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An Approach to Anemia (MED 341)

An Approach to Anemia (MED 341). Abdul-Kareem Al- Momen , MD,FRCPC College of Medicine, KSU 1430-1431 H(2009-2010) . Definition:. Anemia is defined as a reduction in one or more of the major RBC measurements:

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An Approach to Anemia (MED 341)

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  1. An Approach to Anemia(MED 341) • Abdul-Kareem • Al-Momen, MD,FRCPC • College of Medicine, KSU 1430-1431 H(2009-2010)

  2. Definition: Anemia is defined as a reduction in one or more of the major RBC measurements: hemoglobin concentration, hematocrit, or RBC count to a degree lower than normal values for the tested population :newborn, childhood, adulthood (males & females), and sea level

  3. Anemia? Production? Destruction? The key test is the …..

  4. The reticulocyte count • Increased reticulocytes (greater than 2-3% or 100,000/mm3 total) are seen in blood loss and hemolytic processes.

  5. The reticulocyte count • To be useful the reticulocyte count must be adjusted for the patient's hematocrit, because when hematocrit is low, reticulocytes are released earlier (faster) from the marrow so one can adjust for this phenomenon as follows: • Corrected retic. = Patients retic. x (Patients Hct/45) Example: Hb 70 g/L, PCV (Hct) = 20, Retics.= 16 % Corrected Retics.= 16 X 20/45 = 7

  6. The reticulocyte count • Reticulocyte Production index (RPI) = corrected retic. count/Maturation time (Maturation time = 1 for Hct=45%, 1.5 for 35%, 2 for 25%, and 2.5 for 15%.) Example: PCV = 20 %, Retics.= 16, Corrected Retics=7 RPI = 7/2 = 3.5 • Absolute reticulocyte count = retic x RBC number.

  7. Causes of Anemia (kinetic approach) Decreased erythrocyte production Bone marrow suppression Bone marrow infiltration Nutritional deficiencies Decreased erythropoietin production Inadequate marrow response to erythropoietin

  8. Causes of Anemia • Erythrocyte loss • Hemorrhage : • Bleeding tendencies, • Menorrhagea, • Anticoagulation • Liver disease • Hemolysis: • Autoimmune, • None-immune, (MAHA, • RBC defects, Hypersplenism)

  9. Dilutional Anemia • Dilutional- A patient's plasma volume increases with pregnancy, laying down possibly responsible for as much as a 3-6% drop in the hematocrit in the first two days of hospitalization.

  10. Morphological Approach (big versus small) • First, measure the size of the RBCs: •    MCV  (femtoliters) = 10 x HCT(percent) ÷ RBC (millions/µL)

  11. High MCV MCV>115 • B12, Folate • Drugs that impair DNA synthesis (AZT, chemo., azathioprine) • MDS

  12. Normal MCV Normocytic normocytic • Anemia of chronic disease • Mixed deficiencies • Renal failure • Endocrinopaties

  13. Low MCV Microcytic • Iron deficiency • Thalassemia trait • Anemia of chronic disease (30-40%) • Sideroblastic anemias • Lead poisoning

  14. Iron deficiency anemia • Iron deficiency is a common form of malnutrition that affects more than 2 billion people globally.

  15. Iron Deficiency Anemia • Smear: • hypochromic and microcytic (low MCV) RBCs, usually not seen unless Hct  30% • platelet count is often elevated •  Ferritin: a measure of total body iron stores, but also an acute phase reactant • <15g/l = Fe deficiency, 150 g/l = Not Fe deficiency15-150 g/l = ?

  16. Iron Deficiency Anemia • Low Iron Saturation (Fe/TIBC ratio) •  Fe (not reliable) •  TIBC • Fe/TIBC (% saturation) 15% • BM bx: absent Fe stores • Gold standard • Therapeutic Trial of Oral Iron

  17. Iron Compartments in a 70 kg person

  18. Increased iron requirements • Blood loss • Gastrointestinal disorders (esophageal varices, hemorrhoids) • Extensive and prolonged menstruation • Pulmonary (hemoptysis, pulmonary hemosiderosis), urologic, or nasal disorders • Dialysis • Hookworm infestation • Intravascular hemolysis with hemoglobinuria • Paroxysmal nocturnal hemoglobinuria • Cardiac valve prostheses • Rapid growth in body size between 2 and 36 months of age • Pregnancy and lactation

  19. Inadequate iron supply • Poor nutritional intake in children (not a common independent mechanism in adults but often a contributing factor) • Malabsorption • Gastric bypass surgery for ulcers or obesity • Achlorhydria from gastritis or drug therapy • Severe malabsorption (for example, celiac disease [nontropical sprue]) • Abnormal transferrin function • Congenital atransferrinemia • Autoantibodies to transferrin receptors

  20. Oral iron failure? • Incorrect diagnosis (eg, thalassemia) • anemia of chronic disease? • Patient is not taking the medication • Not absorbed (enteric coated?) • Rapid iron loss?

  21. Intravenous Iron Therapy • Iron sacharate (Ferrosac), 200 mg in 100-250 cc normal saline IV over one hour daily to the total dose required • (Weight {kg} x Hb deficit {target Hb-current Hb] x 4). • Ferric gluconate (Ferrlecit ) in patients on renal dialysis. The number of allergic reactions is lower than that from iron dextran

  22. Differentiation of anemia of chronic disease and iron deficiency anemia by laboratory measures

  23. Utility of supraphysiologic doses of erythropoietin in the setting of inflammatory block.

  24. B12/Folate Deficiency • Etiology: • Anemia-- Vitamin B12 and folate are needed for DNA synthesis deoxyuridate to thymidylate , including RBC precursors • Deficiency • B12 - Dietary intake, acid-pepsin in the stomach, pancreatic proteases, gastric secretion of intrinsic factor, an ileum with Cbl-IF receptors (fish tapeworm) • Folate-- Poor dietary intake  EtOH, malabsorption, increased demand (pregnancy, hemolytic anemias), inhibitors of DHFR

  25. B12/Folate Deficiency (2) • Dx: • Smear: Macrocytic (High MCV) RBCs, +/- hypersegmented neutrophils, +/- modest neutropenia, but… • the diagnosis of B12 def. was made in patients in whom only 29 percent had anemia, and only 36 percent had a MCV greater than 100 fL (Pruthi RK, Tefferi A, Mayo Clin Proc 1994 Feb;69(2):144-50) • B12 • Low serum B12, elevated serum methylmalonic acid levels • Anti-IF Abs, Schilling test (?), PA accounts for 75% • Folate • Serum folate level-- can normalize with a single good meal

  26. B12/Folate Deficiency (3) • Tx: • B12 deficiency: B12 1 mg/month IM, or 1-2 mg/day po • Folate deficiency: Improved diet, folate 1 mg/day • Monitor for a response to therapy. • Pernicious Anemia – monitor for gi cancers.

  27. Cobalamin deficiency and neurological problems • Subacute combined degeneration of the dorsal and lateral spinal columns. • Well known study of B12 deficiency in the nursing home population (Carmel R Karnaze DS, JAMA 253:1284, 1985) • Vitamin B-12 deficiency is present in up to 15% of the elderly population as documented by elevated methylmalonic acid in combination with low or low-normal vitamin B-12 concentrations. • Is oral B12 good enough? • Association between nitrous oxide anesthesia and development of neurological symptoms responsive to B12 in patients with subclinical cobalamin deficiency (methionine?).

  28. Diagnostic tests for Vit. B12 Deficiency

  29. Sideroblastic Anemias • Heterogenous grouping of anemias defined by presence of ringed sideroblasts in the BM • Etiologies: • Hereditary (rare), type of porphyria • Myelodysplasia • EtOH • Drugs (INH, Chloramphenicol) • Tx: • Trial of pyridoxine for hereditary or INH induced SA

  30. Hemolytic Anemias Hemolytic anemias are either acquired or congenital. The laboratory signs of hemolytic anemias include: 1. Increased LDH (LDH1) - sensitive but not specific. 2. Increased indirect bilirubin - sensitive but not specific*. 3. Increased reticulocyte count - specific but not sensitive 4. Decreased haptoglobin - specific but not sensitive. 5. Urine hemosiderin - specific but not sensitive. *The indirect bilirubin is proportional to the hematocrit, so with a hematocrit of 45% the upper limit of normal is 1.00 mg/dl and with a hematocrit of 22.5% the upper limit of normal for the indirect bilirubin is 0.5mg/dl. Since tests for hemolysis suffer from a lack of sensitivity and specificity, one needs a high index of suspicion for this type of anemia.

  31. Hereditary anemias • 1- RBC memberane defects :e.g.Heriditary Spherocytosis • 2-Reduced Globin Chains:e.g. α thalassemia ( reduced α chain ) ,& β thalassemia ( reduced β chain) • 3-Abnormal amino-acid sequence e.g. Sickle Cell Anemia • 3-Enzymopathies :e.g G6PD deficiency

  32. Hemoglobinopathies • Sickle cell disease/anemia • Thalassemias

  33. The hemoglobin electrophoresis reveals HbA2 is 1%, HbF is 0.5%, and HbH is 16%.

  34. Sickle Cell Anemia / Disease • Hb SS due to replacement of glutamic acid by valine at position 6 on the β globin chain • HbS molecule are less soluble ,tend to form crystals and fibers,which leads to RBC deformity ,sickling ,vaso-occlusion & hemolysis

  35. Complications of Sickle Cell Disease • 1- Vaso-occlusion ,with recurrent painful episodes (mild-moderate-severe ) • Acute chest syndrome • Recurrent infection (URT & chest ) • Splenic sequestration • Priapism • Thrombo-embolic disease (CVA,PE,DVT)

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