This document discusses the approach to anemia. It defines anemia as having insufficient red blood cells or hemoglobin to meet physiological needs. Common symptoms include fatigue, shortness of breath, and palpitations. Clinical evaluation involves assessing symptoms to determine the potential cause, such as blood loss, inflammation, or nutritional deficiencies. Laboratory investigations include complete blood count, iron studies, bone marrow examination, and tests for hemolysis. Anemia is classified as hypo-proliferative, maturation disorders, blood loss, or hemolysis. Treatment depends on the underlying cause and may involve iron supplementation, erythropoietin, vitamin B12/folate, or splenectomy.

1. APPROACH TO ANEMIA
DR. V. B. KASYAPA. J
1st year GM PG
Date : 05/08/16

2. ERYTHROPOESIS
Erythroid/Megakaryocytic
Progenitor
Erythroid Cells
Pronormoblast
RBC
GATA-1 & FOG-1
EPO
4-5 DIVISIONS

3. WHO Definition :
Anaemia is a condition in which the
number of red blood cells (and
consequently their oxygen-carrying
capacity) is insufficient to meet the body’s
physiologic needs.

4. Clinical Key
• Classical symptoms :
– Fatigue, Malaise
– Dyspnoea on exertion
– Loss of stamina
– Palpitations
– Complaints related to Exertion
– Reduced exercise capacity
– Pounding sensation in ears
– Night sweats
• Symptoms suggestive of Inflammation :
– Fever
– Weight loss

5. Clinical Key
• Symptoms suggestive of Nutritional anemia :
– Blood in stools
– Loose stools/ Clay colour stools
– Constipation
– Blood in urine
– Pregnancy
– Recurrent/Recent foetal loss
– History of Neural Tube Defects in offspring
– Cleft palate/lip in offspring
– Tingling and Numbness of bilateral limbs
– Infertility
– Prematurity

6. Clinical Key
• Symptoms of Haemolysis :
– Yellowish discoloration of eyes and skin
– Reversible skin pigmentation
• Symptoms suggestive of marrow disorders :
– Recurrent upper respiratory tract infections
– Episodic jaundice/ abdominal pain/ lumbar pain/
hematuria
– Easy bruising/ Gum bleed/ Nose bleed/ Heavy
menstrual flow/ Hemiparesis/ Vision loss
– Recent viral illness aggravating anemia symptoms
– Stunted growth
– Priapism

7. Clinical Key
• Symptoms suggestive of genetic disorders :
– Early hair greying
– Short stature
– Dystrophic nails
• Past History :
– Blood donation history
– Phlebotomy history
– Drug History
– Surgical history
– Chemical exposure history
– Smoking, Alcoholism

8. Clinical Key
• O/e :
– Mental state
– Signs of dehydration
– Cheilosis (Fissures at corners of mouth)
– Koilonychia (Spooning of finger nails)
– Pallor ( < 8-9 gm/dL )
• Mucus membranes
– Palpebral conjunctiva
– Soft palate
• Skin
– Nail beds
– Palmar creases (lighter than surrounding skin when
hyperextended)

9. Clinical Key

10. Clinical Key
– Icterus
– Clubbing
– Cyanosis
– Lymphdenopathy
– Pedal edema
– Petechiae/ Ecchymosis
• Systemic Examination :
– Splenomegaly
– Hepatomegaly
– Forceful Heart beat
– Strong peripheral pulses
– Systolic Flow murmur
– Bony deformities

11. Clinical Key
• Also Look for :
– Ascites
– Heart failure
– Cirrhosis
– Endocrinopathies
– Pseudoxanthoma elasticum
– Neoplasms

12. Lab Investigations
• Complete Blood counts
– Hb :
Occasion Normal Value (mg/dL)
At Birth 17
Childhood 12
Adolescence 13
Adult Man 16 ± 2
Menstruating Adult Female 13 ± 2
Post Menopausal Adult
Female
14 ± 2
During Pregnancy 12 ± 2

13. Lab Investigations
– Hematocrit :
– Reticulocyte Count
– Absolute reticulocyte Count
– Recticulocyte Production Index
Normal Values (%)
Adult Male 47 ± 5
Adult Female 42 ± 5

14. • RBC Indices
• Other Counts
– TLC
– DLC
– Nuclear Segmentation of Neutrophils
– Platelet Count
Lab Investigations
Indices Normal
MCV 90 ± 8 fL
MCH 30 ± 3 pg
MCHC 33 ± 2 %
RDW 11.5 – 14.5 %

15. • Red cell Morphology
– Cell size
– Mirocytic (<80 fL)
– Macrocytic (>100 fL)
– Anisocytosis ( Variable size )
– Poikilocytosis ( Variable Shape )
– Polychromasia
» ( Slightly larger than normal cells, greyish blue in Wright
Giemsa stain
» Prematurely released Reticulocytes having residual
ribosomal RNA
» After EPO stimulation/ architectural damage of BM )
Lab Investigations

16. • Iron Studies
Lab Investigations
Study Normal Range
Serum Iron 50-150 µg/dL
TIBC 300-360 µg/dL
Serum Ferritin Males – 100 µg/ L
Females – 30 µg/ L
Transferrin Saturation 25-50 %

17. • Marrow Examination
– Aspirate :
– M/E ratio (1:1)
– Cell Morphology
– Iron Stain
– Biopsy
– Cellularity (1:1)
– Morphology
• Signs of Hemolysis
– ↑ Unconjugated bilirubin, urobilinogen, S.LDH
– ↓ Haptoglobins
– Positive Urine hemsiderin
Lab Investigations

18. Lab Investigation

19. Lab Investigation

20. Clinical Classification of Anaemia

21. Reticulocyte Count
• By Supra vital stains – Blue, black punctate
spots (precipitated rRNA)
• Life – 24 to 36 hrs
• Normal range – 1-2%
• Daily replacement – 0.8 to 1%
• Response depends on
– Availability of EPO
– Availability of Iron
– Healthy Bone marrow

22. Reticulocyte count

23. Reticulocyte count
• Correction for Anemia
– 𝐴𝑏𝑠𝑜𝑙𝑢𝑡𝑒 𝑅𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒 𝑐𝑜𝑢𝑛𝑡 =
𝑟𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒 𝑐𝑜𝑢𝑛𝑡 𝑥 𝐻𝑏/15 𝑜𝑟 𝐻𝑚𝑡/45
• Correction for prematurely released
reticulocytes (only when you see ‘shift’ cells)
– 𝑅𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒 𝑃𝑟𝑜𝑑𝑢𝑐𝑡𝑖𝑜𝑛 𝐼𝑛𝑑𝑒𝑥 =
𝑅𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒 𝑐𝑜𝑢𝑛𝑡 𝑥 𝐻𝑏/15 𝑥 1
/ 𝑀𝑎𝑡𝑢𝑟𝑎𝑡𝑖𝑜𝑛 𝑡𝑖𝑚𝑒 𝑐𝑜𝑟𝑟𝑒𝑐𝑡𝑖𝑜𝑛(2)

24. Clinical Classification of Anaemia

25. Hypo-proliferative Anemia
• Causes :
– Mild to Moderate Anemia
– Marrow Damage
– Inadequate EPO stimulation
• Inflammation (IL -1, TNF α, etc..)
• Metabolic Disorders ( Hypothyrodism, ..)
• Renal Failure ( in DM & Myeloma – marked EPO def seen
than actual failure )
• Usually – Normocytic, Normochromic
• Marrow is Hypocellular (M/E > 2:1)

26. Hypoproliferative Anemia
Parameter Mild – Mod Iron Def Chr. Inflammation
S.Iron ↓ ↓
TIBC ↑↑ ↓/N
% Saturation ↓ ↓
S.Ferritin ↓ ↑/N

27. Maturation Disorder
• BM shows erythroid hyperplasia (M/E < 1:1)
– But fails to release into peripheral circulation
Nuclear maturation defects Cytoplasmic maturation defects
Macrocytosis Microcytic, Hypochromic
Vit B12/ Folate Deficiency Severe Iron Deficiency
Drugs ( Methotrexate/ Alkylating agents/
Alcohol)
Globin chain/Heme synth Defects
Myelodysplasia

28. Blood Loss
• Normocytic/ Slightly Macrocytic
Acute Blood
Loss
• No Increase in RPI
• Signs of
Hypovolemia
dominate
Sub Acute
Blood Loss
• Modest
Reticulocytosis
• May show Iron
def
Chronic Blood
Loss
• Iron Deficiency
picture dominates

29. Intra Vascular
(Iron loss may limit the
Marrow response)
Acute
(Autoimmune hemolysis/
Pathway defects )
Extra Vascular
(Efficient recycling of
Iron)
Chronic
(Membrane Defects/
Hemoglobinopathies)
Hemolysis

30. Iron Deficiency Anemia
• C/f :
– Pregnancy/ Adolescence/ Blood Loss/ Phlebotomy
– Advanced tissue iron def
» Cheilosis
» Koilonychia
– In adult male – GI loss, until proven otherwise

31. Iron Deficiency Anemia
• RBC Indices
– Microcytic, Hypochromic, Aniso-Poikilocytosis
• Iron Studies
• Marrow Iron (Normal : 20-40% sideroblasts,
with ferritin granules)
– Decreases
• RBC protoporphyrin Level (Normal : <30µg/dL)
– Impaired heme synth (>100 µg/dL).

32. Iron Deficiency Anemia

33. DD for Microcytic Anemia

34. Iron Deficiency Anemia
Red cell infusion
(Symptomatic/ CV instability/
Elder/ Continued blood loss)
Oral Iron
(Young/ Asymptomatic)
Parenteral Iron
(Oral iron intolerance/ Acute need/ Persistent
GI loss/ Malabsorption/ EPO therapy
Rx

35. • Oral Iron:
– 200mg elemental Iron/day
– Absorption will be upto 50mg/d (with good retention
capacity)
– Supports 2-3x production
– Add Ascorbic acid for increased absorption (if cost
effective)
– 3-4 tabs/day for 6-12 months
– GI disturbances (15-20%)
– First response : ↑ Retic count in 4-7 days; peak in 7-
10 days
Iron Deficiency Anemia

36. – Iron Tolerance test
• 2 Iron tabs on empty stomach
• Serial S.Iron for 2 hrs
• At least 100 mcg/dL increase
Iron Deficiency Anemia
Preparation Amount (Elemental Iron)
Ferrous sulphate 325 (65)
Ferrous Fumarate 325 (107)
Polysaccharide Iron 150 (150)

37. • Parenteral Iron :
Needed = { Body wt in Kg x 2.3 x (15 – pt. Hb)}
+ 500-1000mg for stores
– 500mg at a time/ repeated small doses
Iron Deficiency Anemia
Preparation Amount of Iron per injection
Sodium ferric gloconate 125 mg
Iron sucrose 200 mg
Ferrumoxytol 510 mg
Ferric carboxy maltose 750 mg

38. Anemia of chronic inflammation
• Iron restricted erythropoesis with
inflammation.
• IL – 1 -> INF ᵞ
• TNF α -> INF β
• Suppresses EPO
• Mixed blood picture
• Inflammatory component (Normocytic Normochromic)
• Iron deficiency (Microcytic Hypochromic)
• Acute infection can cause 2-3 g/dL fall in 1-2
days ( d/t death of senile RBC)

39. Anemia of chronic inflammation

40. • Rx :
– Transfusion : symptomatic/ terminal disease
• Wait up to 7-8 g/dL
• If compromised, maintain at 11 g/dL
• Liberal use in ICU leads to ↑ morbidity & mortality
– EPO : Glycoprotein, from peritubular capillary cells
in kidney & hepatocytes, regulated by HIF 1 α
• Normal – 10-25 U/L; t ½ - 6-9 hrs
• Up to 4-5x production in 1-2 weeks
Anemia of chronic inflammation

41. • Recombinant EPO therapy :
– Check for iron stores
– 50-150 U/kg 3 times/week IV
– Up to 300 U/kg, (in chemo induced anemia)
– 10-12 g/dL Hb in 4-6 weeks
– Stop if acute inf/ iron depletion/ Al toxicity/
hyperpaarthyroidism
– Thrombo embolic events, Tumor progression
– Long acting : DARBEPOETIN α
Anemia of chronic inflammation

42. Megaloblastic Anemia
Megaloblastic Megaloblastoid
Immature appearing nuclei with large
blast like cells with normal
hemoglobinisation.
Seen in B12/Folate deficiency.
Immature appearing nuclei with defective
hemoglobinisation.
Seen in Myelodysplasia.
CLINICAL FEATURES
Anorexia, Wt. loss, Diarrohea/ constipation, Mild fever
Tissue effects Hematological effects
Mucosal damage Macrocytsis
Pregnancy related complications Hyper segmented neutrophil (>5)
CVS disorders Leucopenia, thrombocytopenia
Malignancies (ALL, Follicular lymphoma,
breast & gastric)
Hyper cellular marrow
CNS abnormalities Signs of hemolysis

43. Megaloblastic Anemia
HYPER SEGMENTED NEUTROPHILS

44. B12 deficiency Folate Deficiency
S.Cobalamin <100 ng/L S. Folate < 2µg/L
↑ - severe B12 def & Intestinal stagnant
loop synd
S. MMA & Homocystein – Increases S. MMA & Homocystein – Increases
B12 absorption tests are obsolete
S. Gastrin ↑
S. Pepsinogen I ↓
(for Pernicious Anemia)
RBC Folate < 160 µg/L
False + in Recent transfusion/ ↑Retic
count
GI endoscopy & Biopsy (for
malabsorption)
Diet history
Transglutaminase Ab (celiac disease)
Duodenal biopsy
Megaloblastic Anemia

45. Megaloblastic Anemia

46. Megaloblastic Anemia
• Rx :
– Treat appropriate vitamin only (always B12 first)
– Transfusion is usually unnecessary & inadvisable
– ↑ platelet count after 1-2 weeks (start aspirin, if >8
lakh/cumm)
B12 deficiency Folate deficiency
Hydroxy/ cyano cobalamine life long
therapy is best
Routinue in GIT resections/ longterm PPI
therapy
Always low threshold for therapy
(prevent neuropathy)
Oral 5-15 mg/ day
For 4 months
Replenishment : 6 x 1000 µg IM/ week
Maintenance : 1000 µg IM/ 3 monthly
Pregnancy
Preventive – 400 µg/day
Prev NTD history – 4 mg/day
Sub-lingual therapy/ Large oral dose (for
bleeding disorders)

47. Hemolytic Anemias

48. Hereditary Spherocytosis
Family
History
±
Jaundice
Gall stonesSplenomegaly
Mild : Young
adult/ adult
Severe : Infancy

49. Hereditary Spherocytosis

50. Hereditary Spherocytosis
↑ MCHC with Normal
blood counts
↑ Osmotic fragility
SDS – gel electrophoresis
of membrane proteins
Eosin 5’ maleimide (EMA)
binding test
Acid glycerol Test

51. Hereditary Spherocytosis
• Rx:
– No causal treatment
– Splenectomy
– Mild cases : Defer Splenectomy
– Moderate cases : delay until puberty
– Sever cases : delay until 4-6 years of age
– Anti pneumococcal vaccination before surgery

52. G6PD Deficiency
• Asymptomatic
• Classical :
– Malaise, weakness, abd & lumbar pain
– In 3 days
– Jaundice & dark urine
• Primaquine mass prophylaxis is a danger
• Blood :
– Normocytic Normochromic (Mod to Severe)
– Heinz bodies ( denatured Hb & hemichromes in
supravital staining with methyl violet)
– Hemighosts (bizarre, RBC with uneven Hb)
– Bite Cell/Blister cell

53. G6PD Deficiency

54. G6PD Deficiency
• Diagnosis :
– DNA testing
– During hemolytic attack – quantitative test done
for heterozygotes and hemi zygotes
• Rx :
– No cure
– Severe – Transfusions, Splenectomy.
– Good prognosis – if No Kidney damage

55. AIHA
Anemia + Splenomegaly + Jaundice
Warm Ab disease Cold Ab disease
• Ig G1/ G3 mediated
• 37⁰ C
• Extravascular hemolysis
• Phagocytosis
• Fragmentation
• Cytotoxicity
• Acute, Moderate to Severe
• Hepatosplenomegaly
• Fatigue, SOB
• Ig M mediated
• 0-4⁰C
• Intravascular hemolysis
• Membrane attacking complex
• Mild to moderate, acute
• Acrocyanosis

56. AIHA

57. AIHA

58. AIHA
• Medical Emergency, needs transfusion.
• Abs are commonly non specific against ‘e’ Ag of
Rh system.
• So all most all the blood groups will be
incompatible
• Start incompatible blood transfusion to keep the
pt alive (with hold when condition improves)
• Prednisolone 1mg/kg/day +
• Rituximab 100 mg/week x 4
• Splenectomy, Allogenic BMT.

59. PNH
Hemolysis + Pancytopenia + Venous thrombosis
• Classical :
– Early morning bloody urine
• Recurrent severe abdominal pain (thrombotic
event)
• Acute hepatomegaly, ascites without liver or
cardiac disease
• MC COD : Venous thrombosis > Infections
(Neutropenia) > Haemorrhage
(Thrombocytopenia)

60. PNH
• Reticulocytosis (up to 400,000/µL)
• ↑ MCV, Normo-Macrocytic
• Signs of Hemolysis
• Signs of Iron def (persistent loss)
• BM : cellular with massive erythroid hyperplasia
• Definitive : ↑susceptibility to complement
– Sucrose hemolysis (not reliable)
– Acidified serum (Ham) test (Not available)
– Flow cytometry (Gold standard) : CD59 -, CD 55- (>5%
RBC, >20% granulocytes)

61. PNH
• Life long condition
• Filtered RBC (retain WBC)
• S. Iron maintanance
• Folate >3mg/d
• Never long term corticosteroids
• ECULIZUMAB IV/ Fort night (↓Compliment
mediated hemolysis)
– ↑ Extra vascular hemolysis
• Allogenic BMT (definitive)

62. Aplastic Anemia
• Sudden/ insidious Bleeding (MC 1st symp)
• Easy bruising, gum bleed, nose bleed, heavy menstrual
flow, petechia, Hemorrhagic CVA, Retinal hemorrhage
• Symptoms of Anemia
• History of Drugs (allopurinol, gold, pencillamine)/ Viral
illness/ Chemical exposure
• Early hair greying – telomeropathy
• Peculiar nails & leukoplakia – Dyskeratosis congenita
• Café au lait spots & short stature – Fanconi anemia

63. Aplastic Anemia
• PS : large RBC, paucity of platelets &
granulocytes, ↓↓↓ Retic count
• Immature myeloid forms – Leukaemia/MDS
• Nucleated RBC – Marrow fibrosis/ tumor invasion
• Abnormal platelets - MDS

64. Aplastic Anemia
Aplastic anemia Hypocellular MDS/Leukemia
• ↓ myeloid/ megakaryocytes
• Normal eyrthroblasts
• ↑ myeloblasts
• Abnormal karyotype of erythroblasts
Aplastic anemia Hairy cell leukaemia
• No splenomegaly
• No lymphadenopathy
• Splenomegaly
• lymphadenopathy

65. Aplastic Anemia
• Supportive
• Epoetin/ Darbepoetin + Filgrastim/ Sargramostim
• Transfusions, AMD
Mild
• <40 yrs + HLA matched donor = allogenic
BMT
• <40 yrs – HLA matched donor/
• >40 yrs
=Immunosuppressive therapy
Severe
(<500/µL
neutrophils
<20000/µL
thrombocytes
<1% retic count
<20% BM cellularity)
• Transfusions
• ELTROMBOPAG
Refractory

66. Aplastic Anemia
Immunosuppressive therapy
Initially
• Equine Anti thymocyte globulin (40mg/kg/day x 4)
• Cyclosporin A (6mg/kg BD x 6months)
• Methyl prednisolone (1-2mg/kg/day x 7day)
After 1-3
months
• Patient becomes partially transfusion free
After 4
months
• Complete remission can be seen

67. Thalassemia
α- thalassemia β- thalassemia
• (α, α/α,-) Silent carrier (β0/β0 or β +/β +) Thalassemia Major
Transfusion dependent
• (α,-/α,-) type I α- thalassemia trait
• (α, α/-,-) type II α- thalassemia trait
Mild Microcytic anemia
(β+/β+ with more β chain synth) T.
Intermedia
Transfusion at aplastic crisis/ stress
• (α,-/-,-) Hb H disease
Chronic hemolytic anemia of variable
severity
± transfusion dependance
(β/β0 or β/β+) T. Minor
Mild Microcytic hypochromic anemia
• (γ, γ/γ, γ) Hb Barts/ Hydrops fetalis
Still born

68. Thalassemia
• C/f : Onset 4-6 months
• Stunted growth
• Bony deformities
• Hepatosplenomegaly
• Jaundice (gallstones, hepatitis)
• Thrombophilia
– Over load symptoms
• Heart failure
• Arrhythmias
• Cirrhosis
• Endocrinopathies
• Pseudoxanthoma elasticum

69. Thalassemia
• Microcytic hypochromic
• 60 – 70 fL MCV
• 22-32 % Hematocrit
• Target cells
• Acanthocytes (irregular spikes)
• Basophilic stippling (β thalassemias)
• Retic count (depends on severity)

70. Thalassemia

71. Thalassemia

72. Thalassemia
• Electrophoresis (definitive)

73. Thalassemia
• Mild – No Rx
• Hb H
– Folate 1mg/day oral
– No oxidative drugs/ iron
– Transfusion
• Splenectomy (if hypersplenism is seen)
• Iron chelation
– Oral DEFERASIROX 20 – 30mg/kg/day
• Allogenic BMT ( Definitive )

74. Sickle Cell Anemia
• C/f : Onset 4 – 6 months
– Chronic hemolytic jaundice
– Aplastic crisis with viral illness
– Acute painful syndrome ( acute vaso occlusion)
• Episodes last for hrs to days + low grade fever
– Repeated occlusion
• Enlarged heart
• PAH
• Cirrhosis liver
• Osteonecrosis (salmonella > staph)
• Renal papillary infarction ( gross hematuria)
• Retinopathy ( similar to DM)
• Auto splenectomy ( initially enlarged )
– Repeated infections
– Strokes
• Sagittal sinus thrombosis
• Priapism

75. Sickle Cell Anemia
• Sickled cells (5 – 50%)
• Reticulocytes (10 – 25%)
• Howel jolley bodies (d/t hyposplenism)
• Target cells
• Leukocytosis (12000 -15000/cumm)
• Reactive thrombocytosis
• Hb Electrophoresis (Definitive)

76. Sickle Cell Anemia

77. Sickle Cell Anemia

78. Sickle cell anemia
• Allogenic BMT
(Curative in child)
• Omega 3 FA
• Folate 1mg/day
• Transfusions
• Pneumococcal
vaccination
• Iron chelation
• Hydroxy Urea 500-
750 mg/OD
• Painful crisis :
– Hydration, NSAIDS, O2
• Vaso-occlusive/
Intractable pain/
Acute chest synd/
priapism/ stroke
– Exchange transfusion
Prevention of stroke : 2-16 yr age annual trans-cranial doppler
>200 cm/sec velocity ----- start transfusions

79. THANK YOU