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
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
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.