autoimmune diseases and lymphoproilferative
diseases that may be underlying in many
cases, a workup including chest and abdominal
tomography, ANA studies, serum protein, and
immunoglobulin electrophoresis have been
proposed as part of the initial workup.[5]
A diagnosis of ES against one of either
AIHA or ITP alone has important
implication on the treatment and prognosis
of the patient. Although steroids remain
the firstline of management and despite
a good initial response (as high as 80% in
most series), sustained response rates are
lower, and secondline agents like danazol,
dapsone, azathioprine, cyclophosphamide,
mycophenolatemofetil, cyclosporine have been
used with varying degrees of success and
need to be considered early.[5] Splenectomy is
an established form of secondline therapy,[5]
but responses are poorer than in AIHA or
ITP individually. In patients who are reluctant
to undergo splenectomy and/or in those
with an underlying condition(SLE, common
variable immunodeficiency, chronic lymphocytic
leukemia) or comorbidities that may increase
the risk of infections, or may not be improved
by the procedure, other therapeutic options
must be considered. Rituximab has been

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EVANS SYNDROME

tried and found to be at least as successful as


splenectomy.[6,7]
Our patient was a young female, who presented
with both features of bleeding and hemolytic
anemia. Laboratory markers of hemolysis,
a positive Coombs test combined with
thrombocytopenia established the diagnosis.
Although the ANA test was positive, two of the 11
criteria proposed by the American Rheumatologic
Association were fulfilled precluding a diagnosis
of SLE, other features may, however, develop
in the future. She responded dramatically to
steroids and sustained that response over 6
months of tapering. She is now asymptomatic
and on regular followup.
ES is no longer considered to be a coincidental
association but rather manifestation of severe
immune dysregulation.[8] Underlying diseases
have been shown to be common;[5] older patients
need to be carefully evaluated for an underlying
lymphoproliferative disease while in younger
patients, an associated connective tissue
disease needs to be ruled out. Adiagnosis of ES
demands lifelong followup and treatment owing
to its low incidence, most recommendations
remain observationbased, and randomized
trials will be difficult to realize in the future.

REFERENCES
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Primary thrombocytopenic purpura and acquired
haemolytic anemia: Evidence for a common
etiology. AMA Arch Intern Med 1951;87:4865.

85

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How to cite this article: Dosi RV, Ambaliya AP, Patell RD, Patil
RS, Shah PJ. A case report of evans syndrome. Indian J Med Sci
2012;66:82-5.
Source of Support: Nil. Conflict of Interest: None declared.

Indian Journal of Medical Sciences, Vol. 66, No. 3 and 4, March and April 2012