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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