Bleeding Disorders in Adults

1. Clinical Overview

Summary

Bleeding disorders encompass a heterogeneous group of conditions characterized by impaired haemostasis, leading to excessive or prolonged bleeding. These disorders result from defects in primary haemostasis (platelets, von Willebrand factor), secondary haemostasis (coagulation factors), or both. The clinical spectrum ranges from mild mucocutaneous bleeding to life-threatening haemorrhage. Understanding the coagulation cascade is fundamental: the intrinsic pathway (factors XII, XI, IX, VIII) and extrinsic pathway (factor VII, tissue factor) converge on the common pathway (factors X, V, II, fibrinogen) to form a stable fibrin clot. [1]

Bleeding disorders can be inherited (haemophilia A/B, von Willebrand disease, rare factor deficiencies) or acquired (anticoagulant-related, liver disease, disseminated intravascular coagulation, acquired haemophilia). The pattern of bleeding often provides diagnostic clues: mucocutaneous bleeding (petechiae, purpura, epistaxis, menorrhagia) suggests platelet or von Willebrand factor defects, whereas deep tissue bleeding (haemarthroses, muscle haematomas, retroperitoneal bleeding) indicates coagulation factor deficiencies. [2]

Prompt recognition and appropriate management are critical. Severe bleeding in haemophilia can lead to joint destruction and disability. Anticoagulant-related bleeding is increasingly common with the widespread use of warfarin and direct oral anticoagulants (DOACs). Acquired bleeding disorders in critically ill patients (DIC, massive transfusion, liver failure) carry high mortality. The key to management is identifying the underlying defect through clinical assessment and coagulation testing, followed by targeted replacement therapy (factor concentrates, DDAVP, platelet transfusion) and treatment of the underlying cause. [1,2,3]

Key Facts

• Incidence (Inherited): Haemophilia A 1:5,000 male births; Haemophilia B 1:30,000 male births; von Willebrand disease 1-2% of population (most mild/asymptomatic) [4]
• Incidence (Acquired): Anticoagulant-related bleeding 2-3% per year; DIC 1% of hospitalized patients [5,6]
• Mortality: less than 1% for mild bleeding; 10-20% for severe bleeding with shock; >50% for DIC with multi-organ failure [5,6]
• Peak age: Inherited disorders present in childhood/early adulthood; acquired disorders any age
• Sex: Haemophilia A/B X-linked (males affected); von Willebrand disease autosomal (equal sex distribution)
• Critical diagnostic tests: PT (extrinsic pathway); APTT (intrinsic pathway); fibrinogen; factor assays; platelet count and function
• First-line treatment: Factor replacement (haemophilia); DDAVP (mild haemophilia A, von Willebrand disease type 1); reversal agents (anticoagulant bleeding); treat underlying cause

Clinical Pearls

"Pattern of bleeding predicts the defect" — Mucocutaneous bleeding (petechiae, epistaxis, menorrhagia) suggests platelet or von Willebrand defect. Deep tissue bleeding (haemarthroses, muscle haematomas) indicates factor deficiency.

"PT vs APTT localizes the problem" — Isolated prolonged APTT: intrinsic pathway (factors VIII, IX, XI, XII) or heparin. Isolated prolonged PT: extrinsic pathway (factor VII) or warfarin. Both prolonged: common pathway (factors II, V, X, fibrinogen), liver disease, DIC, or combined defects.

"Mixing studies distinguish deficiency from inhibitor" — If prolonged APTT corrects with 50:50 mix with normal plasma → factor deficiency. If doesn't correct → inhibitor (lupus anticoagulant, factor VIII inhibitor).

"DDAVP only works for mild haemophilia A and von Willebrand type 1" — Releases endogenous von Willebrand factor and factor VIII from endothelial stores. Dose: 0.3 μg/kg IV/SC. Tachyphylaxis occurs with repeated dosing. [7]

"Haemarthrosis = haemophilia until proven otherwise" — Recurrent spontaneous joint bleeding in young males is pathognomonic of severe haemophilia (less than 1% factor activity).

"Life-threatening bleeds need immediate factor replacement before test results" — Don't wait for factor assays in severe bleeding. Give factor concentrate or prothrombin complex concentrate (PCC) immediately.

Why This Matters Clinically

Bleeding disorders represent both chronic management challenges and acute medical emergencies. Early diagnosis of inherited disorders enables prophylactic treatment to prevent joint damage and disability. Recognition of acquired bleeding is crucial as these patients are often critically ill with multi-system pathology. With the increasing use of anticoagulants in an aging population, anticoagulant-related bleeding is a growing problem requiring familiarity with reversal strategies. Advances in haemophilia treatment (extended half-life factors, emicizumab, gene therapy) are transforming outcomes, but require specialized knowledge for optimal use. [1,2,8]

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2. Epidemiology

Incidence & Prevalence

Inherited Bleeding Disorders:

Acquired Bleeding Disorders:

Demographics

Risk Factors

Inherited Bleeding Disorders:

Non-Modifiable:

• Family history (X-linked pattern for haemophilia, autosomal for others)
• Male sex (for X-linked disorders)
• Genetic mutations (specific factor gene defects)

Acquired Bleeding Disorders:

Severity Classification

Haemophilia (based on factor VIII or IX level):

von Willebrand Disease:

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3. Aetiology & Pathophysiology

Normal Haemostasis Overview

Haemostasis involves three integrated processes: [1,2]

Primary Haemostasis (Platelet Plug Formation):

1. Vascular injury exposes subendothelial collagen
2. von Willebrand factor (vWF) binds to collagen and platelet GPIb receptor
3. Platelet adhesion, activation, and aggregation form platelet plug
4. Timeline: seconds to minutes

Secondary Haemostasis (Coagulation Cascade):

1. Intrinsic pathway: Activated by contact with negatively charged surfaces; involves factors XII, XI, IX, VIII
2. Extrinsic pathway: Activated by tissue factor (TF) released from damaged cells; involves factor VII
3. Common pathway: Both pathways activate factor X → factor Xa converts prothrombin (II) to thrombin (IIa) → thrombin converts fibrinogen to fibrin
4. Timeline: minutes

Fibrinolysis:

1. Plasminogen converted to plasmin
2. Plasmin degrades fibrin clot
3. Regulated by tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI)

Classification of Bleeding Disorders

By Mechanism:

Inherited Bleeding Disorders

Haemophilia A (Factor VIII Deficiency):

• F8 gene on X chromosome (Xq28)
• 50% of cases have intron 22 inversion
• Factor VIII is a cofactor for factor IXa in activating factor X
• Without factor VIII, intrinsic pathway impaired, reduced thrombin generation
• Severity correlates with residual factor VIII activity [1,4]

Exam Detail: Molecular Pathophysiology:

Factor VIII circulates bound to von Willebrand factor (which stabilizes it and prevents degradation). In the coagulation cascade:

• Factor IXa + Factor VIIIa + calcium + phospholipid = "tenase complex"
• This complex activates factor X (rate-limiting step)
• Without factor VIII, this amplification step fails
• Result: 50-fold reduction in thrombin generation, inadequate fibrin formation

Haemophilia B (Factor IX Deficiency):

• F9 gene on X chromosome (Xq27)
• Factor IX is a serine protease that activates factor X
• Clinically indistinguishable from haemophilia A
• Treatment requires factor IX concentrate (NOT factor VIII)

von Willebrand Disease:

Three major types based on pathophysiology: [2,7]

vWF:Ag = von Willebrand factor antigen; vWF:RCo = ristocetin cofactor activity; RIPA = ristocetin-induced platelet aggregation

Type 2B von Willebrand disease is critical to recognize: giving DDAVP can precipitate thrombocytopenia by releasing abnormal vWF that spontaneously binds platelets. [7]

Acquired Bleeding Disorders

Anticoagulant-Related Bleeding:

Liver Disease Coagulopathy:

The liver synthesizes most coagulation factors (except vWF and factor VIII). In cirrhosis: [13]

• Reduced synthesis of factors II, V, VII, IX, X, XI → prolonged PT and APTT
• Reduced synthesis of protein C, protein S, antithrombin → paradoxical prothrombotic risk
• Thrombocytopenia (portal hypertension, splenic sequestration, reduced thrombopoietin)
• Dysfibrinogenaemia
• Result: "rebalanced" but fragile haemostasis with both bleeding and thrombotic risk

Disseminated Intravascular Coagulation (DIC):

Pathophysiology: Widespread activation of coagulation → consumption of platelets and factors → microvascular thrombosis AND bleeding: [6]

• Triggers: Sepsis (endotoxin), trauma (tissue factor release), malignancy (procoagulants), obstetric (amniotic fluid embolism)
• Microvascular thrombosis: Ischaemic organ damage (renal failure, ARDS, hepatic dysfunction)
• Consumptive coagulopathy: Thrombocytopenia, low fibrinogen, prolonged PT/APTT
• Fibrinolysis: Elevated D-dimer, fibrin degradation products (FDPs)

Acquired Haemophilia A:

Autoantibodies (typically IgG4) against factor VIII: [14]

• Incidence 1-2 per million per year
• 50% idiopathic; associations: postpartum, autoimmune disease, malignancy, drugs
• Unlike inherited haemophilia: patients are elderly with no prior bleeding history
• Bleeding can be severe and atypical (soft tissue, mucocutaneous more common than joints)
• Inhibitor titre measured in Bethesda units (BU)
• Management: control bleeding (bypassing agents: activated PCC, recombinant FVIIa) + immunosuppression to eradicate inhibitor

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4. Clinical Presentation

Symptoms: The Patient's Story

History Taking Framework:

1. Bleeding History:

   • Spontaneous vs provoked (trauma, surgery, dental extraction)
   • Sites: mucocutaneous (epistaxis, gingival, menorrhagia, GI, bruising) vs deep tissue (joints, muscles, retroperitoneum)
   • Duration: immediate (platelet/vWF defect) vs delayed (factor deficiency - bleeding hours after trauma)
   • Severity: required transfusion? Hospital admission?
   • Response to haemostatic challenges: circumcision, dental extractions, surgery, childbirth

2. Family History:

   • Bleeding in male relatives (X-linked haemophilia)
   • Consanguinity (autosomal recessive disorders)
   • Pedigree pattern

3. Medications:

   • Anticoagulants (warfarin, DOACs, heparin)
   • Antiplatelet agents (aspirin, clopidogrel)
   • NSAIDs
   • Antibiotics (high-dose beta-lactams can cause platelet dysfunction)
   • Chemotherapy

4. Medical History:

   • Liver disease (reduced factor synthesis)
   • Renal failure (platelet dysfunction)
   • Autoimmune disease (acquired haemophilia)
   • Malignancy (DIC)
   • Recent infection (DIC)
   • Obstetric history (postpartum acquired haemophilia, HELLP syndrome)

Typical Presentations by Disorder:

Signs: What You See on Examination

Vital Signs:

General Inspection:

• Pallor: Anaemia from chronic or acute blood loss
• Jaundice: Liver disease, haemolysis (DIC)
• Cachexia: Malignancy (DIC trigger)
• Fever, hypotension: Sepsis (DIC)

Skin and Mucosal Bleeding:

Pattern Recognition:

• Petechiae + purpura (especially dependent areas, pressure points): Think platelet problem (thrombocytopenia or dysfunction)
• Large ecchymoses, haematomas: Think factor deficiency (haemophilia, anticoagulation)
• Bleeding from multiple sites (venepuncture, wounds, mucosa): Think DIC
• Delayed bleeding (hours after trauma): Think factor deficiency
• Immediate bleeding (oozing at injury site): Think platelet/vWF defect

Musculoskeletal Examination:

Haemarthrosis (Pathognomonic of Haemophilia):

• Swollen, warm, painful joint
• Restricted range of movement
• Held in flexed position (position of maximum capsular volume)
• Target joints: Ankles, knees, elbows most common (weight-bearing and mobile)
• Chronic haemarthroses → haemophilic arthropathy (joint destruction, contractures)

Muscle Haematomas:

• Palpable mass, tender
• Iliopsoas haematoma: Hip flexion, palpable mass, femoral nerve compression (foot drop)
• Forearm compartment syndrome: Tense, painful forearm, neurovascular compromise

Abdominal Examination:

• Hepatosplenomegaly: Liver disease (coagulopathy cause), portal hypertension (thrombocytopenia)
• Abdominal distension, flank bruising: Retroperitoneal haemorrhage (medical emergency)
• Peritonism: Intra-abdominal bleeding
• Rectal examination: Melaena (upper GI bleed), fresh blood (lower GI bleed)

Neurological Examination:

Critical in suspected intracranial haemorrhage:

• Reduced GCS, focal neurology, headache, vomiting, seizures
• Fundoscopy: Retinal haemorrhages
• Femoral nerve palsy: Iliopsoas haematoma (cannot extend knee, reduced knee reflex, numbness anterior thigh)

Red Flags - Require Immediate Action

[!CAUTION] Life-Threatening Presentations Requiring Immediate Senior Review and Treatment:

Haemodynamic Instability:

• Hypotension (SBP less than 90 mmHg), tachycardia (HR >120), shock
• Requires: Massive transfusion protocol, haematology/critical care input

Intracranial Haemorrhage:

• Headache, reduced GCS, focal neurology, seizures
• Requires: Urgent CT head, neurosurgical review, immediate factor replacement/reversal

Retroperitoneal Bleeding:

• Abdominal/flank pain, flank bruising, unexplained anaemia, iliopsoas sign
• Requires: CT abdomen/pelvis, surgical review, factor replacement

Compartment Syndrome:

• Tense, painful muscle compartment, neurovascular compromise
• Requires: Urgent orthopaedic review, measure compartment pressures, consider fasciotomy + factor cover

Neck/Airway Bleeding:

• Expanding neck haematoma, stridor, dysphagia
• Requires: Secure airway, ENT review, factor replacement

Bleeding with Factor Level less than 1%:

• In known severe haemophilia with head injury or major trauma
• Requires: Immediate factor replacement (do NOT wait for imaging)

Acute DIC:

• Bleeding + thrombosis + organ dysfunction
• Requires: ICU admission, treat underlying cause, blood product support

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5. Differential Diagnosis

When assessing a patient with bleeding, systematically consider:

Always Consider First (Most Common/Must Not Miss)

1. Anticoagulant-Related Bleeding (Most common cause of acquired bleeding)

• Key features: Known anticoagulant use, supratherapeutic levels, recent dose change, drug interactions
• Distinguishing: INR elevated (warfarin), anti-Xa elevated (LMWH, DOACs), APTT elevated (dabigatran, heparin)

2. Thrombocytopenia (Must not miss - can be rapid onset and severe)

• Key features: Petechiae, purpura, mucosal bleeding, platelet count less than 50 × 10⁹/L
• Distinguishing: Isolated low platelets, normal PT/APTT, normal factor levels

3. Liver Disease (Often missed as cause of bleeding)

• Key features: Known cirrhosis, alcohol excess, jaundice, stigmata of chronic liver disease
• Distinguishing: Prolonged PT AND APTT, low albumin, deranged LFTs, low platelets

4. DIC (Must not miss - high mortality)

• Key features: Critically ill, sepsis, trauma, malignancy, obstetric emergency
• Distinguishing: Low platelets, prolonged PT/APTT, low fibrinogen, HIGH D-dimer, schistocytes on film

Differential Diagnosis by Laboratory Pattern

Isolated Prolonged APTT (Normal PT, Normal Platelets):

Isolated Prolonged PT (Normal APTT, Normal Platelets):

Prolonged PT AND APTT (Normal Platelets):

Low Platelets (Normal PT/APTT initially):

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6. Investigations

First-Line (Bedside) - Do Immediately

Clinical Assessment (Most Important):

1. Focused History:

• Bleeding site, duration, severity, triggers
• Previous bleeding episodes, family history
• Medications (especially anticoagulants)
• Comorbidities (liver disease, renal failure, malignancy)

2. Examination:

• Vital signs (HR, BP, RR - assess haemodynamic status)
• Pattern of bleeding (mucocutaneous vs deep tissue)
• Signs of underlying disease (liver disease, sepsis)
• Assess for compartment syndrome, intracranial bleeding

3. Venous Access:

• Large bore IV access (14-16G) if active bleeding
• Blood samples for urgent tests

Laboratory Tests

Initial Coagulation Screen (Do in ALL patients with bleeding):

Second-Line Tests (Guided by Initial Results):

If Isolated Prolonged APTT:

If Prolonged PT and/or APTT:

Specific Tests for von Willebrand Disease:

Note: von Willebrand disease testing can be affected by blood group (type O have 25% lower vWF), acute phase response (vWF rises with inflammation), menstrual cycle, pregnancy. Repeat testing may be needed. [7]

DIC Scoring System (ISTH):

Score ≥5 = Overt DIC [6]

Imaging

Usually not required for diagnosis of bleeding disorders, but essential for assessing complications:

CT Head (Non-Contrast):

CT Abdomen/Pelvis (With IV Contrast):

Ultrasound (Musculoskeletal):

Diagnostic Criteria and Algorithms

Diagnosing Haemophilia:

• Male with bleeding (or positive family history)
• Prolonged APTT, normal PT, normal platelets
• Factor VIII less than 40% (haemophilia A) OR Factor IX less than 40% (haemophilia B)
• Severity: less than 1% severe, 1-5% moderate, 5-40% mild

Diagnosing von Willebrand Disease:

• Mucocutaneous bleeding, family history (autosomal)
• vWF:Ag less than 50 IU/dL AND/OR vWF:RCo less than 50 IU/dL
• Type 1: Parallel reduction in vWF:Ag and vWF:RCo
• Type 2: Disproportionate reduction in vWF:RCo vs vWF:Ag (ratio less than 0.6)
• Type 3: Virtually absent vWF, very low FVIII, severe bleeding

Diagnosing Acquired Haemophilia:

• Sudden onset bleeding in elderly with no prior history
• Prolonged APTT not correcting with mixing study
• Low factor VIII (less than 50%)
• Positive Bethesda inhibitor assay (>0.6 BU)

Diagnosing DIC:

• Clinical context (sepsis, trauma, malignancy, obstetric)
• ISTH DIC score ≥5
• Low platelets, prolonged PT/APTT, low fibrinogen, very high D-dimer
• Schistocytes on blood film

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7. Management

Management Algorithm

           PATIENT WITH BLEEDING
     (Active bleeding or high risk)
                   ↓
┌────────────────────────────────────────────┐
│  IMMEDIATE ASSESSMENT (FIRST 15 MINUTES)   │
│  • ABC - secure airway, breathing, IV access │
│  • Vital signs - assess shock               │
│  • Examine - site/severity of bleeding      │
│  • Bloods - FBC, coag screen, G&S/X-match   │
│  • History - medications, liver disease     │
└────────────────────────────────────────────┘
                   ↓
      ┌───────────┴───────────┐
      │                       │
  ACTIVE BLEEDING        RISK OF BLEEDING
      │                       │
      ↓                       ↓
┌─────────────────────┐  ┌──────────────────┐
│ RESUSCITATION       │  │ PROPHYLAXIS      │
│ • IV access 14-16G  │  │ • Factor replace │
│ • Fluid/blood       │  │ • Pre-procedure  │
│ • Tranexamic acid   │  │ • Surgery cover  │
│ • STOP anticoag     │  └──────────────────┘
└─────────────────────┘
      ↓
┌────────────────────────────────────────────┐
│  SPECIFIC TREATMENT (Based on Cause)       │
├────────────────────────────────────────────┤
│  INHERITED DISORDERS                       │
│  ├─ Haemophilia A                          │
│  │  → Factor VIII concentrate 50 IU/kg     │
│  │  → Target >100% for major bleeding [1]  │
│  │                                         │
│  ├─ Haemophilia B                          │
│  │  → Factor IX concentrate 100 IU/kg      │
│  │  → Target >100% for major bleeding [1]  │
│  │                                         │
│  ├─ Mild Haemophilia A / vWD Type 1        │
│  │  → DDAVP 0.3 μg/kg IV/SC [7]            │
│  │  → Tranexamic acid 1g TDS PO/IV         │
│  │                                         │
│  └─ von Willebrand Disease (Type 2/3)      │
│     → vWF/FVIII concentrate (e.g. Haemate P)│
│     → 40-80 IU/kg vWF:RCo [7]              │
│                                            │
│  ACQUIRED DISORDERS                        │
│  ├─ Warfarin                               │
│  │  → Vitamin K 10mg IV                    │
│  │  → PCC 25-50 IU/kg (urgent) [9,10]      │
│  │  → FFP 15 mL/kg if no PCC               │
│  │                                         │
│  ├─ Dabigatran                             │
│  │  → Idarucizumab 5g IV [11]              │
│  │  → Haemodialysis if no antidote         │
│  │                                         │
│  ├─ Rivaroxaban/Apixaban                   │
│  │  → Andexanet alfa (if available) [12]   │
│  │  → PCC 50 IU/kg (off-label)             │
│  │                                         │
│  ├─ DIC                                    │
│  │  → Treat underlying cause (sepsis, etc) │
│  │  → Platelets if less than 50 + bleeding [6]      │
│  │  → Cryoprecipitate if fibrinogen less than 1.5   │
│  │  → FFP 15 mL/kg if ongoing bleeding     │
│  │                                         │
│  ├─ Liver Disease                          │
│  │  → Vitamin K 10mg IV (may help)         │
│  │  → FFP 15 mL/kg for procedures/bleeding │
│  │  → Platelets if less than 50 + active bleeding   │
│  │  → Fibrinogen (cryoprecipitate) if less than 1.5 │
│  │                                         │
│  └─ Acquired Haemophilia                   │
│     → Bypassing agents (FEIBA, rFVIIa) [14]│
│     → Immunosuppression (steroids, rituximab)│
└────────────────────────────────────────────┘
                   ↓
┌────────────────────────────────────────────┐
│  MONITOR AND REASSESS                      │
│  • Vital signs, bleeding sites             │
│  • Repeat coag screen 1-2h after treatment │
│  • Factor levels (maintain >50% initially) │
│  • Consider complications (compartment syndrome)│
└────────────────────────────────────────────┘

Acute/Emergency Management - The First Hour

For ALL patients with significant bleeding:

1. Resuscitation (ABC Approach):

• Airway: Assess and secure if compromised (neck haematoma, massive haematemesis)
• Breathing: High-flow oxygen, assess for pulmonary haemorrhage
• Circulation:
  • Two large bore IV cannulas (14-16G)
  • IV fluid bolus 500mL crystalloid if hypotensive
  • Activate major haemorrhage protocol if shocked
  • Blood products as per protocol (see below)

2. Stop Bleeding at Source:

• Direct pressure: Most effective for accessible bleeding
• Tranexamic acid: 1g IV over 10 minutes, then 1g over 8h (give within 3 hours of bleeding onset) [15]
• Topical agents: Thrombin, fibrin glue for mucosal/surgical bleeding
• Interventional radiology: Embolization for GI, retroperitoneal bleeding if haemodynamically stable

3. Immediate Bloods:

• FBC: Hb, platelets
• Coagulation: PT, APTT, fibrinogen, D-dimer
• Group & Save or Cross-match (4-6 units if severe)
• Factor assays if known haemophilia (but don't delay treatment)
• U&E, LFT: Renal/liver function
• Venous/arterial blood gas: Lactate (marker of tissue perfusion), base deficit

4. Specific Treatment (Do NOT Wait for Full Results in Life-Threatening Bleeding):

If Known Haemophilia:

• Give factor concentrate IMMEDIATELY (before imaging for head injury)
• Factor VIII 50 IU/kg (haemophilia A) or Factor IX 100 IU/kg (haemophilia B)
• Target factor level >100% for major bleeding [1]

If On Anticoagulation:

• STOP anticoagulant
• Warfarin: PCC 25-50 IU/kg IV + Vitamin K 10mg IV [9,10]
• Dabigatran: Idarucizumab 5g IV [11]
• Rivaroxaban/Apixaban: Andexanet alfa OR PCC 50 IU/kg [12]
• Heparin: Protamine 1mg per 100 units heparin (max 50mg)

If Suspected DIC:

• Treat underlying cause (antibiotics for sepsis, delivery in obstetric DIC)
• Platelets if less than 50 × 10⁹/L AND bleeding
• Cryoprecipitate if fibrinogen less than 1.5 g/L
• FFP 15 mL/kg if ongoing bleeding with prolonged PT/APTT [6]

Medical Management

Factor Replacement Therapy:

Haemophilia A (Factor VIII Deficiency):

Dose calculation: 1 IU/kg factor VIII raises plasma level by ~2%. Half-life ~12 hours. [1]

Haemophilia B (Factor IX Deficiency):

Dose calculation: 1 IU/kg factor IX raises plasma level by ~1% (lower recovery than FVIII). Half-life ~18-24 hours. [1]

Products:

• Recombinant factor VIII/IX: Preferred (no viral transmission risk)
• Extended half-life factors: Require less frequent dosing (e.g., once weekly for prophylaxis)
• Cryoprecipitate/FFP: Only if factor concentrate unavailable (volume overload risk)

von Willebrand Disease:

Type 1 (Mild):

• DDAVP (Desmopressin): 0.3 μg/kg IV over 30 minutes OR 300 μg intranasal [7]
  • Releases endogenous vWF and factor VIII from endothelial Weibel-Palade bodies
  • Increases vWF 3-5 fold within 30-60 minutes
  • "Duration of effect: 6-12 hours"
  • Tachyphylaxis with repeated doses (give no more frequently than 48h apart)
  • "Side effects: Facial flushing, headache, hyponatraemia (restrict fluids), rarely seizures"
  • "Test dose: Give trial dose and measure vWF/FVIII response before relying on DDAVP for surgery"
  • "Contraindications: Type 2B (can worsen thrombocytopenia), cardiovascular disease, age less than 2 years"

Type 2A, 2M, 2N, Type 3 (Moderate-Severe):

• vWF/FVIII concentrate: e.g., Haemate P, Wilate
  • "Dose: 40-80 IU/kg vWF:RCo (contains both vWF and FVIII)"
  • "For major bleeding: 50-80 IU/kg, then 40-60 IU/kg 8-12 hourly"
  • "For surgery: 50-60 IU/kg pre-op, maintain vWF:RCo >50% for 5-10 days"
  • Do NOT use factor VIII concentrate alone (lacks vWF)

Adjunctive therapy (all types):

• Tranexamic acid: 1g TDS PO or 1g IV TDS (antifibrinolytic) [15]
• Hormonal therapy: Combined oral contraceptive for menorrhagia
• Local measures: Pressure, nasal packing, dental wax

Novel Therapies for Haemophilia:

Emicizumab (Haemophilia A with/without inhibitors):

• Bispecific antibody mimicking factor VIII function (bridges factor IXa and X)
• Subcutaneous injection weekly/fortnightly/monthly
• Dramatically reduces bleeding rate (87% reduction vs no prophylaxis) [8]
• Use: Prophylaxis in haemophilia A (NOT haemophilia B)
• Caution: If bleeding occurs, use rFVIIa (NOT factor VIII or aPCC - thrombosis risk)

Anticoagulation Reversal

Warfarin Reversal:

PCC (Prothrombin Complex Concentrate):

• Contains factors II, VII, IX, X (the vitamin K-dependent factors)
• Beriplex/Octaplex: 4-factor PCC (also contains protein C, S)
• Dose: 25-50 IU/kg (max 5000 IU)
• Onset: 10-15 minutes
• Advantage: Rapid, small volume (1-2 vials)
• Disadvantage: Thrombosis risk 1-2%, expensive
• Alternative if PCC unavailable: FFP 15 mL/kg (large volume, slower)

DOAC Reversal:

General DOAC reversal measures:

• Stop DOAC (short half-life 5-17h depending on agent and renal function)
• Activated charcoal if less than 2-4h since ingestion
• Tranexamic acid 1g IV TDS
• Monitor anti-Xa or thrombin time (check reversal achieved)

Blood Product Support

Indications for Transfusion in Bleeding Disorders:

Massive Transfusion Protocol:

In massive haemorrhage (>10 units pRBC in 24h or >4 units in 1h), use balanced resuscitation:

• Red cells : FFP : Platelets = 1:1:1 ratio
• Aim fibrinogen >1.5 g/L (give cryoprecipitate early)
• Tranexamic acid 1g IV stat, then 1g over 8h [15]
• Monitor: FBC, coag screen every 30-60 minutes
• Avoid: Hypothermia (warm fluids), acidosis (permissive hypotension), hypocalcaemia (calcium 1g IV every 4 units FFP)

Acquired Haemophilia Management

Two goals: Control bleeding AND Eradicate inhibitor [14]

Control Bleeding:

• DO NOT give factor VIII (inhibitor neutralizes it, may boost inhibitor titre)
• Use bypassing agents:
  • "Activated PCC (FEIBA): 50-100 IU/kg every 8-12h (max 200 IU/kg/day)"
  • "Recombinant factor VIIa (NovoSeven): 90 μg/kg every 2-3h until bleeding controlled"
  • Choice depends on local availability, clinical response

Eradicate Inhibitor (Immunosuppression):

• First-line: Prednisolone 1 mg/kg/day PO + Cyclophosphamide 1.5-2 mg/kg/day PO
• Second-line: Rituximab 375 mg/m² IV weekly × 4 weeks
• Target: Inhibitor titre less than 0.6 BU, factor VIII >50%
• Duration: Often 6-12 weeks of treatment
• Monitoring: Factor VIII level and inhibitor titre weekly

Disposition and Follow-Up

Admit to Hospital If:

• Active major bleeding (ICH, GI, retroperitoneal, compartment syndrome)
• Haemodynamic instability
• Severe anaemia requiring transfusion
• Newly diagnosed severe haemophilia
• Intracranial bleeding or head injury in haemophilia (even if no bleed on CT)
• DIC
• Acquired haemophilia with bleeding
• Post-procedure bleeding requiring factor replacement

Critical Care/HDU If:

• Haemodynamic instability despite resuscitation
• Ongoing major bleeding requiring massive transfusion
• DIC with organ dysfunction
• Intracranial haemorrhage requiring ICP monitoring

Outpatient Management:

• Mild bleeding (e.g., haemarthrosis) in known haemophilia if self-treated promptly
• Minor bleeding controlled with DDAVP/tranexamic acid
• Warfarin over-anticoagulation with minor bleeding (give vitamin K, ensure INR corrected, follow-up)

Discharge Criteria:

• Bleeding controlled
• Haemodynamically stable
• Hb stable
• Factor levels adequate (>30-50% if haemophilia)
• Safe to discharge with outpatient follow-up

Follow-Up:

Haemophilia:

• Specialist haemophilia centre - all patients should be registered
• Prophylaxis: Severe haemophilia - factor VIII/IX 2-3× weekly to maintain trough >1% (prevents joint bleeds) [1]
• Home therapy: Trained patients self-administer factor at first sign of bleeding
• Annual review: Joint examination, inhibitor screen, viral serology
• Multidisciplinary: Haematologist, physiotherapist, orthopaedic surgeon, psychologist

von Willebrand Disease:

• Mild (type 1): Often only requires treatment for procedures/bleeding episodes
• Moderate-severe: May need prophylaxis pre-menstruation, procedures
• DDAVP test dose: Document response for future use
• Genetic counseling: For family planning

Acquired Bleeding:

• Anticoagulation: Review need for anticoagulation, consider alternative (e.g., DOAC to warfarin), optimize INR monitoring
• Liver disease: Treat underlying liver disease, avoid unnecessary procedures
• DIC: Treat underlying cause, monitor for resolution
• Acquired haemophilia: Monitor factor VIII and inhibitor titre until eradicated

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8. Complications

Immediate (Hours-Days)

Compartment Syndrome:

• High suspicion in forearm/calf haematomas
• 6 Ps: Pain (out of proportion), Pressure (tense compartment), Paraesthesia, Pallor, Pulselessness (late), Paralysis (late)
• Measure compartment pressure: >30 mmHg absolute or less than 30 mmHg difference from diastolic BP = indication for fasciotomy
• Critical: Give factor replacement to 100% BEFORE surgery, maintain >50% during perioperative period

Early (Days-Weeks)

Inhibitor Development:

• Alloantibody (typically IgG) against factor VIII (haemophilia A) or factor IX (haemophilia B)
• Measured in Bethesda units (BU): less than 5 BU low titre, >5 BU high titre
• High titre inhibitors: Very difficult to treat; require bypassing agents (FEIBA, rFVIIa) or immune tolerance induction
• Immune tolerance induction (ITI): High-dose factor VIII daily/alternate days for months-years to induce tolerance; success 60-80% [1]

Late (Months-Years)

Haemophilic Arthropathy:

• Target joints: Ankles, knees, elbows (weight-bearing and mobile joints)
• Pathophysiology: Iron from haemolysed blood → synovial hypertrophy → cartilage damage → osteoarthritis
• Classification: Pettersson score (radiographic), Haemophilia Joint Health Score (clinical)
• Prevention is key: Prophylaxis from age 1-2 years reduces joint bleeds by 90% and prevents arthropathy [1]

Mortality

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9. Prognosis & Outcomes

Natural History (Without Treatment)

Severe Haemophilia (Untreated):

• Recurrent spontaneous haemarthroses from age 1-2 years
• Progressive joint destruction → wheelchair-bound by adolescence/early adulthood
• Muscle haematomas, compartment syndrome
• Life expectancy: Historically 20-30 years (ICH, bleeding complications)
• Now with treatment: Near-normal life expectancy [1]

von Willebrand Disease:

• Type 1 (mild): Often asymptomatic, normal life expectancy
• Type 2/3: Moderate bleeding, manageable with treatment
• Main impact: Menorrhagia (iron deficiency, reduced QoL), bleeding with procedures

Acquired Bleeding Disorders:

• DIC: 30-50% mortality (depends on underlying cause) [6]
• Anticoagulant bleeding: Variable; ICH 40-60% mortality
• Liver disease coagulopathy: Mortality relates to liver disease severity

Outcomes with Treatment

Haemophilia with Prophylaxis:

Prophylaxis regimens (factor VIII/IX 2-3× weekly to maintain trough >1%) have transformed haemophilia outcomes. [1]

Novel therapies (emicizumab, extended half-life factors, gene therapy) further improving outcomes:

• Emicizumab: 87% reduction in bleeding vs no prophylaxis; subcutaneous dosing (weekly/monthly) improves adherence [8]
• Gene therapy: Emerging; AAV-mediated factor VIII/IX gene transfer achieving sustained factor levels >5% in many patients (converts severe to mild phenotype) [16]

von Willebrand Disease:

• Type 1: Excellent prognosis with DDAVP/tranexamic acid for bleeding episodes
• Type 2/3: Good outcomes with vWF/FVIII concentrate availability
• Pregnancy: vWF and FVIII rise in pregnancy (especially 3rd trimester), but may need supplementation at delivery [7]

Anticoagulant Bleeding:

• If bleeding controlled and anticoagulation reversed: good prognosis
• ICH: 40-60% mortality; survivors often have significant disability
• Recurrence risk: 2-3% per year if anticoagulation restarted; risk-benefit assessment crucial [5]

DIC:

• Mortality 30-50%, depends on underlying cause [6]
• Survival factors: Early treatment of underlying cause (antibiotics for sepsis), blood product support
• Non-survivors: Multi-organ failure (renal, respiratory, hepatic)

Acquired Haemophilia:

• Bleeding-related mortality: 10-20% [14]
• Inhibitor eradication: 60-80% with immunosuppression (median 5 weeks)
• Recurrence: 10-20% (monitor factor VIII level)

Prognostic Factors

Good Prognosis:

• Early diagnosis and treatment
• Prophylaxis in severe haemophilia (started before age 3 years)
• Mild haemophilia or von Willebrand type 1
• Good adherence to treatment
• No inhibitor development
• Access to specialist haemophilia centre
• Supportive family/social environment

Poor Prognosis:

• Delayed diagnosis
• Severe haemophilia without prophylaxis
• Inhibitor development (high titre, refractory to immune tolerance)
• Advanced chronic arthropathy
• Intracranial haemorrhage
• DIC with multi-organ failure
• Elderly with acquired haemophilia
• Limited access to treatment

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10. Prevention & Screening

Primary Prevention

Genetic Counseling:

• Haemophilia: X-linked; daughters of affected males are obligate carriers; 50% chance male offspring of carriers affected
• von Willebrand disease: Autosomal; offspring have 50% chance if one parent affected (types 1,2)
• Prenatal diagnosis: Chorionic villus sampling (CVS) at 11-14 weeks, amniocentesis at 15-20 weeks for fetal DNA analysis
• Pre-implantation genetic diagnosis (PGD): For families wishing to select unaffected embryos (IVF)

Carrier Testing:

• Female relatives of haemophilia patients should be offered carrier testing
• Factor VIII level less than 50% suggests carrier (but not definitive; Lyon hypothesis means variable X-inactivation)
• Genetic testing definitive

Prevention of Bleeding in Known Patients:

Haemophilia:

• Prophylaxis: Factor VIII/IX 2-3× weekly from age 1-2 years (prevents joint bleeds, maintains trough >1%) [1]
• Avoid trauma: No contact sports, protective equipment
• Avoid medications: NSAIDs, aspirin, intramuscular injections
• Immunizations: Subcutaneous route (not IM)
• Dental care: Excellent oral hygiene to avoid extractions; prophylactic factor cover for dental work
• Home therapy: Patients/families trained to administer factor at first sign of bleeding
• Medical alert: Bracelet/card identifying haemophilia

von Willebrand Disease:

• Avoid medications: NSAIDs, aspirin
• DDAVP test: Trial dose to assess response (for type 1)
• Pre-procedure planning: DDAVP or vWF/FVIII concentrate for surgery/dental work

Secondary Prevention (Prevent Complications in Established Disease)

Prevent Inhibitor Development:

• Controversial: Some evidence that continuous prophylaxis (vs on-demand) may reduce inhibitor risk
• Immune tolerance induction (ITI): If inhibitor develops, start ITI early (within 1 year)

Prevent Joint Damage:

• Prophylaxis: Most effective prevention [1]
• Physiotherapy: Strengthen muscles, maintain range of movement
• Treat bleeds promptly: Early factor replacement minimizes joint damage
• Avoid immobilization: Prolonged immobilization weakens muscles

Prevent Infection (Transfusion-Transmitted):

• Recombinant factors: No viral transmission risk (vs plasma-derived)
• Pathogen inactivation: If using plasma-derived products
• Vaccinations: Hepatitis A and B for all haemophilia patients

Screening

No population screening for bleeding disorders.

Case-finding:

• Pre-operative screening: Many centres screen with PT/APTT before surgery; identifies unsuspected bleeding disorders
• Heavy menstrual bleeding: Consider von Willebrand disease screening (affects 10-20% of women with menorrhagia)
• Family history: Offer carrier testing to female relatives of haemophilia patients

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11. Key Guidelines & Evidence

Major Society Guidelines

1. World Federation of Hemophilia (WFH) Guidelines for the Management of Hemophilia, 3rd Edition (2020) [1]

Key Recommendations:

• Prophylaxis: Start from age 1-2 years in severe haemophilia; target trough factor level >1%
• Treatment of bleeding: Factor VIII 50 IU/kg or factor IX 100 IU/kg for major bleeds; target level >100% initially
• Inhibitors: Immune tolerance induction first-line; bypassing agents for bleeding
• Novel therapies: Emicizumab as prophylaxis option for haemophilia A
• Evidence Level: 1A for prophylaxis, treatment protocols

2. NICE Guidelines: Haemophilia (Congenital Factor VIII or IX Deficiency) (2020)

Key Recommendations:

• Home treatment for bleeding episodes
• Specialist haemophilia centre care
• Prophylaxis for severe haemophilia
• Annual review and monitoring

3. British Committee for Standards in Haematology (BCSH) Guidelines

von Willebrand Disease (2021): [7]

• Type 1: DDAVP first-line for minor bleeding/procedures
• Type 2/3: vWF/FVIII concentrate
• DDAVP test dose: Assess response before relying on for surgery

4. ASH Guidelines: Management of DIC (2018) [6]

Key Recommendations:

• Treat underlying cause (most important)
• Platelet transfusion if less than 50 × 10⁹/L AND bleeding
• Fibrinogen replacement (cryoprecipitate) if less than 1.5 g/L
• Do NOT use heparin routinely (controversial)

5. European Society of Cardiology (ESC) Guidelines: Anticoagulation Reversal (2022) [9,10,11,12]

Key Recommendations:

• Warfarin major bleeding: PCC 25-50 IU/kg + vitamin K 10mg IV
• Dabigatran: Idarucizumab 5g IV
• Rivaroxaban/apixaban: Andexanet alfa OR PCC 50 IU/kg
• Tranexamic acid: Consider in all anticoagulant-related bleeding

Landmark Trials and Studies

1. Joint Outcome Study (2007) - Prophylaxis vs on-demand treatment in haemophilia [17]

• Design: RCT, 65 boys with severe haemophilia A
• Intervention: Prophylaxis (factor VIII 25 IU/kg 3× weekly) vs on-demand treatment
• Results: 93% reduction in joint bleeds (0.4 vs 5.9 bleeds/year); prevention of joint damage on MRI
• Impact: Established prophylaxis as standard of care

2. HAVEN 1 Study (2017) - Emicizumab for haemophilia A [8]

• Design: Open-label trial, haemophilia A with inhibitors
• Intervention: Emicizumab prophylaxis vs no prophylaxis or bypassing agent prophylaxis
• Results: 87% reduction in bleeding vs no prophylaxis; 79% reduction vs bypassing agents
• Impact: Emicizumab now widely used; subcutaneous, long-acting, effective

3. CRASH-2 Trial (2010) - Tranexamic acid in trauma bleeding [15]

• Design: RCT, 20,211 adults with traumatic bleeding
• Intervention: Tranexamic acid 1g IV bolus + 1g over 8h vs placebo
• Results: Reduced all-cause mortality (14.5% vs 16.0%, p=0.0035); benefit if given less than 3h
• Impact: Tranexamic acid now standard in major bleeding

4. ANNEXA-4 Study (2019) - Andexanet alfa for factor Xa inhibitor reversal [12]

• Design: Prospective cohort, 352 patients with major bleeding on rivaroxaban/apixaban
• Intervention: Andexanet alfa bolus + infusion
• Results: Median 92% reduction in anti-Xa activity within 2-5 minutes; effective haemostasis in 82%
• Impact: Licensed for rivaroxaban/apixaban reversal (though expensive, limited availability)

5. RE-VERSE AD Study (2015) - Idarucizumab for dabigatran reversal [11]

• Design: Prospective cohort, 503 patients on dabigatran with major bleeding or requiring urgent surgery
• Intervention: Idarucizumab 5g IV
• Results: Median 100% reversal of anticoagulant effect within minutes; effective in 68-93%
• Impact: Specific reversal agent for dabigatran

Evidence Strength for Key Interventions

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12. Common Exam Questions & Viva Points

Typical MRCP/FRACP Viva Questions

Q1: "A 4-year-old boy presents with recurrent knee swelling. What is your differential diagnosis and how would you investigate?"

Viva Point: Opening Statement: "Recurrent knee swelling in a young boy raises the possibility of haemophilia, but I would also consider other causes of monoarthritis. The key features I'd want to elicit are whether this is recurrent in the same joint, any history of trauma, presence of pain, and any family history of bleeding disorders."

Differential Diagnosis:

1. Haemophilia A or B (most likely if recurrent spontaneous haemarthroses)
2. Juvenile idiopathic arthritis
3. Trauma/post-traumatic effusion
4. Septic arthritis (if acute, febrile)
5. Osteomyelitis
6. Pigmented villonodular synovitis (rare)

Investigations:

• Bedside: Examine joint (swelling, warmth, range of movement, pain)
• Bloods: FBC (platelets), coagulation screen (PT, APTT), factor VIII and IX assays if APTT prolonged
• Imaging: Ultrasound joint (confirm haemarthrosis), X-ray (exclude fracture, assess for chronic changes)

If Haemophilia Confirmed:

• Factor level less than 1% = severe (explains spontaneous bleeds)
• Refer to specialist haemophilia centre
• Start prophylaxis (factor 2-3× weekly)
• Genetic counseling for family

Q2: "An 80-year-old man on warfarin for AF presents with extensive bruising. INR is 8.5. He is haemodynamically stable. How would you manage him?"

Viva Point: Assessment: "This is warfarin over-anticoagulation with bleeding. My priorities are to assess the severity of bleeding, identify the cause of the high INR, reverse the anticoagulation appropriately, and prevent further bleeding."

Immediate Management:

1. Assess bleeding severity: Is this minor (just bruising) or major (GI, ICH)? Haemodynamically stable vs shocked?
2. Stop warfarin
3. Bloods: FBC (Hb, platelets), U&E, LFT, coagulation (INR 8.5 known)
4. Vitamin K 5-10mg IV (slow infusion to avoid anaphylaxis)
   • Will take 12-24h to work
   • Dose 5mg for minor bleeding, 10mg for major bleeding

If Major Bleeding (e.g., GI bleeding, ICH):

• Prothrombin complex concentrate (PCC) 25-50 IU/kg IV (rapid reversal in 10-15 min)
• FFP 15 mL/kg if PCC not available (but large volume, slower)
• Tranexamic acid 1g IV TDS

Identify Cause of High INR:

• Recent antibiotics (erythromycin, metronidazole, ciprofloxacin inhibit warfarin metabolism)
• Alcohol binge (inhibits metabolism)
• Reduced dietary vitamin K
• Liver disease, renal impairment
• Drug interactions, missed doses then double-dosing

Follow-Up:

• Recheck INR at 6h, 12h, 24h (vitamin K slow onset)
• Restart warfarin when INR less than 5 (if still indicated for AF)
• Optimize INR monitoring: Consider DOAC if poor INR control

Q3: "How would you distinguish between haemophilia A and von Willebrand disease?"

Viva Point: Key Distinguishing Features:

Laboratory Diagnosis:

• Both can have prolonged APTT and low factor VIII
• Key test: von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo)
  • Low in von Willebrand disease, normal in haemophilia A

Clinical Pearls:

• Haemarthrosis strongly suggests haemophilia (NOT typical of von Willebrand disease)
• Menorrhagia in female suggests von Willebrand disease (can't have haemophilia A as female unless Turner syndrome/X-inactivation)
• Family history pattern: X-linked (males, maternal grandfather/uncles) vs autosomal (both sexes, parents)

Common Mistakes (What Fails Candidates)

❌ Not giving immediate factor replacement in severe bleeding in haemophilia

• "Waiting for factor assay results" is wrong - give factor IMMEDIATELY in severe bleeding

❌ Giving DDAVP in type 2B von Willebrand disease

• Can precipitate severe thrombocytopenia (abnormal vWF binds platelets)

❌ Giving factor VIII concentrate in acquired haemophilia

• Inhibitor neutralizes it; use bypassing agents (FEIBA, rFVIIa)

❌ Using FFP alone for warfarin reversal in major bleeding

• Too slow, large volume; PCC is superior

❌ Not checking mixing studies when APTT is prolonged

• Distinguishes factor deficiency (corrects) from inhibitor (doesn't correct)

❌ Assuming low platelets always cause bleeding

• HIT, TTP cause thrombosis MORE than bleeding
• Lupus anticoagulant prolongs APTT but causes thrombosis (not bleeding)

❌ Forgetting DIC in the differential of prolonged PT/APTT

• Always consider in sepsis, trauma, obstetric emergency

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13. Patient/Layperson Explanation

What is a Bleeding Disorder?

A bleeding disorder is a condition where your blood doesn't clot properly, which means you might bleed more easily, for longer, or more heavily than normal after an injury. Some people are born with bleeding disorders (like haemophilia), while others develop them later in life (like from liver disease or blood-thinning medications).

Think of it like this: Normal blood clotting is like building a wall to stop a leak. It needs bricks (platelets) and cement (clotting factors) to seal the hole. If you're missing bricks or cement, or they don't work properly, the wall won't form and the bleeding continues.

Types of Bleeding Disorders

Haemophilia:

• You're missing one of the clotting factors (like missing the cement)
• Mostly affects boys/men (passed down from mothers)
• Causes bleeding into joints and muscles
• Treated with injections of the missing clotting factor

von Willebrand Disease:

• You don't have enough "von Willebrand factor" (a protein that helps platelets stick together)
• Can affect anyone (boys or girls)
• Causes nosebleeds, easy bruising, heavy periods
• Often mild; treated with a medication called DDAVP or clotting factor injections

Acquired Bleeding (from other causes):

• Liver disease (liver makes most clotting factors)
• Blood-thinning medications (warfarin, DOACs)
• Serious infections
• These can affect anyone at any age

Why Does It Matter?

Without treatment, bleeding disorders can cause:

• Joint damage from repeated bleeding (haemophilia)
• Dangerous bleeding after surgery or injury
• Rarely, life-threatening bleeding into the brain or abdomen

With treatment, most people with bleeding disorders can live normal, active lives.

How is it Treated?

For Haemophilia:

• Factor replacement: Injections of the missing clotting factor (like adding the missing cement)
• Prophylaxis: Regular injections 2-3 times a week to prevent bleeding (especially important for children)
• Home treatment: Many people learn to give their own injections at the first sign of bleeding
• Newer treatments: Long-acting injections (weekly or monthly) and other medications that help blood clot

For von Willebrand Disease:

• DDAVP: A medication (injection or nasal spray) that releases your body's stored clotting factors
• Tranexamic acid: Helps stabilize clots (stops them breaking down)
• Clotting factor injections if DDAVP doesn't work

For Bleeding on Blood Thinners:

• Stop the medication (temporarily)
• Reversal agents: Medications that quickly reverse blood thinners
• Vitamin K: For people on warfarin (takes 12-24 hours to work)

What to Expect

If You Have Haemophilia:

• Regular hospital visits to a specialist centre
• Injections 2-3 times a week if on prophylaxis
• Avoid contact sports (rugby, boxing), but most other activities are safe
• Medical alert bracelet
• Good dental care (to avoid extractions)
• Most people with haemophilia can work, study, and have families

If You Have von Willebrand Disease:

• Often only need treatment for surgery, dental work, or heavy periods
• Avoid aspirin and anti-inflammatory medications (make bleeding worse)
• Tell doctors/dentists before any procedures

When to Seek Help Urgently

Call 999 immediately if:

• Severe headache, vomiting, confusion (could be brain bleeding)
• Heavy bleeding that won't stop with pressure
• Bleeding after a head injury
• Severe abdominal pain
• Feeling dizzy, faint, or short of breath (could be major blood loss)
• Swollen, tense, painful muscle or limb

See Your Doctor Soon if:

• Easy bruising or frequent nosebleeds
• Heavy or prolonged periods
• Bleeding more than normal after cuts or dental work
• Joint swelling or pain (in haemophilia)

Living with a Bleeding Disorder

Good News:

• Modern treatments mean most people can live normal lives
• Prophylaxis prevents joint damage in haemophilia
• New treatments are easier to use (subcutaneous injections weekly/monthly)
• Gene therapy is being researched and may cure haemophilia in the future

Important:

• Always tell doctors, dentists, and paramedics about your bleeding disorder
• Carry a medical alert card or bracelet
• Avoid medications that increase bleeding (aspirin, ibuprofen) unless approved by your doctor
• If you have haemophilia, get vaccinations by injection under the skin (not into muscle)

Support and Resources

• Haemophilia centres: Specialist teams (doctors, nurses, physiotherapists) to support you
• Patient organizations: Support groups, information, advocacy
• Genetic counseling: If you're planning a family, to understand risks to children

Remember: With proper treatment and care, people with bleeding disorders can live full, active, and healthy lives. The key is early diagnosis, regular treatment, and prompt management of any bleeding.

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14. References

1. Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1-158. doi:10.1111/hae.14046

2. Leebeek FWG, Eikenboom JCJ. Von Willebrand's Disease. N Engl J Med. 2016;375(21):2067-2080. doi:10.1056/NEJMra1601561

3. Castaman G, Linari S. Diagnosis and Treatment of von Willebrand Disease and Rare Bleeding Disorders. J Clin Med. 2017;6(4):45. doi:10.3390/jcm6040045

4. Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016;388(10040):187-197. doi:10.1016/S0140-6736(15)01123-X

5. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. doi:10.1016/S0140-6736(13)62343-0

6. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. Br J Haematol. 2009;145(24):24-33. doi:10.1111/j.1365-2141.2009.07600.x

7. Laffan MA, Lester W, O'Donnell JS, et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol. 2014;167(4):453-465. doi:10.1111/bjh.13064

8. Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017;377(9):809-818. doi:10.1056/NEJMoa1703068

9. Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol. 2011;154(3):311-324. doi:10.1111/j.1365-2141.2011.08753.x

10. Sarode R, Milling TJ Jr, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128(11):1234-1243. doi:10.1161/CIRCULATIONAHA.113.002283

11. Pollack CV Jr, Reilly PA, van Ryn J, et al. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med. 2017;377(5):431-441. doi:10.1056/NEJMoa1707278

12. Connolly SJ, Crowther M, Eikelboom JW, et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2019;380(14):1326-1335. doi:10.1056/NEJMoa1814051

13. Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med. 2011;365(2):147-156. doi:10.1056/NEJMra1011170

14. Collins PW, Hirsch S, Baglin TP, et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007;109(5):1870-1877. doi:10.1182/blood-2006-06-029850

15. CRASH-2 trial collaborators, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. doi:10.1016/S0140-6736(10)60835-5

16. Nathwani AC, Reiss UM, Tuddenham EGD, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371(21):1994-2004. doi:10.1056/NEJMoa1407309

17. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-544. doi:10.1056/NEJMoa067659

18. Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004;104(5):1243-1252. doi:10.1182/blood-2004-02-0595

19. Chee YL, Crawford JC, Watson HG, Greaves M. Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures. Br J Haematol. 2008;140(5):496-504. doi:10.1111/j.1365-2141.2007.06968.x

20. Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014;370(9):847-859. doi:10.1056/NEJMra1208626

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Last Reviewed: 2026-01-10 | MedVellum Editorial Team - Haematology

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and current guidelines. This information is not a substitute for professional medical advice, diagnosis, or treatment.