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  1. 1. ANAEMIA: Preventable, Yet a Problem!!
  2. 2. RETICULOCYTES Reticulocytes are premature red blood cells, typically composing about 1% of the red cells in the human body. Reticulocytes develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells, reticulocytes do not have a cell nucleus. They are called reticulocytes because of a reticular (mesh-like) network of ribosomal RNA that becomes visible under a microscope with certain stains such as new methylene blue.
  3. 3. Remember that the bonemarrow has the capacity to increase RBC production 5-10 times the normal production. Thus, if all necessary raw products are available, the RBC life span can decrease to about 18 days before bone marrow compensation is inadequate and anemia develops.
  4. 4. RBC “rule of 3’s” For normal erythrocytes: hemoglobin (g/dL) hematocrit (%) 3 x RBC count (millions) 3 x hemoblobin (g/dL) 3% Failure to obey this “rule of 3’s” suggests an abnormality in erythrocytes (sickle cells, etc)
  5. 5. Normal range : In male : 5 - 6 millions/cmm of blood In female :4 – 5 millions/cmm of blood Decrease in Hemoglobin concentration Normal range : In male : 15 -18 gm/100ml of blood In female : 12 – 15 gm/100ml of blood
  6. 6. Introduction In its broadest sense, anemia is a functional inability of the blood to supply the tissue with adequate O2 for proper metabolic function. Anemia is not a disease, but rather the expression of an underlying disorder or disease.
  7. 7. ENTOMOLOGY -from Ancient Greek ἀναιμία anaimia, meaning "lack of blood")
  8. 8. Magnitude of Problem Globally, is about 30 % In developing countries & India, incidence is around 40 – 90%. Responsible for 40% of maternal deaths in third world countries. Important cause of direct and indirect maternal deaths - Vitere FE Adv Exp Med Biol 1994;352:127
  9. 9.  Anemia is a common condition.  It occurs in all age groups and all racial and ethnic groups.  Both men and women can have anemia, but women of childbearing age are at higher risk for the condition.  This is because women in this age range lose blood from menstruation.  Researchers continue to study how anemia affects older adults.  More than 10 percent of older adults have mild forms of anemia.  Many of these people have other medical conditions as well.
  10. 10. Definition Anemia - insufficient Hb to carry out O2 requirement by tissues. WHO definition : Hb conc. 11 gm % For developing countries : cut off level suggested is 10 gm % - WHO technical report Series no. 405, Geneva 1968 Centre for disease control, MMWR 1989;38:400-4
  12. 12. WHO Classification of Anaemia Degree Hb% Moderate 7-10.9 24-37% Severe 4-6.9 13-23% Very Severe <4 Haematocrit (%) <13%
  13. 13. ANEMIA Morphologic classification macrocytic normocytic microcytic MCV <80 MCV 80-100 MCV >100
  14. 14. ANEMIA Classification by volume I. Microcytic Anemia (MCV <80) II. Normocytic Anemia (MCV 80-100) III. Macrocytic Anemia (MCV >100)
  18. 18. ANEMIA Pathophysiologic classification I RBC loss 1. blood loss 2. ↑ RBC destruction a. intrinsic abnormality b. extrinsic abnormality II ↓RBC production 1. stem cell abnormality 2. erythroblast abnormality 3. unknown/multiple mechanism
  19. 19. ANEMIA Pathophysiologic classification I RBC loss 1. blood loss a. acute : trauma, massive hemorrhage b. chronic : GI lesion, GYN lesion
  20. 20. ANEMIA pathophysiologic classification 2.↑ RBC destruction a. intrinsic abnormality b. extrinsic abnormality
  21. 21. ANEMIA pathophysiologic classification 2.↑ RBC destruction a. intrinsic abnormality i. membrane disorder ii.enzyme disorder iii.Hgb synthesis disorder iv.acquired memb. defect
  22. 22. Classification of Anemia Based on cell size (MCV) Macrocytic (large) MCV 100+ fl (femtoliters) Normocytic (normal) MCV 8-99 fl Microcytic (small) MCV<80 fl Based on hemoglobin content (MCH) Hypochromic (pale color) Normochromic (normal color) Hyperchromic cell
  27. 27. The Three Causes of Anemia Decreased red blood cell production Increased red blood cell destruction Red blood cell loss
  28. 28. Decreased RBC production Lack of iron, B12, folate Marrow is dysfunctional from myelodysplasia, tumor infiltration, aplastic anemia, etc. Bone marrow is suppressed by chemotherapy or radiation Low levels of erythropoeitin, thyroid hormone, or androgens
  29. 29. Increased RBC destruction RBCs live about 100 days Acquired: autoimmune hemolytic anemia, TTP-HUS, DIC, malaria Inherited: spherocytosis, sickle cell, thalassemia
  30. 30. Symptoms Irritability Lack of Concentration Fatigue Infection Palpitation Weakness Dizziness
  31. 31. Clinical Features Pallor of skin And m/m Soft ejection systolic murmur Edema Signs Platynychia Koilonychia Tachycardia Glossitis Stomatitis
  32. 32. DIAGNOSIS
  33. 33. ASSESSMENT – Patient history – Patient physical exam – Signs and symptoms exhibited by the patient – Hematologic lab findings Identification of the cause of anemia is important so that appropriate therapy is used to treat the anemia.
  34. 34. Before making a diagnosis of anemia, one must consider: Age Sex Geographic location Presence or absence of lung disease
  35. 35. DIAGNOSIS OF ANEMIA How does one make a clinical diagnosis of anemia? Patient history – Dietary habits – Medication – Possible exposure to chemicals and/or toxins – Description and duration of symptoms
  36. 36. DIAGNOSIS OF ANEMIA • Tiredness • Muscle fatigue and weakness • Headache and vertigo (dizziness) • Dyspnia (difficult or labored breathing) from exertion • G I problems • Overt signs of blood loss such as hematuria (blood in urine) or black stools
  37. 37. Physical examination –General findings might include • Hepato or splenomegaly • Heart abnormalities • Skin pallor –Specific findings may help to establish the underlying cause: • In vitamin B12 deficiency there may be signs of malnutrition and neurological changes • In iron deficiency there may be severe pallor, a smooth tongue, and esophageal webs • In hemolytic anemias there may be jaundice due to the increased levels of bilirubin from increased RBC destruction
  38. 38. Laboratory investigation A complete blood count, CBC, will include: –An RBC count: • At birth the normal range is 3.9-5.9 x 106/ul (1012/L) • The normal range for males is 4.5-5.9 x 106/ul • The normal range for females is 3.8-5.2 x 106/ul • Note that the normal ranges may vary slightly depending upon the patient population.
  39. 39. DIAGNOSIS OF ANEMIA –Hematocrit (Hct) or packed cell volume in % or (L/L) • At birth the normal range is 42-60% (.42.60) • The normal range for males is 41-53% (.41-.53) • The normal range for females is 38-46% (.38-.46) • Note that the normal ranges may vary slightly depending upon the patient population.
  40. 40. DIAGNOSIS OF ANEMIA –Hemoglobin concentration in grams/deciliter - the RBCs are lysed and the hemoglobin is measured spectrophotometrically • At birth the normal range is 13.5-20 g/dl • The normal range for males is 13.5-17.5 g/dl • The normal range for females is 12-16 g/dl • Note that the normal ranges may vary slightly depending upon the patient population. –RBC indices – these utilize results of the RBC count, hematocrit, and hemoglobin to calculate 4 parameters:
  41. 41. DIAGNOSIS OF ANEMIA • Mean corpuscular volume (MCV) – is the average volume/RBC in femtoliters (10-15 L) • Hct (in %)/RBC (x 1012/L) x 10 • At birth the normal range is 98-123 • In adults the normal range is 80-100 • The MCV is used to classify RBCs as: • Normocytic (80-100) • Microcytic (<80) • Macrocytic (>100)
  42. 42. DIAGNOSIS OF ANEMIA •Mean corpuscular hemoglobin concentration (MCHC) – is the average concentration of hemoglobin in g/dl (or %) • Hgb (in g/dl)/Hct (in %) x 100 • At birth the normal range is 30-36 • In adults the normal range is 31-37 • The MVHC is used to classify RBCs as: • Normochromic (31-37) • Hypochromic (<31) • Some RBCs are called hyperchromic
  43. 43. DIAGNOSIS OF ANEMIA • Mean corpuscular hemoglobin (MCH) – is the average weight of hemoglobin/cell in picograms (pg= 1012 g) • Hgb (in g/dl)/RBC(x 1012/L) x 10 • At birth the normal range is 31-37 • In adults the normal range is 26-34 • This is not used much anymore because it does not take into account the size of the cell.
  44. 44. DIAGNOSIS OF ANEMIA • Red cell distribution width (RDW) – is a measurement of the variation in RBC cell size • Standard deviation/mean MCV x 100 • The range for normal values is 11.5-14.5% • A value > 14.5 means that there is increased variation in cell size above the normal amount (anisocytosis) • A value < 11.5 means that the RBC population is more uniform in size than normal.
  46. 46. DIAGNOSIS OF ANEMIA –Reticulocyte count gives an indication of the level of the bone marrow activity. • Done by staining a peripheral blood smear with new methylene blue to help visualize remaining ribosomes and ER. The number of reticulocytes/1000 RBC is counted and reported as a %.
  47. 47. DIAGNOSIS OF ANEMIA • At birth the normal range is 1.8-8% • The normal range in an adult (i.e. in an individual with no anemia) is .51.5%. Note that this % is not normal for anemia where the bone marrow should be working harder and throwing out more reticulocytes per day. In anemia the reticulocyte count should be elevated above the normal values.
  49. 49. DIAGNOSIS OF ANEMIA –Blood smear examination . The smear should be evaluated for the following: • Poikilocytosis – describes a variation in the shape of the RBCs. It is normal to have some variation in shape, but some shapes are characteristic of a hematologic disorder or malignancy.
  52. 52. DIAGNOSIS OF ANEMIA •Erythrocyte inclusions – the RBCs in the peripheral smear should also be examined for the presence of inclusions or a variation in erythrocyte distribution :
  53. 53. DIAGNOSIS OF ANEMIA •A variation in size should be noted (anisocytosis) and cells should be classified as •Normocytic •Microcytic •Macrocytic •A variation in hemoglobin concentration (color) should be noted and the cells should be
  55. 55. DIAGNOSIS OF ANEMIA •The peripheral smear should also be examined for abnormalities in leukocytes or platlets. •Some nutritional deficiencies, stem cell disorders, and bone marrow abnormalities will also effect production, function, and/or morphology of platlets and/or granulocytes. •Finding abnormalities in the
  56. 56. •In a bone marrow sample, the following things should be noted: • • • • • • Maturation of RBC and WBC series Ratio of myeloid to erythroid series Abundance of iron stores (ringed sideroblasts) Presence or absence of granulomas or tumor cells Red to yellow ratio Presence of megakaryocytes – Hemoglobin electrophoresis – can be used to identify the presence of an abnormal hemoglobin (called hemoglobinopathies). Different hgbs will move to different regions of the gel and the type of hemoglobin may be identified by its position on the gel after electrophoresis.
  57. 57. DIAGNOSIS OF ANEMIA – Evaluation of RBC enzymes and metabolic pathways – enzyme deficiencies in carbohydrate metabolic pathways are usually associated with a hemolytic anemia. – Evaluation of erythropoietin levels – is used to determine if a proper bone marrow response is occurring. •Low levels of RBCs could be due to a bone marrow problem or to a lack of erythropoietin production. – Serum iron, iron binding capacity and % saturation – used to diagnose iron deficiency anemias (more on this later) – Bone marrow cultures – used to determine the viability of stem cells.
  58. 58. Management Options Pre – pregnancy : Treat the cause before conception Pre-pregnancy balanced diet, education and health support. Build up iron stores during adolescent phase
  59. 59. Modalities of Management Oral Iron Parenteral Injectable Iron Blood transfusion Human Recombinant Erythropoietin
  60. 60. Oral Iron Therapy Ideal dose – 100mg per day (prophylactic) Ferrous gluconate, ferrous fumarate, ferrous succinate, ferrous sulphate, ferrous ascorbate citrate Rise in Hb – 0.8 gm / dl / week Side effects -G I upset most common Pt. compliance not guaranteed Ineffective in pts with worm infestations Inconclusive evidence on benefit of controlled release Iron preparation
  61. 61. Absorption of Ferrous Salts Uncontrolled Passive Absorption Iron salts are dissociated into bivalent or trivalent iron salts Diffuses as free iron ions through the upper part of the gastrointestinal mucosa Taken up by transferrin and incorporated into ferritin. For binding to ferritin and transferrin ferrous iron has to be converted into ferric iron by oxidation Highly reactive free radicals are produced during this process All ionic iron including carbonyl iron are absorbed similarly • Borbolla JR. Cicero RE, Dibilox MM, Sotres RD et al.. Rev Mex Pediatr 2000; 67(2): 63-67 • Heubers KA, Brittenham GM, Csiba E, Finch CA. J Lab Clin Med 1986 ; 108 ; 473-8.
  62. 62. Parenteral Therapy : Traditional Indications Intolerance to oral iron Poor compliance to oral iron Gastrointestinal disorders Malabsorption syndromes Rapid blood loss
  63. 63. Parenteral Therapy : Traditional Indications Inability to maintain iron balance (haemodialysis) Patient donating large amount of blood for auto-transfusion programme ? Pregnant women with severe IDA, presenting late in pregnancy
  64. 64. The World Health Organisation states… ‘transfusion should be prescribed ONLY for conditions for which there is NO OTHER TREATMENT’
  65. 65. PREVENTION Some common forms of anemia are most easily prevented by eating a healthy diet and limiting alcohol use. All types of anemia are best avoided by seeing a doctor regularly and when problems arise. In the elderly, routine blood work ordered by the doctor, even if there are no symptoms, may detect anemia and prompt the doctor to look for the underlying causes.
  66. 66. SUMMARY Preventing anemia and having the correct number of red blood cells requires cooperation among the kidneys, the bone marrow, and nutrients within the body. If the kidneys or bone marrow are not functioning, or the body is poorly nourished, then normal red blood cell count and function may be difficult to maintain. Anemia is actually a sign of a disease process rather than a disease itself. It is usually classified as either chronic or acute. Chronic anemia occurs over a long period of time. Acute anemia occurs quickly. Determining whether anemia has been present for a long time or whether it is something new, assists doctors in finding the cause. This also helps predict how severe the symptoms of anemia may be.
  67. 67. Take Home Message Anaemia although preventable is a global problem Anaemia still is the commonest cause of maternal mortality and morbidity in spite of easy diagnosis and treatment Anaemia can be due to a number of causes, including certain diseases or a shortage of iron, folic acid or Vitamin B12. The most common cause of anemia in pregnancy is iron deficiency. Iron therapy is best given orally
  68. 68. Take Home Message The youth need to be educated about diet, sanitation and personal hygiene Hookworm infestation should be treated Pregnant women should be given Iron and folate supplements