A Practical Approach to Anemia

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A Practical Approach to Anemia
How to efficiently and accurately work up an
anemic patient ?

• Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada)
• Consultant Physician Chest Specialist
• Visit us at www.drsarma.in

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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 !! Well 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 packets Biconcave discs Haem
Gl Center 1/3 pallor Pink cytoplasm (Hb
filled) Cell size 7- 8 µ - capill. 2 µ EM
pathway, HMP Negative charge no phago Na less,
K more inside 100-120 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
13 EG 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 lt 13.5 g WHO lt 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
• RBC count (RCC) 5 million 4 to 5.7
• Hemoglobin 15 g 12 to 17
• 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
• RCC 5 million 4 to 5.7
• Hemoglobin 15 g 12 to 17
• Hematocrit 45 38 to 50
• MCV C A x 10 90 fl
• MCH B A x 10 30 pg
• MCHC () B C x 100 33

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Types of Anemia
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Causes of Anemia

• Decreased production of Red Cells
• - Hypo proliferative, marrow failure
• Increased destruction of Red Cells
• - Hemolysis (decreased survival of RBC)
• Loss of Red Cells due to bleeding
• - Acute / chronic blood loss (hemorrhagic)
• M P x S ( L)

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Hypoproliferative Anemias
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Anemia Second Test

• RETICULOCYTE COUNT

• RBC to be or Apprentice RBC
• Fragments of nuclear material
• RNA strands which stain blue

Normal Less than 2
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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
Leishmans
Supravital
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Reticulocyte Production Index

• For example, the RPI is calculated as follows
• Reticulocyte count 9
• Hb content 7.5 g
• Correction for Anemia
• 9 x (7.5 15) 9 x 0.5 4.5
• Correction for life span
• 4.5 2 2.25
• 3. Thus, the RPI is 2.25

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Anemia
Hb lt 12, Hct lt 38
Hemolytic
Hypoproliferative
RPI lt 2
RPI gt 2
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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

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Anemia Workup - MCV
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Anemia Workup 4th TestRed cell Distribution
Width RDW
RDW lt 13 Mean 90 fl
RDW is 13 MCV 90 fl
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Red cell Distribution Width - RDW
MCV
Microcytic
Normocytic
Macrocytic
Left
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
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IDA Summary

• Microcytic MCV lt 80 fl, RBC lt 6 µ
• RDW Widened and shifted to left
• Hypochromic MCH lt 27 pg, MCHC lt 30
• RPI lt 2
• Retic. count May be gt 2
• Serum ferritin Very low lt 33 (p mols/L)
• TIBC Increased gt 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 gt Fe gt 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 lt 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
• Liver disease/alcohol
• Hemoglobinopathies
• Metabolic disorders, Hypothyroidism
• Myelodystrophy, BM infiltration
• Accelerated Erythropoesis - ?destruction
• Drugs (cytotoxics, immuno suppressants, AZT,
  anticonvulsants)

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Anemia - Macrocytic (MCV gt 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 gt 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
• Crohns 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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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 Smear Microcytic hypochromic DD of Microcytic
Serum Ferritin 46 pmol/l Boarderline
TIBC 390 µg/dl Elevated
BM Iron stain Absent Clinches IDA
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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 Smear Microcytic hypochromic DD of Microcytic
Serum Ferritin 320 pmol/l High
TIBC 300 µg/dl Normal
BM Iron stain Ringed sideroblasts Clinches SBA
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Test Done Value Remarks
RBC 2.69 million/c mm Decreased
Hb 10.6 g Decreased
Hematocrit 31.6 Decreasd
MCV 117.5 fl Macrocytosis (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/l Normal (Not required)
TIBC 338 µg/dl Normal (Not required)
BM Exam Megaloblastic BM Clinches 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 fl Macrocytosis (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/l Normal (Not required)
TIBC 338 µg/dl Normal (Not required)
BM Exam Normoblastic BM Clinches 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/l Normal (Not required)
TIBC 338 µg/dl Normal (Not required)
BM Exam Normoblastic BM CLD, ALD, CKD, Drugs
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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/l Normal (Not required)
TIBC 338 µg/dl Normal (Not required)
BM Exam E G Ratio is 2 1 Hypercellular marrow
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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 lt 2 or gt
  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

• Liver Disease
• Thalassemia
• Hb D Disease
• Post splenectomy

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Tear Drop Cells

• Myelofibosis
• Infiltration of BM
• Tumours of BM
• 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 Hb
3. Hemoglobin electrophotesis
4. Serum LDH
5. Serum bilirubin
6. Haptoglobin
7. Urine hemosiderin
8. 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 (ßeta-Thalassemia trait)
3. RBC enzymes (G6PD, PK, etc)
4. Direct indirect antiglobulin tests (immune)
5. Cold agglutinins
6. 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

• Liver Disease
• Acute Alcoholism
• H Stomatocyosis
• Malignancies

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EchinocytesEvenly distributed spicules gt 10

• Uremia
• Peptic ulcer
• Gastric Ca
• 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
Fragmented, Helmet or triangle shaped RBC

• MAHA
• Prosthetic valves
• Uremia
• Malignant HT

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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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