Approach to anemia

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Approach to anemia

• Abdul-Kareem Al-Momen, MD, FRCPC
• KSU-MED 341
• 17-04-2011 (13-05-1432)

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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
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Newborn Chld. Adult Male Female Sea Level Jeddah Hi.Alt.Albaha Hb (gm/L) 200 /- 20 110 /- 10 160 /- 20 14 /- 20 150 g/L 190 G/l PCV (Hct) 60 /- 20 33 /- 3 48 /- 5 42 /- 5 47 58
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Anemia?
Production?
Destruction?
The key test is the reticulocytic count
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The reticulocyte count

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

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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
  

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The reticulocyte count

• Reticulocyte Production index (RPI) corrected
  retic. count/Maturation time
• (Maturation time 1 for Hct45, 1.5 for
  35, 2 for 25, and 2.5 for 15.)
• Example PCV 20 , Retics. 16, Corrected
  Retics7
• RPI 7/2 3.5
• Absolute reticulocyte count retic x RBC number.

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Causes of Anemia (kinetic approach) Decreased
erythrocyte production Bone marrow suppression
Bone marrow infiltration Nutritional
deficiencies Decreased erythropoietin production
Inadequate marrow response to erythropoietin
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• Causes of Anemia
• Blood loss
• Hemorrhage
• Bleeding tendencies,
• Menorrhagea,
• Anticoagulation
• Liver disease
• Hemolysis
• Autoimmune,
• None-immune, (MAHA,
• RBC defects, Hypersplenism)

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Dilutional Anemia

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

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Morphological Approach (big versus small)

• First, measure the size of the RBCs
•    MCV  (femtoliters) 10 x HCT(percent) RBC
  (millions/µL)

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High MCV

• MCVgt115
• B12, Folate
• Drugs that impair DNA synthesis (AZT, chemo.,
  azathioprine)
• MDS

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Normal MCV

• Normocytic normocytic
• Anemia of chronic disease
• Mixed deficiencies
• Renal failure
• Endocrinopaties

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Low MCV

• Microcytic
• Iron deficiency
• Thalassemia trait
• Anemia of chronic disease (30-40)
• Sideroblastic anemias
• Lead poisoning

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Iron deficiency anemia

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

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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
• lt15?g/l Fe deficiency, ?150 ?g/l Not Fe
  deficiency 15-150 ?g/l ?

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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

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• 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

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• 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

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Oral iron failure?

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

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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

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

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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 Feb69(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

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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.

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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
  2531284, 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?).

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Diagnostic tests for Vit. B12 Deficiency
Test
Serum methylmalonic acid and serum homocysteine
MCVgt115, smear, CBC
Antibodies to IF and Parietal cells
Schilling test
Spot urine for homocysteine
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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

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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.
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Hereditary anemias

• 1- RBC memberane defects e.g.Heriditary
  Spherocytosis
• 2-Reduced Globin Chainse.g. a
  thalassemia ( reduced a chain ) , ß
  thalassemia ( reduced ß chain)
• 3-Abnormal amino-acid sequence e.g. Sickle Cell
  Anemia
• 3-Enzymopathies e.g G6PD deficiency

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Hemoglobinopathies

• Sickle cell disease/anemia
• Thalassemias

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Sickle Cell Anemia / Disease

• Hb SS due to replacement of glutamic acid by
  valine at position 6 on the ß globin chain
• HbS molecule are less soluble ,tend to form
  crystals and fibers,which leads to RBC deformity
  ,sickling ,vaso-occlusion hemolysis

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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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SCD Complication (cont.)

• Avascular necrosis (head of femur humerus)
• Tendency for Osteo-myelitis ( salmonella)
• Leg ulcers
• Gall stones

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Presipitators of Vaso-Occlusive Episodes

• 1-Hypoxia - low atmospheric oxygen , Lung
  diseases ,heart diseases
• 2-Increased blood viscosity increased Hb/Hct
  ,dehydration, infection ,general anesthesia
• 3-Extreme hot/cold weather
• 4-Unknown causes

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Management of SCD

• Vaccination
• Antibiotic prophylaxis
• Avoidance of hypoxia and extreme weathers
• Increase fluid intake
• Treatment of acute episodes
• Exchange transfusion /transfusion
• Prevention premarital screening genetic
  counseling

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ß Thalassemia

• 2 ß genes on chromosome 11 give 2 ß globin
  chains.
• ßß normal
• -ß ß thalassemia trait (hypochromic ,
  microcytic anemia, asymptomatic , confused with
  iron deficiency anemia )

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Thalassemia Major (Homozygous ß Thalassemia )

• No ß chains
• Severe intramedullary hemolysis
• Severe hemolytic anemia
• Jaundice Pallor
• Bone marrow expansion
• Hepatosplenomegaly
• Delayed puperty
• Iron overload ( absorption hemolysis )

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H. Spherocytosis

• RBC Spheres (not biconcave )_
• Reduced survival (hemolytic anemia )
• Jaundice,
• Splenomegaly
• Gall stones
• Reticulocytosis
• Increased direct billirubin

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Treatment

• 1-Folic acid
• 2-Splenectomy after vaccination against
  S.Pneomoniae H.Influenzae?
• Malaria avoidance / prophylaxis

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Enzymopathies G6PD Deficiency

• G6PD is essential for the production of the
  anti-oxidant Glutathione
• Acute hemolysis upon exposure to oxidative stress
  food (fava beans),drugs (e.g.sulfa derivatives
  ),chemicals or infection
• X- linked

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Approach to anemia

• History Onset (acute versus chronic),Age at
  onset, character, associations (splenomegally,
  growth retardation, painful episodes,
  transfusions, dietary habits, family history,
  consanguinity, involvement of other systems, drug
  history ASA, anticoagulantsetc )
• Symptoms (fatigue, exercise intolerance,
  headache, palpitation, lack of concentration,
  poor appetite,
• Adaptation

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Approach to anemia

• Signs (physical exam)
  Pallor, dry skin, smooth tongue, thin
  hair, hair loss, splenomegally, neuropathy,
• Signs of systemic diseases ( renal, hepatic,
  musculoskeletal, cancer, infection, etc )

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Approach to anemia

• Laboratory RBC, Hb, Hct (PCV), MCV, MCH, MCHC,
  RDW, Reticulocytes, WBC, Platelets, blood filnm (
  smear)
• Fe, Transferrin, ferritin, B12, folates (RBC)
• ESR, ANA, RF, BUN, Cr,
• Hb electrophoresis (Hb A, A2, S, F, )

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• Good Luck