Nathalie Moulin

Thrombophilia and risk of venous thrombosis in patients with cancer

Venous thrombosis is a common and severe complication in patients with cancer. We reviewed studies assessing whether a state of acquired or congenital thrombophilia influenced the risk of thrombosis in patients with cancer. The results are equivocal. However, the majority of studies were of limited size. The influence of thrombophilia in patients with cancer may be more difficult to demonstrate than in the general population, the risk of thrombosis due to cancer per se possibly outweighing the contribution of thrombophilic factors. Moreover, the results may depend on the genetic background of the population, the type of cancer, the type of thrombosis, and the chemotherapeutic treatment. Nevertheless, it appears that factor V Leiden or G20210A prothrombin gene mutation increases the risk of venous thromboembolism about 2- to 4-fold, compared with patients with cancer without either of these mutations. Similar results were observed for the occurrence of central venous catheter-associated thrombosis. Antiphospholipid antibodies and acquired resistance to activated protein C were frequently observed in patients with cancer and appeared to favor the occurrence of thrombosis. The role of hyperhomocysteinemia deserves further investigation. Since the clinical implications of these findings remain to be clarified, routine screening of cancer patients for thrombophilia cannot yet be recommended on the basis of these studies. Studies designed to assess the value of thromboprophylaxis in high-risk patients, including thrombophilic patients, with long-term central venous catheters may be valuable.

Recent findings in the epidemiology, diagnosis and treatment of superficial-vein thrombosis

Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially impact its clinical management. Thus, the clear confirmation that SVT is closely linked to deep-vein thrombosis (DVT) or pulmonary embolism (PE) highlights the potential severity of the disease. DVT or PE are diagnosed in 20-30% of SVT patients. Moreover, clinically relevant symptomatic thromboembolic events complicate isolated SVT (without concomitant DVT or PE at diagnosis) in 4-8% of patients. For the first time, an anticoagulant treatment, once-daily 2.5 mg fondaparinux for 45 days, was demonstrated to be effective and safe for preventing these symptomatic thromboembolic events in patients with lower-limb isolated SVT in the randomized placebo-controlled CALISTO study. Based on these recent findings, new recommendations on the management of SVT patients, including complete ultrasonography examination of the legs, and in patients with isolated SVT, prescription of once-daily 2.5 mg fondaparinux subcutaneously for 45 days on top of symptomatic treatments, may be proposed.

Clinical efficacy and safety of fondaparinux in the prevention and treatment of venous and arterial thrombosis

Fondaparinux (Arixtra) is a synthetic, selective Factor Xa inhibitor. Its pharmacokinetic profile allows once-daily subcutaneous administration of the drug without any laboratory monitoring. The benefit-to-risk ratio of fondaparinux in the prevention of venous thromboembolism has been extensively studied in both surgical and acutely ill medical patients at risk of thrombosis. Its efficacy and safety have also been investigated in the initial treatment of symptomatic deep-vein thrombosis and pulmonary embolism. Finally, a number of Phase II trials investigated the safety and efficacy of fondaparinux in patients with acute coronary syndromes, and a large Phase III program is ongoing in this setting. This review focuses on the use of fondaparinux in the prevention and treatment of thromboembolic disorders.

Screening cancer after venous thromboembolism: How many abnormal tests before diagnosing cancer? An analysis of practice

INTRODUCTION Since Trousseau, we knows that venous thrombemboembolism (VTE) can reveal occult cancer. Different strategies of cancer screening have been evaluated: they are often time-consuming, cause stress and anxiety, and frequently require second-look examinations (due to the risk of false positives), with ultimately a very low yield (about 5%). We evaluated the number of suspect cancer tests before reporting them to the number of cancers finally diagnosed, after a VTE, in the setting of practices analysis. METHODS We studied retrospectively patients hospitalized for a VTE and with a cancer screening, between 2011 and 2012. Screening cancer was defined by performing at least one of the following tests: PSA, fecal occult blood test, mammography, abdominopelvic iconography (abdominal ultrasound and/or abdominal CT scan). We recorded the suspected cancer tests, the cancers diagnosed, their stage and the survival. These results were expressed as a percentage with a 95% confidence interval. RESULTS Out of the 491 patients treated for a VTE, screening cancer was performed on 295 patients (median age 66.2 years). Nineteen PSA (16.7%, 95% CI [10.3-25]) were abnormal, with 2 localized prostate cancers. Nineteen fecal occult blood tests (15.3%, 95% CI [9.5-23]) were positive, with 2 local cancers. Five mammograms suspected cancer (4.7% 95% CI [1.6-10.8]) for one confirmed. Thirty-eight abdomino-pelvic iconographies (14.4% 95% CI [10.4-19.2]) were suspect, with 7 confirmed cancers, 6 being metastatic at times of diagnostic. CONCLUSION Among the 607 tests performed, 81 were suspected of cancer (13.3%) for only 12 cancers confirmed (2.0%). Screening cancer exposes patients to several false positive tests.