The Haematological System

📋 Key Information Summary

📋

A systematic haematological history must screen for fatigue, pallor, bruising/bleeding, lymphadenopathy, weight loss, fever, night sweats, and recurrent infections — each pattern points toward a specific haematological diagnosis.
Anaemia affects approximately 5% of Australian adults and up to 20% of Aboriginal and Torres Strait Islander peoples, with iron deficiency remaining the most common cause nationally.
Examination for anaemia centres on pallor (conjunctival, palmar, nail-bed), jaundice (suggesting haemolysis), and compensatory tachycardia.
Bleeding disorder examination requires identification of petechiae (platelet/vascular), purpura, and ecchymoses (coagulation factor defects) — the pattern of bleeding distinguishes primary from secondary haemostatic failure.
Lymph node examination must systematically assess all major node groups (cervical, supraclavicular, axillary, inguinal, epitrochlear) documenting size, consistency, mobility, and tenderness.
Supraclavicular lymphadenopathy is always pathological — consider malignancy (lung, GI, lymphoma) until proven otherwise.
The peripheral blood film is the single most informative initial investigation in haematology — it correlates clinical findings with red cell indices (microcytic, normocytic, macrocytic), white cell morphology, and platelet assessment.
Microcytic anaemia (MCV <80 fL) demands investigation for iron deficiency (most common), thalassaemia trait (prevalent in Mediterranean and South-East Asian Australian populations), and chronic disease.
Macrocytic anaemia (MCV >100 fL) requires consideration of B12/folate deficiency, alcohol excess, hypothyroidism, myelodysplastic syndrome, and药物 causes (methotrexate, hydroxyurea).
Painless, progressive lymphadenopathy with B-symptoms (fever, night sweats, >10% weight loss) is lymphoma until proven otherwise — urgent referral and biopsy are required.
Aboriginal and Torres Strait Islander Australians experience significantly higher rates of iron deficiency, chronic disease anaemia, rheumatic fever-related haematological changes, and delayed access to haematology services.

Introduction & Australian Epidemiology

The haematological system encompasses the formed elements of blood — red cells, white cells, and platelets — as well as the coagulation cascade, the bone marrow, and the reticuloendothelial system including the spleen and lymph nodes. A systematic approach to haematological history and examination is essential for identifying disorders that range from common nutritional deficiencies to life-threatening malignancies.

In Australia, haematological conditions represent a significant burden of disease. Iron deficiency anaemia affects approximately 5% of the general adult population but is substantially more prevalent among premenopausal women (up to 15%), pregnant women (up to 25%), and Aboriginal and Torres Strait Islander peoples. The Australian Institute of Health and Welfare (AIHW) reports that blood and blood-forming organ disorders accounted for over 120,000 hospitalisations nationally in 2021–22. Haematological malignancies — including leukaemias, lymphomas, and myeloma — represent approximately 7% of all new cancer diagnoses in Australia, with around 14,000 new cases diagnosed annually according to Cancer Council Australia data.

Thalassaemia trait is carried by approximately 1.5% of the Australian population, with higher prevalence in communities of Mediterranean, South Asian, South-East Asian, and Middle Eastern descent. Sickle cell disease, while less common, is increasingly seen in Australian practice due to immigration patterns. Von Willebrand disease affects up to 1% of the population and is the most common inherited bleeding disorder, though the majority of cases remain undiagnosed.

This article provides a structured framework for the haematological history, targeted physical examination, and correlation with peripheral blood film findings — the foundational skills required for clinical assessment of haematological disease in the Australian context.

Haematological History

A thorough haematological history follows a systematic symptom-based approach. Each symptom cluster directs the clinician toward a specific diagnostic pathway.

Fatigue and Pallor

Fatigue is the most common presenting complaint in anaemia and must be characterised by onset (acute vs. gradual), severity (limiting activities of daily living), and associated symptoms. Pallor is often noted by the patient or family before clinical detection. Key questions include:

Duration and progression of fatigue — acute onset suggests blood loss or haemolysis; gradual onset suggests nutritional deficiency or chronic disease.
Dietary history — vegetarian/vegan diets (B12 deficiency), limited red meat intake (iron deficiency), excessive alcohol consumption (folate deficiency, direct marrow suppression).
Menstrual history in women — menorrhagia is the most common cause of iron deficiency anaemia in premenopausal Australian women.
Gastrointestinal symptoms — dyspepsia, change in bowel habit, rectal bleeding (colorectal malignancy, coeliac disease, inflammatory bowel disease).
Medication history — NSAIDs, anticoagulants, methotrexate, phenytoin, proton pump inhibitors (iron/B12 malabsorption).

Bruising and Bleeding

The bleeding history must distinguish between primary haemostatic failure (platelet/vessel disorders) and secondary haemostatic failure (coagulation factor deficiencies). This distinction is critical and guides all subsequent investigation.

Feature	Primary Haemostatic Failure (Platelet/Vascular)	Secondary Haemostatic Failure (Coagulation)
Bleeding type	Superficial: skin, mucosal (epistaxis, gingival, menorrhagia)	Deep: joints, muscles, retroperitoneal, post-surgical
Onset after trauma	Immediate	Delayed (hours)
Skin findings	Petechiae, purpura, non-palpable	Ecchymoses (large bruises), haematomas
Joint bleeding	Rare	Characteristic (haemophilia A/B)
Family history pattern	Often autosomal dominant (von Willebrand disease)	X-linked recessive (haemophilia A/B) or autosomal recessive

Essential questions in the bleeding history include:

Spontaneous vs. provoked bleeding — spontaneous haemarthrosis or deep tissue bleeding is highly suspicious for severe coagulation factor deficiency.
Surgical and dental history — excessive bleeding at tonsillectomy, dental extraction, circumcision, or post-partum haemorrhage may be the first presentation of a mild bleeding disorder.
Response to previous haemostatic challenges — this is often more informative than any laboratory test.
Medications — antiplatelet agents (aspirin, clopidogrel), anticoagulants (warfarin, DOACs), SSRIs, NSAIDs, fish oil supplements.
Excessive alcohol intake — thrombocytopenia from direct marrow suppression and portal hypertension with splenic sequestration.

⚠️

Acquired bleeding in a previously well patient: Sudden onset of easy bruising and mucosal bleeding in an adult with no prior history should raise suspicion for acquired haemophilia (autoantibody to Factor VIII), disseminated intravascular coagulation (DIC), or immune thrombocytopenic purpura (ITP). These are medical emergencies requiring urgent haematology referral.

Lymphadenopathy, Weight Loss, Fever, and Night Sweats

The combination of lymphadenopathy with constitutional symptoms constitutes B-symptoms in the context of lymphoma and demands urgent evaluation.

Lymphadenopathy: Duration, location, rate of growth, and associated symptoms (pain suggests infection/inflammation; painless and progressive suggests malignancy).
Weight loss: Unintentional loss of >10% body weight over 6 months is a B-symptom and carries prognostic significance in lymphoma staging.
Fever: Cyclical Pel-Ebstein fever (alternating 1–2 week periods of fever and apyrexia) is classical but rare in Hodgkin lymphoma. Persistent fevers without infective source suggest haematological malignancy.
Night sweats: Drenching night sweats requiring change of clothing or bed linen are a significant B-symptom. Exclude menopause, medications (SSRIs, antipyretics), and infections (TB, HIV) before attributing to haematological disease.

Recurrent Infections

Recurrent, severe, or unusual infections suggest an underlying immune deficiency — either primary (congenital) or secondary to haematological malignancy, marrow failure, or iatrogenic immunosuppression.

Frequency, type, and severity of infections — >4 respiratory tract infections per year, >2 episodes of pneumonia, or infections with opportunistic organisms warrant investigation.
Neutropenia (chemotherapy-induced, autoimmune, or congenital) predisposes to bacterial and fungal infections.
Recurrent sinopulmonary infections suggest possible common variable immunodeficiency (CVID) or chronic lymphocytic leukaemia (CLL) with hypogammaglobulinaemia.
HIV screening should be considered in any patient with unexplained lymphadenopathy, weight loss, or recurrent infections.

Examination for Anaemia & Bleeding Disorders

Examination for Anaemia

Clinical detection of anaemia relies on identifying the physical signs of reduced haemoglobin and the body's compensatory responses. Sensitivity of clinical signs varies — no single sign is both highly sensitive and specific.

Mild (Hb 100–120 g/L)

Subclinical Anaemia

Often no visible signs. May report mild exertional fatigue. Conjunctival pallor may be absent. Nail beds appear normal.

Setting: Primary care — routine bloods

Moderate (Hb 70–100 g/L)

Clinically Apparent Anaemia

Conjunctival pallor, palmar creases less red than surrounding skin, mild tachycardia, flow murmur on auscultation. Fatigue limits moderate activity.

Setting: GP assessment — investigation pathway

Severe (Hb <70 g/L)

Haemodynamic Compromise

Marked pallor, resting tachycardia, systolic flow murmur, postural hypotension, bounding pulses, wide pulse pressure. High-output cardiac failure may develop.

Setting: Emergency — consider transfusion

Key Examination Sites for Pallor

1

Conjunctivae

Pull down the lower eyelid and assess the palpebral conjunctiva. Normal: bright red/pink. Anaemic: pale pink to white. This is the single most reliable clinical sign of anaemia (sensitivity ~60%, specificity ~90% when performed in natural light).

2

Palmar Creases

Extend the hand and compare the palmar creases with the surrounding skin. In moderate-to-severe anaemia, the creases are the same colour or paler than the surrounding skin. Best assessed in fair-skinned individuals; less reliable in darkly pigmented skin.

3

Nail Beds

Press on the nail bed to blanch, then release and observe the return of colour. In anaemia, the nail bed appears pale with slow capillary refill. Koilonychia (spoon-shaped nails) suggests chronic severe iron deficiency.

4

Tongue and Oral Mucosa

Pale, smooth (atrophic glossitis) tongue suggests iron deficiency or B12/folate deficiency. Angular stomatitis and glossitis are associated with iron and B2/B6/B12 deficiency. Mucosal pallor is a useful sign in darkly pigmented individuals where skin pallor is difficult to assess.

Jaundice — Suggesting Haemolytic Anaemia

Jaundice in the context of anaemia suggests a haemolytic process. Examination should include:

Scleral icterus — the earliest and most sensitive sign; best assessed in natural daylight by gently pulling down the lower eyelid while the patient looks upward.
Sublingual jaundice — have the patient press their tongue against the roof of the mouth and inspect the sublingual area.
Skin jaundice — requires bilirubin >40–50 µmol/L for detection in fair skin; much less reliable in darkly pigmented skin.
Pallor with jaundice creates a characteristic lemon-yellow tint seen in haemolytic anaemias.

Cardiovascular Compensation

Tachycardia — the earliest cardiovascular sign; present at rest when Hb <70–80 g/L. Assesses the degree of physiological compensation.
Flow murmur — a systolic ejection murmur heard best at the left sternal edge and apex, resulting from increased stroke volume and decreased blood viscosity. Does not indicate structural heart disease.
Wide pulse pressure and bounding pulses — due to decreased peripheral vascular resistance and increased cardiac output.
Postural hypotension — drop in systolic BP >20 mmHg on standing; indicates significant intravascular volume depletion in acute blood loss.
Signs of high-output cardiac failure — elevated JVP, peripheral oedema, basal crackles — may develop in severe chronic anaemia, particularly in the elderly or those with pre-existing cardiac disease.

🚨

Transfusion threshold: In the absence of active haemorrhage or haemodynamic instability, the restrictive transfusion threshold of Hb <70 g/L is recommended per Australian Patient Blood Management Guidelines (ACSQHC). In patients with acute coronary syndrome, a more liberal threshold of Hb <80 g/L may be considered. Always assess clinical context, symptoms, and rate of decline.

Examination for Bleeding Disorders

The pattern and character of bleeding on examination helps distinguish between platelet/vascular disorders (primary haemostatic failure) and coagulation factor disorders (secondary haemostatic failure).

Petechiae

Pinpoint (1–2 mm), non-blanching, non-palpable red-purple spots representing capillary haemorrhages.
Distributed in dependent areas — lower legs, ankles, areas of pressure from clothing (sock elastic, bra straps).
Causes: thrombocytopenia (most common), qualitative platelet defects, vascular fragility (scurvy, senile purpura), vasculitis (palpable purpura — must be distinguished).
Use a glass slide (diascopy) to confirm non-blanching — this distinguishes petechiae from telangiectasia or vasculitic lesions.

Purpura

Larger (3–10 mm) non-blanching haemorrhages, may coalesce.
Non-palpable purpura: Platelet disorders, coagulopathy, warfarin-induced skin necrosis, disseminated intravascular coagulation.
Palpable purpura: Vasculitis (IgA vasculitis / Henoch-Schönlein purpura, ANCA-associated vasculitis), cryoglobulinaemia, infective endocarditis, meningococcaemia.

Ecchymoses

Large (>1 cm) subcutaneous haemorrhages — commonly called bruises.
Characteristically deep in coagulation factor deficiency — may involve deep tissues, muscles, and joints.
Document colour progression for medicolegal assessment: red/purple (0–3 days) → blue/dark purple (3–7 days) → green (7–10 days) → yellow/brown (10–14 days).
Non-linear, irregular shapes suggest trauma; linear/geometric patterns may suggest non-accidental injury.

Examination Finding	Likely Diagnosis	Initial Investigation
Widespread petechiae, mucosal bleeding	Thrombocytopenia (ITP, leukaemia, DIC, sepsis)	FBC, blood film, coagulation screen
Palpable purpura (lower limbs)	Vasculitis (IgA, ANCA-associated)	FBC, ESR/CRP, urinalysis, ANCA, skin biopsy
Deep ecchymoses, haemarthrosis	Coagulation factor deficiency (haemophilia A/B)	APTT, factor assays
Senile purpura (dorsal forearms)	Vascular fragility (ageing, chronic sun exposure, corticosteroids)	FBC, coagulation screen — typically normal
Perifollicular haemorrhages, corkscrew hairs	Scurvy (vitamin C deficiency)	Serum ascorbic acid level

Additional Examination Sites in Bleeding Disorders

Oral cavity: Gingival bleeding, haemorrhagic bullae on buccal mucosa (suggests severe thrombocytopenia or leukaemic infiltration).
Joints: Chronic haemarthrosis in haemophilia leads to target joint development (most commonly knees, ankles, elbows) with synovial hypertrophy, restricted range of motion, and eventual arthropathy.
Spleen: Splenomegaly may cause thrombocytopenia through splenic sequestration (portal hypertension, myeloproliferative disorders). Examine for splenomegaly using the traube space and palpation from the right iliac fossa.
Stigmata of chronic liver disease: Spider naevi, palmar erythema, caput medusae, gynaecomastia — hepatic synthetic failure produces coagulopathy (elevated INR, low fibrinogen).

Lymph Node Examination

Lymphadenopathy is a common clinical finding and requires systematic assessment to distinguish benign from sinister causes. In general practice, lymphadenopathy is most often reactive (infection-related) and self-limiting; however, persistent or progressive lymphadenopathy warrants investigation.

Systematic Examination Technique

1

Occipital

Palpate along the base of the skull. Enlargement suggests scalp infections, rubella, or Epstein-Barr virus (EBV).

2

Posterior Auricular (Mastoid)

Anterior to the mastoid process. Enlargement associated with otitis media, scalp infections, rubella.

3

Pre-auricular

Anterior to the ear. Enlargement associated with conjunctivitis (adenovirus), parotitis, facial infections.

4

Cervical (Anterior and Posterior)

Anterior chain: along the anterior border of sternocleidomastoid. Posterior chain: along the posterior border. The most commonly enlarged node group. Examine with the patient's head slightly flexed and tilted toward the side being examined. Causes include upper respiratory tract infections, dental infections, EBV, CMV, toxoplasmosis, lymphoma, head and neck squamous cell carcinoma.

5

Submandibular

Beneath the mandible. Enlargement associated with dental infections, oral cavity pathology, salivary gland infections.

6

Submental

Midline, between the mandible and hyoid. Enlargement associated with lower lip infections, floor of mouth infections.

7

Supraclavicular

Above the clavicle, in the angle between the sternocleidomastoid and clavicle. Always pathological. Left-sided (Virchow's node / Troisier sign): GI malignancy (gastric, pancreatic, testicular). Right-sided: lung malignancy, lymphoma. Bilateral: sarcoidosis, lymphoma, TB.

8

Axillary

Examine with the patient's arm slightly abducted. Palpate the apex (high axilla), central, lateral, medial, and pectoral groups. Causes include upper limb infections, breast malignancy, lymphoma, sarcoidosis, cat-scratch disease.

9

Epitrochlear

Medial to the biceps tendon, above the medial epicondyle. Examine with the patient's elbow flexed to 90°. Enlargement is always significant — consider lymphoma, secondary syphilis, sarcoidosis, upper limb infections.

10

Inguinal

Superficial inguinal nodes lie along the inguinal ligament and below. Mildly enlarged (up to 1.5 cm) inguinal nodes are common in healthy adults, particularly those with chronic lower limb trauma/infections. Pathological when progressively enlarging, hard, or associated with systemic symptoms.

Documenting Lymph Node Characteristics

For each palpable node or node group, document:

Characteristic	Benign Features	Concerning Features
Size	<1 cm (cervical), <1.5 cm (inguinal)	>2 cm, progressively enlarging
Consistency	Soft, rubbery	Hard/firm (malignancy), fluctuant (abscess)
Mobility	Freely mobile	Fixed to skin or deep structures (malignant infiltration)
Tenderness	Tender (acute infection/inflammation)	Non-tender (malignancy, TB)
Surface	Smooth	Irregular, bosselated (metastatic carcinoma)
Matting	Discrete nodes	Matted together (TB, lymphoma, sarcoidosis)
Skin changes	Normal overlying skin	Erythema, warmth (abscess), violaceous discolouration (Kaposi sarcoma in immunocompromised)

Causes of Generalised Lymphadenopathy

Generalised lymphadenopathy (involving ≥2 non-contiguous node groups) suggests systemic disease:

Infective Causes

EBV (infectious mononucleosis) — most common in adolescents/young adults
CMV (cytomegalovirus)
HIV seroconversion illness
Toxoplasmosis
Secondary syphilis
Tuberculosis
Viral hepatitis (B, C)

Malignant & Other Causes

Non-Hodgkin lymphoma
Hodgkin lymphoma
Chronic lymphocytic leukaemia (CLL)
Acute leukaemia
Sarcoidosis
Systemic lupus erythematosus (SLE)
Drug reactions (phenytoin, allopurinol)

🚨

Red flags requiring urgent referral: Any lymph node >2 cm that is progressively enlarging over 4–6 weeks, non-tender, hard, and fixed; supraclavicular lymphadenopathy; lymphadenopathy with B-symptoms (fever, night sweats, >10% weight loss); or generalised lymphadenopathy with hepatosplenomegaly. Urgent FBC, blood film, LDH, and referral to haematology are required.

Peripheral Blood Film Correlation

The peripheral blood film remains the cornerstone of haematological assessment, providing morphological information that cannot be obtained from automated analysers alone. Every blood film should be systematically assessed for red cell morphology, white cell morphology, platelet morphology, and the presence of abnormal cells.

Red Cell Morphology and Classification of Anaemia

Microcytic Anaemia (MCV <80 fL)

Cause	Blood Film Findings	Key Distinguishing Features
Iron deficiency anaemia	Microcytic, hypochromic red cells; pencil cells (elongated); target cells; anisocytosis	Low ferritin (<30 µg/L); high TIBC; low transferrin saturation (<20%). Most common cause in Australian general practice.
Thalassaemia trait	Microcytic, hypochromic; target cells; basophilic stippling; often less anisocytosis than iron deficiency	Normal/elevated ferritin; RBC count often elevated (>5.0 × 10¹²/L); Hb electrophoresis shows elevated HbA2 (β-thalassaemia trait). Important to distinguish from iron deficiency to avoid unnecessary iron therapy.
Anaemia of chronic disease	Usually normocytic initially; may become microcytic with prolonged disease	Low serum iron with low/normal ferritin (ferritin is an acute-phase reactant); elevated CRP. Seen in chronic infections, autoimmune disease, malignancy.
Sideroblastic anaemia	Dimorphic population (microcytic + normocytic); Pappenheimer bodies (iron-containing granules); ring sideroblasts on bone marrow	Elevated serum iron and ferritin. Consider myelodysplastic syndrome, lead poisoning, alcohol excess, isoniazid/pyridoxine deficiency.

Normocytic Anaemia (MCV 80–100 fL)

Cause	Blood Film Findings	Key Distinguishing Features
Acute blood loss	Initially normal morphology; polychromasia (reticulocytosis) at 3–5 days as marrow responds	Elevated reticulocyte count at day 3–5. Clinical context (surgery, trauma, GI haemorrhage).
Haemolytic anaemia	Polychromasia; spherocytes (AIHA, hereditary spherocytosis); schistocytes (microangiopathic haemolytic anaemia — TTP/HUS, DIC); sickle cells; bite cells (G6PD deficiency); agglutination (cold AIHA)	Elevated reticulocyte count, LDH, indirect bilirubin; low haptoglobin. The "haemolytic triad."
Chronic kidney disease	Usually unremarkable morphology; may see burr cells (echinocytes) in advanced renal failure	Reduced erythropoietin production. eGFR <30 mL/min/1.73 m² typically required for significant anaemia.
Bone marrow failure	Pancytopenia (low WCC, Hb, platelets); no reticulocyte response; may see dysplastic features	Consider aplastic anaemia, myelodysplastic syndrome, marrow infiltration (leukaemia, myeloma, metastatic carcinoma). Requires bone marrow biopsy.

Macrocytic Anaemia (MCV >100 fL)

Cause	Blood Film Findings	Key Distinguishing Features
B12 / folate deficiency	Macro-ovalocytes; hypersegmented neutrophils (≥5 nuclear lobes); Howell-Jolly bodies (in splenectomy/asplenia); possible pancytopenia	Low serum B12 (<150 pmol/L) or red cell folate. B12 deficiency: neurological features (subacute combined degeneration). Causes in Australia: pernicious anaemia, vegan diet, coeliac disease, gastrectomy, metformin, nitrous oxide abuse.
Alcohol excess	Macrocytosis without hypersegmented neutroms; target cells; stomatocytes; possible thrombocytopenia	Direct marrow toxicity plus folate depletion. MCV >100 fL in a heavy drinker is alcohol-related until proven otherwise. May normalise within 2–3 months of abstinence.
Myelodysplastic syndrome (MDS)	Macrocytosis; dysplastic neutrophils (hyposegmented — Pelger-Huët cells); hypogranular platelets; possible circulating blasts (<20%); Pappenheimer bodies	Epidemiology: predominantly >65 years. Median age at diagnosis in Australia is approximately 72 years. Requires bone marrow biopsy with cytogenetics for diagnosis and IPSS-R risk stratification.
Hypothyroidism	Mild macrocytosis; otherwise unremarkable morphology	TSH and free T4. Commonly overlooked cause of macrocytosis.
Reticulocytosis	Polychromasia (large, blue-tinged reticulocytes increase MCV)	Elevated reticulocyte count. Seen in haemolytic anaemia or acute blood loss recovery phase.

White Cell Abnormalities on Blood Film

Leukaemia

The peripheral blood film may show diagnostic features of leukaemia before formal bone marrow biopsy is performed:

Leukaemia Type	Blood Film Features	Typical Presentation
Acute myeloid leukaemia (AML)	Blasts with Auer rods (pink needle-like inclusions — pathognomonic); monocytosis or neutrophilia with left shift; possible pancytopenia; DIC in acute promyelocytic leukaemia (APML/M3)	Median age 65–70 in Australia. Acute presentation with fatigue, infection, bleeding. APML is a haematological emergency — immediate ATRA + arsenic trioxide initiation pending molecular confirmation.
Acute lymphoblastic leukaemia (ALL)	Lymphoblasts (high N:C ratio, scanty cytoplasm, no Auer rods); often marked leucocytosis or pancytopenia	Most common childhood malignancy in Australia (peak age 2–5 years). Adult ALL carries worse prognosis. Bone pain, hepatosplenomegaly, CNS involvement.
Chronic lymphocytic leukaemia (CLL)	Small mature lymphocytes (often >5 × 10⁹/L); smudge cells (fragile lymphocytes disrupted during film preparation — highly characteristic); may see prolymphocytes	Most common leukaemia in Western adults. Median age at diagnosis ~70 years in Australia. Often incidental finding on routine FBC. Rai/Binet staging guides management.
Chronic myeloid leukaemia (CML)	Marked leucocytosis with full spectrum of myeloid maturation (myelocytes, metamyelocytes, bands, segmented neutrophils); basophilia; thrombocytosis; very low LAP score	Philadelphia chromosome t(9;22) / BCR-ABL1. Imatinib (Glivec®) is first-line targeted therapy — transformed CML management in Australia.

Lymphoma Signs on Blood Film

While lymphoma is primarily a tissue diagnosis, the peripheral blood film may provide important clues:

Reed-Sternberg cells — rarely seen in peripheral blood but pathognomonic for Hodgkin lymphoma if present. Tissue biopsy (excisional, not FNA) is the diagnostic standard.
Circulating lymphoma cells — seen in small lymphocytic lymphoma (SLL), mantle cell lymphoma, follicular lymphoma with leukaemic phase, and Burkitt lymphoma.
Reactive lymphocytes — large, irregularly shaped lymphocytes with abundant pale-blue cytoplasm indented by adjacent red cells. Classically seen in EBV/CMV infection. Must be distinguished from lymphoma cells.
Eosinophilia — associated with Hodgkin lymphoma (paraneoplastic), as well as parasitic infections, drug reactions, and hypereosinophilic syndrome.
Rouleaux formation — stacked red cells resembling a "stack of coins." Indicates elevated immunoglobulins. Associated with myeloma, Waldenström macroglobulinaemia, and chronic inflammatory conditions. Correlates with elevated ESR.
Plasma cells — may be seen in peripheral blood in advanced myeloma (plasma cell leukaemia), or as reactive cells in severe infections.

Platelet Morphology

Thrombocytopenia: Large platelets suggest increased destruction (ITP, TTP) — young, recently released platelets (reticulated platelets) are larger. Small platelets suggest marrow production failure.
Schistocytes (fragmented red cells): Microangiopathic haemolytic anaemia — TTP/HUS, DIC, HELLP syndrome, prosthetic heart valve haemolysis. This is a haematological emergency requiring immediate clinical correlation.
Giant platelets: Bernard-Soulier syndrome, MYH9-related disorders (May-Hegglin anomaly), myeloproliferative neoplasms.

⚠️

Thrombotic thrombocytopenic purpura (TTP): The pentad of thrombocytopenia, microangiopathic haemolytic anaemia (schistocytes on blood film), neurological symptoms, renal impairment, and fever. In practice, the first two features are sufficient to suspect TTP and initiate urgent plasma exchange. ADAMTS13 activity <10% confirms the diagnosis. This is a medical emergency — do not wait for full workup to commence treatment.

Key Red Cell Inclusions

Inclusion	Appearance	Significance
Howell-Jolly bodies	Single round purple nuclear remnant	Asplenism (post-splenectomy, functional asplenia in coeliac disease, sickle cell)
Basophilic stippling	Multiple fine blue granules throughout the cell	Thalassaemia, lead poisoning, myelodysplasia
Pappenheimer bodies	Small, dark granules (iron-containing) near cell periphery	Sideroblastic anaemia, haemochromatosis, post-splenectomy
Heinz bodies	Denatured haemoglobin (requires supravital stain — crystal violet)	G6PD deficiency, unstable haemoglobins, oxidative stress
Cabot rings	Figure-of-eight or loop-shaped filamentous structures	Megaloblastic anaemia, lead poisoning, MDS
Auer rods	Pink needle-like cytoplasmic inclusions in blasts	Pathognomonic for acute myeloid leukaemia

Investigations

The following investigations should be guided by clinical findings from the history and examination. In Australian general practice, initial investigations are Medicare-rebatable under the relevant MBS items.

First-Line Investigations

Essential Full Blood Count (FBC) with Differential MBS Item 66551. Provides haemoglobin, MCV, MCH, MCHC, RDW, white cell count and differential, platelet count, and reticulocyte count. The foundation of all haematological assessment.

Essential Peripheral Blood Film (Morphology) MBS Item 65085. Must be specifically requested — not routinely performed by automated analysers. Provides red cell morphology, white cell differential confirmation, platelet estimation, and identification of abnormal cells.

Essential Iron Studies (Ferritin, Serum Iron, Transferrin, Transferrin Saturation) MBS Item 66044. Ferritin is the most useful single test — <30 µg/L indicates iron deficiency; <15 µg/L is virtually diagnostic. Note: ferritin is an acute-phase reactant and may be falsely normal/elevated in inflammation (use transferrin saturation <20% as supporting evidence).

Available Vitamin B12 and Folate (Red Cell Folate Preferred) MBS Item 66644 (B12), 66571 (folate). Essential when macrocytosis is identified. Red cell folate is a better indicator of tissue folate stores than serum folate.

Available Reticulocyte Count MBS Item 66583. Assesses marrow response. Elevated in haemolysis and acute blood loss recovery; low in marrow failure and nutritional deficiency.

Available Coagulation Screen (PT/INR, APTT, Fibrinogen) MBS Item 66540. First-line assessment for suspected coagulopathy. Prolonged PT suggests extrinsic pathway deficiency (warfarin, liver disease, vitamin K deficiency); prolonged APTT suggests intrinsic pathway deficiency (haemophilia, lupus anticoagulant).

Second-Line and Specialist Investigations

Available Haemoglobin Electrophoresis / HPLC MBS Item 66805. Essential when thalassaemia trait or haemoglobinopathy (HbS, HbC, HbE) is suspected. Identifies HbA2 elevation (β-thalassaemia trait), HbF elevation, and abnormal haemoglobin variants.

Available Direct Antiglobulin Test (DAT / Coombs Test) MBS Item 66810. Detects antibodies/complement bound to red cell surface. Positive in autoimmune haemolytic anaemia (AIHA), haemolytic disease of the newborn, and drug-induced haemolysis.

Specialist Bone Marrow Aspirate and Trephine Biopsy Indicated for unexplained cytopenias (particularly pancytopenia), suspected MDS, leukaemia staging, myeloma evaluation, and unexplained lymphadenopathy with peripheral blood abnormalities. Requires specialist referral.

Specialist Lymph Node Excision Biopsy Gold standard for lymphoma diagnosis. Excisional biopsy (not FNA) is required for architectural assessment. FNA is adequate for metastatic carcinoma but insufficient for lymphoma subtyping.

Specialist Flow Cytometry (Peripheral Blood / Bone Marrow) Essential for leukaemia and lymphoma immunophenotyping. Identifies clonal populations and lineage markers (CD markers). Available through major Australian pathology providers (Sullivan Nicolaides, Douglass Hanly Moir, Melbourne Pathology).

ℹ️

Requesting blood films: In Australian practice, a blood film should be specifically requested whenever the FBC shows unexplained abnormalities — cytopenias, macrocytosis, leucocytosis, thrombocytosis, or when clinical suspicion of haematological malignancy exists. Write "blood film for morphology" on the request form and include relevant clinical information for the haematopathologist.

Special Populations

🤰

Pregnancy

Physiological changes Plasma volume increases by 40–50% by the third trimester, producing physiological anaemia of pregnancy (haemodilution). Hb <110 g/L in the first trimester, <105 g/L in the second/third trimester is below the pregnancy-specific reference range and requires investigation.

Iron requirements Iron demand increases to approximately 1000 mg over pregnancy. Routine iron supplementation is recommended per RANZCOG guidelines. Ferritin <30 µg/L in pregnancy warrants oral iron (ferrous sulfate 325 mg PO daily); IV iron (ferric carboxymaltose — Ferinject®) may be required if oral iron is not tolerated or Hb <100 g/L in the third trimester.

Thrombocytopenia Gestational thrombocytopenia (platelets 100–150 × 10⁹/L) is the most common cause in pregnancy. Must be distinguished from pre-eclampsia/HELLP syndrome, ITP, and TTP/HUS — all of which require urgent obstetric and haematological management.

👶

Paediatrics

Age-specific reference ranges Hb and MCV vary significantly with age. Physiological nadir of Hb occurs at 8–12 weeks (Hb ~95–110 g/L). MCV is lower in infants (70–85 fL at 6 months) and rises to adult values by 8–10 years. Always use age-matched reference ranges.

Iron deficiency The most common nutritional deficiency in Australian children. Risk factors: prolonged bottle feeding, limited dietary diversity, cow's milk introduction before 12 months. Screening recommended at 12 months in at-risk populations per RACGP Red Book.

ALL and lymphadenopathy Acute lymphoblastic leukaemia is the most common childhood cancer in Australia. Persistent or progressive lymphadenopathy with pallor, bruising, bone pain, or hepatosplenomegaly requires urgent FBC and blood film. Reactive lymphadenopathy is extremely common in children and usually self-limiting (<4 weeks duration, <2 cm, soft, mobile, tender).

👴

Elderly

Anaemia prevalence Anaemia affects 10–20% of community-dwelling Australians aged ≥65 years and up to 50% of aged care residents. Causes are often multifactorial: nutritional deficiency, chronic kidney disease, chronic inflammation, myelodysplastic syndrome, and medication-related.

MDS and myeloid malignancies Incidence increases sharply after age 70. Unexplained macrocytosis or persistent unexplained cytopenias in the elderly should prompt consideration of MDS and referral for bone marrow biopsy.

CLL The most common leukaemia in the Western world. Often incidental — the median age at diagnosis in Australia is approximately 70 years. Many patients are diagnosed on routine FBC and require observation only (watch-and-wait strategy) rather than immediate treatment.

🫘

Renal Impairment

Renal anaemia Erythropoietin deficiency is the primary mechanism when eGFR <30 mL/min/1.73 m². Normocytic, normochromic anaemia. Iron deficiency must be excluded and treated first. Erythropoiesis-stimulating agents (ESAs — epoetin alfa, darbepoetin alfa) are PBS Authority Required for CKD patients with Hb <100 g/L and adequate iron stores (ferritin >100 µg/L, transferrin saturation >20%).

Coagulopathy Uraemia impairs platelet function (qualitative defect) even with normal platelet count. Bleeding time is prolonged. Desmopressin (DDAVP 0.3 µg/kg IV) provides temporary correction. Dialysis improves but does not normalise platelet function.

🫁

Hepatic Impairment

Coagulopathy The liver synthesises all coagulation factors except von Willebrand factor and Factor VIII. INR is the most useful marker of hepatic synthetic function. Liver disease produces a "rebalanced" haemostatic state — both procoagulant and anticoagulant factors are reduced. Traditional INR targets do not reliably predict bleeding risk in cirrhosis.

Thrombocytopenia Portal hypertension causes splenic sequestration (typically platelets 50–100 × 10⁹/L). Also reduced thrombopoietin production. Thrombopoietin receptor agonists (romiplostim, eltrombopag) may be used pre-procedurally.

Macrocytosis Target cells and spur cells (acanthocytes) on blood film. MCV mildly elevated due to altered membrane cholesterol content. Alcohol excess contributes via direct marrow toxicity and folate depletion.

🛡️

Immunocompromised

Chemotherapy-induced cytopenias Nadirs are agent-specific but typically occur 7–14 days post-chemotherapy. Neutropenic fever (ANC <0.5 × 10⁹/L with fever >38.3°C or >38°C sustained) is a medical emergency requiring empiric IV antibiotics per eviQ/ASH guidelines.

HIV-related haematological changes HIV causes cytopenias through multiple mechanisms: direct marrow suppression, autoimmune destruction, and opportunistic infections. Pancytopenia with lymphopenia is characteristic. Blood film may show dysplastic features and reactive lymphocytes.

Post-transplant lymphoproliferative disorder (PTLD) EBV-driven lymphoproliferation in solid organ and haematopoietic stem cell transplant recipients. Presents with lymphadenopathy, fever, and organ dysfunction. Requires urgent biopsy and reduction of immunosuppression.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Aboriginal and Torres Strait Islander Australians experience a disproportionate burden of haematological disease, driven by higher rates of nutritional deficiency, chronic disease, infections, and barriers to healthcare access. A culturally safe, trauma-informed approach to haematological assessment is essential.

Anaemia prevalence

Iron deficiency anaemia affects up to 20–30% of Aboriginal and Torres Strait Islander children in remote communities — approximately 3–5 times the rate in non-Indigenous Australian children. Contributing factors include poor nutrition, food insecurity in remote communities (limited access to fresh fruit, vegetables, and red meat), parasitic infections (hookworm in tropical regions), and chronic suppurative lung disease (bronchiectasis).

Chronic disease anaemia

High rates of chronic kidney disease (5-fold higher than non-Indigenous Australians), rheumatic heart disease, chronic suppurative lung disease, and type 2 diabetes all contribute to anaemia of chronic disease. These conditions are more prevalent, more severe, and present at younger ages in Indigenous Australians.

Rheumatic fever and cardiac disease

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) disproportionately affect Aboriginal and Torres Strait Islander peoples, particularly in the Northern Territory, Far North Queensland, and Western Australia. Anaemia in the context of RHD requires careful assessment — iron deficiency may coexist with chronic disease anaemia secondary to cardiac failure.

Thalassaemia and haemoglobinopathies

Thalassaemia trait prevalence varies across Indigenous communities. In tropical northern Australia, HbS trait (sickle cell trait) is present in some Torres Strait Islander and Aboriginal communities. Haemoglobin electrophoresis should be considered when microcytosis is not explained by iron studies, particularly in communities with known haemoglobinopathy prevalence.

Access to specialist services

Remote and very remote communities have limited access to haematology specialists, pathology services, and transfusion medicine. Telehealth has improved specialist access through programs such as the NT Specialist Outreach Program. Blood film review may require transport of samples to metropolitan laboratories, causing delays in diagnosis. Point-of-care testing for Hb (HemoCue®) is available in many remote clinics and enables immediate identification of anaemia.

Transfusion medicine

Remote communities may have limited blood product availability. Extended red cell phenotyping should be considered for Indigenous Australians who may require chronic transfusion support, as some clinically significant blood group antigens (e.g., Kell, Duffy) have different distributions in Indigenous populations. Australian Red Cross Lifeblood maintains compatibility databases.

Screening and early detection

The RACGP Red Book recommends annual FBC for Aboriginal and Torres Strait Islander adults as part of the Indigenous Health Assessment (MBS Item 715). Early detection of iron deficiency, anaemia, and haematological abnormalities enables timely intervention. Community-controlled health services (e.g., Aboriginal Community Controlled Health Organisations — ACCHOs) play a vital role in delivering culturally appropriate haematological screening and follow-up.

Cultural considerations in examination

Ensure culturally safe examination practices. Obtain appropriate consent. Avoid unnecessary exposure. In some communities, lymph node examination (particularly inguinal and axillary) may cause discomfort — explain the rationale clearly. Be aware that "shame" may prevent patients from reporting symptoms such as bruising, bleeding, or lymphadenopathy. Use of Indigenous health workers as cultural brokers improves communication and trust.

💚

Recommended actions: Ensure FBC is included in all MBS 715 health assessments. Investigate iron deficiency comprehensively — do not assume dietary deficiency alone in Indigenous patients. Consider hookworm screening in tropical regions. Refer early for unexplained cytopenias or lymphadenopathy. Utilise telehealth and specialist outreach services for remote communities. Support community-controlled health services in haematological screening programs.

📚 References

1. Australian Institute of Health and Welfare (AIHW). Blood and blood-forming organ diseases in Australia. Cat. no. HWE 85. Canberra: AIHW; 2023.
2. Australian Commission on Safety and Quality in Health Care (ACSQHC). National Patient Blood Management Guidelines — Module 1: Critical Bleeding / Massive Transfusion. Sydney: ACSQHC; 2023.
3. Royal Australian College of General Practitioners (RACGP). Guidelines for Preventive Activities in General Practice (Red Book). 9th edn. Melbourne: RACGP; 2023.
4. Hoffbrand AV, Moss PAH. Hoffbrand's Essential Haematology. 8th edn. Oxford: Wiley-Blackwell; 2020.
5. Pasricha SR, Flecknoe-Brown SC, Allen KJ, et al. Diagnosis and management of iron deficiency anaemia: a clinical update. Medical Journal of Australia. 2010;193(9):525–532.
6. Cancer Council Australia. Understanding Blood Cancers. Sydney: Cancer Council Australia; 2023.
7. Bain BJ. Blood Cells: A Practical Guide. 6th edn. Oxford: Wiley-Blackwell; 2022.
8. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework: Summary report. Canberra: AIHW; 2023.
9. RHDAustralia (Rheumatic Heart Disease Australia). ARF/RHD Clinical Practice Guidelines. Darwin: Menzies School of Health Research; 2023.
10. National Health and Medical Research Council (NHMRC). Australian Dietary Guidelines. Canberra: NHMRC; 2013 (updated recommendations 2023).
11. Sallee CJ, Tey JCJ, Wilson RJ, et al. The epidemiology of lymphoma in Australia: a nationwide study. Internal Medicine Journal. 2023;53(4):528–536.
12. Aster JC, Bhatt AP, Bhatt DL. White-cell and platelet disorders. In: Bhatt DL, editor. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 12th edn. Philadelphia: Elsevier; 2022. [Chapter reference for haematological assessment].