This potential to diagnose occult malignancy in patients with idiopathic thromboembolic events stimulates debate around the usefulness of extensive cancer screening for these patients. One large systematic review compared routine and extensive cancer screening strategies following an unprovoked VTE. An extensive screening strategy consisting of CT scans of the abdomen and pelvis significantly increased the proportion of previously undiagnosed cancers; however, the authors did not determine complication rates, cost effectiveness, or difference in morbidity and mortality associated with extensive screening strategies.7
Other studies have demonstrated that extensive screening with CT, endoscopy, and tumor markers finds more previously undetected cancers; however, up to half of these malignancies could have been identified without resorting to such expensive and invasive workups.12 Additionally, no prospective data demonstrate improved outcomes or increased survival from these diagnoses. Likewise, no cost-effectiveness data exist to support this expensive and aggressive screening approach.7
All patients with an idiopathic VTE should undergo a complete history and physical examination with attention to common areas of malignancy. Patients should have basic lab work and be recommended for age-appropriate cancer screening (see Table 2). Any abnormalities uncovered on this initial workup should be aggressively investigated.13 If overt cancer is detected, then low molecular weight heparin would be preferred over oral anticoagulation as treatment for the VTE.14 Extensive malignancy evaluation in all patients with unprovoked VTE is not warranted, however, given the lack of data regarding efficacy of extensive screening, the potential for increased harms, and the costs associated with this approach.
Antiphospholipid syndrome: Antiphospholipid syndrome is the most common acquired cause of thrombophilia.15 Characterized by the presence of antiphospholipid antibodies (e.g. lupus anticoagulant antibodies or anticardiolipin antibodies), this syndrome is usually secondary to cancer or an autoimmune disease.
Antiphospholipid antibody syndrome is a thrombophilic disorder in which both venous and arterial thrombosis may occur. Patients with this disorder are considered at high risk for thrombotic events. Data suggest that antiphospholipid antibody syndrome also increases the risk of VTE recurrence. In one retrospective study, cessation of warfarin therapy in patients with antiphospholipid antibodies after a VTE resulted in 69% of patients having recurrent thrombosis in the first year.16 Given this substantial risk, antiphospholipid antibody testing is recommended in those with a suggestive history, including patients with 1) recurrent fetal loss, 2) fetal loss after 10 weeks, or 3) known collagen vascular disease.16 Lifelong anticoagulation is recommended for these patients.
Inherited hypercoagulable states: The most frequent causes of an inherited hypercoagulable state are the factor V Leiden mutation and the prothrombin gene mutation, accounting for 50% to 60% of hereditary thrombophilias. Protein S, protein C, and antithrombin defects account for most of the remaining cases of inherited thrombophilias.15
Currently, there is no consensus regarding who should be tested for inherited thrombophilia. Testing for an inherited thrombophilia would be indicated if the results added prognostic information or changed management. Arguments against testing hinge on the fact that neither prognosis nor management is affected by the presence of an inherited thrombophilia.
The presence of a thrombophilia also does not change the method or intensity of anticoagulation.17 The risk of recurrence after discontinuing anticoagulation therapy is not affected.17,18 The strongest predictor of VTE recurrence is the unprovoked VTE itself, regardless of an underlying thrombophilia.15 Recurrent VTE is nearly twice as frequent in patients with idiopathic VTE compared to those with provoked VTE.15