Craig D. Seaman

Cost-effectiveness of rivaroxaban versus warfarin anticoagulation for the prevention of recurrent venous thromboembolism: a U.S. perspective.

INTRODUCTION Rivaroxaban is an oral direct factor Xa inhibitor that is noninferior to warfarin in the prevention of recurrent venous thromboembolism (VTE). Whether rivaroxaban is cost-effective in the prevention of recurrent VTE, however, is not known. MATERIAL AND METHODS To assess the cost effectiveness of rivaroxaban compared with warfarin in the prevention of recurrent VTE, we built a Markov state-transition model over a 10-year time horizon. The base case analysis consisted of a hypothetical cohort of 60-year-old patients with an initial VTE who received secondary prophylaxis with either rivaroxaban or warfarin for 3 to 12months. Cost estimates were derived from the Healthcare and Utilization Project and other sources. Probabilities were based on literature values. Outcomes included costs in 2011 United States dollars, quality-adjusted life-years (QALYs), and incremental cost effectiveness ratios (ICERs) over 10years from a societal perspective. RESULTS Compared with warfarin, the rivaroxaban strategy cost less (

Does Deficiency of von Willebrand Factor Protect Against Cardiovascular Disease? Analysis of a National Discharge Register

3,195 vs.

Venous thromboembolism in pregnant women with sickle cell disease: A retrospective database analysis☆

6,188) and was more effective (9.29 QALYs vs 9.14 QALYs). Our results were highly robust in sensitivity analyses. Warfarin was no longer dominated by rivaroxaban when the risk of major bleeding with rivaroxaban exceeds 3.8% (base case estimate: 0.96%). CONCLUSION In summary, prophylactic anticoagulation with rivaroxaban appears to be a cost effective, and perhaps cost saving, alternative to warfarin for the prevention of recurrent VTE.

Feasibility of the Von Willebrand disease PREVENT trial

von Willebrand factor (VWF) plays a critical role in platelet adhesion and aggregation after vascular injury and at sites of high shear rate. Elevated VWF levels are associated with an increased risk of ischemic cardiovascular events; however, it is unclear whether VWF deficiency is protective against atherosclerosis. We aimed to compare the prevalence of cardiovascular disease (CVD) among patients with and without von Willebrand disease (VWD).

Prevalence and Risk Factors Associated With Hypertension in Hemophilia: Cross-Sectional Analysis of a National Discharge Register.

INTRODUCTION The risk of venous thromboembolism (VTE) is higher during pregnancy, with an incidence between 0.05 and 0.2%, and among persons with sickle cell disease (SCD), yet the rates and risk factors, such as pneumonia, vasooclusive crisis (VOC), and acute chest syndrome (ACS), associated with pregnancy-related VTE are not firmly established in SCD. METHODS Inpatient hospital discharge data from 2007-2011 were obtained from the Pennsylvania Health Care Cost Containment Council to estimate the rate of VTE among African American delivery hospitalizations with SCD and to compare pregnancy complications and medical comorbidities among pregnant women with SCD. RESULTS Among 212 hospitalized deliveries in African-American women with SCD, 6 (2.8%, 95% CI 1.0%-5.9%) had VTE compared to 0.05 to 2.0% in the general population. Risk factors for VTE included pneumonia and diabetes mellitus. Overall, the prevalence of VTE, among hospitalized deliveries in SCD women with pneumonia, VOC, and/or ACS, 6.6%, was significantly greater than among those without these conditions, 2.2%, p<0.001. CONCLUSION Pregnancy-related VTE in women with SCD appears to be 1.5 to 5 times greater than pregnancy-related VTE in the general population. The higher prevalence of VTE among pregnant women with pneumonia, VOC, and/or ACS, and their potential clinical overlap, suggests that VTE may be missed in such women. We conclude that VTE in pregnant women with SCD may be more common than previously reported, and such women might be candidates for thromboprophylaxis.

Thrombin generation and bleeding in haemophilia inhibitor patients during immune tolerance induction

BACKGROUND Despite treatment, women with von Willebrand disease (VWD) have lower von Willebrand factor (VWF) levels and greater blood loss at delivery than controls. Current weight-based dosing does not account for the ~1.5-fold increase in blood volume in pregnancy. METHODS To evaluate the feasibility of a trial to prevent postpartum hemorrhage (PPH), we reviewed pre-pregnancy and 8th month VWF levels in women with VWD with and without PPH following vaginal delivery, assessed VWF concentrate use at delivery by U.S. hemophilia treatment center physician survey, and reviewed thrombosis risk with VWF concentrate by literature review. We determined trial interest and acceptability by structured interviews of physicians and patients. Analysis was by Students t-test for continuous data, and chi-square or Fishers exact test for discrete data. RESULTS PPH was associated with lower pre-pregnancy VWF:RCo, p<0.005; higher pre-pregnancy, 8th and 9th-month weight, each p<0.001; a family bleeding history, p=0.036; and VWF concentrate treatment, p=0.005. Surveyed physicians reported first-line therapy at delivery was VWF concentrate, at a mean dose 50IU/kg. A trial of a 1.5-fold volume-based dose increase was acceptable to physicians and patients, if it is safe and if costs and visits are minimized. A literature review determined thrombosis risk with VWF concentrate is low, 0.4%. CONCLUSIONS This study suggests pre-pregnancy VWF:RCo may predict PPH, but 50-80IU/kg VWF concentrate dosing may not prevent PPH. If pharmacokinetic modeling confirms volume-based dosing achieves VWF levels comparable to pregnant controls, it may be possible to determine if volume-modified VWF concentrate dosing will reduce PPH in VWD.

The Association of Aging With Von Willebrand Factor Levels and Bleeding Risk in Type 1 Von Willebrand Disease

Introduction: Improved life expectancy of persons with hemophilia (PWHs) has led to a greater interest in the role of age-related chronic diseases, such as hypertension, in this cohort. Several observational studies have reported an increased prevalence of hypertension in PWHs; however, this has not been assessed using a large, national database in the United States. Aims: We hypothesized the prevalence of hypertension is increased in PWHs and compared the prevalence of hypertension and associated risk factors among patients with and without hemophilia. Methods: A cross-sectional analysis was performed using discharge data among adult males from the National Inpatient Sample over the 3-year period, 2009 to 2011. Hypertension was compared across groups using Rao-Scott χ2 test. Multivariable logistic regression was used to estimate the odds of hypertension in patients with hemophilia after adjustment for hypertension-associated risk factors. Results: The prevalence of hypertension in patients with hemophilia was less than the prevalence of hypertension in patients without hemophilia (39.5% vs 56.3%, P < .001). Hemophilia was associated with a decreased odds of hypertension after adjusting for associated risk factors (odds ratio: 0.87; 95% confidence interval: 0.81-0.94). Conclusion: In contrast to the findings of several other recent studies, we report a decreased prevalence of hypertension in PWHs. The discrepancy among the reported prevalence of hypertension in our study and several others highlights the potential biases inherent to retrospective and cross-sectional studies and underscores the need for well-designed prospective studies to determine the true incidence of hypertension in PWHs, which may lie somewhere in between our findings and the findings of others.

Prevalence and Risk Factors Associated With Hypertension in von Willebrand Disease.

Inhibitor formation complicates haemophilia treatment and requires immune tolerance induction to rid inhibitors over 5 BU. In the prospective, randomized International Immune Tolerance Study, immune tolerance induction was equally effective with high‐dose (HD) (200 IU kg−1 day−1) and low‐dose (LD) (50 IU kg−1 3× per week) factor VIII, but haemorrhages were twofold higher in the LD arm. This finding was unexpected as inhibitors neutralize FVIII activity. We hypothesized that the thrombin generation assay (TGA), a global measure of clot formation, might predict bleeding better than FVIII levels.

Coagulopathy in Cirrhosis

Little is known about aging in von Willebrand disease (VWD). It is uncertain whether VWD patients experience an age-related increase in von Willebrand factor (VWF) levels, and if so, it is unknown whether normalization of VWF levels with aging ameliorates bleeding risk. We aimed to determine the association of age with VWF levels and bleeding risk in patients with type 1 VWD. This is a retrospective chart review of patients with type 1 VWD presenting to the Hemophilia Clinic of Western Pennsylvania for regularly scheduled clinic visits. Data collected included VWF antigen level and condensed molecular and clinical markers for the diagnosis and management of Type 1 (MCMDM-1) VWD bleeding assessment tool (BAT) bleeding score based on bleeding symptoms during the previous 3 years. Thirty-nine patients participated in the study, and 32 were female. The average age of participants was 41.8 ± 18.0 years. The mean VWF antigen level was 0.83 ± 0.37 IU/mL, and the mean bleeding score was 2.51 ± 2.90. The bleeding score was inversely associated with age, β = −0.080 (SE = 0.023), P < .01. There was a nonsignificant association between VWF antigen levels and age. To our knowledge, this is the first report showing an association between aging and decreased bleeding symptoms in patients with type 1 VWD. Determining whether or not bleeding risk is reduced in older patients with type 1 VWD is essential for optimal clinical management. Moreover, VWF concentrate is costly, and unwarranted use represents a significant waste of health-care dollars. These findings warrant further investigation.

Bleeding Disorders: Diagnosis and Treatment of Hemorrhagic Complications in the Intensive Care Unit

Background: von Willebrand factor (VWF) is a biomarker for endothelial damage. Increased VWF levels are observed in hypertension (HTN) and disorders of endothelial dysfunction, for example, atherosclerotic heart disease (ASHD) and diabetes. Whether low VWF protects against HTN is unknown. Methods: To determine prevalence and risk factors for HTN in patients with von Willebrand disease (VWD), we conducted a cross-sectional analysis of discharge data from the National Inpatient Sample, 2009 to 2011. Group comparisons were performed by Rao-Scott χ2 test. Odds of HTN and HTN outcomes in VWD were estimated by weighted multivariable logistic regression. Results: The prevalence of hypertension in patients with VWD (N = 7556), 37.35%, was significantly lower than that in non-VWD patients (N = 19 918 970), 49.40%, P < .0001. Hypertension risk factors (hyperlipidemia, diabetes, smoking, hepatitis C, and HIV) and HTN outcomes (ASHD, myocardial infarction [MI], ischemic stroke, and renal failure) were less common in patients with VWD than in non-VWD patients, all P ≤ .0001. Patients with VWD were younger, 49.67 versus 57.30 years, Caucasian, 82.23% versus 68.35%, and female, 75.44% versus 59.61%, P < .0001. Patients with HTN were older, 67.55 versus 47.29 years, male, 45.99% versus 34.90%, and had more HTN risk factors and HTN outcomes than those without HTN, all P < .0001, including male and female subgroups, each P < .0001. The unadjusted odds of HTN in patients with VWD (odds ratio [OR] = 0.611, P < .0001) and of HTN outcomes in patients with VWD (ASHD, OR = 0.509; MI, OR = 0.422; ischemic stroke, OR = 0.521; renal failure, OR = 0.420, all P < .0001) became insignificant after adjustment for HTN risk factors plus demographics (age/race/gender), OR = 1.035, P = .260. Conclusion: The risk of HTN is reduced in patients with VWD, but not after adjustment for HTN risk factors plus demographics, as patients with VWD not having HTN are also typically young, Caucasian, and female.