Anemia by f2gfdPJ4


         Jenny Wright, MD
Acting Instructor, Dept of Medicine
          Lecture Outline
 Casebased presentation highlighting
 common causes of anemia, including
 evaluation and treatment
                 Case 1
 26 year old female presents to clinic for
  evaluation after attempting to donate blood
  and being was told that she was anemic.
  What labs would you order at this visit?
 A) Hematocrit
 B) CBC, iron, TIBC, and ferritin
 C) CBC, reticulocyte count
 D) CBC, reticulocyte count, peripheral
  blood smear, iron, TIBC and ferritin
 Definition: Low oxygen carrying capacity in the
  blood due to low erythrocyte mass.
 We use the hematocrit or hemoglobin as
  surrogate markers for the erythrocyte mass
  because that it too difficult to measure.
 Hemoglobin of < 12 g/dL in women or a
  Hemoglobin of <13 g/dL in men is considered
  abnormal (WHO criteria).
 The hematocrit is approximately 3 x the
          Overview of Causes
 Bloodloss
 Decreased production of RBCs:
     decreased erythropoetin (epo)
     Normal production of epo but decreased
      ability to respond to epo
 Destruction   of RBCs:
     intravascular
     extravascular
 History:  Patient reported symptoms will
  vary greatly based on the rapidity of the
  change in Hct, medical co-morbidities and
  the cause of the anemia.
 Physical exam findings: conjunctival rim
  pallor is the physical exam finding with the
  highest positive likelihood ratio (16.7)
Conjunctival rim pallor
    Initial laboratory evaluation
 Reticulocyte count: this may be reported as the
  absolute count (determined by flow cytometry) or
  the reticulocyte count as a percentage of the
  total erythrocytes – in this case you want to
  calculate the reticulocyte index
  (RI=reticulocyte% x pt’s Hct/45 x 0.5).
 If low (RI<2), bone marrow hypoproliferation:
  production problems
 If normal (RI>2), bone marrow
  hyperproliferation: hemolytic anemia, acute
  blood loss
   Initial laboratory evaluation
 Peripheral blood smear:
 Offers important additional information
  regarding the morphology of the cells that
  cannot be obtained from other laboratory
 Examples include differentiation between
  types of hemolytic anemia, different types
  of macrocytic anemias.
Example normal smear

   From UpToDate,;jsessionid=B
        Red blood cell indices
 Microcytic (MCV<81): iron deficiency,
  thalassemia, sideroblastic anemia, anemia of
  chronic disease
 Normocytic (MCV 81-98): anemia of chronic
  disease, aplastic anemia, bone marrow
  infiltration, kidney disease, acute blood loss
 Macrocytic (MCV >98): alcohol, B12 deficiency,
  folate deficiency, myelodysplasia, drug toxicity,
  reticulocytosis, liver disease
     Our patient’s smear

26 year old female presenting for evaluation after
attempting to donate blood and being was told that she
was anemic.
             Case 1, cont.
 Her  labs reveal: low reticulocyte count, Hct
  33%, MCV 74, iron 35 (low), TIBC 540
  (high), ferritin 14 (low). What do you do
 A) treat with oral iron
 B) order a colonoscopy
 C) order a transfusion
 D) start oral contraceptive pills
    Dx of Fe deficiency anemia
 Ferritin can be the most useful single test,
  though due to the fact that this is an acute phase
  reactant, only in patients without
 All pt’s with ferritin <15 are iron deficient (highly
  specific but not sensitive), values >100
  essentially rule out iron deficiency.
 Other characteristic iron study results are:
  elevated TIBC, low transferrin saturation and low
  serum iron level
          Fe Def. Smear
Progression of
(increased RDW)
              Fe Def Anemia
   In severe cases may
    have additional
    physical exam
    Management of Fe deficiency
   Evaluate for cause:
       In post-menopausal females and males you have to
        evaluate for GI blood loss.
       In menstruating females, menses is a common cause;
        the most common cause of anemia overall in females.
   Treat: Iron replacement can typically be given
    orally, ferrous sulfate or gluconate 325 mg, 1-3
    times a day.
       Ideally pts are treated with TID medication though this
        is rarely tolerated
       Sulfate salt is cheaper but generally less well
              Case 1, cont.
 Three  months later pt returns, still being
  told she can’t give blood! Her Hct is 34%
  and ferritin 15. What do you do now?
 A) review how she’s taking her
 B) transfusion
 C) give it more time
 D) start vitamin C
                       Iron therapy
   Side effects of oral iron replacement lead to low
       Constipation, stomach upset
       May have less symptoms if they take it with food (though this
        decreases absorption)
   Consider other causes of poor absorption: celiac sprue,
    IBD, taking with an antacid, PPI, calcium.
   If not a compliance issue consider w/u for celiac disease
   Vitamin C enhances absorption
   Expect Hct to improve within a few weeks of therapy
    though pts should continue treatment for 6 mo -1 yr,
    would like to see ferritin level normalized
                Case 2
A  52 year-old woman with lupus is
 admitted to the hospital for pneumonitis.
 During her evaluation she is found to have
 a Hct of 30 and MCV of 80. What is the
 differential diagnosis of her anemia?
          Case 2, continued
 What   additional labs would you order to
  work up her anemia?
 A. reticulocyte count, iron, vitamin B12,
  and folate
 B. reticulocyte count, epo level
 C. reticulocyte count, smear, ferritin, iron
  and TIBC
 D. reticulocyte count, smear and ferritin
      Anemia of Chronic Disease
   Lab findings:
    Hypoproliferative anemia (low reticulocyte count)
    Typically a normocytic anemia, though 25% of cases are
    Classically labs will reveal an normal - elevated ferritin,
    and low serum iron and TIBC.
    Bone marrow stores of iron are normal (though testing
    for this is not indicated)
   Etiology: multiple contributing factors including
    decreased transfer of iron to red blood cells, decreased
    response to Epo, decreased Epo release
   Treatment: Treat underlying cause
ACD +/- Fe def.
ACD +/- Fe def.
       over half
 You’re
 way there!
     Fe def is most
      common anemia in
     Anemia of chronic
      disease is the most
      common anemia in
                         Case 3
   48 year old female is admitted to the hospital for severe
    alcohol withdrawal. She is experiencing alcoholic
    hallucinosis and you are unable to obtain a reliable
    history. Admission labs are remarkable for: Hct 34%,
    MCV 105, RI <2 . Her PMHx is remarkable for
    rheumatoid arthritis.
             Case 3, cont.
 The  most likely diagnosis is:
 A. chronic GI blood loss due to gastritis
 B. dietary B12 deficiency
 C. folate deficiency
 D. anemia of chronic disease
           Macrocytic anemia
 Other   causes include:
     Alcohol
     Drug toxicity: zidovudine (AZT), hydroxyurea
     Hypothyroidism
     Liver disease
     Myelodysplasia
 Besure to assess reticulocyte count to
 eval for stress erythropoiesis
    Megaloblastic macrocytosis
 The smear in a patient with macrocytic anemia is
  helpful in identification of megaloblastic changes
  – macro-ovalocytes and hypersegmented
  neutrophils (>5 lobes)
 Etiologies include: B12 deficiency, folate
  deficiency, drugs that cause abnl DNA synthesis
  or folate metabolism, and myelodysplastic
 Non-megaloblastic macrocytosis is typical of
  liver disease and hyposplenism, on smear
  patients may have large target cells,
  acanthocytes, and Howell-Jolly bodies.
Megaloblastic Macrocytic Anemia
Non-megaloblastic macrocytosis
                 Folate deficiency
 Found in: Fruits (e.g. citrus, melon, bananas),
  leafy green vegetables, and fortified grain
 Causes include:
       alcohol due to both a decreased ability to absorb
        folate and, frequently, decreased intake of folate rich
       Malabsorption (celiac disease, IBD)
       Diseases/conditions associated with rapid cell
        turnover such as sickle cell disease, psoriasis,
       Medications: trimethoprim, phenytoin, methotrexate
       Vitamin B12 deficiency
 The body stores large amounts of B12 therefore
  decreased dietary intake rarely lead to
  deficiency, typically due to decreased absorption
  due to pernicious anemia and intrinsic factor
  deficiency, atrophic gastritis or IBD.
 Medications to decrease stomach acid can also
  contribute to B12 deficiency (PPIs, antacids)
 In addition to causing anemia, B12 deficiency
  can lead to a metabolic peripheral neuropathy
  and neuropsychiatric disease (not the case for
  folate deficiency)
             Case 3, cont.
 Labs  reveal a low folate level and a normal
  B12 level (450). You initiate folic acid
  supplementation with 1 mg po q day.
 As was done here, you always want to
  assure that pts don’t also have B12
  deficiency prior to treating for folate
  deficiency, you may be able to improve a
  patients anemia but the neurologic
  symptoms will progress
                 Vitamin B12
 Iflevels are at the lower limits of normal
  (200-300), then consider checking
  methylmalonic acid and homocysteine
  levels, these will be elevated in the case of
  B12 deficiency
 Should be given orally, IM in rare
      Oral dosing is 1000 – 2000 mcg po q day
      IM dosing is 1000 mcg IM q day x 7 days,
       then q wk x 4 wks then q month
                     Case 4
   A 28 year African American old female presents
    to clinic with fatigue. She has a history of
    cellulitis and just finishing a 14 day course of
    therapy with Bactrim. TSH is normal, Hct is 25%,
    MCV 98. What do you think is the most likely
    cause of her anemia?
   A. hemolysis
   B. iron deficiency
   C. folate deficiency
   D. anemia of chronic disease
            Hemolytic anemia
     to order: reticulotye count, peripheral
 Labs
 smear, haptoglobin, indirect bilirubin and
     The peripheral smear will help you
      differentiate between causes of hemolysis
Extravascular Hemolytic Anemia
   Etiologies of extravascular hemolysis include:
       Congenital hemoglobin abnormalities:
       Erythrocyte membrane abnormalities: hereditary
       Erythrocyte metabolic abnormalities: G6PD deficiency
       Auto-immune process: idiopathic, underlying
        malignancy, CVD, lymphoproliferative disorders,
        medications (PCN, cephalosporins, NSIADs)
Extravascular Hemolysis
What’s going on here?;jsessionid=49B7B6DD5EECE1FD7800F
      Glucose 6-phospate
    dehydrogenase deficiency
 X-linked enzyme deficiency that results in
  decreased glutathione levels
 Most common form results in severe
  hemolysis with medications (primaquine,
  sulfa, dapsone), fava beans and some
 Dx: enzyme activity testing, may have
  false negative test in the setting of acute
  hemolysis, re-test at 2-3 months
Intravascular hemolytic anemia
 Etiologies   include:
     Microangiopathic hemolytic anemia – TTP,
     Shearing due to malfunctioning mechanical
      heart valves
Intravascular Hemolysis
           Case 4, cont.
 She has labs consistent with hemolytic
 anemia, and the following smear. What do
 you think is going on and what test can
 you send to confirm this?

                           From UpToDate,
            Case 4, cont.
 You send a direct antiglobulin test
 (Coombs test) and it is positive, confirming
 the diagnosis of auto-immune hemolytic
 anemia. She is treated with steroids and
 does well.
 When    to transfuse?
    General rule: Hct <21%, consider at <25% in
     pt’s with multiple medical problems
    Other times to consider: on-going rapid blood
     loss, highly symptomatic patients, patient with
     low Hct and severe cardiovascular disease
    You expect the Hct to increase 3% for each
     unit of blood transfused
                     Case 5
   63 year old female with DM and CKD presents
    for evaluation of fatigue. Labs reveal Hct 31%,
    MCV 87, iron 43 (40-155), TIBC 241 (270-535),
    ferritin 95 (10-180), transferrin sat. 18% (10-
    45%). How can you treat her anemia?
   Transfusion
   Epo
   Epo and iron
   Iron replacement
Anemia of Chronic Kidney Disease

             Burr cells
Anemia of Chronic Kidney Disease
 Hypoproliferative (low reticulocyte count),
  normocytic anemia
 For erythropoietin therapy to be effective
  need adequate iron stores – ferritin >100
  and transferrin saturation >20%
 Treatment goal is hemoglobin of 11-12
  (Hct 33-36%), higher levels are associated
  with increased morbidity and mortality –
  carries a Black Box warning
 Can use darbopoetin or epoetin
                 Case 6
A 27 yr old man of SE Asian descent comes
  in for a routine exam required for
  employment. He is in good health, without
  weight loss, fatigue or bleeding sx. FH
  negative for anemia. Exam is
  unremarkable and pt has no HSM. Neg
  stool guaiac.

WBC 5.3, HCT 35%, MCV 65, plts 330K,
Retic index 0.8.
              Case 6, cont.
 What   is the best test to confirm the most
  likely cause of this patient’s anemia?
 Obtain CBC on siblings
 Perform ultrasound for spleen size
 Measure serum ferritin and iron studies
 Check glucose-6-phosphate
            dehydrogenase screen
 Perform hemoglobin electrophoresis
   Thalassemia trait: mild anemia with pronounced
    microcytosis (MCV <70)
      Ethnicity: Mediterranean, Asian, African

      Pt are asymptomatic

      FamHx is often negative

      Dx thal trait: Hemoglobin electrophoresis

   Thalassemia intermedia:
         • Ineffective erythropoiesis, more severe anemia,
           often require frequent transfusions, at risk of
           development of iron overload
   Iron deficiency anemia: usually more pronounced
    microcytic anemia than thal trait

Microcytic, hypochromic RBC, target and
teardrop cells
            Anemia Summary
 Evaluation:
     CBC – eval. RBC data alongside WBC and Plt
      counts, RBC indices
     Reticulocyte count – if bone marrow is
      responding appropriately
     Smear – morphologic clues to etiology
             Anemia Summary
 Most    common etiologies:
     Females – Iron deficiency
     Men – Anemia of chronic disease
     Hx and labs, possibly including soluble
      transferrin receptor will help you differentiate
            Anemia by size
 Microcytic:iron def., thalassemia trait,
  thalassemia intermedia
 Normocytic: anemia of chronic disease
  (25% microcytic), chronic renal failure,
  hemolytic anemia, acute blood loss
 Macrocytic anemia: Folate def., B12 def.

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