Anemias

Sample CaseA 25 year old female sought consult due to fatigue which was noted 3 months ago. Patient is not taking any medications. She occasionally consumes a pack of smokes and is an avid alcohol consumer. No history illicit drug use. Menses were noted to be heavier than normal over the past few months. She eats a well balanced diet. She used to go to the gym 5 times per week but is now unable to do so because she feels she cannot keep up. Her vitals signs included a heart rate of 88/min, respiratory rate of 20/min, and blood pressure of 130/80 mmHg. Examination was generally unremarkable except for the finding of pallor on the palpebral conjunctivae.

Major Classifications1. Hypoproliferative Anemia2. Anemia Due to Ineffective Erythropoeisis3. Hemolytic Anemia

Approach to the Patient with AnemiaHistory Nutritional history Alcohol intake Family history Exposure to drugs or toxic agentsPhysical Examination Strong peripheral pulses Systolic murmur Pale skin and mucous membranes Hemoglobin < 8-10 g/dl

Reticulocyte Count and Index

ARC = retic count x 1000 x ( hgb of patient / expected hgb for weight and age ) Choose maturation time Compute for RI RI = ARC / MT

Sample Case

Patient T.P, 30/F, presents with pallor, HGB 91, HCT 25%, retic count 0.015ARC = 0.015 x 1000 x (91/120) = 11.375MT = 2.0RI = 11.375/2.0 = 5.7

Iron Deficiency and Other Hypoproliferative Anemias The most common anemia; anemia associated with chronic inflammation is the most common of these Associated with normocytic and normochromic red cells and an inappropriately low reticulocyte response (reticulocyte index Supply (blood loss, pregnancy, rapid growth spurts, low dietary iron) Red cell morphology and indices are normalIron-Deficient Erythropoiesis Transferrin saturation falls to 15-20% impaired Hb synthesis First appearance of microcytic cellsIron-Deficiency Anemia Decreased hemoglobin and hematocrit Transferrin saturation is 10-15%

Moderate anemia ( Hb 10-13 g/dl ) Hypoproliferative marrowSevere anemia ( Hb 7-8 g/dl ) Hyperplastic marrow ( appearance of target cells, poikilocytes )

Clinical Presentation Signs depend of chronicity and severity of the anemia Fatigue, pallor, reduced exercise capacity Cheilosis and koilonychia are signs of advanced tissue iron deficiency Diagnosis is based on laboratory results Decreased serum iron < 30 g/dl ( 50-150 g/dl ) Increased TIBC > 360 g/dl ( 300-360 g/dl) Transferrin Saturation < 20 % ( 25-50% ) SI X 100 / TIBC Serum ferritin < 15 g/dl ( 100 g/dl for males ; 30 g/dl for females )

Treatment Severity and causes determines appropriate approach CV instability Transfusions Young, stable Fe replacement Oral iron therapy usually suffices in the absence of unusual blood loss or malabsorption Red cell transfusion CV instability, continued and excessive blood loss Acutely corrects anemia and provides a source for iron utilization Hemoglobin < 11 g/dl 8 g/dl Oral Iron Therapy Fe Sulfate 325 mg in 3-4 divided doses daily Provides 65 mg elemental iron per tablet Best absorbed with an empty stomach Ascorbic acid enhances absorption GI upset (15-20%) Pain, nausea, vomiting, constipation may lead to non-compliance

Parenteral Iron Indications: Intolerance to oral iron Refractory response to oral iron Gastrointestinal disease Rapid continued blood loss Body weight (kg) 2.3 (15patients hemoglobin, g/dL) +500 or 1000 mg (for stores) Anaphylaxis is a concern Chest pain, wheezing, hypotension Stop transfusion*May have arthralgias, skin rashes, and low-grade fever may appear several days after iron infusion

Other Hypoproliferative Anemias Anemia of Inflammation Often encountered in the clinical setting Low SI, hypoproliferative marrow, normal-increased ferritin Interleukin 1, TNF decreases EPO production in response to anemia Hepcidin suppress iron absorption and iron release from storage sites Anemia of CKD Anemia in Hypometabolic States EPO sensitive to need for O2 not just O2 levels ( decreased metabolic activity decreased O2 demand decreased EPO production )

Megaloblastic Anemia Characterized by presence of distinctive morphologic appearance of the developing red cells in the bone marrow Macro-ovalocytes and hypersegmented neutrophils Due to deficiency in Vitamin B12 or folic acid

Cobalamin (Vitamin B12) Deficiency Cofactor for methianonine synthetase in the conversion of homocysteine to methionine (methylcobalamine) Conversion of methylmalonylcoenzyme A (CoA) to succinyl-CoA (adenosylcobalamin) Both enzymatic steps are critical for annealing Okazaki fragments during DNA synthesis, particularly in erythroid progenitor cells Present in foods of animal origin Dietary deficiency is extremely rare and is seen only in strict vegans Daily requirements are 1-3 g

Pteroylmonoglutamic Acid (Folic Acid) Deficiency Act as coenzymes involved in purine and pyramidine synthesis necessary for DNA and RNA replication Coenzyme for methionine synthesis Present in most fruits and vegetables Especially citrus fruits and green leafy vegetables Daily adult requirements are ~ 100 g

Clinical Features Elevated MCV on routine CBC ( >100 fL ) Hypersegmentation of neutrophils Marked anorexia, weight loss, diarrhea, or constipation Glossitis, angular cheilosis, mild fever, jaundice, reversible skin hyperpigmentation Neurologic manifestations (Cobalamin deficiency) Bilateral peripheral neuropathy or degeneration peripheral nerves affected first paresthesias Involvement of the posterior column of the spinal cord difficulty with balance or proprioception Causes of Cobalamin Deficiency Inadequate dietary intake Pernicious anemia Total or partial gastrectomy Intestinal causes (Intestinal stagnant loop syndrome, ileal resection, tropical sprue, fish tapeworm)

Diagnosis COBALAMIN Serum cobalamin < 170 pg/ml ( >210 pg/ml ) Confirmed by elevated serum methylmalonic acid (MMA) (>1000 nmol/L) LDH and indirect bilirubin may be elevated FOLIC ACID RBC Folic Acid level < 150 ng/ml RBC is preferred over serum because the former reflects body stores over the life span of the RBC, while the latter reflects immediate labile serum levels rather than body stores

Treatment Cobalamin Deficiency Lifelong cobalamin injections Replenishment of body stores with 1000 g IM injections given at 3-7 days intervals ( more frequent doses if with neuropathy ) For maintainance: 1000 g hydroxocobalamin IM once every 3 months is satisfactory Oral or SL cobalamin (1 mg/day) may be used instead of parenteral therapy once correction of the deficiency has occurred CNS symptoms reversible if they are of relatively short duration (