Anemia Goals Definition of anemia - PowerPoint Presentation

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Anemia

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Goals

Definition of anemia

.Epidemiology.Classification. Review the terminology used to discuss anemia.Evaluation:.

• Address clues in the history and exam that can direct the evaluation. • Describe one approach to using lab tests to make the diagnosis. Review some anemia& aspects of treatment of common anemia.

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Definitions

A.

Anemia refers to a reduction in the number or volume of RBCs to less than a normal level. May occur due to: Acute/chronic blood loss Decreased production Breakdown of blood (hemolysis)

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B

.

Strictly defined by decreased Hgb relating to a value 2SD below a mean .

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AGE

Hgb

Mean/ (-2SD)

HCT%

Mean/ (-2SD)

MCV

Mean/ (-2SD)

Newborn

16.5 (13.5)

51 (42)

108 (96)

1 Month13.9 (10.7)44 (33)101 (91) 2 Months11.2 (9.4) 35 (28)95 (84) 6 Months12.6 (11.0)36 (31)76 (68) > 6 Months12.5 (11.0)36 (33) 81 (70+ age per yr)AdultMaleFemale15.5 (13.5)14.0 (12.0)47 (40)41 (36)90 (80) 90 (80)

1. Normal values vary according to age and gender (and lab)

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2 . Specific lab values must be interpreted in context of :

patient and illness;

ie, are Hgb levels of 14.0 in a male smoker, or of 12.5 in a severely volume contracted woman, “normal?”

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C.

The clinical context and condition of the patient

determine how urgently Dx and Rx must occur.

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EPIDEMIOLOGY

Anemia affects more than 2 billion people worldwide – one-third of the world's population.

Half of these are iron deficiency anemia.

Anemia is common in menstruating women,infant, children and elderly patients.In almost all developing countries, at least 1/3 of the Women and children are anemic.Prevalence among pregnant women and children under 2 years of age is more than 50 %.

Anemia contributes to 20% of all maternal deaths.

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Indices

1. Hgb – most reliable value 2. Hct – reliable if spun; if automated it is an approximation. 3. MCV (mean corpuscular volume) – is a useful index for distinguishing anemias (if homogenous RBC population).

• Normal MCV 82-97 fL • Macrocytosis > 97 fL • Microcytosis < 82 fL

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Mentzer

index = MCV/RBC

Ratio <13: Thalassemia Ratio >13: Iron Deficiency Anemia, Hemoglobinopathy.

Mean corpuscular hemoglobin (MCH) - Average quantity of Hb per red cell MCH (pg) = (Hb x 10) ÷ RBC

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4. MCHC (mean corpuscular

Hgb

concentration) – derived index Grams of hemoglobin per 100 cc packed cells. MCHC = (Hb ÷ PCV) x 100 5. RDW (red blood cell distribution width) – calculated index (

nml 11.5-14.5%); if elevated, indicates variability of RBC (anisocytosis) – unreliable value in diagnosis.It measures RBC size variation (Anisocytosis)Standard deviation of RBC volume x 100

MCV

It is very helpful to distinguish between different types of

microcytic

anemia.

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Reticulocyte

Count:

Decreased:1- Hypoproliferative

2- ineffective erythropoiesisIncreased :1 -Iron deficiency anemia

2 Lead poisoning

3 Condition with high

reticulocyte

count (

thalassemia

minor?)

4

Erythropoietic porphyria5 Inflammation

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E. Remember the value and often the need, to actually examine the peripheral smear Spherocytes/ovalocytes Sickle cells

Schistocytes – traumatic hemolysis (prosthetic valve, DIC, TTP, hemolytic-uremic syndrome) “Teardrop” cells – bone marrow disease (fibrosis, tumor) Oval macrocytes,

hypersegmented

polys

–

megaloblastic

anemia

Immature (blast) cells – leukemia

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RBC MORPHOLOGY ON A PERIPHERAL SMEAR

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classification

Morphologic

MCV,MCHC,RDWFunctionalDecrease productionIncrease destructionUnderlying mechanismImpaired production(proliferation ,differentiation ,maturation )

Increased destruction-hemolytic.Blood loss.

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MORPHOLOGICAL CLASSIFICATION OF ANEMIAS

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Anemia

Microcytic

anemia

(MCV<80)

Normocytic

anemia

(MCV 80–100)

Macrocytic anemia

(MCV>100)

High

reticulocyte

countLow reticulocyte countWith megaloblastic bone marrowWithout megaloblastic bone marrow

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Functional classification

I.

inadequate production of RBCs :

A. deficiency of essential factors

B. toxic factors

C. endocrine causes (thyroid ,pituitary)

D.

erythropoiten

production (renal, starvation)

E. invasion of bone marrow

f. failure of stem cells

II. Increased RBC loss or destruction (hemolytic anemia)III. Blood loss anemia

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FUNCTIONAL CLASSIFICATION OF

ANEMIAS

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II.

Evaluation

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A.

History

1. Hx of chronic anemia or family Hx of anemia – may suggest inherited anemia. Spherocytosis

, ovalocytosis Hemoglobinopathy 2. Medical Hx – many chronic illnesses can be associated with anemia.

Chronic infection

Diabetes, hypothyroid, renal,

hypoadrenal

, collagen

vascular diseases are common causes.

Malignancy

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3. Social

Hx

Nutritional: strict vegan (B12); few fruits/veggies (folate) Alcohol use (folate, marrow suppression, liver disease) .4. Surgical Hx

: partial or total gastrectomy.

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5. Medications can cause

Bone marrow depression

Hemolysis (G-6-PD deficiency) 6. Review of systems Pregnancy Menses Symptoms suggesting undiagnosed medical problem

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B.

Symptoms attributable to anemia alone

1. Usually not present until Hgb level less than 7-8 g/dl. 2. No correlation between level and signs/symptoms.

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C.

Physical findings

1. Pallor of oral mucosa/conjunctiva 2. Palmar crease pallor suggests Hgb < 7 g/dl.

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3.

Volume status:

orthostasis, baseline tachycardia, widened pulse pressure, flow murmurs, flat neck veins, decreased urine output, decreased turgor. 4. Skin: jaundice (hemolysis),

petechiae/ecchymoses (bleeding disorders), lymphadenopathy (malignancy/infection)

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5. Oral

• Glossitis, macroglossia (pernicious anemia) • Angular cheilitis (Fe deficiency)

Glossitis

Angular

Stomatitis

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Angular

Stomatitis

Koilonychia

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6.

Neuro: paresthesias, dementia, ataxia, decreased proprioception/vibration (pernicious anemia). 7. Heme positive stool (GI loss).

8. Splenomegaly (hemolysis, sequestration, malignancy).

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The symptoms can be related to the anemia itself, or the underlying cause:

fatigue.

Dizziness.

headache.

poor concentration

Parasthesia

in fingers and toes.

Irritability

dyspnea. increasing cardiac output: palpitation , intermittent claudication and symptoms of heart failure .Symptoms

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D.

Labs

1. Approach varies greatly depending upon reference, experience, circumstances, etc; regardless of approach, have a rationale for it. Recognize the difference between patient in office vs in hospital (usually acutely ill).

Try not to “shotgun” (even though we all do it!)

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2.

Approach

a. CBC, peripheral smear b. Check retic count 1) Must calculate the corrected absolute

retic count • Abs retic count = retic count x RBC • Abs retic

count

<

100,000 suggests

defect

inRBC

production

•

Abs retic count > 100,000 suggests acute bleeding or hemolysis

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2) Corrected Abs

retic

count = Abs retic count/retic maturity time • Hct 45% Mat time 1 day • Hct 25%, 2.0 days •

Hct 15%, 2.5 days

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c.

Use MCV and

retic count to determine path for workup

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Anemia

Microcytic

anemia

(MCV<80)

Normocytic

anemia

(MCV 80–100)

Macrocytic anemia

(MCV>100)

High

reticulocyte

countLow reticulocyte countWith megaloblastic bone marrowWithout megaloblastic bone marrow

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3). Specific notes

a.

Serum Fe: negative phase reactant – it decreases with any stress (fever, etc).b. TIBC: only elevated in Fe def; however, it is also a negative acute phase reactant.

c. % Sat: decreases in both Fe def and ACD

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d.

Ferritin

: proportional to body’s iron stores generally both increase with age. Less than 16-35 ng/dl suggests depleted stores (if older than 65, less than 45 ng/dl).

Even though it is a positive acute phase reactant, must have Fe to elevate. Can have ferritin of 50-60 ng/mL and still have Fe deficiency.

e.

Bone marrow

iron stores: (gold standard).

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Microcytic

AnemiasDIFFERENTIAL DX:

Iron Deficiency AnemiaThalassemiasSideroblastic Anemia

Lead poisoning

Anemia of chronic disease (usually

normocytic

)

MCV < 80

Check also MCH, MCHC, RDW

Next Lab

testsIron studies Serum Iron TIBC/transferrin Serum Ferritin, % sat

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Microcytic

Anemia (MCV < 82

fL)1. Check ferritin level a. Low value (generally < 30 ng/

mL) suggests/confirms iron def. b. Normal or high value – check serum iron. 1) Low Fe – anemia of chronic disease (ACD) 2) Normal or increased – check serum lead level. • High – lead toxicity • Normal – do Hgb

electrophoresis:

thalassemia

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Iron Deficiency Anemia

Most common cause of anemia worldwide

1. Prevalence:10-25% young women, 1% men, up to 10% elderly 2. Why worry? a. Treatable b. Clue to underlying diseases

• 10-20% pts w/Fe def anemia have CA. • Up to 50% have GERD/PUD 3. Diet 10-15 mg/day – 10% absorbed

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4

. Daily loss 1 mg/d, plus 1 mg/d menstruation

5. FeSO4 20% elemental iron: 180 mg = 36 mg elemental Fe 6. Replace Fe at 6 mg/kg/day up to 200 mg/d elemental Fe 7. Consider Feosol elixir to minimize GI side effects common with FeSO4 tablets.

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Iron deficiency anemia

Iron deficiency anemia is the most common type of anemia

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8.

Vitamin C increases absorption of non-

heme Fe; literature implies little clinical significance, but antioxidant Rx is becoming a hot topic. 9. Retic count up by 2 weeks 10. Anemia corrected by 6 weeks 11.

4-6 months to correct depleted Fe stores of 500 mg 12. In questionable cases, especially of distinguishing Fe-def vs ACD in an elderly ill patient, consider empiric trial of Fe replacement. Be sure to follow retic and Hgb

; if no

change, stop Fe

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PREVALENCE OF ID

Region

0-4yr 5-12yr

WomenSouth Asia 56% 50% 58%

Africa

56% 49% 44%

Latin Am

26% 26% 17%

Gulf Arabs

40% 36% 38%

Developed

12% 7% 11% World 43% 37% 35%

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Causes of iron-deficiency anemia

1. Increased need Pregnancy Normal growth 2. Decreased intake or absorption Childhood Gastric surgery, achlorhydria

Celiac sprue 3. Increased blood loss GERD, PUD, gastritis IBD Malignancy Menstruation

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Clinical Signs to be looked for

Skin / mucosal pallor,

Skin dryness, palmar creases

Bald tongue, GlossitisMouth ulcers, Rectal exam

Jaundice,

Purpura

Lymph

adenopathy

Hepato-splenomegaly

Breathlessness

Tachycardia, CHF

Bleeding, Occult Blood

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TREATMENT:

Oral iron replacement (ferrous sulfate)

Side effects: constipation, nausea, dyspepsiaIV or IM iron dextran—

If pt cannot tolerate PO, poor PO absorption, or greater requirements than PO can provideBlood transfusion—NOT recommended unless anemia is severe or pt has cardiopulmonary disease

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Short term prevention of IDA in infancy

Avoid gestational ID

Try to prevent premature delivery and LBW (pregnancy care)

Increase birth spacingBreast feeding also reduces or delays the onset of IDAIron supplement after 6 months

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Thalassemia

Inherited disorders

Classified according to deficient chain, severity varies based on mutationsα

-thalassemiaβ-thalassemia

Inadequate production of either the alpha- or beta-

globin

chain of

Hb

Microcytic

,

hypochromic

RDW usually normalHigh RBC countCan see tear drop cells, target cellsNormal or increased ironDx by Hb electrophoresis“Thalassa” means “sea” in Greek

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Normocytic

AnemiasDIFFERENTIAL DX:Anemia of chronic disease

Aplastic AnemiaRenal, liver, or endocrine disease

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Normocytic Anemia (MCV 82-97

fL) 1. Check corrected absolute reticulocyte count a. Low or normal 1) Any changes of marrow failure

a) Yes – do bone marrow biopsy • Myelodysplasia • Infiltrative disease • Aplastic anemia b) No – Dx is ACD.

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b. High

1) Check LDH,

haptoglobin Normal – can be expected response to blood loss. Abnormal – check Coombs’

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2) Any

splenomegaly

? a) Yes – check RBC morphology and Coombs’ • Negative Coombs’ – hypersplenism, drug effect, infection, hemoglobinopathy • Positive Coombs’ – hemolytic disease b) No – hemolytic disease

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Causes

1. Decreased RBC production Bone marrow failure Aplastic anemia 2. RBC destruction/loss a. Acute blood loss (may be occult) b. Hypersplenism

c. Hemolytic anemia 1) Intrinsic RBC anomalies • Spherocytosis • G6PD defects • Hemoglobinopathies

2) Extrinsic factors

• Mechanical

• Infectious (DIC)

• Autoimmune antibodies

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Aplastic

Anemia

RareLow reticulocyte % accompanied by pancytopenia

Causes:Idiopathic (majority)Congenital—Fanconi

anemia

Radiation exposure

Meds—

chloramphenicol

, sulfonamides, gold,

carbamazepine

Viral infection—human parvovirus,

HepB, HepC, EBV, CMV, HZV, HIVChemicals—benzene, insecticides

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Aplastic

Anemia

Clinical:Fatigue, dyspnea, petechiae

, easy bruising, frequent infectionsCan transform into acute leukemiaDiagnosis: Bone marrow biopsy—definitive—hypocellular marrow, absence of progenitors

Treatment:

Bone marrow transplant, transfuse with PRBCs and platelets if necessary,

immunosuppression

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Treatment

Directed at cause

If ACD, iron replacement doesn’t help and may be detrimental. Consider erythropoietin

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Macrocytic

AnemiasDIFFERENTIAL DX:

Vitamin B12 Deficiency (MCV>115)Folate Deficiency (MCV>115)Liver disease (MCV up to 115)

Stimulated

erythropoiesis

(MCV up to 110)

MCV > 100

Next labs to check:

serum

vit

B12 serum folate serum homocysteine serum methylmalonic acid Intrinsic factor Ab

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Macrocytic

Anemia (> 97 fL

) 1. Evaluate peripheral smear for macrocytes,

hypersegmented polys a. Present – megaloblastic anemia

1) Check B12,

folate

levels

• One or both low – deficiency (replace): consider

Schilling’s test.

• Normal – consider due to drug or idiopathic:

referral for

eval, bone marrow

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b. Absent –

nonmegaloblastic

anemia 1) Review Abs corrected retic count a) Low or normal • Eval for liver disease, hypothyroidism • If absent, aplastic

anemia b) High • Hemolytic disease • Acute blood loss • Hypersplenism

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2

.

Many drugs can cause macrocytosis without megaloblasts. • Phenytoin, OCs, MTX, barbiturates, TMP-SMX,

zidovudine • Alcohol is the most common cause of macrocytosis.

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Vitamin B

12

DeficiencyCauses—

most due to poor absorptionPernicious anemia (lack of intrinsic factor)GastrectomyPoor diet

Alcoholism

Crohn’s

disease,

ileal

resection

Organisms competing for

Vit

B12If untreated can lead to demyelination in posterior columns, lateral corticospinal tracts, spinocerebellar tracts

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Causes of B12 deficiency

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Vitamin B

12

DeficiencyDiagnosis:Peripheral blood smear—macrocytic

RBCs, hypersegmented neutrophilsLow serum vitamin B

12

(<100pg/

mL

)

Methylmalonic

acid,

homocysteine

levels are elevatedShilling testTreatment:Cyanocobalamin (vit B12) IM once per month

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Normochromic, Macrocytic, hypersegmentation of nuetrophils

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Folate

Deficiency

Stores are limited, can become depleted over 3 month periodMain source—green vegetablesCauses—“tea and toast” diet, alcoholism, long term oral antibiotic use, increased demand, pregnancy,

hemolysis, methotrexate use, anticonvulsants (phenytoin), hemodialysis

Clinical—similar to

Vit

B

12

deficiency, without the neurologic symptoms

Treat—daily oral folic acid replacement

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Causes of

folate

deficiency

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Sideroblastic

Anemia

Caused by abnormality in RBC iron metabolismHereditary or acquiredAcquired causes include drugs, lead exposure, collagen vascular disease,

neoplastic diseaseLab findings: normal or increased serum iron and ferritin

normal TIBC

ringed

sideroblasts

in bone marrow

normal RDW

Treatment: remove offending agents, consider pyridoxine (Vit.B6)

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Lead Poisoning

One cause of

sideroblastic anemiaCommon in children

May cause microcytosis if lead level in blood >100µg/dL

(could also be

normocytic

)

Can see basophilic stippling

If lead levels 45-69µg/

dL

:Find and remove lead sourceAdminister EDTA 5.0mg/kg in two divided doses, slow IV infusion for 5 days, ample fluidsAlternative—DMSA—orally acting chelating agent, for use in childrenUse both agents if level >69µg/dL

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Treatment

1. Must be tailored to cause

2. Replacement • Folic acid: 1 mg/d • Vit B12: 1000 microgram/d IM for 5 days, then q week until Hct normal, then q month for life (some studies

suggest p.o. replacement as effective)

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3. Discontinue offending drugs/agents.

4. Transfusion

a. Avoid transfusion “triggers.” b. Plan for autologous blood if possible. c. Administer unit-by-unit based on reassessment. d. Transfuse to relieve symptoms related to blood loss when other replacement has failed.

• Syncope • Dyspnea • Shock • Angina/TIA

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HYPOCHROMIC, MICROCYTIC ANEMIAS

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NORMOCHROMIC, NORMOCYTIC ANEMIAS

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MACROCYTIC ANEMIAS

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Thank You ALL