Anemia for final year MBBS

1. • Fatigue and Weakness
• Headache
• Difficulty Concentrating
• Reduced Interest
• Irritability
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2. 2

3. • According to the World Health Organization (WHO), an estimated
1.62 billion people worldwide had anemia in which represents about
25% of the global population.
•
According to the WHO, approximately 47% of preschool children in
developing countries were estimated to be anemic.
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4. • According to the
“National Nutrition Survey” 2018,
 The prevalence of anemia among children aged
6 to 59 months in Pakistan is 62.3%.
 Among women of reproductive age (15-49
years), the prevalence of anemia is 52.1%.
Among pregnant women, it is 62.8%.
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5. Anemia
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6. Learning Objectives
 To define “Anemia”.
 To evaluate patients presenting with anemia.
 To manage patients diagnosed with anemia.
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7. BASIC
CONCEPT
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8. Anemia
 Anemia is a common complaint in primary care.
 Anemia is defined as low hemoglobin concentration or a
low hematocrit/RBC count.
 According to the World Health Organization, anemia is diagnosed
with:
oa hemoglobin concentration <13 g/dL in men
oA hemoglobin concentration <12 g/dL in women 8

9. Sign & symptoms
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10. 10

11. Classification of
Anemia
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12. Classification of Anemia
 Anemia is classified as macrocytic, microcytic or normocytic
anemia based on the MCV.
oMicrocytic anemia: when the MCV is less than 80.
oMacrocytic anemia: when the MCV exceeds 100.
oNormocytic anemia: when MCV is between 80 and 100.
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13. Types of Anemia
Microcytic Anemia Normocytic Anemia Macrocytic Anemia
 Iron deficiency anemia
 Thalassemia & other
hemoglobinopathies
 Sideroblastic anemia
 Lead poisoning
 Copper deficiency
 Porphyria
 Anemia of inflammation
(anemia of chronic
disease)
 Acute bleeding
 Early iron deficiency
 Anemia of chronic
disease/inflammation
 Bone marrow
suppression (cancer,
aplastic anemia,
infection)
 Chronic renal
insufficiency
 Hypothyroidism
 Hypopituitarism
 Excess alcohol
 Vitamin B12 deficiency
 Folate deficiency
 Alcohol abuse
 Liver disease
 Hypothyroidism
 Medications that
interfere with nuclear
maturation
(hydroxyurea,
methotrexate, some
chemotherapy agents)
 Conditions associated
with abnormal RBC
maturation such as
myelodysplastic
syndrome and acute
leukemia
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14. Approach to
anemia
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15. 15
History
Physical Examination

16. 16

17. 17
SxS of Anemia
CBC
MCV
< 80
Iron Studies
Ferritin
TIBC
%Sat
Serum Iron
Iron Deficiency Anemia ACD Thalassemia Sidroblastic Anemia

18. 18
SxS of Anemia
CBC
MCV
> 100
Peripheral Smear
Vit B12 Deficiency Folate Deficiency
Liver Disease
Medication
Alcohol
Megaloblastic Anemia Non-Megaloblastic Anemia
> 5 lobes PMNs

19. Red Blood Cells
Indices
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20. 20

21. Red Blood Cells Indices
 Red blood cell (RBC) count: the number of RBCs contained in a specified
volume of whole blood.
 Mean corpuscular volume (MCV): the average volume or size of the RBCs.
 Mean corpuscular hemoglobin (MCH): the average hemoglobin content in
a RBC. A low MCH indicates decreased hemoglobin content per cell.
 Mean corpuscular hemoglobin concentration (MCHC): the average
hemoglobin concentration per RBC.
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22.  Red cell distribution width (RDW):
 measure of the variation in RBC size.
 (always high in Nutritional Cause of Anemia)
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23. 23
Retic Count ;
Differentiates between Production and destruction
anemia.
Retic Count > 2 % = Destructive Anemia
Retic Count < 2 % = Productive Anemia

24. History
 Check the duration of anemia
 Check for general symptoms of anemia if present such as fatigue, dizziness, pica, craving for ice, or dyspnea
 Check for constitutional symptoms (loss of appetite, weight loss, fever, and/or night sweats), which might indicate an infection or a malignancy.
 Check for other associated symptoms such as abdominal discomfort, hematochezia, and bright red rectal bleeding.
 Check for medical conditions that might be associated with anemia such as chronic kidney disease, rheumatoid arthritis, peptic ulcer etc.
 Check medications intake: Macrocytosis can be caused by Valproic acid, Trimethoprim/ sulfamethoxazole, Biguanides.
 Check family history of anemia, which can indicate hemoglobinopathies.
 Check nutrition, eating habits, alcohol consumption.
 Check exposure to toxins (occupational or environmental exposure to toxins such as Lead)
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25. Physical
examination
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26. Physical Examination
 Check vital signs namely
 heart rate,
 respiratory rate,
 temperature, and
 blood pressure (look for postural hypotension).
 Check for the presence of PALLOR (nail bed, palm crease,
conjunctiva) , jaundice.
 Conduct a comprehensive physical examination to detect signs of
ORGAN INVOLVEMENT (such as splenomegaly) and assess the
severity of the condition.
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27. Microcytic
anemia
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28. Microcytic Anemia- Causes
 MAIN MICROCYTIC ANEMIA
 Iron deficiency anemia
 Thalassemia & other hemoglobinopathies
 Sideroblastic anemia
 Anemia of inflammation (anemia of chronic disease)
 OTHERS
 Lead poisoning
 Copper deficiency
 Porphyria
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29. Approach to
Microcytosis
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30. Approach to Microcytosis
 History
 Tests
o CBC
o MCV+RETIC COUNT
IRON STUDIES
o FERRITIN
o TIBC
o Transferrin
o % Saturation
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31. Iron deficiency
anemia
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32. Definition
 Iron deficiency anemia is due to diminished red blood cell
production as a result of low iron stores in the body.
 It is the most common nutritional disorder worldwide.
 It accounts for approximately one-half of anemia cases.
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33. Iron Journey
 Before discussing causes, let’s review iron journey
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34. Copyrights apply

35. 35

36. 36

37. 37

38. SUMMARY OF RBC
INDICES in iron
deficiency anemia
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39. 39

40. Causes of Iron
deficiency anemia
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41. Causes
1. Inadequate iron intake (Nutrition Problem)
2. Decreased iron absorption like in celiac disease, gastrectomy,
prolong usage of PPIs
1. Increased iron demand
2. Increased iron loss: can be benign (menstrual blood loss) or
malignant (occult gastrointestinal malignancy), or Peptic
Ulcer
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42. 42

43. 43

44. 44

45. 45

46. 46

47. 47

48. Symptoms
 Many patients have no symptoms (asymptomatic)
(Already discussed)
 Symptoms include:
oWeakness
oHeadache
oDecreased exercise tolerance
oFatigue, Vertigo
oIrritability
oDepression
oPica and pagophagia (ice craving)
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49. Physical Examination
 Pallor
 Dry or rough skin
 Blue/Yellow sclerae
 Atrophic glossitis with loss of tongue papillae, which may be accompanied by
tongue pain or dry mouth
 Cheilosis (also called angular cheilitis)
 Koilonychia (spoon nails)
 Esophageal web, which may be accompanied by dysphagia (Plummer-Vinson or
Patterson-Kelly syndrome)
 Alopecia (rare) in especially severe cases
 Chlorosis (pale, faintly green complexion; extremely rare)
 Dermatitis herpetiformis in celiac disease
 Bloody stool or melena
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50. Treatment
 Iron Supplements
 Dose is 120 mg of elemental iron for 3 months, continue for additional 3 months to replenish iron stores
 +
 Stool Softeners
 NOTE
 With oral iron : Reticulocytosis should be seen within 7 days correction of anemia in 6 weeks.
 In 1 month, increase of 1g/dl of Hb is the expected response
 Vitamin C may enhance absorption of oral iron if administered 30 minutes prior to iron.
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51. Copyrights apply

52. IV iron Treatment
 IV iron is appropriate for patients who are unable to tolerate gastrointestinal side effects of oral iron.
 Examples include older individuals, pregnant women (who already have gastrointestinal symptoms related
to the pregnancy), and individuals with existing gastrointestinal disorders that may exacerbate oral iron
side effects.
 IV iron may be needed for those with severe/ongoing blood loss (eg, telangiectasias, varices).
 Gastric surgery (bypass, resection) that reduces gastric acid may severely impair intestinal absorption of
oral iron.
 Malabsorption syndromes (celiac disease, Whipple's disease, bacterial overgrowth) may limit absorption of
oral iron.
 In the second trimester of pregnancy, if the Hb is less than 10.5 g, or at any time in the third trimester, at
which oral iron is unlikely to rapidly supply adequate iron to the developing fetus.
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53. Copyrights apply

54. 54

55. Anemia of
chronic disease
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56. 56

57. 57

58. diagnosis
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59. 59

60. 60

61. treatment
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62. 62

63. Sideroblastic
anemia
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64. 64

65. 65

66. causes
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67. 67

68. 68

69. investigations
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70. 70

71. Thalassemia
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72. Definition of Thalassemia
 A group of inherited autosomal recessive hematologic disorders that
cause hemolytic anemia due to decreased or absent synthesis of a
globin chain.
oAlpha thalassemia is caused by reduced or absent
synthesis of alpha globin chains, resulting in excess
beta globin chains.
oBeta thalassemia is caused by reduced or absent
synthesis of beta globin chains, resulting in excess
beta chains.
 Imbalances of globin chains cause hemolysis and impair
erythropoiesis.
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73. 73

74. Prototypical Forms of Alpha
Thalassemia
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75. Prototypical Forms of Beta
Thalassemia
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76. 76

77. Thalassemia Trait
 Thalassemia Trait is asymptomatic.
 Majority of cases of Thalassemia Trait are discovered
incidentally in the presence of microcytic anemia.
 Microcytic anemia can be caused by iron deficiency,
thalassemia, lead poisoning, sideroblastic anemia, or anemia of
chronic disease.
 RBC count may be increased despite the presence of anemia
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78. diagnosis
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79. Diagnosis of Thalassemia
 The hemoglobin Electrophoresis is the diagnostic test.
 Beta thalassemia
o reduced or absent HbA
o elevated levels of HbA2
o increased HbF.
 Alpha Thalassemia:
 Hemoglobin electrophoresis is usually normal in adults.
Molecular Diagnosis is required and not Hemoglobin
Electrophoresis
 In the newborn period, if the electrophoresis shows Hb
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80. 80

81. Beta Thalassemia Major
 Persons with beta thalassemia major are diagnosed during
infancy.
 Pallor, irritability, growth retardation, abdominal swelling, and
jaundice appear during the second six months of life.
 Persons with a microcytic anemia but milder symptoms that
start later in life have beta thalassemia intermedia.
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82. Thalassemia Trait
 Most persons with thalassemia trait are found incidentally when
their CBC shows a mild microcytic anemia.
 The MCV is usually less than 75 with thalassemia.
 The RDW may assist in differentiating iron deficiency and
sideroblastic anemia from thalassemia.
 The RDW will be elevated in more than 90% of persons with iron
deficiency, but in only 50% of persons with thalassemia.
 Supplemental tests include serum ferritin, the peripheral smear,
hemoglobin electrophoresis, serum lead level, and rarely bone
marrow aspirate.
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83. treatment
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84. 84

85. Complications
 Complications are related to:
ooverstimulation of the bone marrow
oineffective erythropoiesis
oIron overload from regular blood transfusions.
Iron is deposited in visceral organs (mainly the
heart, liver, and endocrine glands). Most
patient deaths are caused by cardiac
complications.
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86. Important
 Persons with anemia from thalassemia trait should not take iron
supplements unless they have coexistent iron deficiency.
 Persons with beta thalassemia major require periodic lifelong blood
transfusions to maintain hemoglobin levels higher than 9.5 g per dL and
sustain normal growth.
 Persons with beta thalassemia major require chelation therapy for iron
overload.
 Folic acid deficiency has been reported in thalassemia major and intermedia
as a result of increased erythropoiesis.
 Therefore, daily oral supplementation with 1 mg of folic acid is
recommended for persons with evidence of folate deficiency.
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87. Normocytic
anemia
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88. Normocytic Anemia- Causes
 Acute bleeding
 Early iron deficiency
 Anemia of chronic disease/inflammation
 Bone marrow suppression (cancer, aplastic anemia, infection)
 Chronic renal insufficiency
 Hypothyroidism
 Hypopituitarism
 Excess alcohol
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89. Approach to Normocytic Anemia
 History
o Symptoms of acute blood loss
o Symptoms of chronic diseases
o Medications intake
 Tests
o BUN, Creatinine
o TSH, Free T4
o Peripheral blood smear
o SPEP/UPEP to rule out multiple myeloma
o PTH
89

90. Macrocytic
anemia
Vitamin B12 Deficiency
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91. Macrocytic Anemia- Causes
 Vitamin B12 deficiency
 Folate deficiency
 Alcohol abuse
 Liver disease
 Hypothyroidism
 Medications: anticonvulsants (valproate, phenytoin),
antimicrobials (valacyclovir, trimethoprim sulfa), antiretrovirals
(zidovudine, stavudine), chemotherapeutic agents (hydroxyurea,
methotrexate)
 Myelodysplastic syndrome and acute leukemia
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92. Approach to Macrocytosis
 History
oCheck diet and nutrition
oCheck for thyroid disease
oEvaluate for alcohol intake
oCheck medications intake
oCheck for chronic diseases namely liver diseases
 Tests
oVitamin B12 level
oOther tests as indicated: TSH, Free T4, Liver function
tests
oNo need to do folate level. If deficiency is suspected,
empiric treatment with folic acid is indicated.
oPeripheral smear : if it shows signs of myelodysplastic
disease, a bone marrow biopsy is indicated.
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93. Vitamin B12
Deficiency
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94. Clinical Manifestations of Vitamin
B12
 Cutaneous: Hyperpigmentation, Jaundice, Vitiligo
 Gastrointestinal: Glossitis
 Hematologic: Anemia (macrocytic, megaloblastic), Leukopenia,
Pancytopenia, Thrombocytopenia, Thrombocytosis
 Neuropsychiatric: Areflexia, Cognitive impairment (including
dementia-like symptoms and acute psychosis), Gait
abnormalities, Irritability, Loss of proprioception and vibratory
sense, Olfactory impairment, Peripheral neuropathy.
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95. History
 Paresthesia
 Memory loss
 Dementia
 Ataxia
 History of malabsorption or gastrectomy
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96. Physical exam
 Glossitis
 Cheleitis
 Decreased proprioception
 Decreased vibratory sense
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97. Screening
 It is not recommended to screen persons at average risk of
vitamin B12 deficiency.
 It is recommended to screen persons with risk factors.
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98. Risk Factors
 Decreased ileal absorption: such as in Crohn disease, Ileal
resection,Tapeworm infection
 Decreased intrinsic factor: Atrophic gastritis, Pernicious anemia,
Postgastrectomy syndrome
 Genetic: Transcobalamin II deficiency
 Inadequate intake: Alcohol abuse, Patients older than 75 years,
Vegans or strict vegetarians (including exclusively breastfed
infants of vegetarian/vegan mothers)
 Prolonged medication use: Histamine H2 blocker use for more
than 12 months; Metformin use for more than four months;
Proton pump inhibitor use for more than 12 months.
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99. Diagnosis
 Diagnostic testing is recommended in persons with suspected
clinical manifestations.
 Testing includes CBC and serum vitamin B12 level.
oA level of 150-399 pg per mL (111-294 pmol
per L) is considered as low-normal.
oA level < 150 pg per mL (<111 pmol per L) is
diagnostic for vitamin B12 deficiency.
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100. Artificial Elevation of Vitamin B12
 Serum vitamin B12 levels may be artificially elevated in patients
with
oAlcoholism
oliver disease
ocancer
 This is due to decreased hepatic clearance of transport proteins
and resultant higher circulating levels of vitamin B12.
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101. Additional Tests
 Methylmalonic acid level: in case of a normal or low-normal
serum vitamin B12 level and macrocytosis in CBC.
 Anti-intrinsic factor antibodies: to test for pernicious anemia in
patients with vitamin B12 deficiency and without evidence of
dietary or malabsorptive causes by history and physical exam. In
case, these antibodies are negative, serum gastrin level can be
requested to check further for presence of pernicious anemia.
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102. Treatment
 Intramuscular injections of cyanocobalamin or oral vitamin B12
therapy.
 Injectable therapy leads to more rapid improvement and should
be considered in patients with severe deficiency or severe
neurologic symptoms.
 Injections three times per week for two weeks in patients
without neurologic deficits.
 If neurologic deficits are present, injections should be given
every other day for up to three weeks or until no further
improvement is noted.
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103. Prevention
 Patients who have had bariatric surgery should receive 1 mg of
oral vitamin B12 per day indefinitely.
 Patients older than 50 years may not be able to adequately
absorb dietary vitamin B12 and should consume food fortified
with vitamin B12.
 Vegans and strict vegetarians should be counseled to consume
fortified cereals or supplements to prevent deficiency.
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104. After initiation of treatment
 Homocysteine or methylmalonic acid level, or reticulocyte
count: improve in 1 week
 Neurologic symptoms improve in 6 weeks to three months
 Anemia, leukopenia, mean corpuscular volume, or
thrombocytopenia improve in 8 weeks.
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105. References
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