This document provides an evaluation approach for classifying and diagnosing different types of anemia based on patient history and examination findings. It outlines a step-wise approach beginning with determining if the anemia is associated with other hematological abnormalities by examining the bone marrow. It then evaluates the anemia based on red blood cell indices to determine if it is macrocytic, microcytic, or normocytic. For each type of anemia, it provides guidance on further tests and evaluations to identify potential underlying causes. The overall approach is to methodically classify the anemia and then investigate potential etiologies through additional lab tests, bone marrow examination, and considering common associated conditions.

1. In the name of God, Most Gracious, Most Merciful

2. EVALUATION OF A CASE OF ANAEMIA
- Dr. Mohammed Sadiq Azam
PG M:1 (Dr. Siraj’s Unit)
DCMS @ PEH

3. CASE HISTORIES:
• 22/F presented with complaints of shortness of breath (NYHA GR IV),
orthopnoea+, chest discomfort and palpitations on exertion which gradually
increased over the last 6 months to attain present severity. H/s/o Pica+, H/o
passing worms in stools+. No h/o rash, photosensitivity or seizures. O/E: Pallor+,
BPPE+, JVP ↑, s3 gallop+, b/l basal creps (fine)+, no organomegaly, no FF.
• 45/F presented with c/o shortness of breath (NYHA GR II-III), no orthopnoea, no
PND. Past h/o jaundice+. H/o blood transfusion in past +. O/E: Pallor++, Icterus++
+, Hepatomegaly~2 cm below C/m, Splenomegaly~15cm, no FF.
• 75/F presented with c/o fatigability and lethargy over last 8 month, initially mild
now increased in intensity. H/o sob on exertion (NYHA GR I-II). No H/o
orthopnoea/PND. No H/o chest discomfort. Not a known diabetic. H/s/o malena+.
H/o loss of appetitie, loss of weight+ over last 5 months. O/E: Pallor++, anicteric
no PE, CVS/RS – NAD, P/A- NAD.

4. EVALUATION – HISTORY:
• Age/Sex
• Rate of onset – Rapid/Slow
• Blood loss – Haematemesis / malena / bleeding piles / menorrhagia /
metorrhagia / epistaxis / hematuria / haemoptysis
• Abdomen – Appetitie / weight loss / dysphagia / regurgitation / dyspepsia / abd
pain / diarrhoea / constipation / jaundice / soreness of tongue / previous abd
surgeries
• Reproductive – Menstrual history in detail / number & interval between
pregnancies / miscarriages
• Urinary system – Nocturnal polyuria
• CNS – Parasthesiae / difficulty in walking

5. EVALUATION – HISTORY:
• Bleeding tendency – Easy bruising / prolonged bleeding after trivial injuries /
bleeding from more than one site
• Skeletal system – Bone pain / Arthritis / Arthralgia
• Temperature – Fever / Night sweats
• Drug ingestion – Previuos / current
• Occupation – Metal dusts / solvent fumes / lead
• Diet
• Social history – Alcoholism
• Past H/o – Previous anaemia: diag & Rx, response to Rx
• Family H/o – Anaemia / recurrent jaundice / IUD & childhood deaths

6. EVALUATION – EXAMINATION:
• Skin – Colour, texture, petechiae, ecchymoses, scratch marks.
• Nails – Brittleness, longitudinal ridging, koilonychia
• Conjunctiva/Sclera – Pallor, icterus, haemorrhages
• Retina – Haemorrhages, s/o HTN/renal failure, other changes
• Mouth – Mucous membrane: Pallor, petechiae
• Gums: Bleeding, hypertrophy
• Tongue: Redness, atrophy of papillae
• Abdomen – HSM, either HM or SM, tenderness, mass, ascites
• CVS – BP, valvular, vascular prosthesis
• CNS – Peripheral neuritis, s/s/o SADSC

7. EVALUATION – EXAMINATION:
• Supf LN – Enlargement of cervical, axillary, inguinal, epitrochlear nodes
• Bones – Tenderness (esp. of sternum), tumour
• Legs – Ulcers / scars of healed ulcers
• P/R – Haemorrhoids / CA Rectum
• Pelvic – Menorrhagia, metorrhagia, uterus, cervix
• Torniquet test
• Urine – Protein, urobilinogen, BS/BP

8. Provisional Diagnosis: Anaemia for evaluation
THE APPROACH …

9. Is anemia associated with other haematological abnormalities?
Yes No
BM Examination Is there an appropriate reticulocyte response to anaemia?
Leukemias
Aplastic anaemias Yes No
MDS / MF
Myelophthisis RBC Indices
Megaloblastic anaemia
Evidence of haemolysis? MCV >100 MCV 80-100 MCV <80
Yes No Evaluate:
Normocytic anemia
Evaluate cause Evaluate: Evaluate: Evaluate:
of haemolysis haemorrhagic causes Macrocytic anemia Microcytic anemia
(Ref: Bertil Glader: Anaemia: General Considerations, Wintrobe’s Clinical Haematology 11/e, 2004: 951-978)

10. RETICULOCYTOSIS: A WORD
• Retic count = % reticulocytes in RBC population
• Retic count corrected for anaemia = % retculocytes x pt Hb/15 or pt Hct/45
• BUT, Retics released under intense EPO stimulation remain in circulation for approx 2x the usual 1 day
survival of non stress retics, so:
• Corrected Retic index = Retic count corrected for anaemia x 0.5
• < 2.5 = inadequate response – hypoprolifertive / maturation disorder (marrow prod impaired)
• ≥ 2.5 = adequate response – haemolytic / haemorrahgic
• Absolute retic count = %retics x RBC count/l3
• Low retic count + active marrow erythropoiesis = ineffective erythropoiesis
• IDA
• Sideroblastic anaemia
• Thalassemias
• (Also associated with ↑ LDH)

11. Macrocytic anaemia
Does the P/S reveal hypersegmented neutrophils / macroovalocytes?
Yes No
Nonmegaloblastic anaemia
Megaloblastic anaemia – BM to confirm
Test for B12/Folate levels
↑ Reticulocytosis
B12 def No def Folate def Haemolytic N/↓
Schilling’s test: Inherited disorders of DNA syn Poor diet Consider:
Corrects with IF Drugs tht interfere with DNA syn Drug induced malabs - Alcohol
Jejuneal resection - Hypothyroidism
Tropical sprue - Liver disease
Yes No Ileal disease
Previous ileal Sx
Gluten sensitivity
Small bowel bac overgrowth ↑ Needs If NO: BM exam
Pernicious anaemia: Fish tapeworm - Pregnancy
Gastric resection Drug induced malabsorption - Chronic hemolysis - MDS
- Red cell aplasia
- Acq siderobl anaemia
- Herid dyserythropoietic
anaemia (I& III)
(Ref: Bertil Glader: Anaemia: General Considerations, Wintrobe’s Clinical Haematology 11/e, 2004: 951-978)

12. Microcytic anaemia Appropriate age: Rule out malignancy
Reticulocytes
Low / N Increased
Iron Profile P/S: Abnorm morphology
Labs for ↑ RBC destruc
↓ Fe ↓ Fe N. Fe ↑ Fe Hb studies
↑ TIBC N/↓ TIBC N. TIBC N. TIBC
↓ Ferritin N/↑ Ferritin N. Ferritin ↑ Ferritin - Homozygous β thal
- Haemolytic elliptocyt
- Herid pyropoikilocytosis
Iron deficiency
↑ ESR, CRP+ Hb electrophoresis
or other studies BM examination with Fe stains
s/o underlying
Inflammatory disorder - α Thal trait
- β Thal trait
- Hb E syn
AOCD - Hb C disorder Sideroblastic anaemia
(Ref: Bertil Glader: Anaemia: General Considerations, Wintrobe’s Clinical Haematology 11/e, 2004: 951-978)

13. Normocytic anaemia
Reticulocytes
↑ RBC prod N./↓ RBC prod
H/o jaundice, splenomegaly - S. Chemistries to screen S.Fe
Presence of P/S abnormalities for renal, hepatic, endocrine
↑ Bilirubin / LDH disease
- Consider EPO levels, thyroid studies
Yes Haemolysis
Low
Positive Negative N. / High
No Haemolytic anaemia AOCD
BM aspirate & Bx Early IDA
- Anaemia of renal disease
- Anaemia of liver disease - Infiltrative disorder
- Anaemia due to endocrine failure (Leuk, myeloma, MF, Mets)
- Red cell aplasia
- MDS
- Dyserythropoietic anaemia (Type II)
(Ref: Bertil Glader: Anaemia: General Considerations, Wintrobe’s Clinical Haematology 11/e, 2004: 951-978)

14. HAEMORRHAGIC ANAEMIA:
• Retic index ≥ 2.5. Polychromatophilic macrocytes ++ in P/S
• Marrow examination is rarely required if retic index is increased appropriately.
• RBC indices are typically normocytic or slightly macrocytic (reflects ↑ retics)
Blood loss
Acute Missed
Subacute Chronic
No reticulocytosis Presents ///ar to IDA
Observe for 2-3 weeks
Signs of recovery
Modest reticulocytosis - Hb ↑
- Retic count ↓

15. HAEMORRHAGIC ANAEMIA:
Volume of Blood Symptoms
blood loss (ml) volume (%)
500-1000 10-20 Few if any symptoms
1000-1500 20-30 Asymptomatic while at rest in a recumbent position; light headedness
and hypotension when upright; tachycardia
1500-2000 30-40 Symptoms present when recumbent; thirst, SOB, clouding or LOC;
BP, CO, venous pressure decrease, pulse usually rapid; extremities
become cold, clammy & pale
2000-2500 40-50 Lactic acidosis, shock; irreversible shock, death

16. HAEMOLYTIC ANAEMIA:
• Least common form of anaemia
• High retic count: Reflects the ability of the erythroid marrow to compensate
for haemolysis, and, in the case of extravascular haemolysis, the efficient
recycling of iron from the destroyed RBC to support RBC production.
• Intravascular haemolysis – PNH – loss of Fe – limits marrow response
• Hence, the level of marrow response depends on:
• The severity of anaemia
• The nature of the underlying disease process
• Hemoglobinopathies – mixed picture. (Retic count is ↑ but ↓ with respect to
degree of marrow erythroid hyperplasia).

17. HAEMOLYTIC ANAEMIA:
• Presentation varies:
• Acute self limiting illness (autoimmune/EM pathway/GR defects)
• Chronic process (Hb defects/ RBC defects) with a typical history
• HS: chronic course – present with complications such as bilirubin
gallstones or splenomegaly and not anaemia per se.
• Chronic haemolysis also prone to aplastic anaemia if infections occur.

18. HAEMOLYTIC ANAEMIA: INTRAVASCULAR LYSIS
• PNH
• Erythrocyte fragmentation disorders
• Transfusion reactions resulting from ABO incompatability
• Paroxysmal cold haemoglobinuria
• AIHA (occasionally)
• Infections:
• Blackwater fever in falciparum malaria
• Clostridial sps
• Chemical mediated:
• Arsine poisoning
• Snake & Spider venoms
• Acute drug reactions with G6PD def
• I.V. admin of distilled water
• Thermal injury

19. HAEMOLYTIC ANAEMIA: LABS
• Morphological abnormalities: Spherocytes, Elliptocytes, Stomatocytes,
Acanthocytes, Echinocytes, Sickle cells, Target cells, Schistocytes
• Direct Antiglobulin test (Coomb’s test): +ve in IHA (2-5% false neg)
• Osmotic fragility test : HS (Osmotic gradient ektacytometry is more sensitve
& specific, but not widely available)
• Tests for Heinz bodies (supravital staining): G6PD def, unstable Hb
disease, thalassemias, chemicals. (Not seen when spleen is intact)

20. HAEMOLYTIC ANAEMIA: D/D
• Asso with anaemia & retculocytosis:
• Hemorrhage
• Recovery from iron, folate or vitamin B12 deficiency
• Recovery from marrow failure
• Asso with jaundice & anaemia:
• Ineffective erythropoiesis (intramedullary erythropoiesis)
• Bleeding into a body cavity or tissue
• Asso with jaundice without anaemia
• Defective bilirubin conjugation
• Crigler-Najjar syndrome
• Gilbert syndrome
• Marrow invasion
• Myoglobinuria

21. CONCLUSION:
• Any case of anaemia requires a detailed work up starting with history.
• Stepwise approach is the golden rule.
• IDA in elderly – avoid being ‘Penny wise, Pound foolish’
• In tropical countries, tropical malabsorption syndromes are more rampant than
we realize – LOOK OUT, it may be missed unless you look for it.
• Better not to start any IFA or B12 supplements until we diagnose the cause of
anaemia.
• Bone marrow is not the answer to every anaemia – AVOID indiscriminate use.
• No cost is greater than the patient’s life. Investigate what’s mandatory.
• Delayed diagnosis is better than a wrong diagnosis – DO NOT hurry to treat.