Síndrome de Evans de aparición súbita en el embarazoResúmenes
La trombocitopenia complica hasta el 10% de los embarazos. El síndrome de Evans es la coexistencia de la trombocitopenia inmune con anemia hemolítica autoinmune. Se presenta un caso de síndrome de Evans durante el embarazo, complicado por preclampsia y neutropenia fetal. Una mujer de 20 años de edad, previamente sana, primigesta, que presentó a las 34 semanas de gestación dolor epigástrico, trombocitopenia y pre eclampsia. Se le realizó parto por cesárea, por presentar síndrome de HELLP. A los 25 días de postparto, reingresó al Hospital con trombocitopenia severa, plaquetas 2000 x mm<span name="style_sup">3</span>, anemia, hemoglobina 5,3 g/dl y fiebre. El Coombs directo fue positivo y el análisis posterior demostró la presencia de anticuerpos anti-plaquetarios, y anticardiolipina. Recibió transfusiones de sangre y plaquetas. Se le trató con prednisona, plasmaferesis, azatioprina y finalmente, resolvió su cuadro clínico después de 10 días de internamiento en una unidad de cuidado intensivo., anemia, hemoglobina 5,3 g/dl y fiebre. El Coombs directo fue positivo y el análisis posterior demostró la presencia de anticuerpos anti-plaquetarios, y anticardiolipina. Recibió transfusiones de sangre y plaquetas. Se le trató con prednisona, plasmaferesis, azatioprina y finalmente, resolvió su cuadro clínico después de 10 días de internamiento en una unidad de cuidado intensivo.
síndrome de Evans; trombocitopenia; anemia hemolítica; embarazo
Thrombocytopenia complicates up to 10% of pregnancies. Evans syndrome is the coexistence of immune thrombocytopenia with autoimmune hemolytic anemia. We report a case of Evans syndrome during pregnancy complicated by preeclampsia and fetal neutropenia. A 20year-old primigravida, previously healthy, presented at 34 weeks of gestation epigastric pain, thrombocytopenia and preeclampsia. She underwent cesarean delivery for HELLP syndrome. In the 25th postpartum day, she was readmitted to the hospital with severe thrombocytopenia, platelet count in 2000x mm<span name="style_sup">3</span>, anemia, hemoglobin 5.3 g/dl and fever. The direct Coombs was positive and subsequent analysis showed the presence of platelet antibodies, and anticardiolipin. She received blood and platelet transfusions. She was treated with prednisone, plasmapheresis, azathioprine, and finally recovered 10 days in an intensive care unit., anemia, hemoglobin 5.3 g/dl and fever. The direct Coombs was positive and subsequent analysis showed the presence of platelet antibodies, and anticardiolipin. She received blood and platelet transfusions. She was treated with prednisone, plasmapheresis, azathioprine, and finally recovered 10 days in an intensive care unit.
Evans syndrome; thrombocytopenia; autoimmune hemolytic anemia; pregnancy
Thrombocytopenia complicates up to 10% of pregnancies. Evans syndrome is the coexistence of immune thrombocytopenia with autoimmune hemolytic anemia. We report a case of Evans syndrome during pregnancy complicated by preeclampsia and fetal neutropenia. A 20year-old primigravida, previously healthy, presented at 34 weeks of gestation epigastric pain, thrombocytopenia and preeclampsia. She underwent cesarean delivery for HELLP syndrome. In the 25th postpartum day, she was readmitted to the hospital with severe thrombocytopenia, platelet count in 2000x mm<sup>3</sup>, anemia, hemoglobin 5.3 g/dl and fever. The direct Coombs was positive and subsequent analysis showed the presence of platelet antibodies, and anticardiolipin. She received blood and platelet transfusions. She was treated with prednisone, plasmapheresis, azathioprine, and finally recovered 10 days in an intensive care unit.
Evans syndrome; thrombocytopenia; autoimmune hemolytic anemia; pregnancy
Caso clínico
Síndrome de Evans de aparición súbita en el embarazo
(Evans Syndrome of Sudden onset Pregnancy)
Jorge Barboza-Retana, Pilar Bogantes-Ledezma,William Carballo-Gutiérrez, Jorge Díaz-Camacho
*Correspondencia
Resumen
La trombocitopenia complica hasta el 10% de los embarazos. El síndrome de Evans es la coexistencia de la trombocitopenia inmune con anemia hemolítica autoinmune. Se presenta un caso de síndrome de Evans durante el embarazo, complicado por preclampsia y neutropenia fetal. Una mujer de 20 años de edad, previamente sana, primigesta, que presentó a las 34 semanas de gestación dolor epigástrico, trombocitopenia y pre eclampsia. Se le realizó parto por cesárea, por presentar síndrome de HELLP. A los 25 días de postparto, reingresó al Hospital con trombocitopenia severa, plaquetas 2000 x mm3, anemia, hemoglobina 5,3 g/dl y fiebre. El Coombs directo fue positivo y el análisis posterior demostró la presencia de anticuerpos anti-plaquetarios, y anticardiolipina. Recibió transfusiones de sangre y plaquetas. Se le trató con prednisona, plasmaferesis, azatioprina y finalmente, resolvió su cuadro clínico después de 10 días de internamiento en una unidad de cuidado intensivo.
Descriptores: síndrome de Evans, trombocitopenia, anemia hemolítica, embarazo
Abstract
Thrombocytopenia complicates up to 10% of pregnancies. Evans syndrome is the coexistence of immune thrombocytopenia with autoimmune hemolytic anemia. We report a case of Evans syndrome during pregnancy complicated by preeclampsia and fetal neutropenia. A 20year-old primigravida, previously healthy, presented at 34 weeks of gestation epigastric pain, thrombocytopenia and preeclampsia. She underwent cesarean delivery for HELLP syndrome. In the 25th postpartum day, she was readmitted to the hospital with severe thrombocytopenia, platelet count in 2000x mm3, anemia, hemoglobin 5.3 g/dl and fever. The direct Coombs was positive and subsequent analysis showed the presence of platelet antibodies, and anticardiolipin. She received blood and platelet transfusions. She was treated with prednisone, plasmapheresis, azathioprine, and finally recovered 10 days in an intensive care unit.
Keywords: Evans syndrome, thrombocytopenia, autoimmune hemolytic anemia, pregnancy
El síndrome de Evans es una condición poco frecuente, inicialmente reportada en población infantil, caracterizada por la aparición simultánea o consecutiva de trombocitopenia y anemia hemolítica; aunque la incidencia real no es bien conocida, se estima que afecta a entre un 1,8% y un 10% de las pacientes con PTI.
El síndrome como tal fue inicialmente descrito por Evans en 1951, y el primer caso publicado en el embarazo data de 1966. Desde entonces, los reportes de casos a nivel mundial, del síndrome de Evans en su asociación con el embarazo han sido casos aislados.En total 14 publicaciones se han reportado entre casos clínicos y revisiones sistemáticas, motivo por lo cual, se presenta un caso valorado en la unidad de Medicina Materno Fetal del HCG.
Caso Clínico
Mujer de 20 años, vecina de Moravia, desempleada, con historia de presentar 34 semanas de gestación, primigesta sin control prenatal, llega referida de la clínica de Curridabat, por dolor abdominal severo, de predominio epigástrico, náuseas y vómitos. Ingresa al Servicio de Emergencias del HCG, donde se le documentan como antecedentes personales no patológicos que es alérgica a la clindamicina, amoxicilina, voltarén; no fuma ni usa drogas; con signos vitales estables con TA 100/70mmHg, FC 88 por minuto, FCF 140 por minuto.
Se le realiza un ultrasonido de abdomen que se reporta como normal; un ultrasonido obstétrico indica: “Fetometria para 28 semanas, peso fetal estimado de 1201 gramos, índice de líquido amniótico normal, perfil biofísico fetal basal normal”.
Internada en salones de maternidad, persiste con dolor epigástrico, se elevan sus cifras tensionales a 167/102 mmHg, presión arterial media de 126mmHg. Se le inicia sulfato de magnesio y los nuevos laboratorios muestran plaquetas en 42000 x mm3.
En sesión de perinatología se decide interrumpir el embarazo por preclampsia severa y síndrome de HELLP. Nace por cesárea Kerr, recién nacida viva, 1200 gramos, Apgar 9-9, pequeña para la edad gestacional, con neutropenia severa; permanece internada durante 11 días por persistir con trombocitopenia severa y dolor epigástrico, mejora su sintomatología y se egresa el 13 de febrero, con referencia para seguir control en la consulta externa de Reumatología.
Reingresa a maternidad del HCG, con historia de dolor abdominal persistente, náuseas, anemia y trombocitopenia severa en el posparto 25, 17 días después de su egreso.
Es ingresada a la unidad de cuidado intensivo, debido a que no mejora sus parámetros y la destrucción de plaquetas y hemoglobina es tan activa que, a pesar de varias transfusiones de plaquetas y glóbulos rojos empacados (GRE) en dos días, las plaquetas persistían en 1000 y Hb en 2g/dl; se le inicia prednisona e inmunoglobulina.
El 28 de febrero se le inician esteroides y gama globulina 20 gramos IV al día, se le transfunden 2 unidades de GRE filtrados y 6 Unidades de plaquetas.
El cuadro clínico mejora espontáneamente a los 10 días de internada y es traslada a Reumatología, con un conteo de plaquetas en 70000 x mm3, y Hb en 9 g/dl., en franca mejoría, para dar de alta y continuar seguimiento en consulta externa.
Discusión
El síndrome de Evans es una condición hematológica crónica, descrita inicialmente como la aparición simultánea o secuencial de anemia hemolítica autoinmune, Coombs positivo y trombocitopenia autoinmune. 1-3
La asociación con el embarazo la reporta en 1966, Silverstein;1,2los casos en la literatura mundial son muy escasos, y la asociación con el embarazo es una entidad aún más rara.
Puede ocurrir solo o en presencia de otra enfermedad autoinmune, como lupus eritematoso sistémico, síndrome anti fosfolípido y el síndrome autoinmune linfoproliferativo.1,3A la paciente se le detectó un síndrome anti fosfolípido activo en el posparto inmediato, con anticuerpos anti-cardiolipina positivos (IgG en 87,62 e IgM mayor de 92, ambos positivos), un VDRL reactivo 1 en 16 con FTA negativo.
En algunos casos, el síndrome de Evans puede preceder el desarrollo de un síndrome mielo displásico, o de un linfoma no Hodgking.
Únicamente un 4% de los casos presentan un conteo plaquetario de menos de 20000 plaquetas/mm3.5,6La paciente llegó a presentar conteos plaquetarios inferiores a 1000 plaquetas/mm3. Al igual que con la anemia hemolítica, el síndrome de Evans puede tener una misma causa inmunológica. En el caso en cuestión, el diagnóstico se efectúa en el periodo puerperal tardío de la paciente.
En una revisión sistemática publicada en 2010, solo se reportaron 10 casos desde el primero descrito por Silberstein,1,4,7cuyos diagnósticos fueron realizados antes de que las pacientes estuviesen embarazadas. La edad media del diagnóstico fue de 21 años, con un rango de 19 a 34; la mayoría de esos casos fueron diagnosticados entre la semana 14 y 38 de gestación. Solo 2 de los casos presentaron, simultáneamente, trombocitopenia y anemia hemolítica. El parto ocurrió entre las semanas 32 y 40 de gestación y fue vaginal en 7 de los 10 casos; 8 de los 10 productos nacieron vivos; uno de los recién nacidos presentó anemia hemolítica hasta 2 meses después del parto. 5,7
Las 10 mujeres recibieron prednisona durante su embarazo, en dosis de entre 10 y 80 mg al día; cuatro respondieron satisfactoriamente, tres lo hicieron cuando se agregó gamma globulina intravenosa (400 mg/día/Kg por 2-3 días), una recibió anti D globulina por 3 días sin respuesta, otra fue esplenectomisada durante el embarazo 9 y otra después de este.8,10En la paciente de este caso, el cuadro no revertió hasta que se le indicó Azatioprina.
El diagnóstico diferencial del síndrome de Evans en el embarazo incluye, en su mayoría, anemia hemolítica microangiopatica, como la que se observa en el síndrome HELLP y raramente en la púrpura trombocitopénica idiopática, o en el síndrome urémico hemolítico, en cuyos casos el Coombs es negativo.9,10
El diagnóstico de Evans se realiza con hallazgos de laboratorio de anemia y trombocitopenia con policromasia, macrocitosis, esferocitosis, conteo de reticulocitos normales, incremento de la bilirrubina indirecta y disminución de las haptoglobulinas.11La mayoría de los pacientes necesitan tratamiento con corticosteroides, pero en casos resistentes o recurrentes, pueden ser necesarios tratamientos intravenosos con γ- globulina, danazol, ciclofosfamida, alcaloides de la vinca y azatioprina, o incluso plasmaferesis o esplenectomía.11,12
En la literatura, el tratamiento de elección durante el embarazo se basa en corticosteroides y gammaglobulina intravenosa. 11La azatioprina ha mostrado ser segura en el embarazo y en la lactancia.
La esplenectomía por laparoscopia es considerada aceptable en pacientes con síndrome de Evans refractario, después del segundo trimestre del embarazo.10,11Se contraindica el parto instrumentado con fórceps o extractores vacuum; el parto por cesárea, únicamente por indicación obstétrica.11,12
Aunque la trombocitopenia autoinmune en la embarazada puede causar una trombocitopenia fetal moderada o severa, en este caso la única manifestación del producto es una neutropenia moderada a los 40 días de nacida.
Referencias
Referencias bibliográficas
-
1. LefKou, Elefdehtheria. Evans syndrome in pregnancy: a systematic literature reviews a two view cases. Eur J Obstet Gynecol Reprod Biol. 2010; 149: 10-17. -
2. Evans, RS. Primary thrombocytopenic purpura and acquired hemolytic anemia: evidence for common etiology. Arch Intern Med 1951; 87:48– 65.
-
3. Silberstein MN, Aaro LA. Evans syndrome and pregnancy. Am J Med Sci. 1966; 252; 206-11.
-
4. Vorapong, Phupong. Evans syndrome and pregnancy: a case report an International. J Obstet Gynecol. 2004; 111:274 –276.
-
5. Savasan S, Warrier I The spectrum of Evans’ syndrome. Arch Dis Child. 1997; 77: 245–248.
-
6. Selcuk Tuncer Z, Buyukasik Y. et al. Pregnancy complicated by Evan’s syndrome. Eur J Obstet Gynecol Reprod Biol 2001; 100:100-101.
-
7. Sherke RR, Rao MS. Anaesthetic management of splenectomy in Evan’s syndrome during pregnancy with pregnancy induced hypertension. J Postgrad Med. 2001; 47:196-198.
-
8. Z. Selçuk, Tuncera. Gestación complicada por el síndrome de Evans. Eur J Obstet Gynecol Reprod Biol 2002; 2: 120-122.
-
9. Passi, Gr. Isoinmunehemolisis in an infant due to maternal Evans síndrome. Indian J Pediatrics 1997; 64: 893-5.
-
10. Sherrke RR, Rao Ms. Anaesthetic management of splenectomy in Evans syndrome during pregnancy with pregnancy induced hypertension. J Postgrad Med 2001; 47:196-8.
-
11. Boren TReyes C, Montenegro R, Raimer K, Acase of Evans syndrome in pregnancy refractory to primary treatment options. J Matern Fetal Neonatal Med 2007; 20:843-5.
-
12. Norton A, Roberts I. Management of Evans syndrome. Br J Haematol 2006; 97:125-37.
Servicio de Obstetricia del Hospital Dr. Rafael A. Calderón Guardia, Caja Costarricense de Seguro Social
Abreviaturas: FUR,fecha de última regla;ILA,índice de líquido amniótico; GRE, glóbulos rojos empacados; HCG, hospital “Dr. Rafael Ángel Calderón Guardia”
*Correspondencia: Pilar Bogantes Ledezma
Clinical case
Evans Syndrome of Sudden Onset in Pregnancy
Jorge Barboza-Retana, Pilar Bogantes-Ledezma, William Carballo-Gutiérrez, Jorge Díaz-Camacho
Contact informationAbstract:
Thrombocytopenia complicates up to 10% of pregnancies. Evans syndrome is the coexistence of immune thrombocytopenia with autoimmune hemolytic anemia. We report a case of Evans syndrome during pregnancy complicated by preeclampsia and fetal neutropenia. A 20year-old primigravida, previously healthy, presented at 34 weeks of gestation epigastric pain, thrombocytopenia and preeclampsia. She underwent cesarean delivery for HELLP syndrome. In the 25th postpartum day, she was readmitted to the hospital with severe thrombocytopenia, platelet count in 2000x mm3, anemia, hemoglobin 5.3 g/dl and fever. The direct Coombs was positive and subsequent analysis showed the presence of platelet antibodies, and anticardiolipin. She received blood and platelet transfusions. She was treated with prednisone, plasmapheresis, azathioprine, and finally recovered 10 days in an intensive care unit.
Keywords: Evans syndrome, thrombocytopenia, autoimmune hemolytic
anemia, pregnancy
The Evans syndrome is a rare condition, initially reported in children, and characterized by the simultaneous or successive occurrence of thrombocytopenia and hemolytic anemia; although the actual incidence is not well known, according to estimations it affects between 1.8% and 10% of patients with ITP.
Evans was the first one to describe the syndrome as such in 1951, and the first published case about its occurrence during pregnancy dates back to 1966. Since then, there have been few worldwide reports about Evans syndrome in association with pregnancy. A total of 14 publications, which include clinical cases and systematic reviews, have been reported. This is why a case diagnosed at the Fetomaternal Medicine Unit of the HCG is presented.
Clinical case
A 20-year old female, resident of Moravia, unemployed, with 34-weeks of gestational age, primigravida without prenatal care; is referred from the clinic of Curridabat due to severe abdominal pain, predominantly epigastric, nausea and vomiting. She is admitted at the Emergency Service of the HCG, where a personal history of allergy to clindamycin, amoxicillin and Voltaren is recorded. She does not smoke or use drugs. Her vital signs were stable, with BP 100/70mmHg, HR 88 per minute, FHR140 per minute.
The abdominal ultrasound is reported as normal; an obstetrical ultrasound indicates: "Fetometry for 28 weeks, estimated fetal weight of 1201 grams, normal amniotic fluid index, fetal biophysical profile normal."
She is admitted to the maternity rooms; epigastric pain persists, her blood pressure rises to 167/102 mmHg, mean arterial pressure of 126 mmHg. She begins treatment with magnesium sulfate and the new laboratory tests show a platelet count of 42 000 x mm3.
In the perinatology session, the decision to interrupt the pregnancy is taken, due to severe preeclampsia and HELLP syndrome. The newborn was born alive through a Kerr caesarean; with a weight of 1200 grams, Apgar 9-9, small for its gestational age, with severe neutropenia; she remains hospitalized for 11 days because of persisting severe thrombocytopenia and epigastric pain. Her symptomatology improved and was discharged on February 13, with a reference for further control in the Rheumatology outpatient clinic.
She is readmitted to the HCG’s maternity with a history of persistent abdominal pain, nausea, anemia and severe thrombocytopenia, in postpartum day 25, 17 days after discharge.
The patient is admitted to the intensive care unit because her parameters do not improve and the destruction of platelets and hemoglobin is so active that, despite several transfusions of platelets and packed red blood cells (PRBC) during two days, platelet count remained in 1000 and Hb in 2g/dl; treatment with prednisone and immunoglobulin is started.
On February 28 she begins treatment with steroids and gamma globulin, 20 grams IV a day; she receives a transfusion of 2 units of filtered PRBC and 6 units of platelets.
The medical condition improves spontaneously after 10 days of hospitalization and the patient is transferred to the Rheumatology unit, with a platelet count of 70 000 x mm3 and Hb of 9 g/dl; because of her improving conditions, she is discharged and continues under control at the outpatient clinic.
Discussion
The Evans syndrome is a chronic hematological condition, initially described as the simultaneous or sequential occurrence of autoimmune hemolytic anemia, Coombs-Positive and autoimmune thrombocytopenia.1-3
The association to pregnancy was reported by Silberstein in 1966;1,2 cases in worldwide literature are scarce, and the association to pregnancy is an even rarer entity.
It may occur alone or together with the presence of another autoimmune disease like systemic lupus erythematosus, antiphospholipid syndrome and autoimmune lymphoproliferative syndrome.1,3 The patient was diagnosed with an active antiphospholipid syndrome in the immediate postpartum period, with positive anticardiolipin antibodies (IgG 87.62 and IgM greater than 92, both positive), a reactive VDRL 1 in 16 with negative FTA.
In some cases, the Evans syndrome may precede the development of a myelodysplastic syndrome, or of a non-Hodgkin lymphoma.
Only 4% of the cases show a platelet count below 20 000 platelets/mm3.5,6 The patient showed platelet counts below 1000 platelets/mm3. As with hemolytic anemia, the Evans syndrome may have one immunologic cause. In the case under discussion, diagnosis occurs on the patient’s late postpartum period.
In a systematic review published in 2010, only 10 cases had been reported since first described by Silberstein,1,4,7whose diagnoses were made before the patients were pregnant. The average age of diagnosis was 21 years, on a range from 19 to 34 years; most of these cases were diagnosed between 14 and 38 weeks of gestation. Only 2 of the cases showed simultaneous thrombocytopenia and hemolytic anemia. Birth occurred between gestation weeks 32 and 40 and it was vaginal in 7 out of the 10 cases; 8 out of 10 products were born alive; one of the newborns suffered from hemolytic anemia until 2 months after delivery.5.7
The 10 women received prednisone during their pregnancy, at doses between 10 and 80 mg per day; four responded satisfactorily, three did so when intravenous gamma globulin (400 mg/day/kg during 2-3 days) was added, one received anti D globulin during 3 days with no response, another one underwent an splenectomy during pregnancy 9 and the other one after pregnancy.8,10 In this case’s patient, the medical condition did not recede until Azathioprine was prescribed.
The differential diagnosis of Evans syndrome in pregnancy includes mainly microangiopathic hemolytic anemia, such as the one observed in HELLP syndrome and in rare cases in idiopathic thrombocytopenic purpura, or in the hemolytic uremic syndrome, in both of these cases, the Coombs is negative.9, 10
The diagnosis for Evans is performed as a result of laboratory findings of anemia and thrombocytopenia with polychromasia, macrocytosis, spherocytosis, normal reticulocyte count, increased indirect bilirubin and decreased haptoglobulin.11 Most patients require treatment with corticosteroids, but in resistant or recurrent cases, treatment with intravenous γ-globulin, danazol, cyclophosphamide, vinca alkaloids and azathioprine; or even plasmapheresis or splenectomy, might be neccesary.11, 12
In the literature, the treatment to be chosen during pregnancy is based on corticosteroids and IVIG.11 Azathioprine has proven to be safe during pregnancy and lactation.
Laparoscopic splenectomy is considered acceptable in patients with refractory Evans syndrome after the second trimester of pregnancy.10,11 Forceps or vacuum extractor delivery is contraindicated; cesarean delivery only if preceded by obstetric recommendation.11, 12
Although autoimmune thrombocytopenia during pregnancy can
cause moderate or severe fetal thrombocytopenia,
in this case the only manifestation in the product is a moderate
neutropenia
at 40 days old.
References
Obstetrics Department, Hospital Dr. Rafael Calderón Guardia, Caja Costarricense del Seguro Social [Dr. Rafael Calderón Guardia Hospital, Costa Rican Social Security Institution]
Abbreviations: DLP, date of last period; ALI, amniotic liquid index; PRBC, packed red blood cells; HCG, "Dr. Rafael Calderón Guardia" Hospital.
*Contact
information: Pilar Bogantes
Ledezma
Fechas de Publicación
-
Publicación en esta colección
08 Feb 2012 -
Fecha del número
Dic 2011
Histórico
-
Recibido
17 Mar 2011 -
Acepto
25 Ago 2011
