A Practical Approach to Anemia Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada) Consultant Physician & Chest...
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A Practical Approach to Anemia Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada) Consultant Physician & Chest Specialist Visit us at : www.drsarma.in How to efficiently and accurately work up an anemic patient ?
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Transcript of A Practical Approach to Anemia Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada) Consultant Physician & Chest...
A Practical Approach to Anemia
Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada)
Consultant Physician & Chest SpecialistVisit us at : www.drsarma.in
How to efficiently and accurately work up an anemic patient ?
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What is Anemia ?
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 !! We’ll make it
• Its very common and imp. in our practice
• Drug Rx. depends on the cause
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Definition of Anemia
• Decrease in the quantum 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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Normal Red Cells
No nucleus, enzyme packetsBiconcave discs – Haem + GlCenter 1/3 pallorPink cytoplasm (Hb filled)
Cell size 7- 8 µ - capill. 2 µEM pathway, HMPNegative charge – no phagoNa less, K more inside100-120 days life span
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The Factory – Bone Marrow
Sternum, pelvis, vertebrae, long bones, skull bones, Tibia (paed)
From stem cells (pleuripotent)
75% of marrow for WBC
25% of BM for Red cells
Erythrod / Granulocyte Ratio 1:3
E:G ratio increases in Anemia
Large white areas are marrow fat
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Hemoglobin (Hb)
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First Question
• The onset of Anemia
• Acute versus chronic
• Clues
– Hemodynamic stability
– Previous CBC
– Overt blood loss
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Screening Tests – Anemia
• Clinical Signs and symptoms of Anemia
• Look for bleeding – all possible sites
• Look for the causes for anemia
• Routine Hemoglobin examination
• Cut off marks for Hb – – US < 13.5 g WHO < 12.5 g
– India (ICMR) Less than 12 g%
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Clinical Signs to be looked for
• 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
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PCV or Hematocrit
• 57% Plasma
• 1% Buffy coat – WBC
• 42% Hct (PCV)
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The Three Primary Measures
Measurement Normal Range
A. RBC count (RCC) 5 million 4 to 5.7
B. Hemoglobin 15 g% 12 to 17
C. Hematocrit (PCV) 45 38 to 50
A x 3 = B x 3 = C - This is the rule of thumb
Check whether this holds good in a given result
If not -indicates micro or macrocytosis or hypochro.
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The Three Derived Indicies
Measurement Normal Range
A. RCC 5 million 4 to 5.7
B. Hemoglobin 15 g% 12 to 17
C. Hematocrit 45 % 38 to 50
MCV C ÷ A x 10 = 90 flMCH B ÷ A x 10 = 30 pgMCHC (%) B ÷ C x 100 = 33%
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Types of Anemia
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Causes of Anemia
1. Decreased production of Red Cells- Hypo proliferative, marrow failure
2. Increased destruction of Red Cells- Hemolysis (decreased survival of RBC)
3. Loss of Red Cells due to bleeding- Acute / chronic blood loss (hemorrhagic)
M = P x S ( L)
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Hypoproliferative Anemias
Failure of cell maturation
Nuclear breakdown
Cytoplasmic breakdown
Megaloblastic Anemia
Defective DNA synthesis
Folate or B12 deficiency Haem defect Globin defect
Thalassemia
Sickle cell AFe Phorph
IDA, SA
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Anemia – Second Test
RETICULOCYTE COUNT %
NormalLess than
2%
• ‘RBC to be’ or Apprentice RBC
• Fragments of nuclear material
• RNA strands which stain blue
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Reticulocyte
No definite nucleus
Reticulum of RNA
Deep blue staining
Light blue cytoplasm
Cell size about 10 µ
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Reticulocytes
Leishman’sSupravital
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Reticulocyte Production Index
For example, the RPI is calculated as follows
Reticulocyte count 9%
Hb content 7.5 g%
1. Correction for Anemia
= 9 x (7.5 ÷ 15) = 9 x 0.5 = 4.5 %
2. Correction for life span
4.5 ÷ 2 = 2.25 %
3. Thus, the RPI is 2.25
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Anemia
Hypoproliferative Hemolytic
RPI < 2 RPI > 2
Hb% < 12, Hct < 38%
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Workup – Third Test
• The next step is ‘What is the size of RBC’ ?• MCV indicates the Red cell volume (size)• Both the MCH & MCHC tell Hb content of RBC• If the RPI is 2 or less• We are dealing with either
– Hypoproliferative Anemia (lack of raw material)
– Maturation defect with less production
– Bone marrow suppression (primary/ secondary)
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Red Cell Size
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Mean Cell Volume (MCV)
• RBC size is measured indirectly by• The Mean Cell Volume (MCV) and RDW
Microcytic
< 80 fl
MCV
Normocytic Macrocytic
80 -100 fl > 100 fl
< 6.5 µ 6.5 - 9 µ > 9 µ
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Anemia Workup - MCV
Microcytic
MCV
Normocytic Macrocytic
Iron Deficiency (IDA)
Chronic Infections
Thalassemias
Hemoglobinopathies
Sideroblastic Anemia
Chronic diseases, CKD
Early IDA
Hemoglobinopathies
Primary marrow disorders
Combined deficiencies
Increased destruction
Megaloblastic anemias
Liver disease/alcohol
Hemoglobinopathies
Metabolic disorders
Marrow disorders
Increased destruction
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Anemia Workup – 4th TestRed cell Distribution Width – RDW
RDW < 13
Mean 90 fl
RDW is 13
MCV 90 fl
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Red cell Distribution Width - RDW
Microcytic
Left
MCV
Normocytic Macrocytic
Mean 90 Right
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Anemia Workup - 5th TestPeripheral Smear Study
• Are all RBC of the same size ?
• Are all RBC of the same normal discoid shape ?
• How is the colour (Hb content) saturation ?
• Are all the RBC of same colour/ multi coloured ?
• Are there any RBC inclusions ?
• Are there any hemo-parasites in the RBC ?
• Are leucocytes normal in number and D.C ?
• Is platelet distribution adequate ?
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IDA -CBC
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Severe Hypochromia
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Microcytic Hypochromic - IDA
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Microcytic Hypochromic Anemia
Serum Ferritin
< 33 pmol / l 33-270 pmol / l > 270pmol / l
Not IDA, Other Mi A
TIBC (300-340)
HIGH N or ↓
BM Fe +-
Iron Deficiency Anemia IDA
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IDA Summary
• Microcytic MCV < 80 fl, RBC < 6 µ
• RDW Widened and shifted to left
• Hypochromic MCH < 27 pg, MCHC < 30%
• RPI < 2
• Retic. count May be > 2 %
• Serum ferritin Very low < 33 (p mols/L)
• TIBC Increased > 340 (µg/dL)
• BM Iron stain Iron is Absent
• Response to Fe Rx. Excellent
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IDA- Some Nuggets
• Look for occult blood loss – 2 days non veg. free
• Pica and Pagophagia – Ice sucking
• Absorption of Haem Iron > Fe ++ > Fe+++
• Food, Phytates, Ca, Phosphate, antacids ↓absorption
• Ascorbic acid ↑absorption
• Oral iron Rx. always is the best, ? Carbonyl Fe
• FeSO4 is the best. Reserve parenteral Rx.
• Packed cell transfusion in emergency
• Continue Fe Rx at least 2 months after normal Hb
• 1 gram ↑in Hb every week can be expected
• Always supplement protein for the Globin component
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Microcytic Anemias
MCV < 80 fl Serum Ferritin TIBC BM Perls stain
Iron Def. Anemia ↓↓ ↑↑ 0
Chronic Infection ↓↓ ↓↓ + +Thalassemia ↑↑ N + + + +
Hemoglobinopathy N N + +Lead poisoning N N + +Sideroblastic ↑↑ N + + + +
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Ringed Sideroblasts in BM
Prussian Blue Stain
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Macrocytic Anemias
A. Megaloblastic Macrocytic – B12 and Folate↓
B. Non Megaloblastic Macrocytic Anemias
1. Liver disease/alcohol
2. Hemoglobinopathies
3. Metabolic disorders, Hypothyroidism
4. Myelodystrophy, BM infiltration
5. Accelerated Erythropoesis - ↑destruction
6. Drugs (cytotoxics, immuno suppressants, AZT, anticonvulsants)
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Anemia - Macrocytic (MCV > 100)
Premature gray hair – consider MBA
Macrocytic anemias may be asymptomatic until
the Hb is as low as 6 grams
MCV 100-110 fl
must look for other causes of macrocytosis
MCV > 110 fl
almost always folate or B12 deficiency
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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)
• Nuclear : Cytoplasmic dyssynchrony in marrow
• Neutrophil hyper segmentation & macro ovalocytes
• Anemia (and often leukopenia & thrombocytopenia)
• Almost always due to B12 or folate deficiency
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MBA
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Macrocytosis -MBA
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Anisocytosis - Macrocytic Anemia
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HSN - MBA
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Basophilic Stippling - MBA
BS occurs in Lead poisoning also
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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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Pernicious Anemia - Tongue
Bald, smooth, lemon yellowish red tongue
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Normocytic Anemias
1. Chronic diseases, CKD
2. Early IDA
3. Hemoglobinopathies
4. Primary marrow disorders
5. Combined deficiencies
6. Increased destruction
7. Anemia of investigations -ICU
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Anemia of Chronic Disease
• Thyroid diseases• Malignancy• Collagen Vascular Disease
– Rheumatoid Arthritis– SLE– Polymyositis– Polyarteritis Nodosa
• IBD
– Ulcerative Colitis
– Crohn’s Disease• Chronic Infections
– HIV, Osteomyelitis
– Tuberculosis• CKD, Renal Failure
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‘Dimorphic’ Anemia
• 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)
• Peripheral smear exam is critical to assess these
• RDW is increased very much
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Anemia Suspected
Thorough Clin, Bleed Hb%, RCC, Hct Decreased
RPI, Retic count <2 RPI, Retic count >2
Hemolytic Anemia
Coombs DAT, IDAT
Hb electrophoresis
Osmotic fragility
MCV, MCH, MCHC, PSE
Microcytic hypochromic Macrocytic hypo/normo
Megaloblastic NormoblasticIron Def. Anemia
Ferritin, TIBC, BM Fe
Thalassemia, Hb pathy
Sederoblastic Anaem.
Chr. Infection, Lead
Folate defici.
B12 def., PA
Ca, Leukemia, Ulcer
Identify the cause
ALD, CLD, Drug
Chr. Renal dis.
Hypothyroid
BM infiltration
Acid hemolysis
Cold agglutinins
Coagulopathy, DIC
Algorithm for Diagnosis of Anemia
LET US LOOK AT SOME REPORTS OF PATIENTS
In order to make a differential diagnosis
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Test Done Value Remarks
RBC 3.96 million/c mm Decreased
Hb% 9.7 g% Decreased
Hematocrit 23.9 % Decreasd
MCV 60.4 fl Microcytosis
MCH 24.6 pg/l Hypochromia
MCHC 40.5 % Not relevant
RC and RPI 4 %, 1.29 Not Hemolytic
Peripheral SmearMicrocytic hypochromic
DD of Microcytic
Serum Ferritin 46 pmol/l Boarderline
TIBC 390 µg/dl Elevated
BM Iron stain Absent Clinches IDAwww.drsarma.in
Test Done Value Remarks
RBC 3.86 million/c mm Decreased
Hb% 10.4 g% Decreased
Hematocrit 26.9 % Decreasd
MCV 69.7 fl Microcytosis
MCH 25.8 pg/l Hypochromia
MCHC 38.66 % Not relevant
RC and RPI 5 %, 1.73 Not Hemolytic
Peripheral SmearMicrocytic hypochromic
DD of Microcytic
Serum Ferritin 320 pmol/l High
TIBC 300 µg/dl Normal
BM Iron stain Ringed sideroblasts Clinches SBAwww.drsarma.in
Test Done Value Remarks
RBC 2.69 million/c mm Decreased
Hb% 10.6 g% Decreased
Hematocrit 31.6 % Decreasd
MCV 117.5 flMacrocytosis (Severe)
MCH 39.4 pg/l Hyperchromia
MCHC 33.5 % Normal
RC and RPI 5 %, 1.76 Not Hemolytic
Peripheral Smear
Macrocytic Hyperchromic
DD of Macrocytic
Serum Ferritin 240 pmol/lNormal (Not required)
TIBC 338 µg/dlNormal (Not required)
BM Exam Megaloblastic BMClinches MBA (F, B12)
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Test Done Value Remarks
RBC 3.09 million/c mm Decreased
Hb% 10.6 g% Decreased
Hematocrit 31.6 % Decreasd
MCV 102.3 flMacrocytosis (Moderate)
MCH 34.3 pg/l Hyperchromia
MCHC 33.5 % Normal
RC and RPI 3 %, 1.06 Not Hemolytic
Peripheral Smear
Macrocytic Hyperchromic
DD of Macrocytic
Serum Ferritin 240 pmol/lNormal (Not required)
TIBC 338 µg/dlNormal (Not required)
BM Exam Normoblastic BMClinches MCA (Chr D)
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Test Done Value Remarks
RBC 3.10 million/c mm Decreased
Hb% 9.3 g% Decreased
Hematocrit 27.9 % Decreasd
MCV 90 fl Normocytosis
MCH 30.0 pg/l Normochromia
MCHC 33.3 % Normal
RC and RPI 1.5 %, 0.47 Not Hemolytic
Peripheral Smear
Normocytic Normochromic
DD of Normocytic A
Serum Ferritin 240 pmol/lNormal (Not required)
TIBC 338 µg/dlNormal (Not required)
BM Exam Normoblastic BMCLD, ALD, CKD, Drugswww.drsarma.in
Test Done Value Remarks
RBC 3.81 million/c mm Decreased
Hb% 11.1 g% Decreased
Hematocrit 33.3 % Decreasd
MCV 87.4 fl Normocytosis
MCH 29.2 pg/l Normochromia
MCHC 33.33 % Normal
RC and RPI 10 %, 3.70 Hemolytic
Peripheral Smear
Piokilo, Aniso, target cells
DD of Hemolytic Anemia
Serum Ferritin 240 pmol/lNormal (Not required)
TIBC 338 µg/dlNormal (Not required)
BM Exam E : G Ratio is 2 : 1 Hypercellular marrowwww.drsarma.in
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Anemia - 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 Anemia• If hypo proliferative – Microcytic or Macrocytic? (MCV, RDW)• If microcytic – IDA or others – Sr Ferritin TIBC, BM Iron• If macrocytic – Megaloblastic (B12, FA) or Normoblastic BM• If normocytic – Anemia of chr. Disease – Liver, CKD, 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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RBC Size – AnisocytosisDifferent sizes of RBC
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PoikilocytosisDifferent Shapes of RBC
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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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Tear Drop Cells
1. Myelofibosis
2. Infiltration of BM
3. Tumours of BM
4. Thalassemia
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Hair on end - Thalassemia Major
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Drepanocytes - SS
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Sickle Cell Anemia
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Autosplenectomy - SS
Normal spleen is 8 to 12 cm
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Hemolytic Anemia
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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Tests Used to Diagnose Hemolysis
1. Reticulocyte count 2. Combined with serial Hb3. Hemoglobin electrophotesis4. Serum LDH5. Serum bilirubin6. Haptoglobin7. Urine hemosiderin8. Hemoglobinuria
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Findings in Hemolytic Anemia
Reticulocyte count and RPI Increased
Serum Unconjugated Bilirubin Increased
Serum LDH 1: LDH 2 Increased
Serum Haptoglobin Decreased
Urine Hemoglobin Present
Urine Hemosiderin Present
Urine Urobilinogen Increased
Cr 51 labeled RBC life span Decreased
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Tests to define the cause of hemolysis
1. Hemoglobin electrophoresis
2. Hemoglobin A2 (βeta-Thalassemia trait)3. RBC enzymes (G6PD, PK, etc)4. Direct & indirect antiglobulin tests (immune)5. Cold agglutinins6. Osmotic fragility (spherocytosis)7. Acid hemolysis test (PNH)8. Clotting profile (DIC)
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MAHA
Micro Angiopathic Hemolytic Anemia
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MAHA
Micro Angiopathic Hemolytic Anemia
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Hyperactive BM – SkullHemolytic Anemia
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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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StomatocytesSlit like central pallor in RBC
1. Liver Disease
2. Acute Alcoholism
3. H Stomatocyosis
4. Malignancies
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EchinocytesEvenly distributed spicules > 10
1. Uremia
2. Peptic ulcer
3. Gastric Ca
4. PK-D
Called Burr Cells
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Acanthocytes5-8 spikes of varying length, irregular intervals
Called Spur Cells, Occur in A H A
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Shistocytes
1. MAHA
2. Prosthetic valves
3. Uremia
4. Malignant HT
Fragmented, Helmet or triangle shaped RBC
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Leukoplakia - Aplastic Anemia
1. Chloramphenicol
2. Neomercazole
3. Sulfonamides
4. Analgin
5. Phenytoin
6. Butazolidin group
7. Anti Ca drugs
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Normal BM High Power
E : G = 1 : 3
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Shift in E : G Ratio
E : G = 2 : 1
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BM - Aplastic Anemia
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Myelofibrosis
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Post transfusion - CBC
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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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Thank You ALL
