Published on November 19, 2016
1. Dipak Yadav MBBS 7th Batch Roll 139
2. Aplastic Anemia • It compromises a group of disorders of the hematopoietic stem cells resulting in the suppression of one or more of erythroid, myeloid and megakaryotic cell lines. • It may be inherited or acquired.
3. History • Paul Ehrlich (1854-1915) described the first case of aplastic anaemia in a pregnant woman who died of marrow failure in1888. • The term “aplastic anaemia” first used by Anatole Chauffard in 1904.
4. Epidemiology • annual incidence in Europe and US - 2 cases per million population, but 4 cases in Bangkok 6 in Thailand and 14 in Japan. • no racial predisposition exists in the United States; however, prevalence is increased in the Far East. • The male-to-female ratio is approximately 1:1 • Aplastic anemia occurs in all age groups. • a small peak in incidence in childhood.
6. Etiopathogenesis Hematopoietic stem cell may be deficient due to : 1. Acquired injury from viruses, toxins, chemicals 2. Abnormal marrow microenvironment 3. Immunological suppression( mediated by Ab or cytotoxic T cells) 4. Mutation in genes controlling hematopoiesis
7. Clinical features • Anemia: pallor and/or signs of congestive heart failure, such as shortness of breath. • Thrombocytopenia: bruising (eg, ecchymoses, petechiae) on the skin, gum bleeding, or nosebleeds. • Neutropenia :fever, cellulitis, pneumonia, or sepsis • jaundice and evidence of clinical hepatitis in subset of patients
8. • adenopathy or organomegaly should suggest an alternative diagnosis. • In any case of aplastic anemia, look for physical stigmata of inherited marrow failure syndromes such as: • skin pigmentation • short stature • microcephaly • hypogonadism • mental retardation • skeletal anomalies
9. Investigations • CBC • PBS • Reticulocyte count • B12/folate. • Liver function tests • Virology • Bone marrow aspirate & biopsy
10. • Anemia is common, and red cells appear morphologically normal. The reticulocyte count usually is less than 1%. • Thrombocytopenia, with a paucity of platelets in the blood smear. • Agranulocytosis (ie. decrease in all granular white blood cells, including neutrophils, eosinophils, and basophils) and a decrease in monocytes are observed. A relative lymphocytosis occurs. • The degree of cytopenia is useful in assessing the severity of aplastic anemia.
11. Bone marrow exam • A bone marrow biopsy is performed in addition to the aspiration. In aplastic anemia, these specimens are hypocellular. • Only fat cells, fibrous stroma, scattered lymphocytes and plasma cells presents • Bone marrow revels little materials (“Dry Tap”) • Hence biopsy is appreciated.
12. BM Aspiration BM Biopsy
13. Normal Bone marrow
14. BM biopsy hypocellular ,increased fat spaces
15. Other investigations • Hemoglobin electrophoresis - may show elevated fetal hemoglobin. • Biochemical profile, including evaluation of transaminases, bilirubin, lactic dehydrogenase, Coombs test, and kidney function, is useful in evaluating etiology and differential diagnosis. • Serologic testing for hepatitis EBV, CMV, and HIV • Autoimmune disease evaluation for evidence of collagen-vascular disease • The Ham test or sucrose hemolysis test frequently is performed for excluding PNH. • Histocompatibility testing should be conducted early to establish potential related donors, especially in younger patients.
16. Diagnosis • Pancytopenia • Bone marrow histology and cytology • - decreased marrow cellularity (< 25%) • - increased fat cells component • - no extensive fibrosis • - no malignancy or storage disease
17. • No preceding treatment with X-ray or antiproliferative drugs • No lymphadenopathy or hepatosplenomegaly • No deficiencies or metabolic diseases • No evidence of extramedullary hematopoiesis
18. Differential Diagnosis • FANCONI ANEMIA • DYSKERATOSIS CONGENITA • Acute Myelogenous Leukemia • Anemia • Aplastic Anemia • Hairy Cell Leukemia • Paroxysmal Nocturnal Hemoglobinuria • Immune pancytopenias in connective tissue disorders (eg, systemic lupus erythematosus, refractory anemia)
19. Fanconi anemia • hyperpigmentation of the trunk, neck, and intertriginous areas, as well as café-au-lait spots and vitiligo, alone or in combination. • Most patients have short stature. Growth failure may be associated with abnormal growth hormone secretion, or with hypothyroidism. Absent radii and hypoplastic, supernumerary, bifid, or absent thumbs are common. Anomalies of the feet, congenital hip dislocation, and leg abnormalities are seen. • Males may have an underdeveloped penis; undescended, atrophic, or absent testes; and hypospadias or phimosis
20. • . Females can have malformations of the vagina, uterus, and ovary. • Many patients have a Fanconi “facies,” including microcephaly, small eyes, epicanthal folds, and abnormal shape, size, or positioning of the ears • Approximately 10% of patients are mentally retarded. • Ectopic, pelvic, or horseshoe kidneys are detected by imaging, as well as duplicated, hypoplastic, dysplastic, or absent organs.
21. café-au-lait spots (coffee in milk) Thumb attached by a thread Short stature Epicanthal fold Broad nasal bridge Microcephaly
22. DYSKERATOSIS CONGENITA an inherited disorder of the mucocutaneous and hematopoietic systems in association with somatic abnormalities. • The diagnostic ectodermal triad is reticulate skin pigmentation of the upper body, mucosal leukoplakia, and nail dystrophy • Skin and nail findings usually become apparent in the 1st 10 yr of life, whereas oral leukoplakia is seen later.
23. • These manifestations tend to progress as patients get older. • DC is a constitutional pancytopenia; aplastic anemia occurs in approximately 50% of cases, usually in the 2nd decade of life Patients also have a predisposition to cancer. Approximately 85% of patients are male, compatible with X-linked recessive inheritance. Approximately 15% of patients appear to have either autosomal dominant or autosomal recessive modes of inheritance
24. Treatment- AA • Supportive care Severe Anemia- packed red cells Sever Thrombocytopenia- Platelets transfusion Infection- Antibiotics Definitive therapy Hematopoietic stem cell transplant (HSCT)
25. Criteria for HSCT 1. Young age 2. Severe aplastic anemia 3. Availability of matched siblings SAA who cannot go for HSCT • Infusion of antithymocyte globulin(ATG) • Or, antilymphocyte Globulin(ALG) with Oral cyclosporine
26. • Pt. with neutropenia with infections • A trial of granulocyte colony stimulating factor (G-CSF) • It should not be continued for >7 days even if neutrophil count does not increase • As prolonged use increase the risk of malignant transformation
27. Harvesting HSCT
29. Prognosis • SAA is at risk of cardiac failure,infections,severe bleeding • The major prognostic determinant is the blood count; severe disease is defined by the presence of two of three parameters: absolute neutrophil count <500/µL, platelet count <20,000/µL, and corrected reticulocyte count <1% (or absolute reticulocyte count <60,000/µL). • with current transplantation regime the survival rate is 60-70%
30. • Survival of patients who fulfill these criteria is ∼20% at 1 year after diagnosis with only supportive care • patients with very severe disease, defined by an absolute neutrophil count <200/µL, fare even more poorly • Treatment has markedly improved survival in this disease.
31. References • Nelson Textbook Of Pediatrics 19th edition • Ghai Essential Pediatrics 8th edition • Harrison's Principles of Internal Medicine, 18edition • Robbins Basic Pathology, 9th Edition