Treatment of Established DVT and PE

The most effective and economical approach to decreasing the burden of venous thromboembolism (VTE) is to prevent the development of deep vein thrombosis (DVT) in patients at high risk.³ However, DVT continues to be a common problem in hospitalised patients because of underutilisation of prophylaxis therapy.⁵⁷ DVT also develops spontaneously in many nonhospitalised patients, whose initial presenting medical problem is either DVT or pulmonary embolism (PE). Prompt diagnosis and treatment of DVT are essential to decrease the risk of potentially fatal PE.²⁰

The goals of treatment are symptom relief, prevention of PE, and prevention of DVT recurrence. Initial treatment is either unfractionated heparin by continuous intravenous infusion, low-molecular-weight heparin (LMWH) by subcutaneous injection (once or twice daily), or fondaparinux by once-daily injections followed by treatment with an oral anticoagulant.²⁰ Major risks associated with heparin are bleeding complications and heparin-induced thrombocytopenia (HIT); these risks are lower with LMWHs and fondaparinux. Patients with a history of HIT should receive an alternative anticoagulant, such as argatroban, lepirudin, or danaparoid. Osteoporosis is another potential adverse effect when heparin is administered for longer than a month. Acute treatment of DVT with thrombolytic therapy should be reserved for patients with limb-threatening thrombosis and a low risk of bleeding.²⁰

Long-term treatment generally requires a transition from heparin or fondaparinux to a vitamin K antagonist (VKA), such as warfarin. VKAs have a delayed onset of anticoagulant effect; following initiation of VKA therapy, heparin can be discontinued once the INR has reached the therapeutic range (2.0 to 3.0).²⁰ Treatment with warfarin for four weeks to twelve months has been shown to reduce the risk of DVT recurrence by 90%. One exception to this general approach is the cancer patient with DVT, in whom long-term treatment with warfarin is less effective in preventing recurrence. LMWH, shown in one study to be roughly twice as effective in preventing this outcome, should be considered in these patients.¹²⁰

Patient Type	Drug	Duration
* Consideration should be given to continuing past 12 months ** Recommended continuation of therapy indefinitely or until cancer resolves
First episode VTE/PE secondary to transient or reversible condition	VKA	At least 3 months
First episode idiopathic VTE/PE	VKA	6-12 months*
Cancer and first episode VTE/PE	LMWH	3-6 months**
First episode VTE/PE and documented thrombophilia condition	VKA	6-12 months*
First episode VTE/PE and antiphospholipid antibodies or 2 thrombophilia conditions	VKA	12 months*
2 or more episodes of DVT/PE	VKA	Indefinite

Compression stockings have also been evaluated for the prevention of post-thrombotic syndrome in patients with VTE. Limited evidence for the efficacy of graduated compression stockings (GCS) in the prevention of post-thrombotic syndrome includes three studies, two of which showed a significant effect. An 800-patient, randomised, double-blind trial is planned to evaluate GCS in the prevention of post-thrombotic syndrome after proximal DVT.¹²¹

For patients with contraindications to anticoagulation, the short-term risk of PE can be reduced by insertion of a filter into the vena cava. However, in one study of 400 patients with vena caval filters, this protective effect did not persist after two years.¹²²

PE can be difficult to diagnose, as the symptoms and signs associated with the condition are not specific. Because of the diagnostic challenges, a number of clinical scoring systems have been devised to help assess the likelihood that a patient has suffered PE and to stratify the associated risks.^{63, 123} These scoring systems incorporate clinical status, lab results (eg, D-dimer assays), imaging study results, and patient characteristics.

The clinical severity of PE varies depending on the patient’s baseline cardiopulmonary reserve, the size of the embolus, and the degree to which the embolus occludes the pulmonary circulation. A massive embolus can cause cardiogenic shock, while small emboli may be asymptomatic. Treatment is based on the patient’s status. For patients with suspected massive PE and cardiogenic shock, treatment options include anticoagulation plus either thrombolytic therapy or embolectomy (via catheterisation or surgery).⁶³ For a haemodynamically stable patient with PE, anticoagulation with a heparin product, followed by an oral VKA anticoagulant, is the standard or care.

The duration of anticoagulation depends on the aetiology of the PE (see table above). For patients whose PE is linked to surgery, trauma, or immobilisation, three to six months of treatment is adequate.^{63, 124} The benefit of treatment beyond 12 months for patients with idiopathic VTE or VTE associated with thrombophilia is not certain, and treatment decisions in these patients must be individualised.⁴¹