Subtitle: Haemostasis and thrombosis quiz 1, rebuilt as a case-based guide to bleeding disorders: the approach to a bleeding patient, haemophilia A and B and inhibitors, the subtypes of von Willebrand disease, inherited platelet function disorders and their aggregation patterns, factor XIII deficiency, acquired bleeding (vitamin K, liver disease, DIC) and 10 case-based MCQs.
Author: PathologyMCQ Editorial Board
Category: Haematology
Last Updated: October 2026
Read Time: 8 minutes
At-a-Glance
- Mucocutaneous bleeding points to platelets or vWF; joint and muscle bleeding points to coagulation factors.
- Isolated long APTT that corrects on mixing: factor VIII, IX, XI or XII deficiency; no correction: inhibitor or lupus anticoagulant.
- vWD: type 1 (quantitative), type 2 (qualitative; activity/antigen below 0.7), type 3 (absent). 2B: low-dose RIPA increased; 2N: mimics haemophilia A.
- Glanzmann: all agonists fail except ristocetin. Bernard–Soulier: only ristocetin fails, giant platelets.
- Normal PT, APTT and platelets with serious bleeding: think factor XIII.
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Approach to the Bleeding Patient
- History first: a bleeding assessment tool (ISTH-BAT) score, age at onset, family history and sex pattern, response to surgery, dental extraction, menstruation and childbirth, drugs (aspirin, NSAIDs, anticoagulants).
- Pattern: petechiae, epistaxis, menorrhagia and bleeding after cuts suggest platelet or vWF problems; haemarthroses, deep muscle haematomas and delayed post-surgical bleeding suggest factor deficiency.
- First-line tests: full blood count and film, PT, APTT, fibrinogen (Clauss), and in many laboratories a vWF screen and PFA-100/200.
- Second line is directed by the pattern: mixing studies, factor assays, inhibitor assays, vWF subtyping, platelet aggregometry and flow cytometry, factor XIII activity.
What the Screening Tests Tell You
Interpreting the coagulation screen
| PT | APTT | Platelets | Fibrinogen | Think of |
|---|---|---|---|---|
| Normal | Normal | Normal | Normal | vWD (mild), platelet function defect, factor XIII deficiency, vascular causes, mild factor deficiency |
| Normal | Long | Normal | Normal | Factor VIII, IX, XI deficiency (bleed); factor XII, prekallikrein, HMWK deficiency or lupus anticoagulant (no bleed); heparin; vWD with low FVIII |
| Long | Normal | Normal | Normal | Factor VII deficiency, early warfarin or vitamin K deficiency, early liver disease |
| Long | Long | Normal | Normal | Factor X, V, II deficiency; warfarin; vitamin K deficiency; DOACs |
| Long | Long | Low | Low | DIC, severe liver disease, massive transfusion |
| Normal | Normal | Low | Normal | Thrombocytopenia: ITP, drugs, marrow failure, hypersplenism |
| Long | Long | Normal | Low | Hypo- or dysfibrinogenaemia (check thrombin time, reptilase) |
Mixing studies: 1:1 with normal plasma, tested immediately and after 1–2 hours at 37 °C. Correction (into the reference range or Rosner index below about 11%) means deficiency; failure means an inhibitor. Factor VIII inhibitors are typically time dependent; lupus anticoagulant is immediate.
Haemophilia and Inhibitors
Haemophilia A and B
| Feature | Haemophilia A | Haemophilia B |
|---|---|---|
| Deficient factor | VIII | IX |
| Inheritance | X-linked recessive; 30% new mutations; intron 22 inversion in about 45% of severe cases | X-linked recessive |
| Severity by factor level | Severe below 1 IU/dL, moderate 1–5, mild 5–40 | Same |
| Screening tests | PT normal, APTT prolonged (may be normal in mild disease), corrects on mixing | Same |
| Inhibitors | About 30% of severe patients; measured in Bethesda units (Nijmegen) | About 3–5%; may cause anaphylaxis to factor IX |
| Treatment | Recombinant or plasma-derived FVIII, extended half-life products, emicizumab, desmopressin in mild disease | FIX concentrates, extended half-life products |
| Carriers | Can have low FVIII and bleed; lyonisation | Same |
| Differential | vWD type 2N and type 3, acquired haemophilia (autoantibody in the elderly, pregnancy, malignancy) | Vitamin K deficiency in neonates |
von Willebrand Disease
Classification of von Willebrand disease
| Type | Defect | vWF:Ag | vWF activity (GPIbR/GPIbM/RCo) | Activity/antigen ratio | FVIII | Multimers | Key test |
|---|---|---|---|---|---|---|---|
| 1 | Partial quantitative deficiency (commonest, 70%) | Low (below 30, or 30–50 with bleeding) | Low proportionately | Above 0.7 | Low or normal | Normal | Desmopressin trial response good |
| 1C | Rapid clearance (Vicenza) | Low | Low | Above 0.7 | Low | Normal | vWFpp/vWF:Ag ratio high; short response to desmopressin |
| 2A | Loss of large multimers | Normal or low | Disproportionately low | Below 0.7 | Normal or low | Large and intermediate absent | RIPA reduced |
| 2B | Gain of function: binds GPIb spontaneously | Normal or low | Low | Below 0.7 | Normal or low | Large absent | Low-dose RIPA increased; thrombocytopenia; avoid desmopressin |
| 2M | Reduced platelet binding with normal multimers | Normal or low | Low | Below 0.7 | Normal or low | Normal | RIPA reduced; collagen binding normal (unless collagen-binding variant) |
| 2N | Reduced FVIII binding | Normal | Normal | Normal | Low (5–40) | Normal | vWF:FVIIIB assay; autosomal recessive; mimics haemophilia A |
| 3 | Complete absence | Undetectable | Undetectable | n/a | Very low (1–10) | Absent | Severe; autosomal recessive; alloantibodies may develop |
- vWF levels rise with stress, pregnancy, oestrogen, inflammation and age, and are lower in blood group O; repeat borderline results.
- Acquired vWS: aortic stenosis, LVAD, myeloproliferative neoplasms with very high platelets, paraproteins, hypothyroidism, Wilms tumour.
Platelet Function Disorders
Light transmission aggregometry patterns
| Disorder | ADP | Collagen | Adrenaline | Arachidonic acid | Ristocetin | Other clues |
|---|---|---|---|---|---|---|
| Glanzmann thrombasthenia | Absent | Absent | Absent | Absent | Normal | Normal count and size; CD41/CD61 absent; clot retraction absent |
| Bernard–Soulier syndrome | Normal | Normal | Normal | Normal | Absent, not corrected by normal plasma | Giant platelets, thrombocytopenia; CD42 absent |
| von Willebrand disease | Normal | Normal | Normal | Normal | Reduced, corrected by normal plasma | Low vWF |
| Storage pool (delta) disease | Reduced second wave | Reduced | Reduced second wave | Normal or reduced | Normal | Low ATP release, Hermansky–Pudlak, Chediak–Higashi |
| Grey platelet (alpha granule) syndrome | Variable | Reduced | Variable | Normal | Normal | Agranular grey platelets, myelofibrosis; NBEAL2 |
| Aspirin / COX-1 defect | Reduced second wave | Reduced | Reduced second wave | Absent | Normal | Drug history |
| Clopidogrel / P2Y12 defect | Reduced | Normal | Normal | Normal | Normal | Drug history |
Acquired Bleeding Disorders
- Vitamin K deficiency: PT prolonged first, then APTT; corrects with vitamin K in 24 hours; causes include newborns, malabsorption, antibiotics, warfarin, rodenticides.
- Liver disease: reduced synthesis of most factors and inhibitors, thrombocytopenia from hypersplenism, dysfibrinogenaemia, low factor V (unlike vitamin K deficiency, where factor V is normal); the INR overstates bleeding risk because anticoagulants fall too.
- DIC: prolonged PT and APTT, low fibrinogen and platelets, raised D-dimer, schistocytes; ISTH score 5 or more is overt DIC. Chronic DIC (malignancy) may show only a raised D-dimer.
- Acquired haemophilia A: autoantibody to FVIII in the elderly, post-partum, autoimmune disease or malignancy; isolated prolonged APTT that does not correct; large soft-tissue bleeds; treat with bypassing agents and immunosuppression.
- Drugs: antiplatelets, anticoagulants, SSRIs, NSAIDs; DOACs prolong PT or APTT unpredictably and need specific anti-Xa or dilute thrombin time assays.
- Massive transfusion and uraemia (platelet dysfunction; desmopressin, dialysis).
Test Yourself: 10 Case-Based MCQs
Bleeding disorders: 10 case-based MCQs
Haemophilia, inhibitors, von Willebrand disease subtypes, platelet function defects, factor XIII and DIC, with instant explanations.
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More practice: the question banks →
Exam Pearls
- Mixing study: corrects = deficiency; fails = inhibitor (FVIII inhibitors are time dependent, lupus anticoagulant immediate).
- Low FVIII with normal vWF: haemophilia A or type 2N vWD; the binding assay decides.
- Activity/antigen ratio below 0.7 = type 2 vWD; 2B is the one with increased low-dose RIPA and thrombocytopenia.
- Glanzmann = everything fails except ristocetin; Bernard–Soulier = only ristocetin fails.
- Normal screen plus severe bleeding = factor XIII, mild vWD, platelet function defect or a vascular cause.
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References
- James PD, et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv. 2021;5:280–300.
- Srivastava A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1–158.
- Bain BJ, Bates I, Laffan MA, eds. Dacie and Lewis Practical Haematology. 12th ed. Elsevier; 2017.
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