8.1 Anaemias, Haemostasis & Thrombosis
Key Takeaways
- Serum ferritin <30 µg/L possesses 92% sensitivity and 98% specificity for absolute iron deficiency, whereas ferritin up to 100 µg/L may still indicate iron deficiency in chronic inflammatory states.
- Immune Thrombocytopenia (ITP) requires treatment when platelets fall below 30 x 10^9/L or in the presence of active mucosal bleeding, utilizing high-dose oral prednisolone (1 mg/kg/day) or IVIG (1 g/kg/day).
- TTP is characterized by severe ADAMTS13 deficiency (<10% activity), presenting with microangiopathic haemolytic anaemia and thrombocytopenia requiring immediate plasma exchange and caplacizumab.
- Unprovoked VTE requires at least 3 to 6 months of therapeutic anticoagulation followed by indefinite extended secondary prevention with DOACs (e.g., apixaban 2.5 mg BD) unless high bleeding risk supervenes.
- Warfarin reversal for major life-threatening bleeding mandates immediate prothrombin complex concentrate (PCC 25-50 IU/kg) and intravenous phytomenadione (Vitamin K1 5-10 mg).
8.1 Anaemias, Haemostasis & Thrombosis
Diagnostic Approach to Anaemias
Anaemia is defined by the World Health Organization (WHO) as a haemoglobin (Hb) concentration <130 g/L in men, <120 g/L in non-pregnant women, and <110 g/L in pregnant women. Initial evaluation requires classification based on the Mean Corpuscular Volume (MCV): microcytic (<80 fL), normocytic (80–100 fL), and macrocytic (>100 fL).
Microcytic Anaemia Differential Diagnostic Panel
The primary causes of microcytic anaemia are iron deficiency anaemia (IDA), anaemia of chronic disease (ACD), thalassaemia trait, and sideroblastic anaemia. Serum ferritin is the single most accurate test for iron deficiency; a level <30 µg/L confirms absolute iron deficiency, though acute phase reactant elevation in chronic illness can falsely elevate ferritin into the normal range (30–100 µg/L).
| Diagnostic Parameter | Iron Deficiency (IDA) | Anaemia of Chronic Disease (ACD) | Thalassaemia Trait | Sideroblastic Anaemia |
|---|---|---|---|---|
| Serum Ferritin | Reduced (<30 µg/L) | Normal or Elevated (>100 µg/L) | Normal or Elevated | Markedly Elevated |
| Serum Iron | Markedly Reduced | Reduced | Normal | Elevated |
| TIBC / Transferrin | Elevated (>70 µmol/L) | Reduced (<45 µmol/L) | Normal | Normal |
| Transferrin Saturation | Reduced (<15%) | Reduced or Low-Normal (15–20%) | Normal (>20%) | Elevated (>50%) |
| Mentzer Index (MCV/RBC) | >13 | >13 | <13 | Variable |
| Hb Electrophoresis | Normal | Normal | Elevated HbA2 (>3.5% in β-thal) | Normal |
MRCPI Exam Pearl: All men and postmenopausal women with newly diagnosed iron deficiency anaemia must undergo upper gastrointestinal endoscopy and colonoscopy to exclude occult gastrointestinal malignancy (e.g., colorectal carcinoma), regardless of bowel symptoms or dietary intake.
Macrocytic Anaemias: Megaloblastic vs. Non-Megaloblastic
Macrocytic anaemia is divided into megaloblastic (impaired DNA synthesis with nuclear-cytoplasmic asynchronous maturation) and non-megaloblastic causes:
- Megaloblastic Anaemia: Vitamin B12 (cobalamin) deficiency and Folate deficiency. Characterized on blood film by hypersegmented neutrophils (≥5 lobes in >5% of neutrophils or ≥1 neutrophil with ≥6 lobes) and oval macrocytes.
- Non-Megaloblastic Anaemia: Alcohol misuse, hypothyroidism, liver disease, reticulocytosis (haemolysis or acute blood loss), and myelodysplastic syndrome (MDS). Neutrophils display normal segmentation, and red cells are round.
In Vitamin B12 deficiency (pernicious anaemia, ileal resection, strict vegan diet), neurological complications include subacute combined degeneration of the spinal cord (SCD), affecting the posterior and lateral columns (loss of vibration/proprioception, upper motor neuron weakness, and extensor plantar responses). Vitamin B12 replacement must always precede or accompany folate repletion to prevent precipitating or worsening neurological degeneration.
Disorders of Primary & Secondary Haemostasis
Haemostasis involves primary haemostasis (platelet plug formation) and secondary haemostasis (coagulation cascade activation). Clinical presentation differs significantly: primary defects present with mucosal bleeding, petechiae, and epistaxis; secondary defects present with deep tissue haematomas and haemarthroses.
Coagulation Profiles & Clinical Correlations
| Clinical Condition | Prothrombin Time (PT) | Activated Partial Thromboplastin Time (aPTT) | Bleeding Time / PFA-100 | Platelet Count |
|---|---|---|---|---|
| Haemophilia A / B | Normal | Prolonged | Normal | Normal |
| von Willebrand Disease (vWD) | Normal | Prolonged or Normal | Prolonged | Normal (except Type 2B) |
| Warfarin / Vitamin K Deficiency | Prolonged | Prolonged | Normal | Normal |
| Unfractionated Heparin (UFH) | Prolonged | Markedly Prolonged | Normal | Normal (unless HIT) |
| Disseminated Intravascular Coagulation (DIC) | Prolonged | Prolonged | Prolonged | Markedly Reduced |
| Immune Thrombocytopenia (ITP) | Normal | Normal | Prolonged | Reduced (<100 x 10^9/L) |
Thrombotic Microangiopathies: TTP vs. HUS
Thrombotic Thrombocytopenic Purpura (TTP) and Haemolytic Uraemic Syndrome (HUS) present with microangiopathic haemolytic anaemia (MAHA) with schistocytes on blood film and severe thrombocytopenia.
- TTP: Mediated by severe deficiency of ADAMTS13 (<10% activity) due to autoantibodies. Classic pentad includes fever, MAHA, thrombocytopenia, neurological deficits, and renal impairment. Treatment is emergency plasma exchange (PEX), corticosteroid therapy, and anti-vWF monoclonal antibody caplacizumab. Platelet transfusions are strictly contraindicated as they precipitate microvascular thrombosis.
- HUS: Shiga-toxin producing E. coli (STEC O157:H7) infection in children/adults, presenting with bloody diarrhoea, renal failure, and MAHA. ADAMTS13 levels are normal (>10%). Supportive care and hemodialysis are mainstay; plasma exchange is not routinely indicated.
Venous Thromboembolism (VTE) & Anticoagulation Management
Deep vein thrombosis (DVT) and pulmonary embolism (PE) management centers on prompt risk stratification using the Wells score and definitive diagnostic testing (D-dimer for low probability, CT pulmonary angiography [CTPA] or compression ultrasonography for high probability).
Direct Oral Anticoagulant (DOAC) Dosing & Reversal Agents
DOACs (apixaban, rivaroxaban, dabigatran, edoxaban) are first-line agents for VTE treatment and non-valvular atrial fibrillation due to predictable pharmacokinetics and lack of routine monitoring requirements.
| Drug | Mechanism | Standard VTE Treatment | Renal Threshold / Adjustment | Reversal Agent |
|---|---|---|---|---|
| Apixaban | Direct Factor Xa Inhibitor | 10 mg BD for 7 days, then 5 mg BD | Reduce to 2.5 mg BD if CrCl 15–29 mL/min | Andexanet alfa |
| Rivaroxaban | Direct Factor Xa Inhibitor | 15 mg BD for 21 days, then 20 mg OD | Avoid if CrCl <15 mL/min | Andexanet alfa |
| Dabigatran | Direct Thrombin (IIa) Inhibitor | LMWH lead-in 5 days, then 150 mg BD | Avoid if CrCl <30 mL/min | Idarucizumab |
| Warfarin | Vitamin K Antagonist (II, VII, IX, X) | Target INR 2.0–3.0 | Safe in severe CKD / ESRD | PCC + Vit K1 |
MRCPI Exam Pearl: For provoked VTE (transient risk factor such as surgery or trauma), anticoagulation is continued for 3 months. For unprovoked VTE or persistent risk factors (active cancer, antiphospholipid syndrome), extended long-term anticoagulation is indicated, provided bleeding risk is acceptable.
A 64-year-old male presents with fatigue and dyspnoea. Laboratory investigations reveal Hb 84 g/L, MCV 71 fL, serum ferritin 12 µg/L (reference range 30-300), and transferrin saturation 9%. What is the most appropriate next step in clinical management?
A 38-year-old female presents with confusion, fever, petechiae, and a reduced urine output. Laboratory testing demonstrates Hb 72 g/L, platelets 14 x 10^9/L, blood film showing numerous schistocytes, normal PT and aPTT, and creatinine 185 µmol/L. Which therapeutic intervention is urgently indicated?
A 52-year-old male with persistent atrial fibrillation and severe chronic kidney disease (eGFR 18 mL/min/1.73m²) requires stroke prevention anticoagulation. Which anticoagulant agent is most appropriate in this clinical scenario?