To the Editor:
A 31-year-old woman with a history of antiphospholipid syndrome and thrombocytopenia in the setting of hemolysis, elevated liver enzymes, and low platelet counts (HELLP syndrome) diagnosed during a prior pregnancy in 2009, was admitted for vaginal and gingival bleeding. Of note, the patient had delivered a baby 1 month prior and had been on Lovenox (Sanofi US, Bridgewater, NJ) throughout the pregnancy and postpartum, maintaining platelet counts of 30k-70k. However, 3 days before admission, the patient began experiencing severe vaginal bleeding.
On admission, the patient had a platelet count of 0/μL and hemoglobin level of 6.3 g/dL. Given the reduced haptoglobin, elevated lactate dehydrogenase, total bilirubin and reticulocytes, and positive direct Coombs test, as well as the presence of spherocytes on peripheral smear, both autoimmune hemolytic anemia and immune thrombocytopenic purpura were identified and thus, the diagnosis of Evans syndrome was made. The patient's anemia was due to both autoimmune hemolytic anemia and vaginal bleeding secondary to low platelets. The absence of schistocytes on peripheral smear and normal fibrinogen and degradation products excluded the diagnoses of thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and disseminated intravascular coagulation. Given active bleeding and lack of prior history of thrombotic events, Lovenox was held. Also, given the severe thrombocytopenia, the patient was transfused with 1 unit of platelets. Cross-matching a unit of red blood cells required sending out a sample to the American Red Cross for a complete antibody work-up. Given the presence of an autoantibody, the patient was eventually transfused with 2 units of packed red blood cells and ultimately achieved a hemoglobin level of 8.0 g/dL. Immediately, the patient was started on intravenous immunoglobulins (IVIG) 0.6 g/kg and dexamethasone 40 mg orally each day. IVIG was eventually increased to 1 g/kg per dose, with 3 total doses given. Dexamethasone was continued at 40 mg daily for 5 days. The patient's hemoglobin improved from 6.3 g/dL to 9.6 g/dL, and platelets increased from 0/μL to 97/μL. Vaginal and gingival bleeding resolved.
Discussion
This presentation is most consistent with Evans syndrome, which is defined by a combination of Coombs positive autoimmune hemolytic anemia, immune thrombocytopenic purpura, and, less commonly, autoimmune neutropenia (∼15%). This case is especially intriguing because we believe that it is the first case in which Evans syndrome occurred in the setting of antiphospholipid syndrome in a patient that also has a history of HELLP syndrome. Also of interest is that this patient's autoimmune hematologic conditions became clinically apparent only during or immediately after pregnancy. The pathophysiology of Evans syndrome is not clearly understood, but likely involves autoantibodies directed against a base protein of Rh blood group, thus destroying red blood cells, and a separate group of autoantibodies directed against platelet GPIIb/IIIa, thus destroying platelets.
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Interestingly, nearly 50% of cases of Evans syndrome are associated with autoimmune conditions such as systemic lupus erythematous, lymphoproliferative disorders, and common variable immunodeficiency.2
First-line treatment is steroids or steroids in combination with IVIG.3
Second-line treatment options include rituximab (which induces remission in the majority of cases, but responses are often sustained for <12 months) and other immunosuppressive agents such as cyclophosphamide, mycophenolate, cyclosporine, vincristine, danazol, and azathioprine.4
Third-line treatment includes splenectomy. For severe and refractory cases, hematopoietic stem cell transplantation offers the only chance for cure, with limited data showing that allogeneic hematopoietic stem cell transplantation may be superior to autologous hematopoietic stem cell transplantation.5
References
- Warm autoimmune hemolytic anemias and Evans syndrome in adults.Rev Med Interne. 2008; 29 ([French]): 105-114
- The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases.Blood. 2009; 114: 3167-3172
- Management of Evans syndrome.Br J Haematol. 2006; 132: 125-137
- A patient with mixed type Evans syndrome: efficacy of rituximab treatment.J Korean Med Sci. 2006; 21: 1115-1116
- Allogeneic stem cell transplantation for Evans syndrome.Bone Marrow Transpl. 2001; 28: 903-905
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Funding: None.
Conflict of Interest: None.
Authorship: All authors have had access and contributed to this manuscript and accept responsibility for the scientific content of the manuscript.
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Published by Elsevier Inc.
