Anemia

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.

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)

B. Strictly defined by decreased Hgb

relating to a value 2SD below a mean .

AGE Hgb

Mean/ (-2SD)

HCT%

Mean/ (-2SD)

MCV

Mean/ (-2SD)

Newborn 16.5 (13.5) 51 (42) 108 (96)

1 Month 13.9 (10.7) 44 (33) 101 (91)

2 Months 11.2 (9.4) 35 (28) 95 (84)

6 Months 12.6 (11.0) 36 (31) 76 (68)

> 6 Months 12.5 (11.0) 36 (33) 81 (70+ age per

yr)

Adult

Male

Female

15.5 (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)

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?‖

C. The clinical context and condition of the

patient

determine how urgently Dx and Rx must

occur.

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.

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

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

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.

Reticulocyte Count: Decreased:

1- Hypoproliferative

2- ineffective erythropoiesis Increased :

1 -Iron deficiency anemia

2 Lead poisoning

3 Condition with high reticulocyte count (thalassemia minor?)

4 Erythropoietic porphyria

5 Inflammation

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

RBC MORPHOLOGY ON A PERIPHERAL SMEAR

classification Morphologic MCV,MCHC,RDW

Functional Decrease production

Increase destruction

Underlying mechanism

Impaired production(proliferation ,differentiation ,maturation )

Increased destruction-hemolytic.

Blood loss.

MORPHOLOGICAL CLASSIFICATION OF

ANEMIAS

Anemia

Microcytic

anemia

(MCV<80)

Normocytic anemia

(MCV 80–100)

Macrocytic

anemia

(MCV>100)

High

reticulocyte

count

Low

reticulocyte

count

With

megaloblastic

bone marrow

Without

megaloblastic

bone marrow

Microcytic Anemia

Retics NOT Elevated Retics Elevated

S.Iron Decreased

Ferritin Decreased

% S.Iron Sat. Decreased

S.Iron N

Ferritin N

% S.Iron Sat. N

Diag. Iron Deff. A.

Evaluate for Bl.loss

Normal Electro. Abnormal Electro.

Diag. Thalassemia B. M.

Ringed Sidroplasts

B. M.

No sidroblast

Urine Heavy Metal +ve Urine Heavy Metal -ve Dig. Sidroblastic A .

Dig. Heavy Metal Poisoning Dig. A. Of Ch. Disease

Retics. Elevated

Abn. R.B.C. forms Spherocytes on per. bl. smear

Evaluate for cell m. defect Coombs +ve Coombs –ve

Diag. Autoimmune Hemoltic A. Diag. herditory Spherocytosis

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

FUNCTIONAL CLASSIFICATION OF

ANEMIAS

II. Evaluation

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

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.

5. Medications can cause

Bone marrow depression

Hemolysis (G-6-PD deficiency)

6. Review of systems

Pregnancy

Menses

Symptoms suggesting undiagnosed medical problem

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.

C. Physical findings

1. Pallor of oral mucosa/conjunctiva

2. Palmar crease pallor suggests Hgb < 7 g/dl.

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)

5. Oral

• Glossitis, macroglossia (pernicious anemia)

• Angular cheilitis (Fe deficiency)

Angular Stomatitis

Angular Stomatitis Koilonychia

6. Neuro: paresthesias, dementia, ataxia, decreased

proprioception/vibration (pernicious anemia).

7. Heme positive stool (GI loss).

8. Splenomegaly (hemolysis, sequestration, malignancy).

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

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!)

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

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

c. Use MCV and retic count to

determine path for workup

Anemia

Microcytic

anemia

(MCV<80)

Normocytic anemia

(MCV 80–100)

Macrocytic

anemia

(MCV>100)

High

reticulocyte

count

Low

reticulocyte

count

With

megaloblastic

bone marrow

Without

megaloblastic

bone marrow

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

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).

Microcytic Anemias

DIFFERENTIAL DX:

Iron Deficiency Anemia

Thalassemias

Sideroblastic Anemia

Lead poisoning

Anemia of chronic disease (usually normocytic)

MCV < 80

Check also MCH, MCHC, RDW

Next Lab testsIron studies

Serum Iron

TIBC/transferrin

Serum Ferritin, % sat

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

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

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.

Iron deficiency anemia Iron deficiency anemia is the most common type of anemia

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

PREVALENCE OF ID Region 0-4yr 5-12yr Women

South 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%

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

Clinical Signs to be looked for

Skin / mucosal pallor,

Skin dryness, palmar creases

Bald tongue, Glossitis

Mouth ulcers, Rectal exam

Jaundice, Purpura

Lymph adenopathy

Hepato-splenomegaly

Breathlessness

Tachycardia, CHF

Bleeding, Occult Blood

TREATMENT:

Oral iron replacement (ferrous sulfate)

Side effects: constipation, nausea, dyspepsia

IV or IM iron dextran—

If pt cannot tolerate PO, poor PO absorption, or

greater requirements than PO can provide

Blood transfusion—NOT recommended unless

anemia is severe or pt has cardiopulmonary

disease

Short term prevention of IDA in infancy

Avoid gestational ID

Try to prevent premature delivery and LBW (pregnancy care)

Increase birth spacing

Breast feeding also reduces or delays the onset of IDA

Iron supplement after 6 months

Thalassemia Inherited disorders

Classified according to deficient chain, severity varies based on mutations

α-thalassemia β-thalassemia

Inadequate production of either the alpha- or beta-globin chain of Hb

Microcytic, hypochromic

RDW usually normal

High RBC count

Can see tear drop cells, target cells

Normal or increased iron

Dx by Hb electrophoresis ―Thalassa‖ means ―sea‖ in Greek

Normocytic Anemias

DIFFERENTIAL DX:

Anemia of

chronic disease

Aplastic Anemia

Renal, liver, or

endocrine disease

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.

b. High 1) Check LDH, haptoglobin

Normal – can be expected response to blood

loss.

Abnormal – check Coombs’

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

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

Aplastic Anemia

Rare

Low 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, HIV

Chemicals—benzene, insecticides

Aplastic Anemia

Clinical:

Fatigue, dyspnea, petechiae, easy bruising, frequent

infections

Can transform into acute leukemia

Diagnosis:

Bone marrow biopsy—definitive—hypocellular

marrow, absence of progenitors

Treatment:

Bone marrow transplant, transfuse with PRBCs and

platelets if necessary, immunosuppression

Treatment Directed at cause

If ACD, iron replacement doesn’t help and may be

detrimental.

Consider erythropoietin

Macrocytic Anemias

DIFFERENTIAL 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

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

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

2. Many drugs can cause macrocytosis without

megaloblasts.

• Phenytoin, OCs, MTX, barbiturates, TMP-SMX,

zidovudine

• Alcohol is the most common cause of macrocytosis.

Vitamin B12 Deficiency

Causes—most due to poor absorption Pernicious anemia (lack

of intrinsic factor) Gastrectomy Poor diet Alcoholism Crohn’s disease, ileal

resection Organisms competing

for Vit B12 If untreated can lead to

demyelination in posterior columns, lateral corticospinal tracts, spinocerebellar tracts

Causes of B12 deficiency

Vitamin B12 Deficiency Diagnosis:

Peripheral blood smear—macrocytic RBCs, hypersegmented neutrophils

Low serum vitamin B12 (<100pg/mL) Methylmalonic acid, homocysteine

levels are elevated Shilling test

Treatment: Cyanocobalamin (vit B12) IM once per

month

Normochromic, Macrocytic, hypersegmentation of nuetrophils

Folate Deficiency Stores are limited, can become depleted

over 3 month period Main source—green vegetables Causes—―tea and toast‖ diet, alcoholism,

long term oral antibiotic use, increased demand, pregnancy, hemolysis, methotrexate use, anticonvulsants (phenytoin), hemodialysis

Clinical—similar to Vit B12 deficiency, without the neurologic symptoms

Treat—daily oral folic acid replacement

Causes of folate deficiency

Sideroblastic Anemia

Caused by abnormality in RBC iron metabolism

Hereditary or acquired

Acquired causes include drugs, lead exposure, collagen vascular disease, neoplastic disease

Lab 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)

Lead Poisoning

One cause of sideroblastic

anemia

Common 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 source

Administer EDTA 5.0mg/kg in two divided doses, slow IV infusion for 5 days, ample fluids

Alternative—DMSA—orally acting chelating agent, for use in children

Use both agents if level >69µg/dL

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)

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

HYPOCHROMIC, MICROCYTIC ANEMIAS

NORMOCHROMIC, NORMOCYTIC

ANEMIAS

MACROCYTIC ANEMIAS

Thank You ALL