HEMATOLOGY Dr. Talib Kamoona

HEMATOPOIESIS

ANEMIA Deficiency of Hb in blood below normal range for age & sex (a decrease in red blood cell mass). MAXIMUM CAPACITY : 34 Gm Hb in 100 ml of red cells. Men: Hb: 15 grams per 100 ml of blood; and Women: Hb: 14 grams per 100 ml.

CLASSIFICATION 1. APLASTIC ANEMIA 2. DEFICIENCY ANEMIA A- IRON DEF B- B12 & FOLATE DEF C- THYROXINE DEF D- VIT C DEF E- EPO DEF (CRF) 3. HEMOLYTIC ANEMIAS A- ABNORMAL RBC MEMBRANE B- ABNORMAL RBC ENZYMES C- ABNORMAL RBC Hb (hemoglobinopathies) D- IMMUNE HA E- INFECTION e.g. Malaria F- HYPERSPLENISM 4. ANEMIA OF CHRONIC DISEASE e.g. RdA

Aplastic Anemia Aplastic anemia is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia.

Etiology A- Congenital or inherited causes (20%) 1. Fanconi anemia 2. Dyskeratosis congenita 3. Cartilage-hair hypoplasia 4. Pearson syndrome B- Acquired causes (80%) 1. Idiopathic factors 2. Infectious causes, such as hepatitis viruses, Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), parvovirus, and mycobacteria 3. Toxic exposure to radiation and chemicals, such as benzene, drugs. 4. Transfusional GVHD 5. Orthotopic liver transplantation for fulminant hepatitis 6. Pregnancy 7. Eosinophilic fasciitis

SYMPTOMS The onset is insidious Anemia may manifest as pallor, headache, palpitations, dyspnea, fatigue, or foot swelling Thrombocytopenia may result in mucosal and gingival bleeding or petechial rashes Neutropenia may manifest as overt infections, recurrent infections, or mouth and pharyngeal ulcerations.

PHSICAL SIGNS * may show signs of anemia, such as pallor and tachycardia, and signs of thrombocytopenia, such as petechiae, purpura, or ecchymoses. Overt signs of infection are usually not apparent at diagnosis. * physical stigmata of inherited marrow-failure syndromes, such as skin pigmentation, short stature, microcephaly, hypogonadism, mental retardation, and skeletal anomalies. * The oral pharynx, hands, and nail beds should be carefully examined for clues of dyskeratosis congenita. Oral leukoplakia in dyskeratosis congenita

Dx 1. Complete Blood Cell Count and Peripheral Smears A paucity of platelets, red blood cells (RBCs), granulocytes, monocytes, and reticulocytes is found in patients with aplastic anemia (PANCYTOPENIA). Mild macrocytosis is occasionally observed. The degree of cytopenia is useful in assessing the severity of aplastic anemia. The corrected reticulocyte count is uniformly low in aplastic anemia. 2. Serologic testing for hepatitis and other viral entities, such as EBV, CMV, and HIV, may be useful. 3. An autoimmune-disease evaluation for evidence of collagen- vascular disease may be performed 4. The Ham test, or the sucrose hemolysis test CD55 and CD59 5. Diepoxybutane incubation is performed to assess chromosomal breakage for Fanconi anemia

Bone Marrow Aspiration and Biopsy *appear hypocellular devoid of active red marrow and replaced by fatty tissue *marrow lymphocytes above 70% is correlated with poor prognosis *Some dyserythropoiesis with megaloblastosis may be observed

Differential Diagnoses Acute Lymphoblastic Leukemia Acute Myelogenous Leukemia Agnogenic Myeloid Metaplasia With Myelofibrosis Lymphoma, Non-Hodgkin Megaloblastic Anemia Myelodysplastic Syndrome Myelophthisic Anemia Osteopetrosis

TREATMENT 1- BMT – YOUNGER THAN 65 Y 2- Diet – Exclude raw meat, dairy products, or fruits and vegetables that are likely to be colonized with bacteria, fungus, or molds 3- Activity -- void any activity that increases the risk of trauma 4- BLOOD TRANSFUSION SUPPORT 5- Treatment of Infections Empirical antibiotic therapy should be broad based, with gram- negative and staphylococcal coverage based on local microbial sensitivities. Especially consider including antipseudomonal coverage at the start of treatment for patients with febrile neutropenia, and consider early introduction of antifungal agents for those with persistent fever. 6- Cytokines – in refractory infections

Immunosuppressive Therapy antithymocyte globulin (ATG) has 2 origins, horse and rabbit Response to ATG is slow, and it usually takes 3-6 months for a response to occur. cyclosporine-A (CSA) is being used as first-line therapy for patients older than 40 years and as second-line therapy in younger patients if a matched sibling donor is not available

alemtuzumab (monoclonal anti CD52 antibody) and daclizumab (anti-interleukin 2 receptor or CD-25 antibody). Mycophenolate mofetil and sirolimus were also used Methylprednisolone (Medrol, Solu-Medrol) Cyclophosphamide (Cytoxan) Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross- linking of deoxyribonucleic acid (DNA), which may interfere with the growth of normal and neoplastic cells.

Fludarabine (Fludara) This agent contains fludarabine phosphate, a fluorinated nucleotide analogue of the antiviral agent vidarabine, 9-b-D-arabinofuranosyladenine (ara-A) that enters the cell and is phosphorylated to form the active metabolite 2-fluoro-ara-ATP, which inhibits DNA synthesis. Fludarabine inhibits DNA polymerase, DNA primase, DNA ligase, and ribonucleotide reductase. This inhibits ribonucleic acid (RNA) function, RNA processing, and mRNA translation. Fludarabine also activates apoptosis.

Prognosis The outcome of patients with aplastic anemia has substantially improved because of improved supportive care. The natural history of aplastic anemia suggests that as many as one fifth of patients may spontaneously recover with supportive care; however, observational and/or supportive care therapy alone is rarely indicated. The estimated 5-year survival rate for the typical patient receiving immunosuppression is 75%. The rate for those receiving a BMT from a matched sibling donor is greater than 90%. However, in cases of immunosuppression, relapse and late clonal disease are risks.

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