Risk Factors for Venous Thromboembolism (VTE)

•    Virchow’s triad:

o    Stasis: immobility, long-haul travel, surgery

o    Endothelial injury: trauma, surgery, central lines

o    Hypercoagulability: pregnancy, malignancy, inherited thrombophilia

•    Other factors:

o    Oestrogen therapy: HRT, combined oral contraceptives

o    Obesity, smoking, increasing age

Thrombophilia

Inherited Thrombophilias:

•    Factor V Leiden mutation: most common inherited cause; activated protein C resistance

•    Prothrombin gene mutation (G20210A): ↑ thrombin production

•    Protein C deficiency

•    Protein S deficiency

•    Antithrombin III deficiency

•    Consider testing if:

o    Unprovoked VTE <40 years

o    Recurrent VTE

o    VTE in unusual sites (e.g. cerebral, mesenteric veins)

o    Strong family history

Acquired Thrombophilias:

•    Antiphospholipid syndrome

•    Malignancy

•    Nephrotic syndrome, myeloproliferative neoplasms

Antiphospholipid Syndrome (APS)

•    Features:

o    Arterial and venous thrombosis

o    Recurrent miscarriages

o    Livedo reticularis, thrombocytopenia

•    Antibodies:

o    Lupus anticoagulant (prolongs APTT but is prothrombotic)

o    Anti-cardiolipin

o    Anti-β2 glycoprotein I

•    Diagnosis: clinical + ≥1 antibody positive on 2 occasions 12 weeks apart

•    Management:

o    Lifelong anticoagulation (warfarin preferred) if thrombosis occurs

o    INR target 2.5–3.5 for recurrent events

Anticoagulants

Heparins:

•    Unfractionated heparin (UFH):

o    IV use, monitor APTT

o    Short half-life, reversible with protamine sulfate

•    Low molecular weight heparin (LMWH):

o    Subcutaneous, predictable dosing

o    No routine monitoring, but check anti-Xa levels in renal failure, obesity, pregnancy

Warfarin:

•    Vitamin K antagonist

•    Monitor INR (target 2.0–3.0 in most cases)

•    Interacts with many drugs and foods (esp. antibiotics, leafy greens)

•    Reversal: vitamin K, prothrombin complex concentrate (PCC)

Direct Oral Anticoagulants (DOACs):

•    Apixaban, rivaroxaban (factor Xa inhibitors)

•    Dabigatran (direct thrombin inhibitor)

•    No routine monitoring; adjust for renal function

•    Reversal:

o    Idarucizumab for dabigatran

o    Andexanet alfa (factor Xa inhibitor reversal)

Therapeutic Fibrinolysis (Thrombolysis)

•    Indications:

o    STEMI (if PCI unavailable within 120 mins)

o    Massive PE with haemodynamic instability

o    Ischaemic stroke: <4.5 hours from onset

•    Agents:

o    Alteplase (tPA): fibrin-specific

o    Streptokinase: antigenic; less commonly used now

•    Major bleeding risk, especially intracranial

Thrombosis and Hormonal Therapy

•    Oestrogen-containing therapy (OCP, HRT):

o    Increases VTE risk

o    Contraindicated in:

    Known thrombophilia

    History of VTE

    Strong family history of VTE

•    Progestogen-only contraceptives are safer alternatives