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What is Anaemia ?
Important to remember Anemia is a clinical sign of disease It is not a single disease by itself Need to look for the underlying cause ! Will we ignore a fever with out investigation ? Its diagnosis is not that simple !! Well make it Its very common and imp. in our practice Drug Rx. depends on the cause
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Definition of Anaemia
Decrease in the number of circulating red blood cell mass and there by O2 carrying capacity Most common hematological disorder by far Almost always a secondary disorder As such, critical for all practitioners to know how to evaluate / determine its cause / treat
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Erythron
1. 2. 3. Erythron is the machinery of RBC production EPO, IL, Growth factors, Cytokines stimulate it Hypoxia is strong stimulus for the Erythron Its functioning is influenced by Normal renal production of EPO A functioning Erythroid marrow An adequate supply of substrates for Hb production
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Pro Erythroblast
Basophilic in stain
Cell > 35
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Early Normoblast
Cell > 25
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Intermediate Normoblast
More cytoplasm
Neutral in stain
Cell > 20
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Late Normoblast
Increased cytoplasm
Pink in stain
Cell > 15
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Reticulocyte
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Hemoglobin (Hb)
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First Question
The onset of Anaemia Acute versus chronic Clues Hemodynamic stability Previous CBC Overt blood loss
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Types of Anaemia
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Skin / mucosal pallor, Skin dryness, palmar creases Bald tongue, Glossitis Mouth ulcers, Rectal exam Jaundice, Purpura Lymph adenopathy Hepato-splenomegaly Breathlessness Tachycardia, CHF Bleeding, Occult Blood
PCV or Hematocrit
C. Hematocrit
45
38 to 50
A x 3 = B x 3 = C - This is the rule of thumb Check whether this holds good in given results If not -indicates micro or macrocytosis or hypochro.
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C. Hematocrit
MCV MCH MCHC
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45
C A x 10 B A x 10 B C x 100 = = =
38 to 50
90 fl 30 pg 33%
Causes of Anaemia
1. Decreased production of Red Cells
- Hypo proliferative, marrow failure
M = P x S ( L)
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Hypoproliferative Anaemias
Failure of cell maturation
Nuclear breakdown
Sickle cell A
Thalassemia
IDA, SA
Reticulocytes
Supravital
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Leishmans
Anaemia
Hb% < 12, Hct < 38%
Hypoproliferative
RPI < 2
Hemolytic
RPI > 2
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Normal CBC
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MCV
Microcytic
Normocytic
Macrocytic
< 80 fl
< 6.5
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80 -100 fl
6.5 - 9
> 100 fl
>9
Microcytic
Iron Deficiency IDA
Chronic Infections Thalassemias
Normocytic
Chronic disease
Early IDA Hemoglobinopathies Combined deficiencies Increased destruction
Macrocytic
Megaloblastic anemias
Liver disease/alcohol Hemoglobinopathies Marrow disorders Increased destruction
Hemoglobinopathies
Sideroblastic Anemia
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Microcytic
Normocytic
Macrocytic
Left
Mean 90
Right
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IDA -CBC
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Severe Hypochromia
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BM Fe
+
Not IDA, Other Mi A
Iron related tests Serum Ferritin (pmo/L) TIBC (g/dL) Serum Iron (g/dL) Saturation % Bone marrow Iron
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IDA Summary
Microcytic MCV < 80 fl, RBC < 6
RDW
Hypochromic RPI
Retic. count
Serum ferritin TIBC Serum Iron BM Fe Stain
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May be > 2 %
Very low < 30 (p mols/L) Increased > 400 (g/dL) Very low < 30 (g/dL) Absent Fe Excellent
Response to Fe Rx.
Microcytic Anaemias
MCV < 80 fl Iron Def. Anemia Chronic Infection Thalassemia Hemoglobinopathy Lead poisoning Serum Iron TIBC BM Perls stain 0
N N
N N N
++
++++
++ ++
++++
Sideroblastic
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Ringed Sideroblasts in BM
Prussian Blue Stain
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Macrocytic Anaemias
A. Megaloblastic Macrocytic B12 and Folate B. Non Megaloblastic Macrocytic Anaemias 1. Liver disease/alcohol 2. Hemoglobinopathies 3. Metabolic disorders, Hypothyroidism 4. Myelodystrophy, BM infiltration 5. Accelerated Erythropoesis - destruction 6. Drugs (cytotoxics, immunosuppressants, AZT, anticonvulsants)
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Macrocytosis of Alcoholism
25-96% of alcoholics MCV elevation usually slight (100-110 fl) Minimal or no anemia Macrocytes round (not oval) Neutrophil hyper segmentation absent Folate stores normal Smoking increases the Red Cell Mass
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Megaloblastic Hematopoiesis
Marrow failure due to
Disrupted DNA synth. & ineffective erythropoesis Giant precursors (Megaloblasts)
MBA
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Macrocytosis -MBA
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HSN - MBA
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HSN - MBA
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Megalocyte in PS
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MBA - BM
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MBA - BM
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Megaloblast FA deficiency
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Normocytic Anaemias
1. 2. 3. 4. 5. 6. 7.
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Chronic disease Early IDA Hemoglobinopathies Primary marrow disorders Combined deficiencies Increased destruction Anaemia of investigations -ICU
IBD Ulcerative Colitis Crohns Disease Chronic Infections HIV, Osteomyelitis Tuberculosis Renal Failure
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Dimorphic Anaemia
Folate & Fe deficiency (pregnancy, alcoholism)
B12 & Fe deficiency (PA with atrophic gastritis) Thalassemia minor & B12 or folate deficiency Fe deficiency & hemolysis (prosthetic valve) Folate deficiency & hemolysis (Hb SS disease)
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Polychromasia - Spherocytosis
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Target Cells
1. Liver Disease
2. Thalassemia 3. Hb D Disease 4. Post splenectomy
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Drepanocytes - SS
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Autosplenectomy - SS
Normal spleen is 8 to 12 cm
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Hemolytic Anaemia
Anemia of increased RBC destruction
Normochromic, normocytic anemia Shortened RBC survival Reticulocytosis due to RBC destruction Will not be symptomatic until the RBC life span is reduced to 20 days BM compensates 6 times
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Reticulocyte count Combined with serial Hb Serum LDH Serum bilirubin Haptoglobin Urine hemosiderin Hemoglobinuria
Urine Urobilinogen
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Increased
Decreased
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MAHA
Micro Angiopathic Hemolytic Anaemia
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MAHA
Micro Angiopathic Hemolytic Anaemia
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Spherocytosis
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Spherocytosis
Hereditary Spherocytosis
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Spherocytosis
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Elliptocytes
Hereditary Elliptocytosis, B12 or Folate
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Stomatocytes
Slit like central pallor in RBC
1. Liver Disease 2. Acute Alcoholism 3. H Stomatocyosis 4. Malignancies
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Echinocytes
Evenly distributed spicules > 10
1. Uremia
2. Peptic ulcer 3. Gastric Ca 4. PK-D Called Burr Cells
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Acanthocytes
5-8 spikes of varying length, irregular intervals
Called Spur Cells, Occur in A H A
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Shistocytes
Fragmented, Helmet or triangle shaped RBC 1. MAHA 2. Prosthetic valves 3. Uremia 4. Malignant HT
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Shift in E : G Ratio
E:G=2:1
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BM - Aplastic Anaemia
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Myelofibrosis
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Howell-Jolly Bodies
Absence of Splenic function; Nuclear chromatin in RBC
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Pelger-Huet Anomaly
Inherited condition
PMN - Spectacles Heterozygous Homozygous fatal Neutrophil Bands
Normal WCC
No e/o infection
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Hb%, RCC, Hct Decreased RPI, Retic count <2 MCV, MCH, MCHC, PSE RPI, Retic count >2 Hemolytic Anaemia Coombs DAT, IDAT Hb electrophoresis Osmotic fragility
Microcytic hypochromic Iron Def. Anaemia Ferritin, TIBC, BM Fe Thalassemia, Hb pathy Sederoblastic Anaem. Chr. Infection, Lead
Macrocytic hypo/normo Megaloblastic Folate defici. B12 def., PA Normoblastic ALD, CLD, Drug Chr. Renal dis. Hypothyroid BM infiltration
Acid hemolysis
Cold agglutinins Coagulopathy, DIC
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Anaemia - Summary
If Hb% is low Do not start on Iron straight away Ask for RCC, Hematocrit Derive MCV, MCH, MCHC Order for Reticulocyte count Is RPI < 2 % or > 2% Thoroughly look for blood loss acute / chronic / occult Is it hypo-proliferative or hemolytic or hemorrhagic anaemia If hypo proliferative Microcytic or Macrocytic? (MCV, RDW) If microcytic IDA or others Spl. Iron tests, BM Iron If macrocytic Megaloblastic (B12, FA) or Normoblastic BM If normocytic Anaemia of chr. Disease Liver, MRD, Ca Peripheral smear study for RBC size, shape, colouration etc. If retic. count is - HA work up; Hb EP, spl. tests
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