November 11, 2007
A Case of Evan’s Syndrome in Pregnancy Refractory to Primary Treatment Options
By Boren, Todd Reyes, Carlos; Montenegro, Raul; Raimer, Karen
Abstract Evan's syndrome is a rare hematological condition defined as immune thrombocytopenic purpura and hemolytic anemia. We describe herein a case of Evan's 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 Evan's syndrome and perinatal outcome.Keywords: Pregnancy, Evan's syndrome, thrombocytopenia, anemia
A 34-year-old G1P0 at 38 estimated weeks of gestation 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 perinatologist 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 intraoperatively. 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 solumedrol 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/mm^sup 3^, and a hematologist was consulted. The patient had no prior knowledge that she had any hematological disorder. The postoperative course was complicated by persistent autohemolysis and severe thrombocytopenia (2000/mm^sup 3^-10 000/mm^sup 3^) despite frequent transfusions, with no evidence of postpartum bleeding. By postoperative day 4, the platelet count continued 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 (antinuclear antibodies), RPR (rapid plasmin reagin), thyroid panel, ANCA (antineutrophil cytoplasmic autoantibodies) C and P, Coombs test, EBV (Ebstein Barr Virus), ESR (Erythrocyte Sedimentation 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 destruction. At this time, the diagnosis of Evan's syndrome was made, which is immune thrombocytopenic 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/mm^sup 3^. 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 discharge, her platelet count was 66 000/mm^sup 3^ and stable.
Using the MEDLJNE search engine, only three previous articles cite Evan's syndrome during pregnancy [1-3]. One describes anesthetic complications with performing a second trimester splenectomy in a patient with Evan's syndrome. The patient responded 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 gestational age with thrombocytopenia . Evan's 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/mm^sup 3^. 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/mm^sup 3^. The third case involved a 26-year-old pregnant patient with Evan's syndrome treated with high dose corticosteroids for severe thrombocytopenia. The patient developed a disseminated gonococcal 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 .
Evan's syndrome involves ITP occurring in sync or sequentially with Coombs positive autoimmune hemolytic anemia (AHA) . This is a rare disease with even fewer patients experiencing associated neutropenia . 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 .
Initial treatment for Evan's syndrome consists of steroid administration such as prednisone. Other therapies include IVIG, chemotherapeutic agents, splenectomy, and plasmaphoresis for refractory cases . 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 concentration 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 antibody production .
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. Complications 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 lifethreatening 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 frequency of which is estimated to be 1-3% . The relative mild maternal thrombocytopenia in the case mentioned above resulted in fetal intracranial hemorrhage, 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 . 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 .
Evan's 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.
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TODD BOREN, CARLOS REYES, RAUL MONTENEGRO, & KAREN RAIMER
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)
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
Copyright Taylor & Francis Ltd. Nov 2007
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