2. Overview
• 1. Basics of hemoglobin synthesis
• 2. Iron profile & its interpretation
• 3. Morphologic classification of anemia
• 4. Anemia of chronic disease
• 5. Sideroblastic anemia
• 6. Iron deficiency anemia
• 7. Lead poisoning & anemia
• 8. Investigations in every microcytic anemia &
interpretation
3. Introduction
• Anemia is a clinical condition due to reduced
oxygen delivery to tissues as a result of a
reduction in the number of red cells and/or
reduction in blood concentration of hemoglobin
below the level that is expected for healthy
person of same age and sex.
• Anemia can grossly be divided into hemolytic,
dyshemopoetic or due to external/internal blood
loss.
• WHO defined anemia as Hb < 13 g/dl (men) &
<12 g/dl (women).
4. Background of HB synthesis
• Heme & globin chains in adults manufactured in
separate cell compartments- mitochondria &
cytoplasm respectively in amazingly accurate
manner.
• 4 principal defects can be seen-
Qualitative defects in globin chain- Sickle cell
Quantitative defects in globin chain- Thalassemia
Defects in heme portion- Porphyria
Defects in incorporating iron into heme-
Sideroblastic anemia
5.
6. Decoding Iron Profile
• Serum Iron- measure of amount of iron bound to
transferrin. Shows diurnal variation- Highest in
morning and lowest in evening.
Influenced by recent ingestion and
absorption of iron medication.
Normal Value- 50-150 µg/dl
• Transferrin saturation- Principal transport protein
for Iron.
Saturation dropping beyond 15-20% produces
iron-deficient erythropoiesis.
7. • Total Iron binding capacity- indirect measurement of
transferrin in terms of amount of iron it will bind
Value- 300-360 µg/dl, starts to increase when iron
deficient erythropoiesis ensues
• Ferritin- Reliable indicator of marrow (intra-cellular)
iron store. Not influenced by recent iron therapy.
Normal Value 50-200 µg/L
Most important acute phase reactant so will increase in
any acute/chronic inflammatory conditions. It has
replaced marrow iron store examination for total body
iron storage measurement.
9. Etiological Classification of Microcytic
Anemia
• Iron Deficiency Anemia
• Anemia of chronic diseases
• Hemoglobinopathy- Thalassemia
• Sideroblastic Anemia
• Long term lead intoxication
10.
11. Anemia of chronic disease
• It mostly encompasses inflammation,
infection, tissue injury & malignancy.
• M/C form of anemia clinically
• Close differential to IDA as inadequate iron
delivery to marrow despite adequate iron
stores.
12. Pathogenesis
• IL-1 directly suppresses EPO production acting
through IFN-ϒ.
• TNF- same mechanism.
• Increased hepcidin via IL-6 pathway
suppresses iron absorption & iron release
from storage sites.
• RBC survival shortening.
• Ongoing blood loss in malignancy
13.
14. Causes asso. with microcytic anemia
A. Chronic inflammation
Rheumatoid arthritis
systemic lupus erythematosis
Crohn’s disease
B. Chronic infection
Tuberculosis
Urinary tract disease
HIV infection
Bacterial endocarditis
pneumonia
C. Neoplasm
Carcinoma
Lymphoma
Myeloma
15. Sideroblastic Anemia
• It indicates defects involving incorporation of
Iron into the heme molecule (dysfunctional
mitochondria) .
• Normally when marrow smear is stained for
iron, 20-40% developing erythroblasts will
have visible ferritin granules in their
cytoplasm-called sideroblasts.
• This represents iron in excess needed for HB
synthesis.
16. Etiology
• It can be congenital-
X-linked
Autosomal recessive
Mitochondrial disorders
Pearson syndrome
DIDMOAD syndrome
• Acquired causes are-
Myelodysplastic syndrome
Nutritional deficiencies (Cu, B6)
Lead Poisoning
Alcoholism
ATD
17. Pathology/ Key features
• All developed due to improper heme synthesis
in presence of adequate Iron.
• Frequently associated with mitochondrial
disorders & cerebellar disorders.
• Drugs- Ab- Tetracycline, linezolid.
Progesterone.
• C/F- Growth retardation, optic atrophy,
porphyria features, ataxia- classical
constellation of symptoms.
18. Treatment
• Removal of toxic agents.
• Pyridoxine, thiamine & Folic acid
supplementation
• Blood transfusion with iron chelation if
needed
• Avoidance of Zn, Alcohol.
19. Iron deficiency Anemia
• Each ml of RBC contains 1 mg of elemental
iron, so daily need of Iron roughly 20 mg for
replacement of cells.
• For addtl production of new RBC’s men need 1
mg & female of child bearing age need 1.4 mg
elemental iron per day respectively.
• Suboptimal supply of Iron during heme
synthesis leads to microcytic hypochromic
anemia.
24. Treatment of IDA
• Oral iron- Typically 3-4 tab( 50-65 mg of
elemental iron each) in empty stomach.
Reticulocyte production begin to increase
within 4-7 days. Goal of the therapy to correct
anemia along with stores of 0.5-1 g.
Duration-atleast 6-12 months depending upon
response.
S/E- GI intolerance, delayed release
preparations preferred.
25. Parenteral Iron therapy
• Main way- Total dose to be given within 2
weeks with atleast 500 mg of body store
• Dialysis associated-100 mg elemental iron
weekly for 10 weeks to augment EPO
response
• Dose- Body weight (kg) × 2.3 × (15- patient’s
Hb, g/dl) + 500 mg.
• To be given with 5D or 0.9%NS over a period
of 60-90 min.
• Iron-Dextran- anaphylaxis a concern.
26. Lead poisoning
• M/C exposures- Pica, industrial exposure,
inhalation in occupational hazards.
• Mechanism- increased generation of ROS.
• It causes impaired synthesis of the Heme
moiety.
• M/C- Neurological manifestations like
temperamental lability, irritability, behavioral
changes, hyperactivity, loss of developmental
milestones.
27.
28. Diagnosis
• Whole blood lead level > 10 µg/dl denotes
significant lead toxicity.
• Elevated free erythrocyte protoporphyrin
levels. Correlates with severity of anemia.
• T/t- Elimination of the exposure along with
chelating agents + iron, Zn.
29. Approach to microcytic anemia
• If we get an anemia with microcytic hypochromic
RBC’s in PBS we should search for-
Menstrual history & blood loss through stool
history
To look for features of malnutrition &
Malabsorption.
To ask for previous/frequent blood transfusion
history. Any similar family history
History suggestive of mitochondrial/cerebellar
disease.
Any joint pains, rashes like inflammatory features
or chronic infective pictures
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37. Routine investigations
Complete RBC indices study (look for MCV)
Iron Profile
HB HPLC
Inflammatory markers- ESR, CRP
Creatinine
Other specific goal directed investigations if
needed.
Bone marrow picture seldom helpful.
Mentzer index- IDA >14, Thalassemia < 12.