1. CBC --- Interpretations

2. Abstract Interpretation of different parameters reported on modern day analyzers is bit tricky and demand continuous monitoring and on-going learning. In present paper interpretation of different reported parameters has been discussed with approach to diagnosis of various abnormalities.

3. The CBC interpretation are useful in the diagnosis of various types of anemias. It can reflect acute or chronic infection, allergies, and problems with clotting.

4. Component of the CBC: Red Blood Cells (RBCs) Hematocrit (Hct) Hemoglobin (Hgb) Mean Corpuscular Volume (MCV) Mean Corpuscular Hemoglobin Concentration (MCHC) - Red cell distribution width (RDW) White Blood Cells (WBCs) Platelet

5. RBC (varies with altitude): –M: 4.7 to 6.1 x10^12 /L –F: 4.2 to 5.4 x10^12 /L Biconcave disc shape with diameter of about 8 µm Function: - transport hemoglobin which carries oxygen from the lung to the tissues -acid –base buffer. Life span 100-120 days.

6. Hemoglobin : M: 13.8 to 17.2 gm/dL F: 12.1 to 15.1 gm/dL Hematocrit : (packed cell volume) It is ratio of the volume of red cell to the volume of whole blood. M: 40.7 to 50.3 % F: 36.1 to 44.3 %

7. –MCV = mean corpuscular volume HCT/RBC count= 80-100fL small = microcytic normal = normocytic large = macrocytic –MCHC= mean corpuscular hemoglobin concentration HB/RBC count= 26-34% decreased = hypochromic normal = normochromic

8. MCH (mean corpuscular hemoglobin) HB/HCT = 27-32 pg RDW (red cell distribution width) It is correlates with the degree of anisocytosis _ Normal range from 10-15%

9. This important value is needed in the evaluation of any anemia. Normal range 1-2% Retic count goes up with –Hemolytic anemia Retic goes down with –Nutritional deficiencies _ Diseases of the bone marrow itself

10. Definition of Anaemia ► Decrease in the number of circulating red blood cell mass and there by O 2 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

11. First Question ► The onset of Anaemia ► Acute versus chronic ► Clues  Hemodynamic stability  Previous CBC  Overt blood loss

12. Types of Anaemia

13. Screening Tests – Anaemia ► 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  Subcontinent Less than 12 g%

14. Clinical Signs to be looked for ► Skin / mucosal pallor, ► Skin dryness, palmar creases ► Bald tongue, Glossitis ► Mouth ulcers, Rectal exam ► Jaundice, Purpura ► Lymphadenopathy ► Hepato-splenomegaly ► Breathlessness ► Tachycardia, CHF ► Bleeding, Occult Blood

15. PCV or Hematocrit ► 57% Plasma ► 1% Buffy coat – WBC ► 42% Hct (PCV)

16. The Three Basic Measures MeasurementNormal Range A. RBC count 5 million 4 to 6 B. Hemoglobin15 g%12 to 17 C. Hematocrit45 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 hypochromia.

17. Causes of Anaemia 1. Decreased production of Red Cells - Hypoproliferative, marrow failure 2. Increased destruction of Red Cells - Hemolysis (decreased survival of RBC) 3. Loss of Red Cells due to bleeding - Acute / chronic blood loss (hemorrhagic)

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

19. Reticulocytes Leishman’sSupravital

20. Anaemia Hypoproliferative Hemolytic Retics < 2Retics > 2 Hb% < 12, Hct < 38%

21. Normal CBC

22. Workup – Second Test ► 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 Retic count 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)

23. Mean Cell Volume (MCV) ► RBC volume (rather) is measured by ► The Mean Cell Volume or MCV and RDW Microcytic < 80 fl MCV NormocyticMacrocytic 80 -100 fl> 100 fl < 6.5 µ6.5 - 9 µ> 9 µ

24. Anaemia Workup - MCV Microcytic MCV NormocyticMacrocytic 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

25. Red cell Distribution Width - RDW Normal Population Uniform RDW High Population Double

26. Anaemia Workup - 4 th Test Peripheral Smear Study ► 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 ?

27. IDA -CBC

28. Microcytic Hypochromic - IDA

29. IDA – Special Tests Iron related tests NormalIDA Serum Ferritin (pmo/L) 33-270 < 33 TIBC (µg/dL) 300-340 > 400 Serum Iron (µg/dL) 50-150 < 30 Saturation % 30-50 < 10 Bone marrow Iron ++Absent

30. IDA Summary ► MicrocyticMCV < 80 fl, RBC < 6 µ ► RDWWidened with low MCV ► HypochromicMCH < 27 pg, MCHC < 30% ► RI < 2 ► Serum ferritinVery low < 30 (p mols/L) ► TIBCIncreased > 400 (µg/dL) ► Serum IronVery low < 30 (µg/dL) ► BM Fe StainAbsent Fe ► Response to Fe Rx.Excellent

31. IDA- Some Nuggets ► 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 ► FeSO 4 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

32. Microcytic Anaemias MCV < 80 fl Serum Iron TIBC BM Perls stain Iron Def. Anemia ↓↓↑↑0 Chronic Infection ↓↓↓↓ + + Thalassemia↑↑N + + + + HemoglobinopathyNN + + Lead poisoning NN + + Sideroblastic↑↑N + + + +

33. Macrocytic Anaemias A. Megaloblastic Macrocytic – B12 and Folate ↓ B. Non Megaloblastic Macrocytic Anaemias 1.Liver disease/alcohol 2.Hemoglobinopathies 3.Metabolic disorders, Hypothyroidism 4.Myelodystrophy, BM infiltration 5.Accelerated Erythropoesis - ↑ destruction 6.Drugs (cytotoxics, immunosuppressants, AZT, anticonvulsants)

34. Anemia - Macrocytic (MCV > 100) 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 B 12 deficiency

35. MBA

36. Macrocytosis -MBA

37. HSN - MBA

38. Basophilic Stippling - MBA BS occurs in Lead poisoning also

39. MBA - BM

40. Pernicious Anaemia - Tongue Bald, smooth, lemon yellowish red tongue

41. Normocytic Anaemias 1. Chronic disease 2. Early IDA 3. Hemoglobinopathies 4. Primary marrow disorders 5. Combined deficiencies 6. Increased destruction 7. Anaemia of investigations - ICU

42. Anaemia of Chronic Disease ► Thyroid diseases ► Malignancy ► Collagen Vascular Disease  Rheumatoid Arthritis  SLE  Polymyositis  Polyarteritis Nodosa IBD – Ulcerative Colitis – Crohn’s Disease Chronic Infections – HIV, Osteomyelitis – Tuberculosis Renal Failure

43. ‘Dimorphic’ Anaemia ► Folate & Fe deficiency (pregnancy, alcoholism) ► B 12 & Fe deficiency (PA with atrophic gastritis) ► Thalassemia minor & B 12 or folate deficiency ► Fe deficiency & hemolysis (prosthetic valve) ► Folate deficiency & hemolysis (Hb SS disease) ► Peripheral smear exam is critical to assess these ► RDW is increased very much

44. RBC Size – Anisocytosis Different sizes of RBC

45. Poikilocytosis Different Shapes of RBC

46. Polychromasia - Spherocytosis

47. Target Cells 1.Liver Disease 2.Thalassemia 3.Hb D Disease 4.Post splenectomy

48. WBCs are involved in the immune response. The normal range: 4 – 11x10^9 /L Two types of WBC: 1) Granulocytes consist of: –Neutrophils: 50 - 70% –Eosinophils: 1 - 5% –Basophils: up to 1% 2) Agranulocytes consist of: - Lymphocytes: 20 - 40% –Monocytes: 1 - 6%

49. The type of cell affected depends upon its primary function: In bacterial infections, neutrophils are most commonly affected In viral infections, lymphocytes are most commonly affected In parasitic infections, eosinophils are most commonly affected.

50. polymorphneuclear leukocytes (PMN,s) Nucleus 3-5 lobes. Diameter 10-14 µm 50-70% WBC =2.5-7.5x10^9/ L Function: Phagocytosis of bacteria and cell debris Numbers rise with all manner of stress, especially bacterial infections

51. Neutrophil disorders –Neutrophilia – an increase in neutrophils –Conditions associated with neutrophilia are: 1-Bacterial infections (most common cause) 2-Tissue destruction e.g. tissue infarctions, burns. 3- leukemoid reaction 4-Leukemia

52. –Neutropenia – this may result from 1-Decreased bone marrow production e.g. BM hypoplasia. 2-Ineffective bone marrow production –E.g. megaloblastic anemias and myelodysplastic syndromes. 3- post acute infection _ e.g. typhoid fever, brucellosis.

53. Bilobed nucleus 1-5% of WBC =0.04-0.4x10^9/L Diameter about 10-14 µm Function: Involved in allergy, parasitic infections Contains: eosinophilic granules

54. –Eosinophilia may be found in Parasitic infections Allergic conditions and hypersensitivity reaction

55. No specific granules 20-40% of WBC =1.55-3.5x10^9/ L Diameter 8-10 µm T cells: cellular (for viral infections) B cells: humoral (antibody) Natural Killer Cells

56. Lymphocytosis – may indicate _ Viral infection e.g. Infectious mononucleosis, CMV or pertussis. _ Bacterial infection e.g. TB Lymphopenia – caused by _Stress. _Steroid therapy _ Irradiation

57. (Leukocytosis) may indicate: _ Infectious diseases _Inflammatory disease (such as rheumatoid arthritis or allergy) _Leukemia _Severe emotional or physical stress _Tissue damage (e.g. necrosis,or burns) (Leukopenia) may result from: _ Decreased WBC production from BM. _ Irradiation. _ Exposure to chemical or drugs.

58. Fever Malaise Weakness Others depend on each system which is involved e.g. » chest: cough, SOB and chest pain » abdomen: diarrhea, vomiting, dehydration. »CNS: headache, visual disturbance, Neck stiffness and so 0n.

59. Infection of the mouth and throat. Painful skin ulceration. Recurrent infection. Septicemia.

60. Small granular non-nucleated discs. Diameter about 2-4 µm Normal range; 150-300x10^9 /L Destroyed by macrophage cells in the spleen. Function; involved in coagulation and blood haemostasis. Life span 7-10 days

61. Numbers of platelets –Increased (Thrombocythemia) Pregnancy. Exercise. High attitudes. splenectomy –Decreased (Thrombocytopenia) Menstruation. Haemorrhage. Bone marrow destruction or suppression e.g. leukemia The values have to fit the clinical situation.

62. Petechial hemorhage. Easy bruising. Mucosal bleeding e.g. _ epistaxes. _ gum bleeding