Key Facts

Haemostasis involves a coordinated interplay between blood vessels, platelets, and the coagulation cascade, balanced by natural anticoagulant and fibrinolytic mechanisms. Disturbances lead to either bleeding or thrombosis.

Epidemiology

VTE (DVT and PE) affects approximately 1-2 per 1,000 population per year in the UK. Haemophilia A affects approximately 1 in 5,000 male births. Von Willebrand disease is the most common inherited bleeding disorder, affecting approximately 1% of the population (most mild). DIC complicates approximately 1% of hospital admissions.

Aetiology

Bleeding disorders:

• Platelet defects: Thrombocytopenia (ITP, TTP/HUS, drugs), platelet dysfunction (aspirin, uraemia)
• Coagulation factor deficiency: Haemophilia A/B, liver disease, vitamin K deficiency, DIC
• Vascular: Hereditary haemorrhagic telangiectasia, vasculitis, scurvy

Thrombotic disorders:

• Inherited thrombophilia: Factor V Leiden (~5% of Caucasians), prothrombin G20210A, protein C/S deficiency, antithrombin deficiency
• Acquired: Antiphospholipid syndrome, malignancy, immobility, oestrogen, surgery

Pathophysiology

Primary haemostasis: Endothelial injury → vWF released → platelet adhesion via GPIb receptor → platelet activation (shape change, granule release: ADP, TXA2) → platelet aggregation via GPIIb/IIIa bridged by fibrinogen

Secondary haemostasis (cell-based model):

• Initiation: TF-VIIa complex generates small amount of thrombin
• Amplification: Thrombin activates platelets, factors V, VIII, XI on platelet surface
• Propagation: Burst of thrombin generation → fibrinogen → fibrin; factor XIII cross-links fibrin

Natural anticoagulants: Antithrombin (heparin cofactor), protein C/S (inactivate Va, VIIIa), TFPI Fibrinolysis: Plasmin degrades fibrin → D-dimers released

Platelet/Primary Haemostasis Disorders

• Mucocutaneous bleeding: Petechiae, purpura, epistaxis, menorrhagia, GI bleeding
• Immediate bleeding after trauma
• Bruising out of proportion to injury

Coagulation/Secondary Haemostasis Disorders

• Deep tissue bleeding: Haemarthroses, muscle haematomas, retroperitoneal bleeds
• Delayed bleeding after trauma or surgery
• Prolonged bleeding from surgical wounds

DIC

• Simultaneous bleeding AND thrombosis
• Petechiae, oozing from venepuncture sites, organ failure from microvascular thrombosis
• Underlying trigger: Sepsis, obstetric emergencies, malignancy, trauma

Red Flags

• Spontaneous haemarthrosis in a child — suspect haemophilia
• New petechiae with rapidly falling platelets — consider TTP/HUS (ADAMTS13)
• Post-operative bleeding with prolonged APTT — exclude acquired factor VIII inhibitor
• Purpura fulminans — consider meningococcal sepsis, protein C deficiency

Bedside

• Observation: Pattern of bleeding (mucocutaneous vs deep tissue)
• Blood pressure: Assess haemodynamic stability

Bloods

• FBC: Platelet count — <150 × 10⁹/L is thrombocytopenia
• Coagulation screen: PT/INR, APTT, fibrinogen
• D-dimer: Raised in DIC, VTE (sensitive but not specific)
• Blood film: Schistocytes (MAHA), platelet morphology
• Mixing studies: APTT corrects = factor deficiency; does not correct = inhibitor (e.g., lupus anticoagulant)
• Factor assays: VIII, IX, vWF antigen and activity
• Thrombophilia screen: Factor V Leiden, prothrombin mutation, protein C/S, antithrombin, antiphospholipid antibodies — test >3 months after acute event, off anticoagulation

Imaging

• Ultrasound: Joint haemarthrosis, DVT assessment
• CTPA: Pulmonary embolism

Special Tests

• Thromboelastography (TEG/ROTEM): Point-of-care viscoelastic testing — guides transfusion in major haemorrhage
• PFA-100: Platelet function analyser — screens for platelet dysfunction/vWD

Non-pharmacological

• Pressure and elevation for acute bleeding
• Avoid NSAIDs and IM injections in bleeding disorders
• Medical alert bracelet for severe haemophilia
• Joint protection and physiotherapy for haemophilic arthropathy

Pharmacological

• Haemophilia A: Factor VIII replacement (recombinant); prophylaxis: 25-40 IU/kg 3×/week; emicizumab (bispecific antibody) for prophylaxis
• Haemophilia B: Factor IX replacement; prophylaxis: 25-40 IU/kg 2×/week
• Von Willebrand disease: Desmopressin (DDAVP) 0.3mcg/kg IV for type 1; vWF-containing factor VIII concentrates for type 2/3
• ITP: Observation if mild; prednisolone 1mg/kg/day; IVIg 1g/kg if urgent; rituximab or TPO-receptor agonists (eltrombopag, romiplostim) for chronic
• DIC: Treat underlying cause; replace factors (FFP, cryoprecipitate if fibrinogen <1.5g/L), platelets if <50 and bleeding
• Warfarin reversal: Vitamin K 5mg IV; prothrombin complex concentrate (Beriplex) 25-50 IU/kg for major bleeding
• VTE treatment (NICE NG158): Apixaban 10mg BD for 7 days then 5mg BD, or rivaroxaban 15mg BD for 21 days then 20mg OD

Referral Criteria

• Suspected inherited bleeding disorder — haematology
• Recurrent VTE or unprovoked VTE — thrombophilia assessment
• TTP — urgent haematology/plasma exchange

• Haemophilia A: Life expectancy near-normal with modern factor replacement; joint disease remains major morbidity
• ITP in children: >80% resolve spontaneously within 6 months; adult ITP is usually chronic
• TTP: Mortality 90% untreated; 10-20% with plasma exchange
• DIC: Mortality 40-80% depending on underlying cause; sepsis-associated DIC has highest mortality
• Factor V Leiden heterozygosity: ~4-7× increased VTE risk; homozygosity ~80× increased risk

Coagulation Cascade Summary

Vitamin K-Dependent Factors