Anaemia

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Anaemia - Overview & Classification

Sources: Harrison's Principles of Internal Medicine 22e (2025) | Robbins & Kumar Basic Pathology | Robbins, Cotran & Kumar Pathologic Basis of Disease

Definition

Anaemia is defined as blood counts below the normal range for a given population. In practice:

Males: Hb < 13.5 g/dL, Hct < 41%
Females: Hb < 12.0 g/dL, Hct < 37%

Note: In pregnancy, a physiological haemodilution occurs (plasma volume rises ~47%, RBC mass only ~17%), making Hb < 10.5 g/dL and Hct < 33% the threshold for pathological anaemia.

Classification - Two Major Systems

There are two complementary ways to classify anaemia. Knowing both is essential for exams.

1. Morphological Classification (by MCV)

This is the classic Wintrobe classification and the most common starting point in clinical workup.

Type	MCV	Common Causes
Microcytic	< 80 fL	Iron deficiency, thalassaemia, sideroblastic anaemia, anaemia of chronic disease (sometimes)
Normocytic	80-100 fL	Aplastic anaemia, renal disease, anaemia of inflammation, endocrinopathies, marrow invasion, myeloma, pure red cell aplasia
Macrocytic	> 100 fL	Megaloblastic (B12/folate deficiency), liver disease, hypothyroidism, reticulocytosis, alcohol, drugs (hydroxyurea, methotrexate), myelodysplasia

Key exam point: In iron deficiency, RDW (red cell distribution width) is high (anisocytosis). In thalassaemia, RDW is low/normal (homogeneous microcytes). This distinction is a classic differentiator.

2. Pathophysiological Classification (by Mechanism)

A. Underproduction (Hypoproliferative) - Reticulocyte count LOW

This accounts for at least 75% of all anaemia cases.

Subcategory	Examples
Nutritional deficiency	Iron, B12, folate, copper, vitamin C
Lack of EPO	Chronic renal disease, anaemia of inflammation, anaemia of ageing
Absence of red cell precursors	Aplastic anaemia, pure red cell aplasia
Stem cell defects	Myelodysplastic syndrome, acute/chronic leukaemia
Marrow replacement	Neoplasm (myelophthisic anaemia), granulomas, infections

B. Increased Destruction / Loss (Hyperproliferative) - Reticulocyte count HIGH

Blood loss (haemorrhage) - acute or chronic
Haemolysis - red cell breakdown exceeds marrow output

Haemolytic Anaemias - Classification

Type	Intrinsic (Corpuscular)	Extrinsic (Extracorpuscular)
Inherited	Hereditary spherocytosis, sickle cell anaemia, thalassaemia, G6PD deficiency	-
Acquired	PNH (paroxysmal nocturnal haemoglobinuria)	Autoimmune, mechanical (prosthetic valves), malaria, drugs

Lab findings in haemolysis: Elevated LDH, low haptoglobin, elevated indirect bilirubin, reticulocytosis, haemoglobinuria (if intravascular).

Key Red Cell Morphology on Peripheral Smear (High-Yield)

Morphology	Association
Microcytic hypochromic cells	Iron deficiency, thalassaemia
Spherocytes	Hereditary spherocytosis, autoimmune haemolytic anaemia
Sickle cells	Sickle cell disease
Target cells	Thalassaemia, liver disease, HbC
Schistocytes (fragmented cells)	Microangiopathic haemolytic anaemia (TTP, DIC, HUS), mechanical valves, burns
Macro-ovalocytes + hypersegmented neutrophils	Megaloblastic anaemia (B12/folate deficiency)
Teardrop cells (dacrocytes)	Marrow fibrosis (myelofibrosis)
Burr cells (echinocytes)	Uraemia
Acanthocytes (spur cells)	Liver disease, abetalipoproteinaemia
Nucleated RBCs in peripheral blood	Asplenia, severe marrow stress, marrow infiltration

Red Cell Indices (MCV Table)

Index	Formula	Normal
MCV	Hct / RBC count × 10	85-95 fL
MCH	Hb / RBC count × 10	27-33 pg
MCHC	Hb / Hct × 100	33.8-34.2 g/dL
RDW	SD of MCV / Mean MCV × 100	11.5-14.5%

Physiological Compensation for Anaemia

The body compensates through three mechanisms (Harrison's 22e):

Increased cardiac output - oxygen delivery = CO × Hb; occurs within minutes
Increased 2,3-DPG - shifts O2 dissociation curve right, releasing more O2 to tissues; occurs over hours to days
Increased plasma volume - preserves BP and cardiac output; occurs over weeks

This explains why chronic anaemia (e.g., thalassaemia, iron deficiency) is often better tolerated than acute anaemia (e.g., haemorrhage).

Clinical Features

Symptom/Sign	Mechanism
Pallor (conjunctiva, palmar creases)	Reduced Hb
Fatigue, lethargy	Tissue hypoxia
Dyspnoea on exertion	Compensatory increased CO
Resting tachycardia	Compensatory increase in CO
Angina / TIA in elderly	Ischaemia due to reduced O2 delivery in atherosclerotic vessels
Pica (craving non-food substances)	Iron deficiency specifically
Peripheral neuropathy	Vitamin B12 deficiency specifically
Jaundice + splenomegaly	Haemolytic anaemia
Bone deformities	Severe congenital haemolytic anaemia (marrow hyperplasia)

Diagnostic Approach (Algorithm)

CBC + Reticulocyte Count
         |
    _____|_____
   |           |
Retic HIGH    Retic LOW (< 2%)
(Haemolysis/   (Hypoproliferative)
 Bleeding)          |
   |           _____|________
Rule out      |              |
bleeding   Low MCV       High MCV
   |       (Microcytic)  (Macrocytic)
Haemolysis      |              |
workup:     Ferritin      B12/Folate
LDH, haptogl.  Low = IDA   Smear for
DAT, smear  Normal = Thal   megaloblasts
            (check RDW)  Normal MCV = Normocytic
                         (Renal fn, EPO level,
                          marrow exam if needed)

Bone Marrow Examination - Indications

Marrow biopsy is indicated when peripheral blood findings suggest:

Circulating blasts
Severe pancytopenia
Very low reticulocyte count (< 0.1%)
Circulating nucleated RBCs
Teardrop cells (marrow infiltration)
Staging lymphoma
Unexplained severe anaemia

Treatment Principles

Cause	Treatment
Iron deficiency	Oral ferrous sulphate 60-120 mg elemental iron/day
B12 deficiency	IM cyanocobalamin or high-dose oral B12
Folate deficiency	Oral folic acid 1-5 mg/day
Anaemia of renal failure	Recombinant EPO + IV iron
Aplastic anaemia	Bone marrow transplant / immunosuppression
Autoimmune haemolytic anaemia	Corticosteroids, rituximab
Blood transfusion	Reserved for Hb-driven haemodynamic compromise, angina, or marrow failure

References:

Harrison's Principles of Internal Medicine 22e (2025), Chapter 66 - Harrison's Principles of Internal Medicine 22E
Robbins & Kumar Basic Pathology, Chapter on Red Cell Disorders - Robbins & Kumar Basic Pathology

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