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Anemia Overview

Anemia Overview. Anu Thummala, M.D. Hematology/Oncology and Internal Medicine Comprehensive Cancer Centers of Nevada. Anemia. Three main mechanisms: DECREASED PRODUCTION OF RBC (HYPOPROLIFERATION) 2. INCREASED DESTRUCTION OF RBC (HEMOLYSIS) 3. ACUTE BLOOD LOSS.

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Anemia Overview

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  1. Anemia Overview Anu Thummala, M.D. Hematology/Oncology and Internal Medicine Comprehensive Cancer Centers of Nevada

  2. Anemia Three main mechanisms: • DECREASED PRODUCTION OF RBC (HYPOPROLIFERATION) 2. INCREASED DESTRUCTION OF RBC (HEMOLYSIS) 3. ACUTE BLOOD LOSS

  3. The most important first step in the diagnosis of Anemias…….

  4. The Peripheral Smear

  5. ? • Young women with surgery as child and was told that she could be at risk for developing infections. • CBC normal

  6. ? • 74 male presents with neuropathy, loss of balance, WBC 1.9, HGB 7, PLT 120,000

  7. ? • A 20 YO woman presents with increasing weakness over six weeks,fever and Hb = 5.9 g/dl., white cells 18.0 x10ˆ9/l., platelets 35 x10ˆ9/l.

  8. ? • Young man with recent travel presents with fever of unknown origin. WBC 18K, HGB 8 g, PLT 461,000

  9. ? • Elderly gentleman presents with fatigue, pallor and SOB. WBC 3K, HGB 6g, PLT 566,000

  10. ? • 70 YO male admitted to ICU with severe pancytopenia, bleeding, hypotensive. Patient is intubated • PT 15, PTT 40, PLT 36,000, WBC 2.2, HGB 8 g.

  11. ? • 46 YO presents with history of alcohol abuse, hypotension. • WBC 3.2, HGB 10g, PLT 72,000 • T. Bili 2.0, creatinine 4, BUN 68

  12. Anemia

  13. Case 1 • 51 YO female presents with fatigue, occasional tingling of her hand and feet. She reports decrease in concentration and memory • PSHx: cholecystectomy, gastric bypass • Social Hx: negative for drug, tobacco and alcohol

  14. Case 1 • LABS: WBC 1.7 HGB 8.9 G/DL PLATELETS 109,000 MCV 109 SEGS 52% LYMPHS 40% MONO 5% EOS 2% METAMYELOCYTES 1%

  15. Case 1 • Additional tests……

  16. SMEAR

  17. Macrocytic Anemia • Abnormal maturation of nucleus in RBC precursors • CAUSES: - Alcoholism • Pernicious Anemia (Vit B12 deficiency) • Folic Acid deficiency • Tropical Sprue • Scandinavia - Fish tapeworm

  18. Macrocytic Anemia Megaloblastic Vitamin B12 (Cobalamin) Deficiency Folate Deficiency MDS Chemotherapy (Methotrexate, Hydroxyurea, Azathioprine SPURIOUS Alcohol, Hypothyroidism, MM, Liver disease, MDS, Aplastic Anemia

  19. MEGALOBLASTIC DISEASE • Diagnosis: MCV> 100 • Macrocytosis may be blunted in presence of Fe deficiency or thalasemia • Low Reticulocyte count • Neutropenia and Thrombocytopenia • WBC :Hypersegmentation. Almost always pathognomonic

  20. FOLIC ACID • FOLIC ACID (pteroylmonoglutamic acid) • Natural Source : fruits / vegetables • May be destroyed by cooking • Minimum daily requirement 50 micrograms/day • Deficiency can develop within months • FDA ordered Folic acid supplementation (January, 1998) to all enriched grains

  21. FOLATE DEFICIENCY • Inadequate Intake • Malabsortion due to Sprue, Celiac disease

  22. FOLATE DEFICIENCY Increased Demand • Cells with high rate of turnover • Chronic hemolytic anemias • Pregnancy • Deficiency in first few weeks - - > neural tube defects in fetus • Malignancy • Chronic Exfoliative Skin Disorders • Hemodialysis pts

  23. FOLATE DEFICIENCY Medications • 6 thioguanine, azathiprine, 6 mercaptopurine • 5 FU, cytosine, arabinoside • Hydroxyurea, procarbazine, AZT • Folate Antagonists - Methotrexate, pentamidine, trimethoprim, triamterene, pyrimethamine, Dilantin

  24. COBALAMIN (VIT B12) • Cobalt cannot be synthesized - required in diet ! • ONLY SOURCE : Animal products (meat and dairy) • Minimum daily requirement: 2.5 micrograms/day

  25. COBALAMIN DEFICIENCY • Inadequate intake “vegetarian” • Malabsorption • Defective Release of Cobalamin from Food • Inadequate Production of Intrinsic Factor

  26. COBALAMIN DEFICIENCY • Disorders of the terminal ileum • Tropical and Non Tropical Sprue • Regional Enteritis, Crohn’s Disease • Intestinal Resection • Competition for cobalamin • Fish Tapeworm (Scandinavian countries) • Bacteria (“blind loop syndrome) • Drugs • p-aminosalicylic acid, colchicine, neomycin

  27. COBALAMIN DEFICIENCY • Blood • Macrocytic Anemia • Pancytopenia, elevated LDH/ Indirect Bilirubin • Clin Sx: weakness, dizziness, vertigo, tinnitus, angina, palpitations and CHF • Physical Exam: pale, icteric, rapid pulse, enlarged heart, systolic flow murmur • GI • Based on rapidly proliferating GI epithelium • SORE TONGUE • ANOREXIA / WEIGHT LOSS • DIARRHEA

  28. COBALAMIN DEFICIENCY • NEURO (may be permanent) • Demyelination -> axonal degeneration -> neuronal death • Peripheral nerves, spinal cord (posterior and lateral columns) , cerebrum • SX: EARLY: Numbness and parethesias in extremities • LATER: weakness, ataxia, sphincter disturbances, • Decreased vibratory sensation • mild irritability --> dementia or psychosis • NEURO SX MAY BE PRESENT IN A PATIENT WHO IS NOT ANEMIC

  29. COBALAMIN DEFICIENCY PERNICIOUS ANEMIA Autoimmune destruction or gastric mucosal atrophy Etio: Lack of Intrinsic Factor (IF) secreted by parietal cells EPIDEMIOLGY • Males = females, often age >60 • See in pts from Northern Europe or African Americans OTHER DISEASE ASSOCIATIONS Graves Disease Myxedema Thyroiditis Vitiligo Hypoparathyroidism Agammaglobulinemia Adrenocortical Insufficiency

  30. PERNICIOUS ANEMIA • ABNORMAL LABS • Anti parietal cell antibody (anti Na,K ATPase (90%) • Anti IF antibody (60%) • RX; Glucocorticoids may reverse disease • H Pylori does NOT cause parietal cell destruction • ANATOMY: Gastric atrophy --> antrum is spared • Tx: All reversible except neurological changes • Complications : Gastric polyps 2x incidence of cancer

  31. Schilling Test (Cobalamin Deficiency verification) • STAGE 1 • STAGE 2 • Give Radioactive Cobalamin bound to IF by mouth • IM injection of nonradioactive B12 • Measure 24 hour urine • Will still be diminished if • Bacterial Overgrowth Syndrome, Blind Loop, Pancreatic insufficiency, Celiac Sprue

  32. FOLATE v COBALAMIN DEFICIENCY STATES

  33. TREATMENT COBALAMIN DEFICIENCY IM Cbl: 1000 µg (1 mg) every day x week, followed by 1 mg every week x four weeks. If the underlying disorder persists (PA) 1 mg every month for life Oral: 1000 to 2000 mcg/day. May not be effective for PA (malabsorption) Do not use timed release preparations Transfusion- watch for CHF

  34. COBALAMIN DEFICIENCY Laboratory response + Anemia--- reticulocytosis in 3-4 days+ Severe Anemia--- serum iron and LDH levels fall Hypokalemia Hypersegmented neutrophils disappear at 10 to 14 days. Neurologic abnormalities often improve but may not reverse fully

  35. TREATMENT Folate Deficiency • Exclude Cobalamin deficiency !! • A dose of 1 mg/day is usually sufficient, even if malabsorption is present. • Neuro symptoms may be exacerbated with therapy

  36. Case 2 • 70 YO male presents with fatigue, weight loss, palpitations • Unremarkable PMHx, PSHx • WBC 1.9, HGB 8, PLT 79,000, MCV 100, ANC 1.0 • Normal B12/folate and iron levels

  37. Case 2 • What is the next diagnostic test…..

  38. Case 2 • Smear • Bone Marrow Biopsy • Ultrasound to evaluate Liver and Spleen • Hepatitis / Viral panel

  39. Case 2

  40. Case 2

  41. Myelodysplasia • Clonal stem cell disorder resulting in multilineage dysplasia • Can transform to acute leukemia • Under diagnosed disorder • Can be secondary to therapy • Multiple bone marrow biopsies required • Cytogenetic abnormalities

  42. Myelodysplasia • WHO system includes: • Refractory anemia (RA) • Refractory anemia with ringed sideroblasts (RARS) • Refractory cytopenia with multilineage dysplasia (RCMD) • Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) • Refractory anemia with excess blasts I and II • 5q- syndrome • Myelodysplasia unclassifiable (seen in those cases of megakaryocyte dysplasia with fibrosis and others

  43. IPSS SCORE • Unfavorable cytogenetics 1 • Age > 60 years 2 • Hgb <10 (g dl-1) 1 • Plt <50 2 • Plt >50 -250 1 • 1BM blasts >4% 1 • diploid and 5q only were favorable cytogenetic, all others were considered as unfavorable cytogenetics.

  44. Myelodysplasia • IPSS Score • Low risk0 • Intermediate risk 1 0.5 – 1 • Intermediate risk 2 1.5 – 2 • High risk  >2.5

  45. Myelodysplasia • Low Risk MDS -Neutropenia or thrombocytopenia -symptomatic anemia is usually the initial problem - Erythropoietin: highest response rate seen in patients with lower endogenous erythropoietin levels (< 500 IU) and lower transfusion requirements. -low-dose granulocyte colony-stimulating factor (G-CSF) -Erythropoietin resistance -Red blood cell transfusions

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