Evan's syndrome is a hematological disorder defined by the simultaneous or sequential presence of autoimmune hemolytic anemia and immune-mediated thrombocytopenia. The pathophysiology and etiology remain unclear.
Evan's syndrome can present in childhood or adulthood. The thrombocytopenic episodes can precede, appear simultaneously with, or follow the episodes of autoimmune hemolytic anemia (AIHA). The severity of symptoms and the time between AIHA and thrombocytopenia episodes can vary. In adult non-simultaneous cases, this delay can last an average of 4 years.
Immune-mediated thrombocytopenia (ITP) often manifests as petechiae, purpura, ecchymoses, epistaxis and mucocutaneous hemorrhage. In severe thrombocytopenia, cerebro-meningeal or gastrointestinal hemorrhage and hematuria may occur.
AIHA is revealed by pallor, unusual weakness, light-headedness, fatigue, exertional dyspnea, tachycardia, jaundice, splenomegaly, and dark urine.
A U.S. and Canada study identified thrombocytopenia in 76% of Evan's syndrome patients and anemia in 67% of these cases [1]. Additionally, the presence of neutropenia was confirmed in 24% of patients while 14% were found to have pancytopenia.
Since its first description, Evan's syndrome has been considered an idiopathic disease. However, it may be associated with other conditions like lymphoproliferative disorders, primary immunodeficiencies, and systemic lupus erythematosus (SLE) [2] [3] [4] [5].
During childhood, the disease may present with an autoimmune lymphoproliferative syndrome (ALPS) that results from a disruption in lymphocyte homeostasis associated with a mutated Fas apoptotic pathway [6].
The spectrum of Evan's syndrome in children has widened recently as there is growing evidence that suggests the syndrome is the reflection of a profound state of immune dysregulation and not a coincidental presentation of immune cytopenias [7].
Evan's syndrome is a diagnosis of exclusion and implies ruling out other conditions including infections, malignancy and autoimmune diseases like thrombotic thrombocytopenic purpura (TTP). To avoid a misdiagnosis, careful analysis of the direct antiglobulin test (DAT) and peripheral blood smear is critical. It is important to distinguish between primary and secondary Evan's syndrome as it can influence the management. The pattern of occurrence of bicytopenia can delay the diagnosis since it may be coincidental, sequential, or separate, and the time frame between episodes can range from months to years [8] [9].
Laboratory tests include CBC, reticulocyte count, lactate dehydrogenase (LDH), direct bilirubin and haptoglobin levels, peripheral blood smear, direct antiglobulin test (Coombs test), and autoantibodies detection.
Th CBC shows anemia (hemoglobin level <12g/dL), thrombocytopenia (platelet count <100,000/microL), neutropenia (neutrophil count <1500/microL), and increased reticulocyte count if anemia is present. It may also reveal combined cytopenias.
Features of hemolysis can be observed as a raised unconjugated bilirubin, decreased haptoglobin levels, elevated lactate dehydrogenase (LDH) and reticulocyte count.
A positive Coombs test confirms that antibodies targeting red blood cell (RBC) antigens are present. Autoantibodies against platelets and neutrophils may be detected.
The identification of thrombocytopenia along with the presence of spherocytes on the blood smear points to an ongoing immune hemolytic anemia, especially when the reticulocyte count is raised. Observing megakaryocytes in the smear suggests an immune origin for the thrombocytopenia. If cytopenia is present, blood smear evaluation can help in ruling out malignancy or proposing its presence.
A variety of antibodies targeting RBCs, white blood tests (WBCs) and platelets have been associated with Evan's syndrome.
The differential diagnoses of Evan's syndrome consists of drug-induced hemolytic anemia, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and chronic cold agglutinin disease.