Treatment of Established DVT and PE

Prompt diagnosis and treatment are critical

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

Goals of DVT treatment: symptom relief, prevention of recurrence

The goals of treatment are symptom relief, prevention of PE, and prevention of DVT recurrence, according to DVT treatment guidelines. 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

Optimal duration of anticoagulation following DVT⁴¹

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

The use of mechanical devices

Compression stockings have also been evaluated for the prevention of post-thrombotic syndrome in patients with DVT. 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, filter insertion was not found to confer a protective effect against PE after two years, and there was an increased risk of DVT in the patients with filters.¹²²

Treatment during pregnancy

The optimal treatment of VTE during and after pregnancy has not been studied in randomised controlled trials, and DVT treatment guidelines are based on expert opinion. According to current guidelines, women with a personal history of DVT or PE or known thrombophilia should start anticoagulant therapy as early as possible during pregnancy.¹⁶¹ Current therapy includes LMWHs or unfractionated heparin (UFH).¹⁶¹ Warfarin also is an option after childbirth.¹⁶¹ The recommended treatment duration for anticoagulants during pregnancy ranges from 3 to 6 months, including 6 weeks after childbirth.^{161, 182} Women receiving adjusted-dose LMWH or UFH should discontinue heparin injections at the onset of labour to decrease the risk of bleeding complications.¹⁸²

Treatment of pulmonary embolism

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 assess the likelihood that a patient has suffered a PE.^{63, 123} These clinical 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 or fondaparinux, 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

Treatment of chronic thromboembolic pulmonary hypertension

Pulmonary hypertension — chronically elevated blood pressure in the pulmonary circulation — occurs as a late complication in 3% to 4% of patients who survive PE.⁷⁷ Pulmonary endarterectomy (PTE, also known as PEA) is the first choice of treatment for chronic thromboembolic pulmonary hypertension.²¹⁹ During this surgical procedure, thrombosis and scar material is removed from the pulmonary arterial tree.²⁷² PTE is relatively safe, and long-term survival, functional status and exercise capacity improve significantly.²¹⁹ The most common postoperative complication is reperfusion pulmonary oedema.²⁷² PTE is currently recommended over lung transplantation, which is associated with high morbidity and mortality.²⁷²

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Article references

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120 - Lee AY, Levine MN, Baker RI, et al;.Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349(2):146-153.
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121 - Kahn SR, Shbaklo H, Shapiro S, et al; SOX Trial Investigators. Effectiveness of compression stockings to prevent the post-thrombotic syndrome (the SOX Trial and Bio-SOX biomarker substudy): a randomized controlled trial. BMC Cardiovasc Disord. 2007;7:21. http://www.biomedcentral.com/1471-2261/7/21. Accessed April 30, 2008.
122 - Decousus H, Leizorovicz A, Parent F, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med. 1998;338(7):409-415.
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Prophylaxis: The prevention of a disease or pathological condition.
Venous thromboembolism: A condition in which a blood clot (thrombus) forms in a vein, which in some cases then breaks free and enters the circulation as an embolus, finally lodging in and completely obstructing a blood vessel, e.g., in lungs causing a PE. The term encompasses both DVT and PE.
Fondaparinux: An indirect Factor Xa inhibitor comprising a synthetic pentasaccharide sequence matching the part of the heparin molecule that binds to antithrombin. It is administered by subcutaneous injection.
Heparin: An anticoagulant that exerts its activity by binding to antithrombin and greatly increasing its activity. The principal coagulation factors inhibited by heparin are Factors IIa and Xa. It is administered by intravenous or subcutaneous injection.
Intravenous: Administration of liquid substances directly into the venous part of the bloodstream.
Subcutaneous: Below the skin.
Vitamin K: An essential cofactor in the carboxylation of glutamic residues on the procoagulant forms of Factors II, VII, IX, and X. This ultimately leads to increased formation of thrombin and fibrin.
Warfarin: A vitamin K antagonist. Most commonly used oral anticoagulant in chronic prevention or treatment of VTE.
International Normalised Ratio: A system for standardising the reports of blood clotting tests and used to monitor the effects of warfarin. INR values should remain within 2.0–3.0 to ensure optimal safety and efficacy in patients with atrial fibrillation.
Low-molecular-weight heparin: An anticoagulant derived from unfractionated heparin (UFH), containing only the low-molecular-weight molecules of heparin. It binds to antithrombin, greatly increasing its activity. It inhibits coagulation Factor Xa and, to a lesser extent, Factor IIa. LMWHs are administered by subcutaneous injection.
Vitamin K antagonists: Vitamin K antagonists block the regeneration of the reduced form of vitamin K.
Post-thrombotic syndrome: A syndrome that can follow a vascular thrombosis. Clinical signs and symptoms of this syndrome include chronic pain, swelling, oedema, discolouration, and in severe cases, venous ulceration. It is likely that valvular incompetence is associated with the clinical manifestations of post-thrombotic syndrome.
Unfractionated heparin: An anticoagulant that exerts its activity by binding to antithrombin and greatly increasing its activity. The principal coagulation factors inhibited by UFH are Factors IIa and Xa. It is administered by intravenous or subcutaneous injection.
Hypertension: Persistently high arterial blood pressure. Hypertension may have no known cause (essential or idiopathic hypertension) or be associated with other primary diseases (secondary hypertension). This condition is considered a risk factor for the development of heart disease, peripheral vascular disease, stroke, and kidney disease.
Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body, usually used to describe demonstrable accumulation of excessive fluid in subcutaneous tissues.