Anemia of Inadequate production Year 4 Paediatrics Notes

Anemia of Inadequate production Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / HAEMATOLOGY -- Slide 1 Anaemias of Inadequate Production Dr Rose Munge Slide 2 Outline Congenital Hypoplastic Anemia Acquired Pure Red Blood Cell Anemia Red Cell Aplasia Associated With Parvovirus B19 Infection Anemia of Chronic Disease Anemia of Renal Disease Megaloblastic Anemias Iron deficiency Anaemia Slide 3 Congenital Hypoplastic Anemia (Diamond-Blackfan Anemia) Diamond-Blackfan anemia (DBA) is a rare, congenital bone marrow failure syndrome that usually becomes symptomatic in early infancy. More than 90% of cases are recognized in the 1st yr of life.\nCharacterized by anemia, usually normochromic and macrocytic; reticulocytopenia; and insufficient or absent red blood cell (RBC) precursors in an otherwise normally cellular bone marrow.\n 50% of affected individuals have additional, extra -hematopoietic anomalies. Slide 4 Since the majority of causative mutations are in RP genes, the disorder is often referred to as a ribosomopathy -identified in up to 70% of cases, most with autosomal dominant inheritance.\nAffects about 7 individuals per 1 million live births.\nProfound anemia usually becomes evident by 2-6 mo of age.\n25% of patients are anemic at birth, and hydrops fetalis occurs rarely; 92% are diagnosed within the 1st yr of life.\n40–50% of patients have congenital anomalies, and 1 anomaly is found in 25% of DBA patients Slide 5 Craniofacial abnormalities -50% of patients- snub nose and high-arched palate.\nSkeletal anomalies, mostly upper limb and hand, affect 30%. Thumb abnormalities, including flattening of the thenar eminence and triphalangeal thumb, may be bilateral or unilateral.\nThe radial pulse may be absent. Genitourinary (38%), cardiac (30%), ophthalmologic, and musculoskeletal anomalies have also been identified.\nShort stature is common. Slide 6 The RBCs are usually macrocytic for age, but no hypersegmented neutrophils or other characteristics of megaloblastic anemia are appreciated on the peripheral blood smear. \n Erythrocyte adenosine deaminase (eADA) activity is increased in most patients with DBA, a finding that helps distinguish congenital RBC aplasia from acquired transient erythroblastopenia of childhood (TEC) Slide 7 Thrombocytosis, or rarely thrombocytopenia, and occasionally neutropenia, may also be present.\n Reticulocyte percentages are characteristically very low despite severe anemia.\n Bone marrow erythrocyte precursors are greatly reduced in most patients; other marrow elements are usually normal.\n Serum iron levels are elevated. Slide 8 Management Corticosteroids are a mainstay of therapy, 80% of patients initially respond.\nBecause corticosteroids impair linear growth as well as physical and neurocognitive development, chronic transfusion therapy and delay the start of steroids until after age 1 yr. Prednisone or prednisolone in doses 2 mg/kg/day.\nAn increase in RBC precursors is usually seen in the bone marrow 1-3 wk. after therapy is begun and is followed by peripheral reticulocytosis.\nThe hemoglobin can reach normal levels in 4-6 wk. Once it is established that the hemoglobin concentration is increasing, the dose of corticosteroid may be reduced gradually by tapering and then by eliminating all except a single, lowest effective daily dose.\nThis dose may then be doubled, used on alternate days, and tapered still further while maintaining the hemoglobin level at ≥9 g/dL. Slide 9 Chronic red cell transfusions required in approximately 35% of patients, including patients who are never steroid responsive (30%), are steroid refractory (15%), or cannot be weaned to acceptable low dose (50%).\nTransfusions are given every 3-5 wk. to maintain a hemoglobin level 8 g/dL. Some younger children may require hemoglobin 9 g/dL to sustain normal growth and activities.\nAppropriate screening and ultimately the initiation of chelation therapy are required for transfusion-related iron overload. Slide 10 Spontaneous remission of anemia with independence from steroid or red cell transfusion therapy has been reported.\n The likelihood of remission is 25% by age 25 yr., with the majority of patients experiencing remission during the 1st decade.\n Hematopoietic stem cell transplantation (HSCT) can be curative. Slide 11 Prognosis DBA is a cancer predisposition syndrome because of the higher risk of myelodysplastic syndrome, acute myeloid leukemia, colon carcinoma, osteogenic sarcoma, and female genital cancers.\n Patients are at risk for iron overload related endocrine abnormalities (diabetes, hypogonadism), especially if transfused. The overall survival is approximately 75% at age 40 yr, with approximately 87% for those maintained on corticosteroids and approximately 57% for transfusion-dependent patients.\n Of reported deaths, 67% were treatment related and 22% were DBA related (malignancy and severe aplastic anemia). Slide 12 Acquired Pure Red Blood Cell Anemia Transie