Approach to Anemia
Definition
Anemia – The World Health Organisation defines anemia as a
hemoglobin level < 130 g/L (13g/dL) in men and <120g/L (12g/dL) in
women.
Approach to anemia Approach to Anemia Approach to Anemia
Clinical Presentation
Often found during routine screening
 Acute blood loss – Hb/HCT does not reflect the volume of blood loss
◦ Mild – No symptoms.
Enhanced oxygen delivery by changes in pH and increased CO2
◦ 10-15% - hypotension and decreased organ perfusion
◦ >30% - postural hypotension, tachycardia
◦ >40% - hypovolemic shock: confusion, dyspnoea, diaphoresis
Acute hemolysis
◦ Intravascular hemolysis: acute back pain, free hemoglobin in plasma
and urine, renal failure
Moderate anemia
◦ Fatigue
◦ Loss of stamina
◦ Breathlessness
◦ Tachycardia on physical exertion
◦ Symptoms may not appear in young, healthy patients until
hemoglobin is 7-8 g/dL
Diseases in which patient presents with anemia
◦ Infections
◦ Rheumatoid Arthritis
◦ Cancer
◦ Lymphoproliferative disorders (CLL, B cell neoplasm)
 Anemia – a major sign of disease
History
Evaluation by History:
◦ Symptoms of known diseases causing anemia: 
Gastric ulceration 
Rheumatoid arthritis 
Renal failure
◦ Duration of symptoms: Hemoglobinopathies in longer duration
◦ Treatment history Medications for pain, hematinics

◦ Nutritional history
Physical examination
Build, nourishment 
Signs of disease 
Vitals – fever, tachycardia, blood pressure 
Pallor 
Jaundice
Lymphadenopathy 
Bone tenderness 
Petechiae 
CVS: Flow murmurs RS: Dyspnoea Abdomen: Splenomegaly
 
Investigations
Hb, Hematocrit 
RBC count 
MCV (Hct x 10 / RBC x 106) [ 90±8 fl ] 
MCH (Hb x 10 / RBC x 106) [ 30 ± 3 pg ]
MCHC (MCH/MCV) [ 33 ± 2 % ] 
Reticulocyte count
 Indices vary with age, gender and pregnancy 
WBC count including differential count, neutrophil segment count
Platelet count
Peripheral smear
Cell size 
Anisocytosis
Cell shape
Poikilocytosis

Polychromasia 
Gives clues to specific disorders.
Approach to anemia Approach to Anemia Approach to Anemia
Approach to anemia Approach to Anemia Approach to Anemia
Approach to anemia Approach to Anemia Approach to Anemia
Approach to anemia Approach to Anemia Approach to Anemia
Reticulocyte count
A reliable measure of red cell production 
Patient’s reticulocyte is compared with expected reticulocyte counts 
In established anemia, reticulocyte count of less than two-three times
is an inadequate marrow response Reticulocyte correction needs to

be done for anemia (1) And shift cells (2), If polychromatophilic cells

are not seen on the blood smear, the second correction is not required.
Corrected Reticulocyte Count
Premature release of recticulocytes are due to EPO stimulation
 Severe chronic hemolytic anemia – RPI increases upto six to
sevenfold. Confirms appropriate response to EPO, normal functioning
marrow and iron availability 
If reticulocyte production index < 2, suggests a defect in marrow
proliferation or maturation
Approach to anemia Approach to Anemia Approach to Anemia
Iron supply and Storage
Serum Iron: 50–150 µg/dL 
TIBC: 300–360 μg/dL 
Serum ferritin (also an acute phase reactant) ◦ 15-20 µg/dL – Lack of
Iron stores ◦ Women: ~30 µg/dL ◦ Men: ~ 100 µg/dL ◦ 200 µg/dL –
adequate iron stores
Serum Transferrin saturation: 25-50%
Bone Marrow Studies
Required in patients with normal iron status with hypoproliferative
anemia Can be used to diagnose primary bone marrow diseases:

myelofibrosis, infiltrative diseases.
Can be stained to confirm iron status (ferritin / hemosiderin). 
Other laboratory tests maybe indicated depending on the type of
anemia.
Approach to anemia Approach to Anemia Approach to Anemia
Hypoproliferative Anemias
75% of all anemias 
Absolute or relative bone marrow failure 
Causes: ◦ Mild to moderate iron defeciency
◦ Inflammation
◦ Marrow damage
◦ Ineffective EPO production (impaired renal function, IL-1,
hypothyroidism, diabetes mellitus, myeloma)
◦ Normocytic normochromic, occasionally microcytic hypochromic
Investigations:
◦ S. Iron
◦ TIBC
◦ RFT
◦ TFT
◦ Bone Marrow biopsy/aspiration
◦ Serum Ferritin
◦ Iron stain of bone marrow
Anemia of chronic inflammation:
◦ S. Iron: Low
◦ TIBC: normal or low
◦ Transferrin saturation: Low
◦ S. Ferritin: Normal – High 
Iron defeciency anemia
◦ S. Iron: Low
◦ TIBC: High
◦ Transferrin: Low
◦ S. Ferritin: Low
Leukemia and lymphoma, marrow aplasia
◦ Peripheral smear
◦ Bone marrow biopsy
Maturation disorders
Features:
◦ Anemia with low reticulocyte count
◦ Macro or microcytosis on smear
◦ Abnormal red-cell indices 
Two categories:
◦ Macrocytic – nuclear abnormalities
◦ Microcytic – cytoplasmic abnormalities 
Ineffective erythropoeisis due to destruction in marrow 
Bone marrow shows erythroid hyperplasia
Nuclear maturation disorders:
◦ Folate or Vitamin B12 defeciency, drug damage (methotrexate),
myelodysplasia
◦ Alcohol causes macrocytosis with variable degree of anemia due to
folate defeciency

Cytoplasmic maturation disorders:
◦ Severe iron defeciency, thallassaemias 
Iron defeciency: Low reticulocyte index, microcytosis, Serum Iron
profile can be used to differentiate from thalassaemias
Myelodysplasia:
◦ Macro or microcytosis
◦ Iron ring in mitochondria
◦ Sideroblasts on marrow stain
◦ Iron studies can help differentiate from other conditions
Blood loss/ Hemolytic Anemia
Red cell production indices > 2.5 or normal
 Polychromatophilic macrocytes on smear 
Red cells indices: Normocytic to Macrocytic due to increased
reticulocytes 
Acute blood loss: Not associated with increased reticulocyte
production because of time required for EPO production 
Subacute blood loss: Moderate reticulocytosis 
Chronic blood loss: Iron defeciency with increased red cell production
Hemolytic disease
Least common form of anemia 
High reticulocyte count – marrow able to sustain erythropoesis with
efficient recycling of iron in case of extravascular hemolysis 
Intravascular hemolysis – Paroxysmal nocturnal hemoglobinuria – Loss
of iron may limit marrow response
 Hemoglobinopathies like sickle cell disease/thallassemias present a
mixed picture and may have a high reticulocyte count which is low
compared to marrow hyperplasia.
Hemolytic Anemias
Acute: specific patterns like autoimmune hemolysis, glutathione
reductase. 
Inherited hemolytic anemias: have a lifelong history of typical of
disease process 
Chronic hemolytic diseases like hereditary spherocytosis may present
with complication of increased red cell destruction (bilrubin gallstones,
splenomegaly). 
Susceptible to aplastic crises
Differential diagnosis of acute or chronic hemolysis requires careful
investigation of family history and specialised laboratory tests like
hemoglobin electrophoresis or screening for red cell enzymes.
 Acquired defects in red cell survival – may requires testing of
indirect antiglobulin test, cold agglutinin titres to detect hemolytic
antibodies or complement mediated destruction.
Approach to anemia Approach to Anemia Approach to Anemia
Treatment
Mild to moderate anemia: Treatment once specific diagnosis in made.
 Acute causes may require treatment before diagnosis is made.
 Some causes of anemia are multifactoral and it is important to check
iron status before and during treatment.
THANK YOU

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Approach to anemia Approach to Anemia Approach to Anemia

  • 2. Definition Anemia – The World Health Organisation defines anemia as a hemoglobin level < 130 g/L (13g/dL) in men and <120g/L (12g/dL) in women.
  • 4. Clinical Presentation Often found during routine screening  Acute blood loss – Hb/HCT does not reflect the volume of blood loss ◦ Mild – No symptoms. Enhanced oxygen delivery by changes in pH and increased CO2 ◦ 10-15% - hypotension and decreased organ perfusion ◦ >30% - postural hypotension, tachycardia ◦ >40% - hypovolemic shock: confusion, dyspnoea, diaphoresis
  • 5. Acute hemolysis ◦ Intravascular hemolysis: acute back pain, free hemoglobin in plasma and urine, renal failure Moderate anemia ◦ Fatigue ◦ Loss of stamina ◦ Breathlessness ◦ Tachycardia on physical exertion ◦ Symptoms may not appear in young, healthy patients until hemoglobin is 7-8 g/dL
  • 6. Diseases in which patient presents with anemia ◦ Infections ◦ Rheumatoid Arthritis ◦ Cancer ◦ Lymphoproliferative disorders (CLL, B cell neoplasm)  Anemia – a major sign of disease
  • 7. History Evaluation by History: ◦ Symptoms of known diseases causing anemia:  Gastric ulceration  Rheumatoid arthritis  Renal failure ◦ Duration of symptoms: Hemoglobinopathies in longer duration ◦ Treatment history Medications for pain, hematinics  ◦ Nutritional history
  • 8. Physical examination Build, nourishment  Signs of disease  Vitals – fever, tachycardia, blood pressure  Pallor  Jaundice Lymphadenopathy  Bone tenderness  Petechiae  CVS: Flow murmurs RS: Dyspnoea Abdomen: Splenomegaly  
  • 9. Investigations Hb, Hematocrit  RBC count  MCV (Hct x 10 / RBC x 106) [ 90±8 fl ]  MCH (Hb x 10 / RBC x 106) [ 30 ± 3 pg ] MCHC (MCH/MCV) [ 33 ± 2 % ]  Reticulocyte count  Indices vary with age, gender and pregnancy  WBC count including differential count, neutrophil segment count Platelet count
  • 10. Peripheral smear Cell size  Anisocytosis Cell shape Poikilocytosis  Polychromasia  Gives clues to specific disorders.
  • 15. Reticulocyte count A reliable measure of red cell production  Patient’s reticulocyte is compared with expected reticulocyte counts  In established anemia, reticulocyte count of less than two-three times is an inadequate marrow response Reticulocyte correction needs to  be done for anemia (1) And shift cells (2), If polychromatophilic cells  are not seen on the blood smear, the second correction is not required.
  • 16. Corrected Reticulocyte Count Premature release of recticulocytes are due to EPO stimulation  Severe chronic hemolytic anemia – RPI increases upto six to sevenfold. Confirms appropriate response to EPO, normal functioning marrow and iron availability  If reticulocyte production index < 2, suggests a defect in marrow proliferation or maturation
  • 18. Iron supply and Storage Serum Iron: 50–150 µg/dL  TIBC: 300–360 μg/dL  Serum ferritin (also an acute phase reactant) ◦ 15-20 µg/dL – Lack of Iron stores ◦ Women: ~30 µg/dL ◦ Men: ~ 100 µg/dL ◦ 200 µg/dL – adequate iron stores Serum Transferrin saturation: 25-50%
  • 19. Bone Marrow Studies Required in patients with normal iron status with hypoproliferative anemia Can be used to diagnose primary bone marrow diseases:  myelofibrosis, infiltrative diseases. Can be stained to confirm iron status (ferritin / hemosiderin).  Other laboratory tests maybe indicated depending on the type of anemia.
  • 21. Hypoproliferative Anemias 75% of all anemias  Absolute or relative bone marrow failure  Causes: ◦ Mild to moderate iron defeciency ◦ Inflammation ◦ Marrow damage ◦ Ineffective EPO production (impaired renal function, IL-1, hypothyroidism, diabetes mellitus, myeloma) ◦ Normocytic normochromic, occasionally microcytic hypochromic
  • 22. Investigations: ◦ S. Iron ◦ TIBC ◦ RFT ◦ TFT ◦ Bone Marrow biopsy/aspiration ◦ Serum Ferritin ◦ Iron stain of bone marrow
  • 23. Anemia of chronic inflammation: ◦ S. Iron: Low ◦ TIBC: normal or low ◦ Transferrin saturation: Low ◦ S. Ferritin: Normal – High  Iron defeciency anemia ◦ S. Iron: Low ◦ TIBC: High ◦ Transferrin: Low ◦ S. Ferritin: Low
  • 24. Leukemia and lymphoma, marrow aplasia ◦ Peripheral smear ◦ Bone marrow biopsy
  • 25. Maturation disorders Features: ◦ Anemia with low reticulocyte count ◦ Macro or microcytosis on smear ◦ Abnormal red-cell indices  Two categories: ◦ Macrocytic – nuclear abnormalities ◦ Microcytic – cytoplasmic abnormalities  Ineffective erythropoeisis due to destruction in marrow  Bone marrow shows erythroid hyperplasia
  • 26. Nuclear maturation disorders: ◦ Folate or Vitamin B12 defeciency, drug damage (methotrexate), myelodysplasia ◦ Alcohol causes macrocytosis with variable degree of anemia due to folate defeciency  Cytoplasmic maturation disorders: ◦ Severe iron defeciency, thallassaemias  Iron defeciency: Low reticulocyte index, microcytosis, Serum Iron profile can be used to differentiate from thalassaemias
  • 27. Myelodysplasia: ◦ Macro or microcytosis ◦ Iron ring in mitochondria ◦ Sideroblasts on marrow stain ◦ Iron studies can help differentiate from other conditions
  • 28. Blood loss/ Hemolytic Anemia Red cell production indices > 2.5 or normal  Polychromatophilic macrocytes on smear  Red cells indices: Normocytic to Macrocytic due to increased reticulocytes  Acute blood loss: Not associated with increased reticulocyte production because of time required for EPO production  Subacute blood loss: Moderate reticulocytosis  Chronic blood loss: Iron defeciency with increased red cell production
  • 29. Hemolytic disease Least common form of anemia  High reticulocyte count – marrow able to sustain erythropoesis with efficient recycling of iron in case of extravascular hemolysis  Intravascular hemolysis – Paroxysmal nocturnal hemoglobinuria – Loss of iron may limit marrow response  Hemoglobinopathies like sickle cell disease/thallassemias present a mixed picture and may have a high reticulocyte count which is low compared to marrow hyperplasia.
  • 30. Hemolytic Anemias Acute: specific patterns like autoimmune hemolysis, glutathione reductase.  Inherited hemolytic anemias: have a lifelong history of typical of disease process  Chronic hemolytic diseases like hereditary spherocytosis may present with complication of increased red cell destruction (bilrubin gallstones, splenomegaly).  Susceptible to aplastic crises
  • 31. Differential diagnosis of acute or chronic hemolysis requires careful investigation of family history and specialised laboratory tests like hemoglobin electrophoresis or screening for red cell enzymes.  Acquired defects in red cell survival – may requires testing of indirect antiglobulin test, cold agglutinin titres to detect hemolytic antibodies or complement mediated destruction.
  • 33. Treatment Mild to moderate anemia: Treatment once specific diagnosis in made.  Acute causes may require treatment before diagnosis is made.  Some causes of anemia are multifactoral and it is important to check iron status before and during treatment.