Aplastic Anemia - Overview

# Aplastic Anemia - Dr Rahul Arya - Assistant Professor - Department of Medicine ## Definition Aplastic anemia is pancytopenia with bone marrow hypocellularity. ## Causes ### Acquired 1. Secondary - Radiation - Drugs and chemicals: Benzene, allopurinol, leflunomide, gold, etc - Vi...

# Aplastic Anemia - Dr Rahul Arya - Assistant Professor - Department of Medicine ## Definition Aplastic anemia is pancytopenia with bone marrow hypocellularity. ## Causes ### Acquired 1. Secondary - Radiation - Drugs and chemicals: Benzene, allopurinol, leflunomide, gold, etc - Viruses - Epstein-Barr virus - Hepatitis (non-A, non-B, non-C hepatitis) - Parvovirus B19 - HIV-1 (AIDS) - Immune diseases - Eosinophilic fasciitis - Hyperimmunoglobulinemia - Large granular lymphocytosis (LGL) - Thymoma/thymic carcinoma - Graft-versus-host disease in immunodeficiency - Paroxysmal nocturnal hemoglobinuria (PNH) - Pregnancy - Idiopathic ### Inherited - Fanconi anemia - Dyskeratosis congenital - Shwachman-Diamond syndrome - Amegakaryocytic thrombocytopenia - Familial aplastic anemias ## Epidemiology - Men and women are affected with equal frequency. - The age distribution is biphasic, with the major peak in the teens and twenties and a second rise in older adults. ## Pathophysiology - Bone marrow failure results from severe damage to the hematopoietic cell compartment. - In aplastic anemia, there is replacement of the bone marrow by fat. - Early hematopoietic cells, committed and primitive progenitor cells, are virtually absent. - An intrinsic stem cell defect exists for the constitutional aplastic anemias. ## Clinical Features - History - Aplastic anemia can appear abruptly or insidiously. - Bleeding is the most common early symptom: easy bruising, oozing from the gums, nosebleeds, heavy menstrual flow, petechiae. - Symptoms of anemia are also frequent, including lassitude, weakness, shortness of breath, and a pounding sensation in the ears. - Patients often feel and look remarkably well despite drastically reduced blood counts. - Prior drug use, chemical exposure, and preceding viral illnesses must often be elicited. ## Physical Examination - Pallor - Petechiae, ecchymoses, retinal hemorrhages. - Lymphadenopathy and splenomegaly are highly atypical of aplastic anemia. ## Laboratory Studies ### Blood - Large erythrocytes and a paucity of platelets and granulocytes. - Mean corpuscular volume (MCV) is commonly increased. - Reticulocytes are absent or few, and lymphocyte numbers may be normal or reduced. ### Bone Marrow - The bone marrow is usually readily aspirated but dilute on smear, and the fatty biopsy specimen may be grossly pale on withdrawal. - In severe aplasia, the smear of the aspirated specimen shows only red cells, residual lymphocytes, and stromal cells. - Biopsy shows mainly fat under the microscope, with hematopoietic cells occupying <25% of the marrow space. ## Treatment ### Hematopoietic Stem Cell Transplantation - This is the best therapy for the younger patient with a fully histocompatible sibling donor. - For allogeneic transplant from fully matched siblings, long-term survival rates for children are approximately 90%. ### Immunosuppression - Antithymocyte globulin (ATG) in combination with cyclosporine. - It induces hematologic recovery in 60-70% of patients. Relapse is frequent. - Horse ATG is administered as intravenous infusions over 4 days. - Methylprednisolone is administered with ATG to ameliorate the immune consequences of heterologous protein infusion. - Cyclosporine is administered orally at an initial high dose, with subsequent adjustment according to blood levels obtained every 2 weeks. ## Supportive Care - Infection in the presence of severe neutropenia must be aggressively treated by prompt institution of parenteral, broad-spectrum antibiotics. - Both platelet and erythrocyte numbers can be maintained by transfusion. - RBCs should be transfused to maintain a normal level of activity, usually at a hemoglobin value of 7 g/dL. - A regimen of 2 units every 2 weeks will replace normal losses in a patient without a functioning bone marrow. - In chronic anemia, the iron chelators, deferoxamine and deferasirox, should be added at approximately the fiftieth transfusion to avoid secondary hemochromatosis. ## Prognosis - The natural history of severe aplastic anemia is rapid deterioration and death. - The major prognostic determinant is the blood count. - Severe disease has been defined by the presence of two of three parameters: - Absolute neutrophil count <500/MI - Platelet count <20,000/μL - Corrected reticulocyte count <1%. ## Thank You