Mainly aimed to Idiopathic (unprovoked) DVT.

Diagnosis and Management of Recurrent Venous Thromboembolism

Evidence-based data provides much-needed guidance.

Recurrences of venous thromboembolism (VTE), which occur in as many as 10% of patients with previously unprovoked thromboses, are often difficult to differentiate from residual clots. However, distinguishing between the two conditions is critical because diagnoses of recurrent VTE imply commitment to life-long anticoagulation. Moreover, when recurrent VTE is diagnosed in a patient who is already receiving anticoagulant therapy, the clinician is faced with a therapeutic dilemma: Should the anticoagulant drug dose be increased, should a different anticoagulant be prescribed, or should an inferior vena cava filter be inserted? Two recent studies provide evidence-based data to assist in diagnosing recurrent VTE and in managing patients with the condition.

In the first study, to develop a prediction model for VTE recurrence, Canadian investigators conducted a multicenter prospective cohort trial involving 398 patients (mean age, 53) who were treated with standard anticoagulant therapy for 5 to 7 months after first episodes of unprovoked VTE. After treatment, patients who initially had deep venous thrombosis (DVT) underwent compression ultrasonography (CUS), and those who had pulmonary embolisms (PEs) received ventilation-perfusion (V/Q) scans. Recurrent DVT was diagnosed if a new noncompressible site was discovered or if the diameter of a preexisting clot had increased by ≥4 mm; recurrent PE was diagnosed if the V/Q scan showed a new mismatched segmental defect or a more pronounced perfusion defect. Patients with nondiagnostic test results had serial CUS, venography, or lung CT scans. Patients with negative test results were not given anticoagulants and were reassessed after 3 months.

During follow-up, recurrent VTE was confirmed in 106 (26.6%) of 398 suspected recurrent VTE events. Of the 284 patients who were not treated after obtaining negative test results, only 8 (2.8%; 95% confidence interval, 1.4%–5.5%) had recurrent VTE; 6 of these patients had superficial thrombophlebitis at the time of suspected recurrence. The investigators concluded that obtaining CUS or V/Q scans after discontinuation of initial anticoagulation and repeating testing if new signs or symptoms appear can safely exclude recurrent VTE; however, if patients with negative test results also have evidence of superficial thrombophlebitis, anticoagulant therapy should be given.

In the second study, a Canadian team that included some of the same researchers performed a retrospective cohort study of the management of 70 cancer patients (median age, 60; 30% had lung cancer; 63% had metastatic disease) in whom VTE recurrences occurred after initial unprovoked episodes. At time of recurrence, two thirds of the patients began receiving low molecular weight heparin (LMWH) and one third began receiving a vitamin K antagonist (VKA). The investigators tested an LMWH dose-initiation or dose-escalation strategy: Patients receiving a VKA or low doses of LMWH were switched to full doses of LMWH; patients receiving less than full doses of LMWH were switched to full doses; and patients receiving full doses of LMWH had doses increased by 20% to 25%. After 4 weeks, LMWH doses were reduced to 75% of the full dose.

During 3-month follow-up, a second recurrent VTE occurred in only 6 patients (8.6%; 95% CI, 4.0%–17.5%) and bleeding complications occurred in only 3 patients (4.3%; 95% CI, 1.5%–11.9%). VTE recurrence portended poor prognosis: Median time between recurrence and death was only 11.4 months.

Comment: Results of these two studies provide much-needed guidance for the diagnosis and management of VTE recurrence. Clinicians should consider performing repeat CUS, V/Q scans, or CT scans in patients with initial unprovoked VTE whose anticoagulation is discontinued. Comparison of new images with those previously obtained can provide evidence to confirm or exclude new disease. If recurrent thrombosis is diagnosed in a patient who is already receiving anticoagulants, switching from an oral anticoagulant to LMWH or escalating the LMWH dose seems to control the condition safely.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology June 23, 2009

Citation(s):

Le Gal G et al. Validation of a diagnostic approach to exclude recurrent venous thromboembolism. J Thromb Haemost 2009 May; 7:752.

Medline abstract (Free)

Carrier M et al. Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients. J Thromb Haemost 2009 May; 7:760.

Medline abstract (Free)