Management of aplastic anemia in a woman during pregnancy: a case report
© Stibbe et al; licensee BioMed Central Ltd. 2011
Received: 21 June 2010
Accepted: 15 February 2011
Published: 15 February 2011
Aplastic anemia is a rare disease caused by destruction of pluripotent stem cells in bone marrow. During pregnancy it could be life-threatening for both mother and child. The only causal therapy for aplastic anemia is bone marrow transplantation, which is contraindicated during pregnancy because of potential embryo toxicity. Treatment options are erythrocytes and platelet transfusions and immunosuppressive therapy. There is, however, no agreement about the optimal supportive care and treatment regime for this disorder during pregnancy.
A 26-year-old nulliparous Asian woman with an uneventful medical history was admitted to the hospital at 14 weeks' gestation because of excessive vomiting. Routine laboratory tests showed pancytopenia (Hb 3.5 mmol/L, leukocytes 3.5 *109/L, platelets 45 *109L). A bone marrow biopsy confirmed aplastic anemia. Methylprednisolon, cyclosporine A, packed cells and platelet transfusions were initiated. At 33 weeks she developed neutropenia (0.1 *109/L) for which oral colistin and tobramycin were given prophylactically. At 35 weeks labor was induced, during which she developed a fever of 38.2°C. She gave birth spontaneously to a healthy son weighing 2415 grams, who had no signs of pancytopenia. After delivery the blood count of the patient did not recover and did not respond to medication. Eighteen weeks after delivery she died of sepsis complicated by cerebral bleeding and infarction due to severe thrombocytopenia and neutropenia, despite optimal supportive treatment.
This potential life-threatening disease has a relatively good prognosis for both mother and child after optimal treatment. Transfusion during pregnancy is the first choice treatment with recommended hemoglobin levels of >5.5 mmol/L and platelet counts of >20 *109/L. Cyclosporine A seems a reasonable alternative therapy with a reported success rate in non-pregnant patients of 70% when combined with antithymocyte globuline. Our patient died 18 weeks postpartum from cerebral bleeding and infarction due to severe thrombocytopenia despite intensive supportive treatment, methylprednisolon and cyclosporine A.
Aplastic anemia is a rare disease caused by destruction of pluripotent stem cells in bone marrow with an annual incidence of 2 to 6/1.000.000 . In contrast to the term 'aplastic anemia', suggesting suppression of erythropoetic cell lines, all cell lines may be affected . Depending on affected cell lines, aplastic anemia is associated with fatigue, bleeding due to thrombocytopenia and recurrent infections due to neutropenia . The diagnosis 'aplastic anemia' is confirmed by hypocellularity of the bone marrow. The remaining cells are morphologically unaffected without malignant infiltration. Potential triggers for the onset of aplastic anemia include T-cell mediated auto-immune disease, iatrogenic agents, viral infection and pregnancy . There is, however, no causal relation between pregnancy and the onset of aplastic anemia . This notion is supported by the similar incidence of aplastic anemia in men and women . During pregnancy bone marrow transplantation is contraindicated because of potential embryo toxicity . There are no clear guidelines for the management of aplastic anemia during pregnancy. Is immunosuppressive treatment more effective than supportive therapy consisting of erythrocytes and platelet transfusion and antibiotics?
Because of the poor prognosis, based on the combination of very severe aplastic anemia and cerebral infarction, further treatment was stopped and the patient died 18 weeks after delivery. At present the child is healthy.
Little research has been published about therapy for aplastic anemia during pregnancy. In fact, only case reports and series with small sample sizes are available. In young non-pregnant patients first choice therapy for aplastic anemia is allogenic stem cell transplantation with a five-year survival of 70 to 80% . However, stem cell transplantation is not feasible during pregnancy because of the teratogenic effects of the immunotherapy and radiotherapy for the unborn child . Pregnancy termination to start bone marrow transplantation was not recommended because of the relatively good prognosis for both mother and child. During pregnancy supportive therapy with erythrocyte and platelet transfusions is a widely used, reasonable alternative. As described in this case, the benefit of transfusions to prevent bleeding should be weighed against the likelihood of developing HLA antibodies and hemochromatosis in the mother . Therefore, we started with a low number and frequency of platelets transfused and increased the frequency after persistent thrombocytopenia . In case the patient responded insufficiently to supportive therapy, immunotherapy with ATG, CsA and/or methylprednisolon could be started. These therapies are used regularly in non-pregnant patients with a hematological response of 40 to 70% . Lesser experience has been gained with ATG treatment during pregnancy, only two cases out of 75. Moreover, both patients died [2, 8]. Outside of pregnancy CsA had comparable results with ATG in a randomized controlled multicenter study . According to this study the hematological responses for CsA and ATG after 12 months were 31.6% and 30% respectively. The one year survival for CsA and ATG was 64 to 70% .
Several case reports refer to Knispel et al. describing a maternal mortality of 20 to 60%. However, the mortality rate in that article published in 1976 differs from the currently reported mortality of 2.7%, probably due to better immunosuppressive treatment and supportive care [2–6, 8, 10, 11]. Unfortunately our pregnant patient with very severe aplastic anemia died after intensive supportive and immunosuppressive treatment with methylprednisolon and CsA during and after pregnancy. She was treated according to the best available treatment based on the literature. She was not treated with ATG during pregnancy because of the bad responses of the two described patients in the literature. Because of the reasonable clinical condition of the patient and good condition of the fetus, there was no indication to terminate the pregnancy early.
Aplastic anemia is a serious condition which may manifest during pregnancy. The seriousness depends on the degree of bone marrow suppression. Most pregnant patients will have full-term pregnancies with a healthy child. Fortunately, aplastic anemia has a low maternal mortality due to treatment. During severe aplastic anemia or complications caused by the supportive therapy (erythrocyte and platelet transfusions and antibiotics) ATG, methylprednisolon and/or CsA could be started. Nonetheless, our patient died 18 weeks postpartum from sepsis, cerebral bleeding and infarction due to severe thrombocytopenia despite intensive supportive treatment, methylprednisolon and CsA. This case shows that aplastic anemia during pregnancy is potentially a life-threatening condition despite the favorable prognosis for both mother and child.
Written informed consent was obtained from the patient and her parents for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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