anaemia comprehensive by dr sarma
DESCRIPTION
anemia on presentationTRANSCRIPT
A Practical Approach to Anemia
How to efficiently and accurately work up an anemic patient ?
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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 !! We’ll 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
• 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
1. Normal renal production of EPO
2. A functioning Erythroid marrow
3. An adequate supply of substrates for Hb production
Let us meet the Grand Parents !
The RBC Lineage
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Haemopoesis in Bone Marrow
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Pro Erythroblast
Large purple nucleus
Thin rim of cytoplasm
Basophilic in stain
Cell > 35 µ
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Early Normoblast
Large purple nucleus
Denser nucleus
Thin rim of cytoplasm
Basophilic in stain
Cell > 25 µ
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Intermediate Normoblast
Medium sized nucleus
Reticulated nucleus
More cytoplasm
Neutral in stain
Cell > 20 µ
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Late Normoblast
Small dense nucleus
Darkly staining
Increased cytoplasm
Pink in stain
Cell > 15 µ
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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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Normal Red Cells
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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 increased in Anaemia
Large white areas are marrow fat
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Normal BM High Power
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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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Screening Tests – Anaemia
• Clinical Signs and symptoms of Anaemia
• 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 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 Basic Measures
Measurement Normal Range
A. RBC count 5 million 4 to 6
B. Hemoglobin 15 g% 12 to 17
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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The Three Derived Indicies
Measurement Normal Range
A. RBC count 5 million 4 to 6
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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Causes of Anaemia
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 Anaemias
Failure of cell maturation
Nuclear breakdown
Cytoplasmic breakdown
Megaloblastic Anaemia
Defective DNA synthesis
Folate or B12 deficiency Haem defect Globin defect
Thalassemia
Sickle cell AFe Phorph
IDA, SA
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Anaemia – First 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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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 Anaemia
= 9 x (7.5 ÷ 15) = 9 x 0.5 = 4.5 %
2. Correction for increased life span
4.5 ÷ 2 = 2.25 %
3. Thus, the RPI is 2.25
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Anaemia
Hypoproliferative Hemolytic
RPI < 2 RPI > 2
Hb% < 12, Hct < 38%
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Normal CBC
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Workup – Second 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 anaemia (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 volume (rather) is measured by• The Mean Cell Volume or 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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Anaemia Workup - MCV
Microcytic
MCV
Normocytic Macrocytic
Iron Deficiency IDA
Chronic Infections
Thalassemias
Hemoglobinopathies
Sideroblastic Anemia
Chronic disease
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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Anaemia Workup – 3rd 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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Anaemia Workup - 4th 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 intra RBC there any hemo-parasites ?
• 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 Anaemia
Serum Ferritin
< 33 pmol / l 33-270 pmol / l > 270pmol / l
Not IDA, Other Mi A
TIBC
HIGH N or ↓
BM Fe +-
Iron Deficiency Anaemia IDA
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IDA – Special Tests
Iron related tests Normal IDA
Serum Ferritin (pmo/L) 33-270 < 33
TIBC (µg/dL) 300-340 > 400
Serum Iron (µg/dL) 50-150 < 30
Saturation % 30-50 < 10
Bone marrow Iron ++ Absent
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IDA Summary
• Microcytic MCV < 80 fl, RBC < 6 µ
• RDW Widened and shift to left
• Hypochromic MCH < 27 pg, MCHC < 30%
• RPI < 2
• Retic. count May be > 2 %
• Serum ferritin Very low < 30 (p mols/L)
• TIBC Increased > 400 (µg/dL)
• Serum Iron Very low < 30 (µg/dL)
• BM Fe Stain Absent Fe
• 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 Anaemias
MCV < 80 fl Serum Iron 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 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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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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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 Anaemia
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HSN - MBA
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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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Pernicious Anaemia - Tongue
Bald, smooth, lemon yellowish red tongue
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Normocytic Anaemias
1. Chronic disease
2. Early IDA
3. Hemoglobinopathies
4. Primary marrow disorders
5. Combined deficiencies
6. Increased destruction
7. Anaemia of investigations -ICU
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Anaemia 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• 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)
• Peripheral smear exam is critical to assess these
• RDW is increased very much
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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 Anaemia
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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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Tests Used to Diagnose Hemolysis
1. Reticulocyte count 2. Combined with serial Hb3. Serum LDH4. Serum bilirubin5. Haptoglobin6. Urine hemosiderin7. Hemoglobinuria
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Findings in Hemolytic Anaemia
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 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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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 Anaemia
1. Chloramphenicol
2. Neomercazole
3. Sulfonamides
4. Analgin
5. Phenytoin
6. Butazolidin group
7. Anti Ca drugs
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Howell-Jolly Bodies
Absence of Splenic function; Nuclear chromatin in RBC
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Anaemia Suspected
Thorough Clin, Bleed Hb%, RCC, Hct Decreased
RPI, Retic count <2 RPI, Retic count >2
Hemolytic Anaemia
Coombs DAT, IDAT
Hb electrophoresis
Osmotic fragility
MCV, MCH, MCHC, PSE
Microcytic hypochromic Macrocytic hypo/normo
Megaloblastic NormoblasticIron Def. Anaemia
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
Anaemia Diagnosis -Algorithm
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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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