Pharmalogical Treatments

Bridging therapy – Heparins and fondaparinux

Most centres have an initial 4-5 day bridging regime of LMWH injections whilst loading with warfarin. Previous use of infusions of unfractionated heparin has been replaced by LMWH, which does not require daily monitoring and allows out-patient anticoagulation suitable for the vast majority of patients.  Unfractionated heparin still has a role in patients with significant renal impairment.

Fondaparinux is now licensed for the treatment of DVT when used in conjunction with warfarin. Trials have compared it with twice daily dosing of enoxaparin to which it is at least comparable.¹⁰

Bridging therapy with LMWH or fondaparinux should continue for at least 5 days or until the INR has been >2 for 24 hours, whichever is longer.⁴

Warfarin

Vitamin K antagonists were previously the mainstay of long-term treatment but are increasingly being replaced by NOACs.  Warfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z. There is a tendency towards a paradoxical pro-thrombotic state during the first few days of warfarin therapy during which time “bridging” therapy is required with a LMWH. This resolves from 36 hours onwards as the levels of stored clotting factors diminish.

Warfarin treatment should be continued for a minimum of three months.⁴ Extended use beyond three months should be considered in patients with an unprovoked (i.e. no clear causative factor) proximal DVT if the risk of recurrence is considered high and there is no major bleeding risk.⁴

Patients with active cancer should receive long term (6 months) anticoagulation with LMWH (rather than warfarin): achieving therapeutic warfarin levels is difficult in cancer patients due to the increased risk of drug interactions, malnutrition, vomiting, and liver dysfunction in these patients. Moreover, cancer patients are at an increased risk of adverse effects of warfarin therapy. In contrast, low-molecular-weight heparins (LMWHs) are associated with a lower risk of adverse events compared with warfarin in patients with cancer. At 6 months, the relative risks and benefits of continuing anticoagulation should be reassessed.⁴

Thrombolysis

Thrombolysis of venous clot is an option rarely used in the UK. In trials it is very effective in restoring blood flow and vessel patency and seems to significantly reduce the long-term post-thrombotic complications of DVT. It carries with it a risk of potentially serious bleeding. A recent meta-analysis supports the use of thrombolysis but the dosing and method of administration remains to be determined. Mortality is comparable to those treated with more conventional anti-coagulation.¹² Local intravascular injection of thrombolytic into the affected vein is an alternative to systemic thrombolysis.

NICE recommends the use of catheter-directed (i.e. local) thrombolytic therapy for highly selected patients: specifically, those with symptomatic iliofemoral DVT who have symptoms of less than 14 day’s duration, good functional status, a life expectancy of greater than one year and a low risk of bleeding.

Aspirin

Aspirin is not recommended for treatment of DVT.⁴

Fig.1 DVT or PE anticoagulation⁴