Predictors of active cancer thromboembolic outcomes: validation of the Khorana score among patients with lung cancer.

UNLABELLED: Essentials Venous thromboembolism (VTE) prevention strategies require effective risk assessment models. We sought to validate the Khorana Risk Score (KRS) in patients with lung cancer. A high KRS was not predictive of VTE but was independently associated with all-cause mortality. Our findings stress the need for a lung cancer-specific VTE risk assessment model. SUMMARY: Objectives Lung cancer is strongly associated with venous thromboembolism (VTE), but primary prevention against VTE is not a validated management strategy. Risk assessment models will be necessary for efficient implementation of preventative strategies. Materials and methods Utilizing a prospectively collected lung cancer database, we aimed to validate the Khorana Risk Score (KRS) in the prediction of VTE among patients with lung cancer. VTE events were retrospectively identified by reviewers unaware of the clinical prediction score calculation. The association between KRS and the risk of VTE was examined using cumulative incidence function with competing risk models. Mortality prediction was evaluated as a secondary outcome. Results We included 719 patients in our review. The patients were predominantly older men with non-small cell lung cancer and 40% had metastatic disease at inception. The median follow-up was 15.2 months. There were 83 VTEs (11.5%) and 568 (78.8%) patients died. A high KRS (cumulative incidence, 12.4%; 95% confidence interval [CI], 6.4-20.5%) was not associated with VTE compared with an intermediate score (cumulative incidence, 12.1%; 95% confidence interval, 9.5-15.0%) in both univariate and multivariable analyses. However, a high KRS was a predictor of mortality (hazard ratio, 1.7; 95% CI, 1.4-2.2). Conclusions Among patients with lung cancer, the KRS did not stratify the patients at the highest risk of VTE. Improved risk stratification methods are needed for this group of patients prior to implementing a primary prevention strategy.

Shear stress-associated acquired von Willebrand syndrome in patients with mitral regurgitation.

BACKGROUND: Mitral valve regurgitation is associated with an acquired hemostatic defect. OBJECTIVE: We sought to assess the prevalence and severity of acquired von Willebrand syndrome in patients with native valve mitral regurgitation (MR). PATIENTS/METHODS: Fifty-three patients were prospectively observed with bleeding questionnaires and laboratory tests when undergoing an echocardiographic assessment of MR. In patients referred for mitral valve surgery, testing was repeated postoperatively. RESULTS: Echocardiography identified 13 patients with mild MR, 14 with moderate MR, and 26 with severe MR. Among patients with mild, moderate or severe MR, loss of the highest molecular weight von Willebrand factor (VWF) multimers occurred in 8%, 64%, and 85%, respectively, median platelet function analyzer collagen ADP closure times (PFA-CADPs) were 84 s (interquartile range [IQR] 73-96 s), 156 s (IQR 104-181 s), and 190 s (IQR 157-279 s), respectively, and the ratios of VWF latex activity to antigen were 0.92 (IQR 0.83-0.97), 0.85 (IQR 0.76-0.89), and 0.79 (IQR 0.75-0.82), respectively (all P < 0.001). Nine patients reported clinically significant bleeding, and seven had intestinal angiodysplasia and transfusion-dependent gastrointestinal bleeding (Heyde syndrome), with the median number of transfusions required being 20 (IQR 10-33; range 4-50). In patients who underwent mitral valve repair (n = 13) or replacement (n = 7), all measures of VWF function reported above improved significantly. CONCLUSION: The high-shear environment of moderate to severe MR is sufficient to produce prevalent perturbations in VWF activity. Acquired von Willebrand syndrome may occur in this setting, and appears to be reversible with mitral valve surgery.

Iliac vein thrombosis: feasibility assessment of randomized controlled trials of endovascular pharmacomechanical thrombolysis.

BACKGROUND: Optimal treatment for iliac vein thrombosis has not been established by randomized clinical trials largely owing to difficulty in patient recruitment. To assess the feasibility of a prospective randomized trial of thrombolysis and stenting, we determined the incidence of iliac vein thrombosis and randomization eligibility based on criteria for two ongoing trials. METHODS: All patients with incident leg deep vein thrombosis during the calendar year 2005 seen at the Mayo Clinic were identified to determine the frequency of iliac vein involvement and the number undergoing endovascular therapies. Each patient was assessed for eligibility for potential randomization into a theoretic trial of thrombolytic therapy. RESULTS: Ninety-five (of 394) patients had iliac vein involvement. Of these, only nine patients would have been suitable for randomization. Of the remaining 86 patients, prolonged symptom duration (n = 28), active cancer (n = 24) and advanced age (n = 19) were the most common exclusion criteria. Of 31 patients who had intervention, 75% had at least one contraindication for randomization. CONCLUSIONS: Despite a philosophy of aggressive treatment for iliac vein thrombosis at this institution, the number of cases that could potentially be randomized into a clinical trial is relatively small. Trial design may require either multicenter cooperation or exclusion criteria revision for adequate recruitment.

Thrombophilia differences in cerebral venous sinus and lower extremity deep venous thrombosis.

OBJECTIVE: To characterize differences in the prevalence of thrombophilic variables in a large cohort of patients with cerebral venous sinus thrombosis (CVST) and lower extremity deep vein thrombosis (DVT). METHODS: An inception cohort of individuals was identified with first lifetime incident CVST between 1995 and 2005 for whom comprehensive thrombophilia testing was available. To test the hypothesis that thrombophilia prevalence differs with respect to thrombus location, test results were compared to a randomly selected group of patients with lower extremity DVT with comprehensive thrombophilia testing. RESULTS: During this time period, 163 patients with CVST were identified who underwent comprehensive thrombophilia testing. Thrombophilia results were abnormal in 29% including anticardiolipin antibodies (17%), heterozygous factor V Leiden (10%), and heterozygous prothrombin G20210A mutation (n = 14/122; 11%). The prothrombin mutation was more than twice as common in patients with CVST (p = 0.04). Activated protein C resistance, factor V Leiden, and protein C deficiency were more common in patients with DVT (p < 0.05 for each comparison). The anticardiolipin antibodies in patients with CVST were primarily low titer IgM isotype. CONCLUSION: The prevalence of selected thrombophilia factors differs comparing patients with cerebral venous sinus thrombosis and deep vein thrombosis. These differences may offer insights into mechanisms governing the geographic distribution of venous thrombosis.