A 32-year-old woman presents with recurrent miscarriages and livedo reticularis. Blood tests show thrombocytopenia and prolonged APTT. What is the most likely diagnosis?

Thrombotic thrombocytopenic purpura

Anaemia investigation for UKMLA AKT: High-Yield Medicine (Core Systems) Lessons

Quick Overview

Anaemia investigation requires systematic interpretation of MCV, blood film morphology, and iron studies to identify underlying causes. NICE NG8 provides referral criteria for suspected haematological malignancy. A structured approach distinguishes microcytic, normocytic, and macrocytic patterns, guiding targeted investigation and timely specialist referral when indicated.

Core Facts & Concepts

📊 Anaemia Definitions (WHO criteria)

Men: Hb <130 g/L | Women: Hb <120 g/L | Pregnancy: Hb <110 g/L

MCV Classification

Microcytic: <80 fL (iron deficiency, thalassaemia, anaemia of chronic disease)
Normocytic: 80-100 fL (acute blood loss, haemolysis, chronic disease, renal failure)
Macrocytic: >100 fL (B12/folate deficiency, alcohol, hypothyroidism, myelodysplasia)

Iron Studies Patterns

Parameter	Iron Deficiency	Anaemia Chronic Disease	Thalassaemia Trait
Ferritin	↓ (<30 μg/L)	Normal/↑ (>100 μg/L)	Normal/↑
Serum Iron	↓	↓	Normal
TIBC	↑	↓	Normal
Transferrin Sat	↓ (<16%)	↓	Normal

Figure 1: Blood film showing microcytic hypochromic red cells with pencil cells and target cells characteristic of iron deficiency anaemia

Key Numbers

Reticulocyte count: Normal 50-100 × 10⁹/L (↑ suggests haemolysis/bleeding, ↓ suggests production failure)
B12 deficiency threshold: <200 ng/L
Folate deficiency: <7 nmol/L

Problem-Solving Approach

Step-by-Step Investigation

Confirm anaemia → Check Hb against age/sex-specific thresholds
Determine MCV category → Microcytic/normocytic/macrocytic
Review blood film → Morphology guides differential diagnosis
Order targeted tests:
- Microcytic: Ferritin, iron studies, haemoglobin electrophoresis (if ferritin normal)
- Macrocytic: B12, folate, TFTs, reticulocytes, LFTs (alcohol screen)
- Normocytic: Reticulocytes, renal function, haemolysis screen if ↑ reticulocytes

Figure 2: Blood film showing macrocytic red cells with hypersegmented neutrophils pathognomonic of megaloblastic anaemia

🚩 NICE NG8 Urgent Referral Criteria (2-week wait)

Hb <100 g/L (men) or <90 g/L (women) without obvious cause
Unexplained lymphadenopathy + anaemia
Splenomegaly + anaemia
Persistent unexplained anaemia after investigation

Red Flags Requiring Immediate Action

Hb <70 g/L → Consider transfusion
Signs of cardiac decompensation
Suspected haemolytic crisis (jaundice + dark urine + ↑ reticulocytes)

⚠️ Warning: Always investigate microcytic anaemia in men and post-menopausal women for GI malignancy (colonoscopy + OGD) after confirming iron deficiency

Analysis Framework

Blood Film Morphology: Discriminating Features

Finding	Primary Differential	Key Associated Tests
Hypochromic microcytic cells	Iron deficiency, thalassaemia	Ferritin, Hb electrophoresis
Hypersegmented neutrophils	B12/folate deficiency	Serum B12, red cell folate
Spherocytes	Hereditary spherocytosis, AIHA	Direct Coombs test, osmotic fragility
Target cells	Thalassaemia, liver disease	Hb electrophoresis, LFTs
Schistocytes	Microangiopathic haemolysis	LDH, haptoglobin, coagulation screen
Rouleaux formation	Myeloma, inflammation	Serum protein electrophoresis, ESR

B12 vs Folate Deficiency

B12: Subacute combined degeneration (posterior columns + corticospinal tracts), glossitis, peripheral neuropathy
Folate: Pregnancy-related, no neurological features
Both: Macrocytosis, hypersegmented neutrophils, ↑ LDH, ↑ bilirubin (ineffective erythropoiesis)

📌 Remember: TAILS for iron deficiency causes - Tea (tannins), Achlorhydria/PPI, IBD, Loss (menstruation/GI bleeding), Surgery (gastrectomy)

Visual Aid

Reticulocyte Response Interpretation

Clinical Scenario	Reticulocyte Count	Interpretation
Acute haemorrhage	↑↑ (>100 × 10⁹/L)	Appropriate marrow response
Iron/B12 deficiency	↓ or normal	Production failure
Post-treatment (Fe/B12)	↑↑ (peak day 7-10)	Confirms diagnosis retrospectively
Aplastic anaemia	↓↓ (<20 × 10⁹/L)	Marrow failure

Key Points Summary

✓ MCV classification is the first step: microcytic (<80), normocytic (80-100), macrocytic (>100 fL)

✓ Ferritin <30 μg/L confirms iron deficiency; investigate GI source in men/post-menopausal women (mandatory colonoscopy + OGD)

✓ NICE NG8: Refer urgently if Hb <100 g/L (men) or <90 g/L (women) without clear cause

✓ Hypersegmented neutrophils (≥6 lobes) are pathognomonic for megaloblastic anaemia (B12/folate deficiency)

✓ Reticulocyte count distinguishes production failure (↓) from haemolysis/bleeding (↑↑)

✓ Thalassaemia trait: microcytosis with normal/raised ferritin and disproportionately low MCV for degree of anaemia

✓ Never treat B12 deficiency with folate alone - risks precipitating subacute combined degeneration

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