A Practical Approach to Anemia

1. A Practical Approach to Anemia Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada) Consultant Physician & Chest Specialist Visit us at : www.drsarma.in How to efficiently and accurately work up an anemic patient ?

2. Important to remember Anemia is a clinical sign of disease It is not a single disease by itself Need to look for the underlying cause ! Will we ignore a fever with out investigation ? Its diagnosis is not that simple !! We’ll make it Its very common and imp. in our practice Drug Rx. depends on the cause What is Anaemia ? www.drsarma.in

3. Decrease in the number of circulating red blood cell mass and there by O2 carrying capacity Most common hematological disorder by far Almost always a secondary disorder As such, critical for all practitioners to know how to evaluate / determine its cause / treat Definition of Anaemia www.drsarma.in

4. Erythron is the machinery of RBC production EPO, IL, Growth factors, Cytokines – stimulate it Hypoxia is strong stimulus for the Erythron Its functioning is influenced by Normal renal production of EPO A functioning Erythroid marrow An adequate supply of substrates for Hb production Erythron www.drsarma.in

5. Let us meet the Grand Parents ! The RBC Lineage

6. Haemopoesis in Bone Marrow www.drsarma.in

7. Pro Erythroblast Large purple nucleus Thin rim of cytoplasm Basophilic in stain Cell > 35 µ www.drsarma.in

8. Early Normoblast Large purple nucleus Denser nucleus Thin rim of cytoplasm Basophilic in stain Cell > 25 µ www.drsarma.in

9. Intermediate Normoblast Medium sized nucleus Reticulated nucleus More cytoplasm Neutral in stain Cell > 20 µ www.drsarma.in

10. Late Normoblast Small dense nucleus Darkly staining Increased cytoplasm Pink in stain Cell > 15 µ www.drsarma.in

11. Reticulocyte No definite nucleus Reticulum of RNA Deep blue staining Light blue cytoplasm Cell size about 10 µ www.drsarma.in

12. Normal Red Cells www.drsarma.in

13. Normal Red Cells No nucleus, Enzyme packets Biconcave discs – Haem + Gl Center 1/3 pallor Pink cytoplasm (Hb filled) Cell size 7 - 8 µ - capill. 2 µ EM pathway, HMP Negative charge – no phago Na less, K more inside 100-120 days life span www.drsarma.in

14. The Factory – Bone Marrow Sternum, pelvis, vertebrae, long bones, skull bones, Tibia (paed) From stem cells (pleuripotent) 75% of marrow for WBC 25% of BM for Red cells Erythrod / Granulocyte Ratio 1:3 E:G ratio increased in Anaemia Large white areas are marrow fat www.drsarma.in

15. Normal BM High Power www.drsarma.in

16. Hemoglobin (Hb) www.drsarma.in

17. The onset of Anaemia Acute versus chronic Clues Hemodynamic stability Previous CBC Overt blood loss First Question www.drsarma.in

18. Types of Anaemia www.drsarma.in

19. Clinical Signs and symptoms of Anaemia Look for bleeding – all possible sites Look for the causes for anemia Routine Hemoglobin examination Cut off marks for Hb – US < 13.5 g WHO < 12.5 g India Less than 12 g% Screening Tests – Anaemia www.drsarma.in

20. 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 Clinical Signs to be looked for www.drsarma.in

21. 57% Plasma 1% Buffy coat – WBC 42% Hct (PCV) PCV or Hematocrit www.drsarma.in

22. Measurement Normal Range RBC count 5 million 4 to 6 Hemoglobin 15 g% 12 to 17 Hematocrit 45 38 to 50 A x 3 = B x 3 = C - This is the rule of thumb Check whether this holds good in given results If not -indicates micro or macrocytosis or hypochro. The Three Basic Measures www.drsarma.in

23. Measurement Normal Range RBC count 5 million 4 to 6 Hemoglobin 15 g% 12 to 17 Hematocrit 45 38 to 50 MCV C ÷ A x 10 = 90 fl MCH B ÷ A x 10 = 30 pg MCHC B ÷ C x 100 = 33% The Three Derived Indicies www.drsarma.in

24. Decreased production of Red Cells - Hypo proliferative, marrow failure Increased destruction of Red Cells - Hemolysis (decreased survival of RBC) Loss of Red Cells due to bleeding - Acute / chronic blood loss (hemorrhagic) M = P x S ( L) Causes of Anaemia www.drsarma.in

25. Failure of cell maturation Nuclear breakdown Cytoplasmic breakdown Folate or B12 deficiency Globin defect Haem defect Sickle cell A Defective DNA synthesis Fe Phorph IDA, SA Megaloblastic Anaemia Thalassemia Hypoproliferative Anaemias www.drsarma.in

26. RETICULOCYTE COUNT % Anaemia – First Test • ‘RBC to be’ or Apprentice RBC • Fragments of nuclear material • RNA strands which stain blue Normal Less than 2% www.drsarma.in

27. Reticulocytes Supravital Leishman’s www.drsarma.in

28. For example the RPI is calculated as follows Reticulocyte count 9% Hb content 7.5 g% Correction for Anaemia = 9 x (7.5 ÷ 15) = 9 x 0.5 = 4.5 % Correction for increased life span 4.5 ÷ 2 = 2.25 % 3. Thus, the RPI is 2.25 Reticulocyte Production Index www.drsarma.in

29. Anaemia Hb% < 12, Hct < 38% Hemolytic Hypoproliferative RPI < 2 RPI > 2 www.drsarma.in

30. Normal CBC www.drsarma.in

31. The next step is ‘What is the size of RBC’ ? MCV indicates the Red cell volume (size) Both the MCH & MCHC tell Hb content of RBC If the RPI is 2 or less We are dealing with either Hypoproliferative anaemia (lack of raw material) Maturation defect with less production Bone marrow suppression (primary/ secondary) Workup – Second Test www.drsarma.in

32. Red Cell Size www.drsarma.in

33. RBC volume (rather) is measured by The Mean Cell Volume or MCV and RDW MCV Microcytic Normocytic Macrocytic < 80 fl 80 -100 fl > 100 fl < 6.5 µ 6.5 - 9 µ > 9 µ Mean Cell Volume (MCV) www.drsarma.in

34. MCV Microcytic Normocytic Macrocytic Iron Deficiency IDA Chronic Infections Thalassemias Hemoglobinopathies Sideroblastic Anemia Chronic disease Early IDA Hemoglobinopathies Primary marrow disorders Combined deficiencies Increased destruction Megaloblastic anemias Liver disease/alcohol Hemoglobinopathies Metabolic disorders Marrow disorders Increased destruction Anaemia Workup - MCV www.drsarma.in

35. Anaemia Workup – 3rd TestRed cell Distribution Width – RDW RDW < 13 Mean 90 fl RDW is 13 MCV 90 fl www.drsarma.in

36. Red cell Distribution Width - RDW MCV Microcytic Normocytic Macrocytic Left Mean 90 Right www.drsarma.in

37. Are all RBC of the same size ? Are all RBC of the same normal discoid shape ? How is the colour (Hb content) saturation ? Are all the RBC of same colour/ multi coloured ? Are there any RBC inclusions ? Are intra RBC there any hemo-parasites ? Are leucocytes normal in number and D.C ? Is platelet distribution adequate ? Anaemia Workup - 4th TestPeripheral Smear Study www.drsarma.in

38. IDA -CBC www.drsarma.in

39. Severe Hypochromia www.drsarma.in

40. Microcytic Hypochromic - IDA www.drsarma.in

41. Serum Ferritin < 33 pmol / l 33-270 pmol / l > 270pmol / l TIBC N or ↓ HIGH - + BM Fe Not IDA, Other Mi A Iron Deficiency Anaemia IDA Microcytic Hypochromic Anaemia www.drsarma.in

42. IDA – Special Tests www.drsarma.in

43. Microcytic MCV < 80 fl, RBC < 6 µ RDW Widened and shift to left Hypochromic MCH < 27 pg, MCHC < 30% RPI < 2 Retic. count May be > 2 % Serum ferritin Very low < 30 (p mols/L) TIBC Increased > 400 (µg/dL) Serum Iron Very low < 30 (µg/dL) BM Fe Stain Absent Fe Response to Fe Rx. Excellent IDA Summary www.drsarma.in

44. Look for occult blood loss – 2 days non veg. free Pica and Pagophagia – Ice sucking Absorption of Haem Iron > Fe ++ > Fe+++ Food, Phytates, Ca, Phosphate, antacids ↓absorption Ascorbic acid ↑absorption Oral iron Rx. always is the best, ? Carbonyl Fe FeSO4 is the best. Reserve parenteral Rx. Packed cell transfusion in emergency Continue Fe Rx at least 2 months after normal Hb 1 gram ↑in Hb every week can be expected Always supplement protein for the Globin component IDA- Some Nuggets www.drsarma.in

45. Microcytic Anaemias www.drsarma.in

46. Ringed Sideroblasts in BM Prussian Blue Stain www.drsarma.in

47. A. Megaloblastic Macrocytic – B12 and Folate↓ B. Non Megaloblastic Macrocytic Anaemias Liver disease/alcohol Hemoglobinopathies Metabolic disorders, Hypothyroidism Myelodystrophy, BM infiltration Accelerated Erythropoesis -↑destruction Drugs (cytotoxics, immunosuppressants, AZT, anticonvulsants) Macrocytic Anaemias www.drsarma.in

48. Premature gray hair – consider MBA Macrocytic anemias may be asymptomatic until the Hb is as low as 6 grams MCV 100-110 fl must look for other causes of macrocytosis MCV > 110 fl almost always folate or B12 deficiency Anemia - Macrocytic (MCV > 100) www.drsarma.in

49. 25-96% of alcoholics MCV elevation usually slight (100-110 fl) Minimal or no anemia Macrocytes round (not oval) Neutrophil hyper segmentation absent Folate stores normal Smoking increases the Red Cell Mass Macrocytosis of Alcoholism www.drsarma.in

50. Marrow failure due to Disrupted DNA synth. & ineffective erythropoesis Giant precursors (Megaloblasts) Nuclear : Cytoplasmic dyssynchrony in marrow Neutrophil hyper segmentation & macro ovalocytes Anemia (and often leukopenia & thrombocytopenia) Almost always due to B12 or folate deficiency Megaloblastic Hematopoiesis www.drsarma.in