Approach to microcytic hypochromic anemia

It encompasses all differential diagnosis & their brief descriptions

1. Approach to microcytic hypochromic anemia Dr. S hinjan Patra 3 rd yr PGT of General medicine Midnapore Medical College

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. 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.

6. 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.

7. Morphologic classification of Anemia Normocytic normochromic/hypochromic Microcytic ( MCV < 80 fl ) Macrocytic (MCV > 100 fl )

8. Etiological Classification of Microcytic Anemia Iron Deficiency Anemia Anemia of chronic diseases Hemoglobinopathy- Thalassemia Sideroblastic Anemia Long term lead intoxication

9. Symptoms

10. 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.

11. 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

12. 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

13. 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.

14. 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

15. 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.

16. Treatment Removal of toxic agents. Pyridoxine, thiamine & Folic acid supplementation Blood transfusion with iron chelation if needed Avoidance of Zn , Alcohol.

17. 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.

18. Iron Metabolism

19. Etiology Increased Demand- Rapid growth in infancy & adolescence Pregnancy Increased loss- Acute/chronic blood loss (upper GI bleeding) Menorrhagia Decreased intake- Malnutrition Malabsorption (chronic inflammatory disease involving jejunum mostly)

20. 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.

21. 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.

22. 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.

23. 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.

24. 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

25. 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.

26. Thank you….