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 Anemia ? www.drsarma.in

3. Decrease in the quantum 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 Anemia www.drsarma.in

4. 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

5. 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 increases in Anemia Large white areas are marrow fat www.drsarma.in

6. Hemoglobin (Hb) www.drsarma.in

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

10. Clinical Signs and symptoms of Anemia 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 (ICMR) Less than 12 g% Screening Tests – Anemia www.drsarma.in

11. 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

12. 57% Plasma 1% Buffy coat – WBC 42% Hct (PCV) PCV or Hematocrit www.drsarma.in

13. Measurement Normal Range RBC count (RCC) 5 million 4 to 5.7 Hemoglobin 15 g% 12 to 17 Hematocrit (PCV) 45 38 to 50 A x 3 = B x 3 = C - This is the rule of thumb Check whether this holds good in a given result If not -indicates micro or macrocytosis or hypochro. The Three Primary Measures www.drsarma.in

14. Measurement Normal Range RCC 5 million 4 to 5.7 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

15. Types of Anemia www.drsarma.in

16. 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 Anemia www.drsarma.in

17. 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 Anemia Thalassemia Hypoproliferative Anemias www.drsarma.in

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

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

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

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

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

23. 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 Anemia (lack of raw material) Maturation defect with less production Bone marrow suppression (primary/ secondary) Workup – Third Test www.drsarma.in

24. Red Cell Size www.drsarma.in

25. RBC size is measured indirectly by The Mean Cell Volume (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

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

27. Anemia Workup – 4th TestRed cell Distribution Width – RDW RDW < 13 Mean 90 fl RDW is 13 MCV 90 fl www.drsarma.in

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

29. 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 there any hemo-parasites in the RBC ? Are leucocytes normal in number and D.C ? Is platelet distribution adequate ? Anemia Workup - 5th TestPeripheral Smear Study www.drsarma.in

30. IDA -CBC www.drsarma.in

31. Severe Hypochromia www.drsarma.in

32. Microcytic Hypochromic - IDA www.drsarma.in

33. Serum Ferritin < 33 pmol / l 33-270 pmol / l > 270pmol / l TIBC (300-340) N or ↓ HIGH - + BM Fe Not IDA, Other Mi A Iron Deficiency Anemia IDA Microcytic Hypochromic Anemia www.drsarma.in

34. Microcytic MCV < 80 fl, RBC < 6 µ RDW Widened and shifted to left Hypochromic MCH < 27 pg, MCHC < 30% RPI < 2 Retic. count May be > 2 % Serum ferritin Very low < 33 (p mols/L) TIBC Increased > 340 (µg/dL) BM Iron stain Iron is Absent Response to Fe Rx. Excellent IDA Summary www.drsarma.in

35. 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

36. Microcytic Anemias www.drsarma.in

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

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

39. 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

40. 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

41. 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

42. MBA www.drsarma.in

43. Macrocytosis -MBA www.drsarma.in

44. Anisocytosis - Macrocytic Anemia www.drsarma.in

45. HSN - MBA www.drsarma.in

46. Basophilic Stippling - MBA BS occurs in Lead poisoning also www.drsarma.in

47. Megalocyte in PS www.drsarma.in

48. MBA - BM www.drsarma.in

49. MBA - BM www.drsarma.in

50. Megaloblast – FA deficiency www.drsarma.in