The Journal of Maternal-Fetal and Neonatal Medicine, November 2007; 20(11): 843845

CASE REPORT

A case of Evans syndrome in pregnancy refractory to primary

treatment options

TODD BOREN, CARLOS REYES, RAUL MONTENEGRO, & KAREN RAIMER

J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Universitat Autonoma Barcelona on 11/04/14

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Bayfront Medical Center, St. Petersburg,
Florida, USA

(Received 26 February 2007; revised 5 June 2007; accepted 8 June 2007)

Abstract
Evans syndrome is a rare hematological condition defined as immune thrombocytopenic purpura and hemolytic anemia.
We describe herein a case of Evans syndrome diagnosed in a term pregnancy that was refractory to primary therapeutic
options. We also describe current treatment options in pregnancy and briefly discuss the pathophysiology of Evans
syndrome and perinatal outcome.
For personal use only.

Keywords: Pregnancy, Evans syndrome, thrombocytopenia, anemia

and a hematologist was consulted. The patient had

Case report
A 34-year-old G1P0 at 38 estimated weeks of ges-
tation presented to our institution as a transfer of
care from a nearby hospital. The patient was
admitted with elevated blood pressures, elevated
liver enzymes (AST 136 U/L and ALT 170 U/L), and
thrombocytopenia (platelet count of 8000/mm3).
The patient had been placed on a prednisone taper
over a three-week period and had received one dose
of intravenous immunoglobulin (IVIG) the week
before by the transferring obstetrician in efforts to
manage the low platelet count. The staff perinatol-
ogist was consulted and the decision was made to
proceed with cesarean section secondary to HELLP
syndrome (hemolysis, elevated liver enzyme levels,
and a low platelet count). Magnesium sulfate was
started on admission. The patient received a total of
20 units of platelets preoperatively and intraopera-
tively. The surgery was uncomplicated and a viable
male infant was delivered with one- and five-minute
Apgar scores of nine and nine.
Postoperatively, the patient was started on solu-
medrol and transfused two units of packed red blood
cells secondary to a postoperative hemoglobin of
6.9 g/dL. The platelets responded to 69 000/mm3,
no prior knowledge that she had any hematological
disorder. The postoperative course was complicated
by persistent autohemolysis and severe thrombocy-
topenia (2000/mm310 000/mm3) despite frequent
transfusions, with no evidence of postpartum bleed-
ing. By postoperative day 4, the platelet count con-
tinued to decline despite solumedrol, frequent doses
of IVIG, and platelet transfusions. The liver enzymes
and blood pressure normalized by postoperative day
3. General surgery was consulted and a splenectomy
was performed without complications. However, the
platelet count did not respond. Multiple labs were
ordered by the hematologist including ANA (anti-
nuclear antibodies), RPR (rapid plasmin reagin),
thyroid panel, ANCA (antineutrophil cytoplasmic
autoantibodies) C and P, Coombs test, EBV
(Ebstein Barr Virus), ESR (Erythrocyte Sedimenta-
tion Rate), CRP (C-reactive Protein), RF (Ristocetin
Factor), AntiDS-DNA (Antidouble-stranded DNA),
and haptoglobin. All labs were normal except the
elevated C3, which is consistent with autohemolysis.
The patient was then started on Rituximab, a
chemotherapeutic agent, with no response.
A bone marrow biopsy was performed that only
showed schistocytes, also consistent with peripheral

Correspondence: Todd Boren, MD, Bayfront Medical Center, 701, 6th Street South, St Petersburg, Florida, 33701. Tel: 727-385-4644. Fax: 727-893-6917.
E-mail: Todd.Boren@moffitt.org
ISSN 1476-7058 print/ISSN 1476-4954 online 2007 Informa UK Ltd.
DOI: 10.1080/14767050701500265
 844 T. Boren et al.
destruction. At this time, the diagnosis of Evans
syndrome was made, which is immune thrombocy-
topenic purpura (ITP) combined with autoimmune
hemolytic anemia. Plasma exchange was initiated
with additional transfusions with packed red cells.
The patient responded well and on hospital day
15 her hemoglobin was stable at 9.2 g/dL with a
platelet count of 22 000/mm3. The patient did not
experience any signs of postoperative hemorrhage
and was discharged home in stable condition.
Over the next several weeks the patient received
weekly courses of plasma exchange. Four weeks after
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Universitat Autonoma Barcelona on 11/04/14
discharge, her platelet count was 66 000/mm3 and
stable.
Discussion
Using the MEDLINE search engine, only three
previous articles cite Evans syndrome during preg-
nancy [13]. One describes anesthetic complications
with performing a second trimester splenectomy in a
patient with Evans syndrome. The patient res-
ponded and went on to deliver a viable infant at
term. The second article documents a 19-year-old
primigravida who presented at 13 weeks estimated
For personal use only.
gestational age with thrombocytopenia [1]. Evans
syndrome had been diagnosed one year earlier. The
platelet count responded to prednisolone 20 mg QD,
which eventually was increased to 60 mg QD at 31
weeks estimated gestational age with platelet counts
ranging from 62 000 to 68 000/mm3. The pregnancy
was unremarkable until she presented at 35 weeks
with a stillborn fetus despite aggressive antenatal
surveillance. The autopsy revealed an intracranial
subdural hematoma as the cause of death. The
patient remained on the same dose of steroids and
at six weeks postpartum had a platelet count of
119 000/mm3. The third case involved a 26-year-old
pregnant patient with Evans syndrome treated with
high dose corticosteroids for severe thrombocyto-
penia. The patient developed a disseminated gono-
coccal infection in the third trimester followed by
preterm labor and abruptio placentae. A cesarean
delivery was performed at 34 weeks estimated
gestational age followed by platelet transfusion. A
viable infant was delivered but the mother eventually
developed delayed postpartum hemorrhage [3].
Evans syndrome involves ITP occurring in sync
or sequentially with Coombs positive autoimmune
hemolytic anemia (AHA) [4]. This is a rare disease
with even fewer patients experiencing associated
neutropenia [5]. The diagnosis is one of exclusion,
made after all other causes of thrombocytopenia are
ruled out. The associated diagnosis of autoimmune
hemolytic anemia can be made with a positive
Coombs test. Although this test was negative in our
case, C3 was elevated. In 10% of cases of AHA, an
elevated complement level will be the only abnormal
finding [6].
Initial treatment for Evans syndrome consists of
steroid administration such as prednisone. Other
therapies include IVIG, chemotherapeutic agents,
splenectomy, and plasmaphoresis for refractory cases
[4]. Glucocorticoids such as prednisone decrease
sequestration and destruction of antibody-sensitized
platelets and red blood cells (RBCs). Splenectomy
removes a primary site of sequestrations as well as a
major site of antibody production. Plasmaphoresis
attempts to replace antibody bound platelets and
RBCs with unbound cells while reducing the con-
centration of IgG. IVIG can lengthen the life span of
bound RBCs and platelets by saturating the Fc
receptors on macrophages and also by inhibiting
sequestration. Immunosuppressive agents such as
rituximab have an inhibitory affect on the immune
system, affecting B cells and T cells and their anti-
body production [6].
In the case described herein, the patient was
refractory to all therapies except plasmaphoresis,
while in the other cases described, the patients
responded to either steroids or splenectomy. Com-
plications in this case and the cases above included
mild preeclampsia, HELLP syndrome, abruption of
placenta, postpartum hemorrhage, and fetal death
in utero [1,3]. Other complications include life-
threatening maternal anemia, severe postpartum
hemolytic anemia in the infant, and maternal and
fetal hemorrhage from severe thrombocytopenia, the
latter being the most severe complication [7,8].
ITP in the pregnant patient can cause moderate to
severe thrombocytopenia in the fetus and neonate
regardless of maternal response to treatment.
The fetal thrombocytopenia cannot be prevented.
The major risk to the fetus is intracranial hemorrhage
with associated neurological impairment, the fre-
quency of which is estimated to be 13% [1]. The
relative mild maternal thrombocytopenia in the case
mentioned above resulted in fetal intracranial he-
morrhage, while the patient in this case experienced
severe thrombocytopenia with no apparent affect on
the fetus.
To date, there is no reliable antenatal measure that
can reliably predict fetal platelet status, and maternal
response to treatment does not guarantee a desired
outcome [9]. Only previous neonatal outcome
provides a useful predictor of fetal and neonatal
platelet count in a subsequent pregnancy [9,10]. The
mode of delivery should be based on obstetrical
indications. Hemorrhagic complications, which are
rare, are not dependent on the choice of cesarean
versus vaginal delivery [8].
Evans syndrome is a rare hematological disease
and even more rare in pregnancy. Diligent antenatal
surveillance of both mother and fetus along with

prompt implementation of treatment protocols by a
multidisciplinary approach is needed to minimize
complications and to improve the chance for a
desired outcome for both mother and child.
References
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