Recurrent bleeding and thrombotic events after resumption of oral anticoagulants following gastrointestinal bleeding: Communication from the ISTH SSC Subcommittee on Control of Anticoagulation.

BACKGROUND: Gastrointestinal bleeding frequently complicates anticoagulant therapy causing treatment discontinuation. Data to guide the decision regarding whether and when to resume anticoagulation based on the risks of thromboembolism and recurrent bleeding are scarce. OBJECTIVES: We aimed to retrospectively evaluate the incidence of these events after anticoagulant-related gastrointestinal bleeding and assess their relationship with timing of anticoagulation resumption. METHODS: Patients hospitalized because of gastrointestinal bleeding during oral anticoagulation for any indication were eligible. All patients were followed up to 2 years after the index bleeding for recurrent major or clinically relevant non-major bleeding, venous or arterial thromboembolism, and mortality. RESULTS: We included 948 patients hospitalized for gastrointestinal bleeding occurring during treatment with vitamin K antagonists (n = 531) or direct oral anticoagulants (n = 417). In time-dependent analysis, anticoagulant treatment was associated with a higher risk of recurrent clinically relevant bleeding (hazard ratio [HR] 1.55; 95% confidence interval [CI] 1.08-2.22), but lower risk of thromboembolism (HR 0.34; 95% CI 0.21-0.55), and death (HR 0.50; 95% CI 0.36-0.68). Previous bleeding, index major bleeding, and lower glomerular filtration rate were associated with a higher risk of recurrent bleeding. The incidence of recurrent bleeding increased after anticoagulation restart independently of timing of resumption. CONCLUSIONS: Anticoagulant treatment after gastrointestinal bleeding is associated with a lower risk of thromboembolism and death, but higher risk of recurrent bleeding. The latter seemed to be influenced by patient characteristics and less impacted by time of anticoagulation resumption.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer disease. The risk is further increased by chemotherapy but the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 3 May 2011) and CENTRAL (2011, Issue 2). The authors searched clinical trials registries and reference lists of relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), direct thrombin inhibitors, direct factor Xa inhibitors or mechanical intervention to no intervention or placebo; or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS: Data were extracted on methodological quality, patients, interventions and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. MAIN RESULTS: Nine RCTs with a total of 3538 patients were considered. None of the RCTs tested UFH, fondaparinux, direct factor Xa inhibitors or mechanical interventions. Overall, the risk of bias was low in most of the studies. LMWH, when compared with inactive control, significantly reduced the incidence of symptomatic VTE (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.41 to 0.93) with no evidence of heterogeneity (I(2) = 0%). The number needed to treat to prevent a symptomatic VTE was 60. LMWH was associated with a 60% increase in major bleeding when compared with inactive control, although this was not statistically significant (RR 1.57, 95% CI 0.69 to 3.60; I(2) = 10%). There was a 45% reduction in overall VTE (RR 0.55, 95% CI 0.34 to 0.88; I(2) = 0%) while for symptomatic pulmonary embolism, asymptomatic VTE, minor bleeding and one-year mortality the differences between the LMWH and control groups were not statistically significant. The effect of the vitamin K antagonist warfarin on preventing symptomatic VTE, measured in only one study, was not statistically significant (RR 0.15, 95% CI 0.02 to 1.20). In one RCT of patients with myeloma, LMWH was associated with a 67% reduction in symptomatic VTE (RR 0.33, 95% CI 0.14 to 0.83) compared with warfarin, with no differences in major bleeding. Antithrombin, evaluated in one study on paediatric patients, had no significant effect on VTE nor major bleeding when compared with inactive control. AUTHORS' CONCLUSIONS: Primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. However, the lack of power hampers definite conclusions on the effects on major safety outcomes, which mandates additional studies to determine the risk to benefit ratio of LMWH in this setting.

Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis.

Thrombophilia has been associated with pregnancy complications and recurrent miscarriage. The aim of this systematic review was to evaluate the controversial association between thrombophilia and failures of assisted reproduction technology (ART). A systematic search of the literature for studies reporting on thrombophilia in women undergoing ART up to April 2011 yielded 33 studies (23 evaluating anti-phospholipid antibodies, 5 inherited thrombophilia, and 5 both) involving 6092 patients. Overall, methodologic quality of the studies was poor. Combined results from case-control studies showed that factor V Leiden was significantly more prevalent among women with ART failure compared with fertile parous women or those achieving pregnancy after ART (odds ratio = 3.08; 95% confidence interval, 1.77-5.36). The prothrombin mutation, methylenetetrahydrofolate reductase mutation, deficiency of protein S, protein C, or anti-thrombin were all not associated with ART failure. Women with ART failure tested more frequently positive for anti-phospholipids antibodies (odds ratio = 3.33; 95% confidence interval, 1.77-6.26) with evidence of high degree of between-study heterogeneity (I(2) = 75%; P < .00001). Prospective cohort studies did not show significant associations between thrombophilia and ART outcomes. Although case-control studies suggest that women experiencing ART failures are more frequently positive for factor V Leiden and anti-phospholipid antibodies, the evidence is inconclusive and not supported by cohort studies.

Obesity, poor muscle strength, and venous thromboembolism in older persons: the InCHIANTI study.

BACKGROUND: Both obesity and the decline in muscle strength, which often occur with aging, are accompanied by functional and metabolic changes that may affect the risk of thrombosis. This study evaluated whether obesity and poor muscle strength are associated with venous thromboembolism (VTE). METHODS: Objectively confirmed VTEs were assessed at baseline and more than a 6-year follow-up in 1,045 participants more than or equal to 60 years enrolled in the InCHIANTI study. RESULTS: At baseline, 97 participants had a positive history of VTE. Obese participants were almost twice more likely (odds ratio 1.76; 95% confidence interval 1.03-3.01) and obese with poor muscle strength were threefold more likely (odds ratio 2.99; 95% confidence interval 1.56-5.73) to have VTE compared with lean participants with normal strength. Fifty-five VTEs occurred during follow-up. History of VTE, obesity, and/or poor strength independently predicted new VTE events. In participants with previous VTE, the odds ratio (95% confidence interval) for thrombosis was 6.64 (1.92-22.95) with poor strength, 9.69 (3.13-30.01) in the obese, and 14.57 (5.16-41.15) in the obese with poor strength as compared with lean participants with normal strength. CONCLUSION: Obesity with or without poor muscle strength is a risk factor for VTE among older persons and significantly amplifies the risk of recurrent thrombosis.

Incidental venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

While the association between cancer and symptomatic venous thromboembolism (VTE) is well established, the incidence and risk factors for incidental VTE in cancer patients remain unclear. The medical records of 1,921 consecutive cancer patients starting chemotherapy from January 2003 up to March 2009 were identified. Patients with a positive history of VTE were excluded. Pre-existing signs of VTE, kind and stage of malignancy, first and subsequent lines of chemotherapy, and all follow-up computed tomography (CT) scans were analysed. The primary outcome was incidental VTE. Overall, there were 101 (5.3%) VTE, 62 (3.2%) incidental and 39 (2.0%) symptomatic during a median of eight months (range 3-72). The incidence on CT scans was 0.58% (95%CI: 0.44-0.74). Incidental VTE included 24 pulmonary embolism, 28 deep venous thrombosis of the extremities, and 10 thromboses of the cava or splanchnic veins. Half of the incidental VTE occurred in the first 3-6 months of chemotherapy with a relatively higher incidence in gynecological and lung cancers. The presence of metastases, high leukocyte count, and platin-based chemotherapy increased the risk up to three-fold. All patients with incidental VTE regardless the location received half to full therapeutic doses of low-molecular-weight heparin for a minimum of three months. In summary, incidental VTE is a relative common finding in patients with solid tumours, especially in the first months of chemotherapy. Further research is needed to understand the natural history of incidental thrombosis in order to develop adequate management guidelines.