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Anemia In The Viewpoint Of Medical, Peadiatrics & Obstetrics


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Anemia In various Aspect & Focusing On Malaysian (South East Asian) opulation

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Anemia In The Viewpoint Of Medical, Peadiatrics & Obstetrics

  2. 2. COMPOSITION OF BLOOD 1. Cellular Portion (45% of total blood volume) -Erythrocytes (RBCs) -Leukocyes (WBCs) -Thrombocytes 2. Fluid portion (Plasma, 55% of total blood volume)
  3. 3. Erythrocytes Biconcave Disk Flattened Flexible Semi-permeable membrane Contains Antigen (ABO & Rh)  Blood type Anuclear No Mitochondria
  4. 4. Erythrocytes Life Span 100-120 days FUNCTIONS Transport O2 to tissues Transport CO2 from tissues Fate Destroyed by macrophage cells (liver, spleen, bone marrow) 33% of RBC cell mass consist of hemoglobin
  5. 5. Normal Erythrocytes Normal Value Male : 4.32 – 5.72 X 1012 cells/L Female : 3.90 – 5.03 X 1012 cells/L Source : procedures/complete-blood- count/basics/results/prc-20014088
  6. 6. Hemoglobin Consist of 4 Globin Adult (HbA) : 2α & 2β Fetal (HbF) : 2α & 2γ 1 Heme bound to each globin
  7. 7. Hemoglobin Normal Values Adults Male 13.5 - 17.5 g/dL Female 12.0 - 15.5 g/dL Source : Children Newborn 14 - 24 g/dL Infant 9.5 – 13 g/dL Pregnancy 11 – 12 g/dL 77% HbF (Newborn) ↓ 23% HbF (after 4 month)
  8. 8. Hemoglobin Synthesis Source : a and β genes mRNAs a and β globins chain Haemoglobin Succinyl CoA+ Glycine Protophophyrins Heme Fe
  9. 9. Erythropoiesis Primitive Hemopoietic Stem Cell (HSC) Proerythroblast Early normoblast Late normoblast Reticulocyte Erythrocyte
  10. 10. Regulators of Erythropoiesis • Erythropoietin (EPO) Synthesis depends on the supply of 1. Iron 2. Folic Acid 3. Vitamin B12 Binds O2 in the Hb within PBC For Thymine synthesis  DNA formation  Normal cell division/maturation Deficiency  ↓Hb Production  ↓Erythropoiesis Stimulate proliferation of erythrocytes progenitor cells & their differentiation into mature RBCs Required for Folic acid function  DNA formation  Normal cell division, maturation
  11. 11. Rate of Erythropoiesis
  12. 12. The Pathology: ANEMIA By Group 1
  13. 13. Anaemia Definition WHO : ANAEMIA is a condition in which the number of red blood cells or their oxygen carrying capacity is insufficient to meet physiologic needs, which vary by age, sex, altitude, smoking and pregnancy status. OXFORD : ANAEMIA is defined as low heamoglobin (Hb) concentration, and may be due either to a low red cell mass or increased plasma volume. Source :
  14. 14. Reduction of Hb concentration below normal ANAEMIA Female Adult : <11.5 g/dL Male Adult : < 13.5 g/dL 2 years – puberty : < 11 g/dL Newborn infants : < 14 g/dL
  15. 15. Types of Anemia Based on Mean Cell Volume (MCV) - Normal MCV : 76-96 fL (femtolitres) Low MCV MICROCYTIC ANAEMIA Normal MCV NORMOCYTIC ANAEMIA High MCV MACROCYTIC ANAEMIA Varying MCV HAEMOLYTIC ANAEMIA
  16. 16. Low MCV MCV < 80fL MCH <27pg MICROCYTIC ANAEMIA Normal MCV MCV 80 – 95 Fl MCH > 27 pg NORMOCYTIC ANAEMIA High MCV MCV > 95 fL MACROCYTIC ANAEMIA 1. Iron-Deficiency Anaemia 2. Thalassemia 3. Sideroblastic Anaemia 1. Acute blood loss 2. Anaemia of Chronic Disease 3. Bone marrow failure 4. Renal failure 5. Hypothyroidism 6. Haemolysis 7. Pregnancy 1. B12 / Folate Deficiency 2. Alcohol excess / Liver Disease 3. Reticulocytosis 4. Cytotoxics 5. Marrow infiltration 6. Hypothyroidism 7. Antifolate drugs (Phenytoin) Source : Murray Longmore, Oxford Handbook of Clinical Medicine, 9th Edition, 2014. MCV: 80 to 100fL MCH: 27 to 31 picograms/cell.
  17. 17. CLASSICAL SIGN AND SYMPTOMS SIGNS SYMPTOMS Pallor Shortness of breath Tachycardia (Compensatory Mechanism) Lethargic Cardiac failure Weakness Palpitation Headaches Angina pectoris Confusion
  19. 19. Iron Deficiency Anemia (IDA) Group 3
  20. 20. • Most common and widespread of nutritional disorder in the world • Affecting large number of women and children in non-industrialized country and virtually all industrialized nations. • Half of pregnant women in the world estimated to be anemic (52% non industrialized, 23% industrialized.) Prevalence
  21. 21. Classification based on WHO Malay N=135 Chinese N=130 Indian N=123 All N=388 Anemia (Hb < 12g/L) 16.4 20.6 26.4 20.9 Depleted iron storage (ferritin <15 22.9 25.2 53.9 33.0 IDA (Hb<12g/L+ferritin <15 + MCV <80 fl 4.3 9.9 18.0 10.3 The prevalence of anaemia and IDA among urban Malaysian women Prevalence of anaemia, depleted iron stores and IDA (Medicine UPM 2010)
  22. 22. WHO regions Children (0-4years) Children (5- 14 years) Pregnant women All women (15- 59years) Men (15- 59years) Elderly Africa 45 228 85 212 10 800 57 780 41 925 13 435 America 14 220 40 633 4 500 53 787 19 443 12 617 South East Asia 111 426 207 802 24 800 214 991 184 752 60 206 Europe 12 475 12 867 2 400 27 119 13 318 18 095 Eastern mediteranian 33 264 37 931 7 700 60 196 41 462 11 463 Western pacific 29 793 156 839 9 700 158 667 174 400 78 211 Overall 245 386 541 284 59 900 572 540 475 300 194 029 Estimated prevalence of anaemia (1990-1995) by WHO Region based on blood haemoglobin concentration (WHO)
  23. 23. Mariah a 17 year old student who has recently migrated from Australia to Malta with her parents. She comes to you complaining of general fatigue and occasional dizziness. Mariah has no significant past medical history and is not any regular medicine. She does not drink alcohol or smoke. Her parents are both healthy. On examination, she has strong peripheral pulses, and her cardiovascular system examination is normal. BP is 115/75mmHg, pulse 90/min and BMI 19.5kg/m2. Mariah has pale skin, conjunctiva and nail beds. Scenario
  24. 24. Poor Diet Intake Pathophysiology& Causes of IDA Loss Of IRON Stores (Depletion Of Hemoglobin Recourse) Malabsorption Increased demands Chronic blood loss
  25. 25. • GIT : peptic ulcer, esophageal varices, aspirin ingestion, stomach/caecum/colon carcinoma, hookworm, angiodysplasia etc. • Uterine menstrual loss (Menorrhagia) • Prolonged hematuria, hemoglobinuria,, pulmonary haemosiderosis ,self inflicted blood loss (rare) Chronic blood loss
  26. 26. • Prematurity • Growth • Pregnancy • Erythropoietin therapy Increased demands
  27. 27. • Gluten-induced enteropathy • Gastrectomy • Autoimmune (atrophic) gastritis Malabsoprtion
  28. 28. • A major factor in many developing countries but rarely the sole cause in developed country Poor diet intake
  29. 29. • Brittle nails • Koilonychia • Atrophy of papillae of the tongue, painless glossitis • Angular stomatitis • Dysphagia ( Plummer Vinson syndrome) • Pica Sign and Symptoms of IDA
  30. 30. • Blood count and film - microcytic (MCV< 80 fl) and hypochromic (MCH < 27pg) anemia - Poilocytosis - Anisocytosis Investigation Iron deficiency anemia, severe. Blood film. The field displays virtually all hypochromic cells with an exaggerated pale center (arrow)
  31. 31. Test Findings MCV Reduced Serum iron Reduced Serum TIBC Raised Serum ferritin Reduced Serum soluble transfer receptor Increased Iron in marrow Absent Iron in erythroblast Absent Investigation cont.
  32. 32. • Treat the underlying causes • Oral iron – ferrous sulphate ( 200mg three times daily, a total of 180mg ferrous iron ) /- ferrous gluconate (300mg twice daily , only 70mg ferrous iron) • Parenteral iron (for high iron requirement)– ferric hydroxide sucrose ( 200mg )/ iron dextran/ ferric carboxymaltose Management
  33. 33. THALASSEMIA Group 1
  34. 34. DEFINITION & EPIDEMIOLOGY DEFINITION Hereditary disease (autosomal recessive) ; Defective in synthesis of globin chain in thalassemia -> imbalance globin chain production-> precipitation of globin chain within red cell precursor-> ineffective erythropoiesis.
  35. 35. CAUSES  Thalassemia is caused by mutations in the DNA of cells that make hemoglobin .  The mutations associated with thalassemia are passed from parents to children.  The mutations that cause thalassemia disrupt the normal production of hemoglobin and cause low hemoglobin levels and a high rate of red blood cell destruction, causing anemia.
  36. 36. CLASSIFICATION thalassemia alpha 1 gene deletion 2 gene deletion 3 gene deletion 4 gene deletion beta major minor Intermedia
  37. 37. CASE SCENARIO Adriana is a 7 –years-old who lives with her parents in a suburban community. Her parents brought Adriana to the US from their homeland in Greece when she was 1-year-old. At the age of 3, Adriana was in the 10th percentile for height and weight, pale, and her Hb was 5.8 g/dl. Following further diagnostic studies, she was diagnosed with beta thalassemia major. Over the cause of the next 4 years, Adriana was hospitalized every 1 – 2 months, so she could be transfused with pack red blood cell.
  38. 38. PATHOPHYSIOLOGY • α-thalassemia  primarily to gene deletion causing reduced α-globin chain synthesis  Since all adult haemoglobin are containing, α-thalassemia produces no change in the percentage distribution of haemoglobin A, A2 and F. In severe form of α- thalassemia, excess β chain may form a β4 tetramere called haemoglobin H. • β-thalassemia Defects that result in absent β globin chain is called as βᴼ Reduced synthesis is termed β
  39. 39. SIGNS AND SYMPTOMS TYPES ( ALPHA THALASSEMIA) SIGNS AND SYMPTOMS Four-gene deletion (Hb Barts) Pale, oedematous, enormous livers and spleen (hydrops fetalis) Three-gene deletion Moderate anaemia and splenomegally Two-gene deletion Mild anaemia One-gene deletion Normal
  40. 40. TYPES ( BETA THALASSEMIA) SIGN AND SYMPTOM Thalassemia minor Anaemia is mild or absent Thalaasemia intermedia -Moderate anaemia - May varies depending on mutation Thalassemia major -severe anaemia -Failure to thrive -recurrent bacteria infection -hepatosplenomegaly -bone expansion -classical thalassemic facies -jaundice
  41. 41. INVESTIGATIONS (Can Be Applied To Both Alpha & Beta) • Complete blood count – Hb, MCV, MCH low – RBC increased – Red cell distribution width (RDW) – normal • Peripheral blood film – Microcytic, hypochromic – Target cells, basophilic stipling, ± nucleated RBC Blood smear showing marked microcytosis, hypochromia, target cell, and anisocytosis. Peripheral blood smear showing basophilic stippling
  42. 42. CONT • Hb analysis – HPLC – No Hb A at all, replaced by Hb F and A2 – Hb electrophoresis – will be further explain after this • DNA analysis – alpha and/or beta gene • Family screening
  43. 43. CONT… •Haemoglobin (Hb) electrophoresis test • Blood test done to check the different types of Hb in the blood. • It uses an electrical current to separate normal and abnormal types of Hb in the blood. Hb types have different electrical charges and move at different speeds. The amount of each Hb type in the current is measured. • An abnormal amount of normal Hb or an abnormal type of Hb in the blood may mean that a disease is present. • Typical finding : HbA decreased or absent, HbF increase, HbA2 variable
  44. 44. CONT… • The most common abnormal Hb are : – Haemoglobin S. This type of haemoglobin is present in sickle cell disease. – Haemoglobin C. This type of haemoglobin does not carry oxygen well. – Haemoglobin E. This type of haemoglobin is found in people of Southeast Asian descent. – Haemoglobin D. This type of haemoglobin is present in some sickle cell disorders.
  45. 45. COMPLICATIONS •Iron overload.  People with thalassemia can get too much iron in their bodies, either from the disease itself or from frequent blood transfusions.  Too much iron can result in damage to : •Infection.  People with thalassemia have an increased risk of infection, especially to those who had splenectomy.
  46. 46. • In cases of severe thalassemia: • Bone deformities.  Thalassemia can make bone marrow expand, which causes bones to widen.  This can result in abnormal bone structure, especially in face and skull.  Bone marrow expansion also makes bones thin and brittle, increasing the chance of broken bones. •Enlarged spleen (splenomegaly).  Thalassemia is often accompanied by the destruction of a large number of red blood cells, making spleen work harder than normal, causing it to enlarge.  Splenomegaly worsen anemia as it can reduce the life of transfused red blood cells.  If spleen grows too big, it may need to be removed.
  47. 47. •Slowed growth rates.  Anemia can cause a child's growth to slow.  Puberty also may be delayed in children with thalassemia. •Heart problems.  Heart problems, such as congestive heart failure and abnormal heart rhythms (arrhythmias), may be associated with severe thalassemia.
  48. 48. Sideroblastic Anaemia Group 4
  49. 49. Aetiology (Hereditary) Structural defect of ALA-S gene Impairment of heme synthesis Accumulation of iron in mitochondria of erythroblasts A ring of iron granules seen in Perls’ stain
  50. 50. Aetiology (Acquired) Malignant diseases Benign conditions
  51. 51. Signs & Symptoms •Shortness of breath •Weakness •Lethargy •Palpitation •Headaches •Visual disturbances – due to retinal haemorrhages •In older pt , symptoms of cardiac failure , angina pectoris or intermittent claudication or confusion may be present. •Pallor of mucous membranes •Tachycardia •Bounding pulse •Systolic flow murmur at apex SignsSymptoms
  52. 52. Laboratory investigations Full blood count Red cell indices Peripheral blood film Bone marrow iron Iron studies
  53. 53. *Presence of 15% or more of ring sideroblasts in bone marrow Basophilic stippling seen in lead poisoning
  54. 54. Sideroblastic anaemia Hb Low MCV Usually low in congenital type but MCV often raised in acquired type MCH Usually low Serum iron Raised TIBC Normal Serum transferrin receptor Normal Serum ferritin Raised Bone marrow iron stores Present Erythroblast iron Ring forms Haemoglobin electrophoresis Normal
  55. 55. Management Pyridoxine therapy Removal of toxic agents Folic acid therapy Blood transfusion + iron chelating agent
  56. 56. • Other factors that have been implicated: – Bone marrow toxins retained in renal failure – BM fibrosis secondary to hyperthyroidism – Haematinic deficiency– iron, vit B12, olate – ↑ red cell distribution – Abnormal red cell membranes causing ↑ osmotics fragility. – ↑ blood loss– occult GIT bleeding, blood sampling, blood loss during haemodialysis or b’coz of platelet dysf(x). – ACE inhibitors(by interfering w control of edogenous erythropoietin release) 11/18/2015
  57. 57. Macrocytic Anaemia
  58. 58. Megaloblastic Anaemia Group 1
  59. 59. Epidemiology • In developing countries, the deficiency of vitamin B12 is significant in Africa, India, and South and Central America due to low intakes of animal products. • In western countries, severe deficiency is usually caused by pernicious anaemia. • B12 deficiency is more common in the elderly because B12 absorption decreases in atrophic gastritis patients which is common in the elderly.
  60. 60. Case Scenario A 70-year-old woman presented with progressive weakness and fatigue. The symptoms had begun about a month earlier, and she no longer felt well enough to do her housework or take her daily walk. She experienced shortness of breath on exertion. Complete blood cell count (CBC) was performed and the results were, hemoglobin, 5.4 gm/dL; mean corpuscular volume (MCV), 103 µm3 (normal 76-96) ; red cell distribution width (RDW), 19.8% (normal, 12%- 15%), She had no history of recent bleeding, jaundice, fever, anemia, or heart disease. She had not been exposed to medications (other than occasional vitamins and aspirin) or toxins.. Findings on the physical examination were unremarkable except for mild tachycardia at rest (96 bpm), a blood pressure of 146/84 mm Hg recumbent and 142/78 mm Hg standing, pallor. Neither the liver nor spleen were palpable. The stool was negative for occult blood. A chest x-ray was normal, and an electrocardiogram showed only sinus tachycardia. The blood urea nitrogen (BUN) level was 15 mg/dL; glucose, 108 mg/dL; and total bilirubin, 1.2 mg/dL (normal, <1.2). Electrolyte levels were normal. A sickle cell preparation was negative. Low serum B12 was notedBlood Film was ordered
  61. 61. Causes of Megaloblastic Anaemias • Vitamin B12 deficiency • Folate deficiency • Abnormalities of vitamin B12 or folate metabolism (eg transcobalamine deficiency , nitrous oxide, antifolate drugs)
  62. 62. Pathophysiology of Vitamin B12 Vitamin B12 is cofactor for: 1) Synthesis of thymidine 2) Normal methionine synthesis In their absence: Cause inadequate DNA synthesis Defective nuclear maturation (Nucleocytoplasmic Ansynchrony) Blockade in cell division Leads to: • Abnormal large RBCs and erythroid precursors (megaloblasts). • Affect granulocyte maturation. • Neurologic complication:- attribute to abnormal myelin degradation.
  63. 63. Vitamin B12 Deficiency Causes of severe vitamin B12 deficiency 1. Nutritional – Inadequate intake – Vegetarianism 2. Malabsorption – Gastric causes – Pernicious anemia – Congenital lack or abnormality of IF – Total or partial gastrectomy – Intestinal causes: chronic tropical sprue, intestinal stagnant loop syndrome, ileal resection, Crohn’s disease, fish tapeworm
  64. 64. Causes of mild vitamin B12 deficiency • Malabsorption of B12 • Elderly • Atrophic gastritis • Severe pancreatitis • Gluten induced enteropathy • HIV infection or therapy with metformin
  65. 65. Pathophysiology of Folate • Folate enter plasma as methyl THF. • Methyl THF is a required in synthesis of thymidine thus, for DNA synthesis. • Lack of folate cause : – Inadequate DNA synthesis thus, abnormal large RBC synthesis.
  66. 66. Folate Deficiency Causes of folate deficiency • Nutritional – Especially old age, institutions, poverty, famine, special diets • Malabsorption – Tropical sprue, gluten induced enteropathy, partial gastrectomy, extensive jejunal resection or Crohn’s disease • Excess urinary folate loss – Active liver disease, CCF • Drugs – Anticonvulsants, sulfasalazine • Excess utilization – Physiological • Pregnancy, lactation, prematurity – Pathological • Haematological disease (haemolytic anaemias, myelofibrosis) • Malignant disease: carcinoma, lymphoma, myeloma • Inflammatory diseases: Crohn’s disease, tb , RA, psoriasis, malaria • Mixed – Liver disease, alcoholism, ICU
  67. 67. Clinical Features • Onset – insidious/ gradually progressive sign and symptoms of anemia • Mildly jaundice- excess breakdown of hb due to increase ineffective erythropoiesis • Glossitis, angular stomatitis, mild symptoms of malabsorption with loss of weight • Neuropathy (severe B12 deficiency) • Neural tube defect in fetus (eg : encephaly, spina bifida) • Increased melanin pigmentation
  68. 68. Glossitis : beefy-red and painful tongue Angular stomatitis Baby with neural tube defect (spina bifida) From : Essential Haematology , 6th Edition
  69. 69. Investigation • FBC: MCV > 98fL • FBP : Oval macrocytic rbcs, hypersegmented neutrophils, pancytopenia • BMA : hypercellular, large erythroblast, failure of nuclear maturation, giant metamyelocytes (BMA is not mandatory in B12/folate deficiency) • Increased serum unconjugated bilirubin, LDH • Reduced serum/ red cell folate and B12 (mandatory test)
  70. 70. Treatment of Megaloblastic Anaemia Vitamin B12 deficiency Folate deficiency Compound Hydroxocobalamin (B12) Folic acid Route Intramuscular Oral Dose 1000ug 5mg Initial dose 6x1000ug over 2-3 weeks Daily for 4 months Maintenance 1000ug every 3 months Depend on underlying disease; lifelong theraphy may be needed in chronic inherited haemolytic anaemias, myelofibrosis, renal dialysis Prophylactic Treatment Given To: Total gastrectomy Ileal resection Pregnancy, severe haemolytic anaemias, dialysis, prematurity
  71. 71. Normochromic & Normocytic Anemia Group 1
  72. 72. Acute of Chronic Disease (ACD) • Common type of anaemia among pt with chronic inflammatory and malignant dz • Causes of ACD : – Chronic iflammatory disease • Infections (pulmonary abcess, tb, osteomyelitis, pneumonia) • Non infectious (RA, SE, CTD, sarcoidosis ) – Malignant disease ( ca, lymphoma, sarcoma ) • Sign and symptoms depends on underlying causes • Not related to bleeding, haemolysis or marrow infiltration • EPIDEMIOLOGY  Most common anemia amongst patients with chronic inflammatory and malignant disease.  2nd commonest anemia after IDA, worldwide.
  73. 73. CASE SCENARIO 1 A 72 - year – old man, previously healthy, presents with fever, chills, cough and SOB. CXR shows a right – middle – lobe infiltrate. He is diagnosed with pneumonia and admitted for iv antibiotics. Blood cultures eventually grow Strep. Pneumoniae. By hospital day 3, he is afebrile but his Hb is 10.5 g/dl, down from 12.4 g/dl on admission and 13.5 g/ dl 1 month ago. He has no evidence of GI blood loss or overt haemolysis. Red cell indices revealed a normocytic normochromic anaemia.
  74. 74. CHARACTERISTIC FEATURES Anemia in chronic disease MCV/MCH Normochromic normocytic anaemia or mildly hypochromic (MCV rarely <75fL) Serum iron Reduced TIBC Reduced Serum ferritin Normal/ raised Bone marrow iron stores Present Eryhtroblast iron Absent Hb electropheresis Normal
  75. 75. • Pathogenesis-  Key regulatory protein – hepcidin which is produced by liver  High levels of production are encouraged by pro-inflammatory cytokines, especially IL- 6.  Hepcidin binds to ferroportin on the membrane of iron exporting cells, and thereby inhibiting the export of iron from these cells into the blood Iron remain trapped inside the cells in the form of ferritin, levels of which are therefore normal or high in the face of significant anaemia • Treatment- treat underlying cause (eg. 60% RA patients). • Inhibition hepcidin and inflammatory modulator → block the inhibition of iron transfer.
  76. 76. EXAMPLE- ANEMIA IN CHRONIC KIDNEY DISEASE(CKD) • Anaemia is a complication of CKD whereby erythropoietin deficiency is the most significant cause. • Insufficient or absent erythropoietin secretion results in normochromic, normocytic anaemia. • The anaemia becomes more severe as the glomerular filtration rate progressively decreases.
  77. 77. Haemolytic Anaemia HERIDATARY ACQUIRED
  78. 78. Loss Of Elasticity:Sickle Cell Anaemia o Sickle cell disease is a group of haemoglobin disorder in which the sickle β-globin gene is inherited. o Homozygous sickle cell anaemia (Hb SS) is the MOST COMMON o Doubly the doubly heterozygote conditions if Hb SC and Hb Sβthal also cause sickling disease o The abnormal red blood cells are rigid and crescent- like shaped that can stuck in the blood vessels resulting in blocking of the blood flow. Hence, distribution of the blood to supply oxygen to all parts of the body might be impaired. Hoffbrand, A., & Moss, P. (2006). Essential haematology (5th ed., p. 85).
  79. 79. Epidemiology o It is believed that the sickle cell abnormal hemoglobin originated in Africa, where it is most commonly encountered, while India is considered as an additional place of origin. HbS is prevalent in Middle East and Mediterranean countries, while population migration has taken the gene to almost all regions of the world, including Western and Northern Europe. o About 7% of the global population carry non-functional hemoglobin gene, with more than 500 000 affected children born annually. More than 80% of these are born and live in the developing countries in the world. o More than 70% of them have a sickle disorder. A number of affected children born in developing countries might be died, misdiagnosed, receiving treatment or left untreated.
  80. 80. Causes Point mutation at 6th codon of β globin (Glutamate  valine)
  81. 81. Pathophysiology
  82. 82. Clinical Features 1. Vaso-occlusive crises The earliest presentation in the first few years of life is acute pain in hand, and feet (dactylitis) dt vaso-occlusion of the small vessels. Severe pain in the other bones occur in older children/adult. Fever often accompanies the pain. 2. Anaemia Hb range from 6-8 g/dL but acute fall in Hb level can occur owing to : • Splenic sequestration • Bone marrow aplasia • Further haemolysis Kumar, P. (n.d.). Kumar & Clark’s clinical medicine (Seventh ed., p. 409, 410)
  83. 83. 3. Splenic Sequestration • Vaso-occlusion causes acute painful enlargement of the spleen • Causing splenic pooling of RBC  hypovolaemia  circulatory collapse  death 4. Aplastic Crises Caused by infection with Parvovirus B19 or Folate deficiency Clinical Features (cont)
  84. 84. Long-term Complications • AFFECT GROWTH AND DEVELOPMENT OF CHILD – Short statue in young children (regain height by adulthood) – weight not appropriate with age (below normal weight) – Delayed sexual maturation (boy- no increase in testicular volume by 14 years; girl- no breast development by 13 and a half years) • BONE – Common site for vaso-occlusive of small vessels. • Avascular necrosis of hips and shoulders • Compression of vertebrae • Shortening of bones in the hands and feet. • Osteomyelitis (by Staphylococcus aureus, Staphylococcus pneumoniae, Salmonella) Kumar, P. (n.d.). Kumar & Clark’s clinical medicine
  85. 85. INFECTIONS • Tissue susceptible to vaso-occlusive (Bones , lungs, kidneys) LEG ULCERS • Occur spontaneously (vaso-occlusive) or following trauma. Then become infected and resistant to treatment. CARDIAC PROBLEMS • Cardiomegaly, arrthymias, iron overload cardiomyopathy. • Myocardial infarction due to thrombotic episodes. NEUROLOGICAL COMPLICATIONS • 25% of patient • Transient ischemic attacks, fits, cerebral infarction, cerebral haemorrhage, coma. • Strokes occur in about 11% of patient under 20 years of age. • Most common finding is obstrustion of a distal intracranial internal carotid artery or a proximal middle cerebral artery.
  86. 86. Cholelithiasis – Pigment stone as a result of chronic haemolysis Liver problems – Chronic hepatomegaly and liver dysfuction caused by trapping of sickle cells. Renal. Chronic tubulointestitial nephritis. Priapism. – Unwanted painful erection as a result of vaso-acclusion. – Impotence Eye – Background retinopathy, proliferative retinopathy, vitreous haemorrhages and retinal detachment all occur Pregnancy – Impaired placental blood flow causes • Spontaneous abortion • Intrauterine growth impairment • Pre-eclampsia • Fetal death
  87. 87. Investigations 1. Complete blood count (CBC) Anaemia (Hb range 6-8 g/dL) High reticulocyte count (10-20%) 2. Blood films (feature of hyposplenic and sickling Sickle cells(arrowed) and target cells. Post splenectomy film with Howell-Jolly bodies(arrowed), target cells and irregular contracted cells. Kumar, P. (n.d.). Kumar & Clark’s clinical medicine (Seventh ed., p. 410)
  88. 88. Investigations (cont) 3. Sickle solubility test A mixture of HbS in a reducing solution (sodium dithionite) gives a turbid apperance because of precipitation of HbS Normal Hb gives clear solution 5. The parents of the affected child will show features of sickle cell trait. Normal Sickle cell trait Sickle cell anaemia Hb electrophoresis 4. Hb electrophoresis to confirm diagnosis Results shows : no Hb A, 80-95% Hb SS, and 2-20% Hb F
  89. 89. Treatment o Prophylactic –to avoid those factors known to precipitate crises, esp dehydration, anoxia, infections, stasis to the circulation and cooling of the cell surface o Folic acid (5 mg once weekly) o Pneumococcal, haemophilus, and meningococcal vaccination and Hepatitis B vaccine if transfusion is needed. o Regular oral penicillin (should start at dx and continue at least until puberty) o Crises –treat by rest, warmth, rehydration by oral fluid and/or IV normal saline (3L in 24H) –blood transfusion is given in severe anaemia o Hydroxyurea (15-20 mg/kg) can increase Hb F levels and have shown to improve the clinical course children/adults who are having 3 or more painful crises each year o For pain –analgesia at appropriate level should be given (NSAID, opiates or paracetamol) Hoffbrand, A., & Moss, P. (2006). Essential haematology (5th ed., p. 89).
  90. 90. 1. Membrane defects : Hereditary Spherocytosis • Most common in northern Europeans Pathogenesis :- • Vertical interactions between the membrane skeleton and the lipid bilayer of the red cell • Loss of membrane because release of parts of the lipid bilayer that are not supported by the skeleton • Normal biconcave red cell but become increasingly spherical as loss of surface area relative to volume as they circulate through spleen and the rest of RE system • Unable to pass through splenic microcirculation where they die prematurely
  91. 91. Blood film of HS
  92. 92. Membrane defects : Hereditary Spherocytosis Molecular basis :- • Ankyrin deficiency/ abnormalities • Alpha or beta – spectrin deficiency / abnormalities • Band 3 abnormalities • Pallidin (protein 4.2) abnormalities
  93. 93. Clinical features :- • Autosomal dominant rarely recessive • Anemia can be present at any age • Fluctuating jaundice (particularly marked if a/w Gilbert’s disease (a defect of hepatic conjugation of bilirubin) ; splenomegaly occurs in most patients • Frequent pigment gallstones Membrane defects : Hereditary Spherocytosis
  94. 94. Investigation :- • A rapid fluorescent flow analysis of eosin-maleimide bound to red cells • Treatment :- • Splenectomy : preferably laparoscopic but only if clinically indicated ;symptomatic anemia/gallstones/leg ulcers/growth retardation – risk of post-splenectomy sepsis particularly in early childhood • Cholecystectomy should be performed with splenectomy if symptomatic gallstones are present Membrane defects : Hereditary Spherocytosis
  95. 95. 2. Defective red cell metabolism : Glucose- 6-phosphate dehydrogenase deficiency Epidemiology :- • 400 million people worldwide are deficient in enzyme activity • Sex-linked • Affecting males • Carried by females (advantage resitance to Falciparum Malaria • Main races :- West Africa, the Mediterranean, the Middle East and SE Asia • Mildly in black Africans, more severe in Orientals and most severe in Mediterranean • Severe deficiency occurs occasionally in white people
  96. 96. Agents that may cause HA in G6PD deficiency (Things that induce OXIDATIVE STRESS) :- • Infections and other acute illnesses eg DKA • Drugs – antimalarials eg primaquine, sulphonamides eg cotrimoxazole, analgesics eg aspirin, antihelminths eg beta-napthol • Fava beans or other vegetables • Miscellaneous eg vit K analogues Defective red cell metabolism : Glucose-6- phosphate dehydrogenase deficiency
  97. 97. Defective red cell metabolism : Glucose-6- phosphate dehydrogenase deficiency Pathogenesis :- • Function of G6PD is to reduce nicotinamide adenine dinucleotide phosphate (NADP) • The only source of NADPH for production of glutathione • Defieciency of G6PD renders the red cell susceptible to oxidant stress • Most common types are B (Western) and type A in Africans
  98. 98. Clinical features :- • Usually asymptomatic • Main syndromes :- 1. Acute HA in response to oxidant stress eg drugs, fava beans or infections – caused by rapidly developing intravascular haemolysis with haemoglobinuria, the anemia maybe self limiting as new young red cells are made with near normal enzyme levels 2. Neonatal jaundice 3. Rarely, a congenital non-spherocytic haemolytic anemia These syndromes may result from different types of severe enzyme deficiency Defective red cell metabolism : Glucose-6- phosphate dehydrogenase deficiency
  99. 99. Diagnosis :- • Between crises the blood count is normal • By screening test or direct enzyme assay on red cells • During crises – ‘bite’ cells/ ‘blister’ cells / contracted and fragmented cells which have had Heinz bodies removed by the spleen. Heinz bodies are oxidized, denatured Hb • Higher enzyme level in young red cells, red cell enzyme assay may give a ‘false’ normal level in the phase of acute hemolysis with a reticulocyte response • Subsequent assay after the acute phase reveals the low G6PD level when the red cell population is of normal age distribution Defective red cell metabolism : Glucose-6- phosphate dehydrogenase deficiency
  100. 100. Treatment :- • Stop offending drugs • Treat underlying infection • Maintain high urine output • Blood transfusion for severe anemia when necessary • Photography and exchange transfusion might be needed in severe cases for neonates as they are prone to neonatal jaundice. The jaundice is usually not caused by excess haemolysis but by deficiency of G6PD affecting neonatal liver function Defective red cell metabolism : Glucose-6-phosphate dehydrogenase deficiency
  101. 101. Haemolytic Anaemia HERIDATARY ACQUIRED Group 4
  102. 102. Autoimmune Hemolytic anemia
  103. 103. A 32-year-old man gradually noticed that he had yellow eyes and dark urine, felt continually tired, and was short of breath when climbing stairs. He had no other symptoms; in particular there was no itching, fever or bleeding, and he was not taking any drugs. On examination, he was anaemic and jaundiced. He was afebrile and had no palpable lymphadenopathy, but evident of splenomegaly
  104. 104. Possible Diagnosis? Possible causes Points Liver disease Jaundice Dark urine Splenomegaly Hemolytic anemia Jaundice Dark urine Shortness of breath Tired Splenomegaly
  105. 105. INVESTIGATION FBC • Haemoglobin 54g/l (130- 180 g/l) • WBC 9.4 x 109/L • Platelets 192 x 109/L • MCV 120 fl (76-96 fl) • Reticulocyte count 9% (<2%) • The blood film shows gross polychromasia and spherocytes; Suspected : Hereditary spherocytosis AIHA
  106. 106. FURTHER INVESTIGATION • LFTs Serum bilirubin 47 umol/L ( 3-17umol/L) • LDH 5721 iu/L (105-333iu/L) • DAT 3+ positive with IgG .
  107. 107. PROVISIONAL DIAGNOSIS Warm AIHA  +ve DAT with IgG
  108. 108. Autoimmune hemolytic anemia • Acquired disorder resulting from increased red cell destruction d/t red cell autoantibodies. • Classification : • Warm AIHA • Cold AIHA • Paroxysmal cold haemoglobinuria (PNH)
  109. 109. Warm AIHA • Autoantibodies predominantly IgG • Possess relatively high affinity for RBCs at 37ºc • Clinical Features • Occur at any age either sex • Short episode of anemia and jaundice. • Generalised symptoms –fatigue, weakness, malaise, fever • Splenomegaly & hepatomegaly common
  110. 110. Cold AIHA Autoimmune predominantly IgM Antibody attach to red cells and cause agglutination – at lower temperature <4◦C • Infection related : Mycoplasma. pneumonia, EBV • Clinical Features • Exacerbation in winter • Cold, painful, often blue fingers, toes, ears or nose (Acrocynosis)
  111. 111. Paroxysmal cold haemoglobinuria (PNH) • Due to a biphase IgG antibodyAttaches with complement to RCs in the cold extremities • Causes lysis when the cell is warmed later from the complement which remains attached • Post-viral phenomenon • Typically an acute self-limiting disease
  112. 112. Clinical features PCH • Presents acutely with leg and back pain, abdominal pain with cramps, nausea/vomiting/diarrhoea and • dark urine (haemoglobinuria) • following exposure to the cold
  113. 113. Investigation for suspected AIHA • FBC and reticulocyte count • Blood film • DAT (Direct Agglutination Test) • Donath Landsteiner Ab (test for PNH) • Blood group specificity • Cold agglutinin titre • Tests for associated infection or disease
  114. 114. Treatment • Corticosteroid (induced remission) • Splenectomy (if fail to respond well to corticosteroid) • Immunosuppressive drugs ( rituximab) • Blood transfusion (if necessary) • Avoidance of Cold ( Cold AIHA & PNH) • Folic acid – as active hemolysis consume folate
  115. 115. Alloimmune Haemolytic Anaemia
  116. 116. Classification (source : Essential Haematology Hoffbrand Moss) Induced by red cell antigens • Haemolytic transfusion reactions • Haemolytic disease of the newborn • Post stem cell grafts Drug-induced • Drug-red cell membrane complex • Immune complex
  117. 117. Haemolytic transfusion reactions (source : Essential Haematology Hoffbrand Moss) Immediate Delayed
  118. 118. Clinical features of a major haemolytic transfusion reaction (source : Essential Haematology Hoffbrand Moss) Haemolytic shock phase Oliguric phase Diuretic phase
  119. 119. Investigations (source : Essential Haematology Hoffbrand Moss) Check for blood compatibility and bacterial contamination of the blood
  120. 120. Management (source : Essential Haematology Hoffbrand Moss) To maintain blood pressure and renal perfusion IV dextran, plasma or saline & frusemide IV hydrocortisone & antihistamine IV adrenaline Compatible transfusion
  121. 121. Drug-induced immune haemolytic anemia
  122. 122. Drug-induced immune haemolytic anemia • Drug-induced immune hemolytic anemia is a blood disorder that occurs when a medicine triggers the body's defense (immune) system to attack its own red blood cells. • Drugs can cause HA by 3 mechanisms. 1)Antibody directed against a drug red-red cell membrane complex – Penicillin, ampicillin 2)Deposition of complement via a drug protein(antigen)- antibody complex onto the red cell surface – Quinidine, Rifampicin 3)A true autoimmune hemolytic anemia with unclear role of the drug – methyldopa
  123. 123. Symptoms • Dark urine • Fatigue • Pale skin color • Rapid heart rate • Shortness of breath • Yellow skin color (jaundice) Investigations Physical examination : enlarged spleen Tests : blood/ urine test - Absolute reticulocyte count - Direct or indirect Coombs test - Indirect bilirubin levels - Red blood cell count - Serum haptoglobin Treatment - Stop taking the drugs -Take a prednisone to suppress the immune response against the red blood cells. Special blood transfusions may be needed to treat severe symptoms.
  124. 124. Red Cell Fragmentation syndromes. DEFINITION • Form of haemolytic anaemia caused by intravascular m echanical trauma resulting in destruction of red cells, re lated to cardiovascular defects and haemolytic anaemia. • Caused by red blood cells passing through abnormal small vessels with also fibrin deposition. • Also known as microangiopathic hemolytic anemia. • Also associated with disseminated intravascular coagulation or platelet adherence.
  125. 125. Infection-induced hemolytic anemia Microorganisms may cause injury to red cells through different mechanisms such as: (1) physical invasion of red cells (e.g. malaria) (2) hemolysin secretions(alpha toxin) to damage the red cells directly (e.g. Clostridium perfringen) (3) infection that triggers formation of antibody (anti-I) against red cells (e.g. mycoplasma) (4) microangiopathic hemolysis caused by disseminated intravascular coagulation associated with infection. (5) may precipitate haemolytic crisis in G6PD deficiency.
  126. 126. Anaemia in infant & children PAEDIATRICS TEAM: Muhammad Faiz Bin Nordin Bibi Afzarina Binti Mohamed Hanafee Hanis Zahirah Binti Baharudin
  127. 127. Definition Anaemia is defined as an Hb level below the normal range. The normal range varies with age, so anemia can be defined as: • Neonate : Hb < 14 g/dl • 1-12 months : Hb < 10 g/dl • 1-12 years : Hb < 11 g/dl
  128. 128. Causes of anaemia in infant & children • Impaired red cell production • Increased red cell destruction (haemolysis) • Blood loss • Anaemia of prematurity
  129. 129. Impaired red cell production May be due to Infective erythropoiesis - iron deficiency red cell aplasia - Fanconi anemia
  130. 130. Infective erythropoiesis: Iron deficiency • Main cause - inadequate intake - malabsorption - blood loss • Common in infants because additional iron is required for ↑ blood volume accompanying growth & to build up
  131. 131. • Diagnostic clue for infective erythropoiesis - normal reticulocyte count - abnormal MCV of RBC : *low in iron deficiency *raised in folic acid deficiency
  132. 132. • Iron may come from - breast milk *low iron content but 50% of iron is absorbed - infant formula: supplement - cow’s milk *higher iron content than breast milk but only 10% is absorbed. - solid introduced at weaning
  133. 133. Dietary sources of iron
  134. 134. Iron requirement during childhood
  135. 135. • Clinical feature - most infant & children are asymptomatic until Hb drop below 6-7 g/dl - When it become worsen, children tire easily & young infant feed more slowly than usual. - appear pale but pallor is an unreliable sign unless confirmed by pallor of conjuctiva, tongue or palmar creases. - children have ‘pica’
  136. 136. • Management - dietary advice and supplementation with oral iron. *except for malabsorption (celiac disease) & chronic blood loss patient (Meckel diverticulum) - should be continue until Hb is normal and then for a minimum of a further 3 months to replenish the iron stores. - Blood transfusion should never be necessary for dietary IDA
  137. 137. Red cell aplasia • Causes - congenital red cell aplasia *Fanconi anaemia - transient erythroblastopenia of childhood - parvovirus B19
  138. 138. • Diagnostic clue - low reticulocyte count despite low Hb - normal bilirubin - negative direct antiglobulin test (Coombs test) - absent red cell precursors on bone marrow examination.
  139. 139. Aplastic anaemia: Fanconi anemia • Most common inherited type • Autosomal recessive diorder due to genetic defect DNA repair. • Usually oocur among 5 to 10 years old children. • 10% developed acute myeloblastic anemia
  140. 140. • Clinical feature - Growth retardation & congenital effect of skeleton - short stature, abnormal thumb and radii, microcephaly, micropthalmia, café au lait & hypopigmented spot, renal structural abnormality
  141. 141. • Management - bone marrow transplantation using normal donor bone marrow from unaffected siblings or matched unrelated marrow donor.
  142. 142. Causes of anaemia in infant & children • Impaired red cell production • Increased red cell destruction (haemolysis) • Blood loss • Anaemia of prematurity
  143. 143. Increased red cell destruction (haemolytic anemia) • Causes - red cell membrane disorders *Hereditary spherocytosis - red cell enzyme disorder *G6PD deficiency - haemoglobinopathies *Sickle cell disease, B-thalassaemia major
  144. 144. red cell membrane disorders: Hereditary spherocytosis • Autosomal dominant inheritance but 25% of cases there is no family history • May cause early, severe jaundice in newborn infants. • Clinical feature - usually asymptomatic - jaundice, anemia, mild to moderate splnomegaly, aplastic crisis & gallstones • Management - oral folic acid, splenectomy if symptomatic
  145. 145. red cell enzyme disorder: G6PD deficiency • Commonest red cell enzymopathy • Is x-linked recessive (predominantly affect male) • May present with neonatal jaundice • Causes acute intermittent hemolysis precipatated by infection, certain drugs, fava bean & naphthalene. • Associated with jaundice, dark urine, fever, malaise • Management - parents should be given advice about the sign of acute hemolysis and give a list of drugs, chemicals and food to avoid.
  146. 146. Haemoglobinopathies: Sickle cell disease • Autosomal recessive • SCD result in ischemia in organ • Clinical feature - anemia, infection, painful crises, squestration crises, splenomegaly, growth failure, gallstone - Serious complication are bacterial infection, acute chest syndrome, stroke and priapism. • Management - Treatment of acute crisis- oral or IV analgesia and good hydration - Treatment of chronic problem- hydroxyurea to increase HbF, bone marrow transplant
  147. 147. haemoglobinopathies: B-thalassaemia major • Mutation of B-globin gene result in an inability to prodece HbA • Clinical feature - severe anemia, growth failure, pallor, jaundice, bossing of skull, maxillary overgrowth, splenomegaly, hepatomegaly, need for repeated blood transfusion
  148. 148. • Management - life long blood transfusion • Complication of long rem-blood transfusion in children - iron deposition - antibody formation - infection
  149. 149. Anaemia in the newborn • Reduced RBC production • Increased RBC destruction • Blood loss • Anaemia of prematurity
  150. 150. Blood loss • Main causes - feto-maternal haemorrhage - twin-to-twin transfussion - blood loss around the time of delivery • Main diagnostic clue - severe anemia with a raised reticulocyte count and normal bilirubin
  151. 151. Anaemia of prematurity • Main causes - inadequate erythropoietin production - reduced red cell lifespan - frequent blood sampling whilst in hospital - iron and folic acid deficiency (after 2-3 months)
  152. 152. Thank You
  154. 154. ESSENTIAL FOR: Support and protection to developing fetus To prepare the mother for labour and delivery CHANGES ARE DUE TO: Hormonal alteration Increased metabolic Mechanical factor of gravid uterus
  155. 155. WHY STUDY THE CHANGES??? To differentiate normal from abnormal To make the process of delivery smooth To anticipate and manage complications
  156. 156. HEMATOLOGICAL SYSTEM 1) Plasma volume o Begin to ↑ to 10% at 7 weeks and increasing rapidly, then plateauing at 40-50% by 32 weeks. o At the same time,red cell volume also ↑ by 15-20% → help to improve utero-placental perfusion
  157. 157. 2) Red cell mass Red cell mass expansion < blood volume expansion Total net of blood conc./viscosity ↓ by 20% (condition known as hemodilution) Dilutional anemia (physiological anemia) Oedema in pregnancy d/t drop colloid oncotic pressure
  158. 158. 3) Blood component o ↑ total vol. RBC up to 25% d/t elevated level erythropoeitin →provide extra O₂ demand o WBC can go up to 15,000-16,000/mm3 o Platelet slightly fall d/t dilutional effect o ↑ clotting factors(VII,VIII,IX,X) and fibrinogen→protect from hemorrhage at delivery
  159. 159. • Severe anemia may weaken the uterine muscle strength which leads to uterine atony, that leads to post partum hemorrhage • Anemia can also lower resistance to infectious disease • However, the impact of anaemia on the extent of blood lost at childbirth and postpartum is not well-understood. How ‘anemia’ cause increased risk of PPH ?
  160. 160. • Check ferritin in early pregnancy: give iron supplements only if iron deficient • Folic acid 5mg daily is required. • Parenteral iron should be avoided • The aim during pregnancy is to maintain pre- transfusion Hb concentration level above 10g/dL How do you manage a patient with thalassemia during pregnancy ?
  161. 161. • Thalassemia screening of the partner; If both positive, the couple need counselling on the risk of pregnancy with thalassemia major. • Evaluation of cardiac function by ECHO, and of liver and thyroid functions, in each trimester (Main risk to the mother is cardiac complications). • Iron chelation therapy is complex and should be tailored to the needs of the individual woman. Others
  162. 162. Anemia in Pregnancy
  163. 163. Contents  Definition of anaemia in pregnancy  Prevalence of anaemia in pregnancy  Causes of anaemia in pregnancy  Iron-deficiency anaemia - factors affecting Iron absorption - types (Prepartum anaemia, IDA during Pregnancy, Anemia + Post partum hemorrhage) - signs & symptoms of IDA - advice on how to take Iron tablet
  164. 164. Definition of anaemia in pregnancy During Pregnancy Haemoglobin (g/dL) WHO < 11 CDC < 11 (1ST trimester) < 10.5 (2nd trimester) < 11 (3rd trimester) Post partum Haemoglobin (g/dL) <10
  165. 165. Prevalence of anemia in pregnancy World 47% 42% 30% Malaysia 32% 38% 30% Pre-school children Pregnant women Non-pregnant women during child bearing age WHO Global Database on Anemia
  166. 166. Prevalence (contd.) • Developing countries – Africa 35% to 56% – Asia 37% to 75% – Latin America 37% to 52% • Industralised countries- mean prevalence 18% • HSNZ- 70.8%
  167. 167.  Insufficient intake/insufficient production : nutrition, blood disease  Increase loss : bleeding, renal disease, infestation of parasites  Increase demand : placenta, fetus, red blood cells expansion Causes of anaemia in pregnancy
  168. 168. Iron-deficiency Anaemia (commonest cause)
  169. 169. The most frequent nutritional disorder How many suffer from iron deficiency anemia? 2 billion peoples 1/3rd of the world’s population
  170. 170. Factors affecting Iron absorption  Iron Absorption Enhancers - Vitamin C; citrus fruit and juice, kiwi, strawberries, tomatoes, etc  Iron Absorption Inhibitors - Iron binding polyphenol: red wine - Coffee & tea - Eggs - Milk
  171. 171. Prepartum anemia • Among fertile, non- pregnant women, ∼40% have ferritin of ≤30 μg/L(low iron status) • Prepartum IDA predisposes to postpartum IDA- some amt blood loss during labour, lactation, dilutional effect of pregnancy Test Level Remarks Serum Ferritin (ug/L) < 30 Low iron status < 15 Iron deficiency
  172. 172. IDA During pregnancy
  173. 173. Iron requirement in pregnancy 100mg/day iron for all women* 9x higher Iron requirement during pregnancy
  174. 174. Anemia and Post Partum Hemorrhage • Anaemia increase the risk of PPH • Unability of uterus to contract • Risk of DIVC higher • Risk of post partum hysterectomy higher
  175. 175. Post-partum Anemia “More than 80 percent of maternal deaths are caused by haemorrhage,…… Most of these deaths are preventable when there is access to adequate reproductive health service”
  176. 176. Post partum anemia • Severe postpartum anemia is a complication of 5% of deliveries • Following delivery, women lose some amount of iron through breastfeeding and lactation • IDA has been associated with impaired cognitive function and behavioral disturbances in postpartum women • Mother’s iron status should be evaluated prior to discharge to monitor postpartum anemia
  177. 177. Post partum anemia • Iron deficiency persists beyond the 4-6 weeks postpartum period – 12% of women are iron deficient up to 12 months after delivery – 8% of women are iron deficient 13-24 months after delivery • Iron supplementation should continue after delivery if iron status remains low or while the mother is breastfeeding
  180. 180. Management of Anemia in pregnancy
  181. 181. Method Pros Cons Oral Iron Cheap, Easy to take, Hardly any serious side effects Slow to act, Compliance issue Parenteral Iron Faster action, ensure compliance Cause anaphylactic reaction, Pain and skin discoloration at injection. Blood Transfusion Treat anemia almost instantly Mismatch, Blood reaction, Disease (Hepatitis, HIV), Fluid Overload
  182. 182. • IDA is treated mainly with iron supplements • Iron supplements have 2 forms, oral and parenteral. Oral iron is most commonly used • Use of iron supplements helps in improving the iron status of the mother during pregnancy and during the postpartum period, even in women who enter pregnancy with reasonable iron stores Iron Supplements
  183. 183. • Oral Iron (200 – 300 mg of elemental iron) with folic acid (500 microgram) prescribed in divided dose • Type of oral supplement available : - Ferrous fumarate - Ferrous gluconate (If the above is not tolerated) - Ferrous glycine sulphate - Ferrous sulphate (dry) - Iron polysaccharide • Why Ferrous fumarate ? - Least expensive and best absorbed form of iron - Newer drugs ? Not proven yet Oral Iron Supplements
  184. 184. • Anorexia • Diarrhea • Epigastric Discomfort (Combination with Vit C supplements) • Nausea, Vomiting • Constipation and Dark colored stool • Temporary staining of teeth *Oral Iron therapy must be continued for at least 12 months after the anemia has been corrected in order to replenish the depleted iron stores Side Effects
  185. 185. • Start with one tablet daily first, then increase gradually until three times daily dosing • Avoid use of high-dose Vit C supplements • Taking with meals (But can also reduced iron absorption) – One hour before meal • Administer at bed time Methods of reducing side effects
  186. 186. • Daily oral iron and folic acid supplementation is recommended as part of the antenatal care to reduce the risk of low birth weight, maternal anaemia and iron deficiency (strong recommendation) WHO Recommendation
  187. 187. • a 30 mg of elemental iron equals 150 mg of ferrous sulfate heptahydrate, 90 mg of ferrous fumarate or 250 mg of ferrous gluconate. Suggested scheme Supplement composition Iron: 30–60 mg of elemental iron Folic acid: 400 μg (0.4 mg) Frequency One supplement daily Duration Throughout pregnancy. Iron and folic acid supplementation should begin as early as possible Target group All pregnant adolescents and adult women Settings All settings
  188. 188. • An agent that increase the hemoglobin level and the number of erythrocytes in the blood • Drug to stimulate RBC formation • Primarily used in treatment of anemia • Example – - Iron (Oral, Parenteral) - Folic Acid - Vit B12 What is ‘hematinic’
  189. 189. According to period of gestation : Less than 30 Weeks – Oral iron with folic acid 30 – 36 weeks – Parenteral Iron Therapy Greater than 36 weeks – Blood Transfusion Management of IDA in pregnancy
  190. 190. Advice on how to take iron tablet: take several times a day on an empty stomach. best to be taken at; -bedtime -or about an hour before a meal and at the same time drink juice that's rich in vitamin C, such as a glass of orange juice for optimum absorption of iron.
  191. 191. • Increased in reticulocytes - Increased 2 – 16%, by 4 – 6 days (earliest), pekas at 9 – 12 days. • Increased in hemoglobin levels (Rising at rate of 2 g/dl after 3 weeks) • Total Plasma Iron will gradually increase and TIBC will return to normal in about a month • Blood ferritin levels return to normal in about 4 – 6 months • Epithelial Changes (eg. Tongue and nails) revert to normal Increased in Hb in oral therapy
  192. 192. *Given over 6 – 8 hours under constant observation Parenteral forms of Iron Iron preparation Route Elemental Iron Content Iron Dextran (Imferon) IM or IV 1ml = 50 mg Ferric Hydroxide + Dextran Iron sorbitol citrate complex (Jectofer) IV 1ml = 50mg Ferric Iron, sorbitol and citric acid Iron sucrose IV 1ml = 2mg Iron-ferric hydroxide in sucrose
  193. 193. • Intolerance to oral form of iron • When iron deficiency is not correctable with oral treatment • Non-compliance on part of the patient (Repeatly fails to heed instructions/incapable of following them) • Patient suffering from Inflammatory Bowel Disease (Aggravated by oral iron therapy) • Patient is unable to absorb iron orally • Patients near term (32 – 36 weeks of pregnancy) Indication of use of parenteral iron therapy
  194. 194. • IM - Pain and staining of the skin at the site of injection + Development of fever, chills, myalgia, athralgia, injection abscess • IV - Serious side effect like anaphylaxis reactions (0.7%) • Both – Systemic reactions Immediate : Hypotension, headache, malaise Delayed : Lymphadenopathy, myalgia, athralgia Side Effects
  195. 195. • There is not enough time to achieve a reasonable Hb level before delivery. (For example, patient presents with severe anemia beyond 36 weeks) • There is acute blood loss or associated infections • Anemia is refractory to iron therapy Indication for blood transfusion