Bleeding phenotype in nonsevere hemophilia by International Society on Thrombosis and Haemostasis bleeding assessment tool, bleeding frequency, and the joint status.

Background: Although the phenotype of severe hemophilia has been well studied, there are still knowledge gaps in nonsevere hemophilia. Objectives: The objective of this study was to characterize the clinical bleeding phenotype in nonsevere hemophilia and its association with different factor VIII/IX assessments. Methods: This was a cross-sectional, multicenter study to investigate the bleeding phenotype in adults with nonsevere hemophilia by the number of bleeding and joint bleeding in the past 5 years, a joint score, and the International Society on Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT). Factor levels were analyzed by 1-stage (lowest in history and at study inclusion) and chromogenic assay (at study inclusion). Patients were enrolled between March 2015 and May 2019. Results: Of the 111 patients (86 with mild and 25 with moderate hemophilia), 57 patients (54.8%) reported any bleeding and 24 (23.1%) any joint bleeding in the past 5 years. A joint score ≥1 was found in 44 patients (41.9%), an ISTH-BAT ≥4 in 100 patients (90.1%), and an ISTH-BAT joint item ≥1 in 50 patients (45.0%). Within the ISTH-BAT, muscle and joint bleeds showed the largest difference between mild and moderate hemophilia. The lowest factor VIII/IX level in patients' history was best associated with bleeding outcomes. Factor was inversely associated with joint bleeds (incidence rate ratio 0.88; 95% CI, 0.79-0.98), joint score, and ISTH-BAT (odds ratios from proportional odds ordinal logistic regression 0.92; 95% CI, 0.87-0.97; and 0.89; 95% CI, 0.86-0.93, respectively). Conclusion: The occurrence of joint bleeding differentiated persons with mild and moderate hemophilia. The ISTH-BAT and lowest factor in patients' history provided valuable information of the bleeding phenotype in nonsevere hemophilia.

Atrial fibrillation and cancer: prevalence and relative risk from a nationwide study.

Background: Atrial fibrillation (AF) is an increasingly recognized codiagnosis in patients with cancer. Objectives: This study aimed to provide a robust and contemporary estimate on the coprevalence and relative risk of AF in patients with cancer. Methods: We conducted a nationwide analysis, utilizing diagnosis codes from the Austrian Association of Social Security Providers dataset. Estimates of the coprevalence of cancer and AF and the relative risk of AF in patients with cancer compared with individuals without cancer were obtained as point prevalences with binomial exact confidence intervals and summarized across age groups and cancer types with random-effects models. Results: Overall, 8,306,244 persons were included in the present analysis, of whom 158,675 (prevalence estimate, 1.91%; 95% CI, 1.90-1.92) had a cancer diagnosis code and 112,827 (1.36%; 95% CI, 1.35-1.36) an AF diagnosis code, respectively. The prevalence estimate for AF in patients with cancer was 9.77% (95% CI, 9.63-9.92) and 1.19% (95% CI, 1.19-1.20) in the noncancer population. Conversely, 13.74% (95% CI, 13.54-13.94) of patients with AF had a concurrent cancer diagnosis. The corresponding age-stratified random-effects relative risk ratio for AF in patients with cancer compared with no cancer diagnosis was 10.45 (95% CI, 7.47-14.62). The strongest associations between cancer and AF were observed in younger persons and patients with hematologic malignancies. Conclusion: Cancer and AF have a substantial coprevalence in the population. This finding corroborates the concept that cancer and AF have common risk factors and pathophysiology.

Relative risk of arterial and venous thromboembolism in persons with cancer vs. persons without cancer-a nationwide analysis.

AIMS: An interrelation between cancer and thrombosis is known, but population-based studies on the risk of both arterial thromboembolism (ATE) and venous thromboembolism (VTE) have not been performed. METHODS AND RESULTS: International Classification of Disease 10th Revision (ICD-10) diagnosis codes of all publicly insured persons in Austria (0-90 years) were extracted from the Austrian Association of Social Security Providers dataset covering the years 2006-07 (n = 8 306 244). Patients with a history of cancer or active cancer were defined as having at least one ICD-10 'C' diagnosis code, and patients with ATE and/or VTE as having at least one of I21/I24 (myocardial infarction), I63/I64 (stroke), I74 (arterial embolism), and I26/I80/I82 (venous thromboembolism) diagnosis code. Among 158 675 people with cancer, 8559 (5.4%) had an ATE diagnosis code and 7244 (4.6%) a VTE diagnosis code. In contrast, among 8 147 569 people without cancer, 69 381 (0.9%) had an ATE diagnosis code and 29 307 (0.4%) a VTE diagnosis code. This corresponds to age-stratified random-effects relative risks (RR) of 6.88 [95% confidence interval (CI) 4.81-9.84] for ATE and 14.91 (95% CI 8.90-24.95) for VTE. ATE proportion was highest in patients with urinary tract malignancies (RR: 7.16 [6.74-7.61]) and lowest in patients with endocrine cancer (RR: 2.49 [2.00-3.10]). The corresponding VTE proportion was highest in cancer of the mesothelium/soft tissue (RR: 19.35 [17.44-21.47]) and lowest in oropharyngeal cancer (RR: 6.62 [5.61-7.81]). CONCLUSION: The RR of both ATE and VTE are significantly higher in persons with cancer. Our population-level meta-data indicate a strong association between cancer, ATE and VTE, and support the concept of shared risk factors and pathobiology between these diseases.Relative risk of ATE and VTE in persons with a cancer diagnosis code versus persons without a cancer diagnosis code.

Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study.

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication of cancer. Elevated D-dimer is associated with an increased risk of cancer-associated VTE. Whether changes in D-dimer over time harbor additional prognostic information that may be exploited clinically for dynamic prediction of VTE is unclear. OBJECTIVES: To explore the potential role of longitudinal D-dimer trajectories for personalized prediction of cancer-associated VTE. PATIENTS/METHODS: A total of 167 patients with active malignancy were prospectively enrolled (gastrointestinal: n = 59 [35%], lung: n = 56 [34%], brain: n = 50 [30%], others: n = 2 [1%]; metastatic disease: n = 74 [44%]). D-dimer (median = 0.8 µg/mL [25th-75th percentile: 0.4-2.0]) was measured at baseline and during 602 monthly follow-up visits. Joint models of longitudinal and time-to-event data were implemented to quantify the association between D-dimer trajectories and prospective risk of VTE. RESULTS: VTE occurred in 20 patients (250-day VTE risk = 12.1%, 95% confidence interval [CI], 7.8-18.5). D-dimer increased by 34%/month (0.47 µg/mL/month, 95% CI, 0.22-0.72, P < .0001) in patients who developed VTE, but remained constant in patients who did not develop VTE (change/month = -0.06 µg/mL, 95% CI, -0.15 to 0.02, P = .121). In joint modeling, a doubling of the D-dimer trajectory was associated with a 2.8-fold increase in the risk of VTE (hazard ratio = 2.78, 95% CI, 1.69-4.58, P < .0001). This finding was independent of established VTE risk factors. Highly personalized, dynamic predictions of VTE conditional on individual patients' D-dimer trajectories could be obtained. CONCLUSIONS: D-dimer increases before the onset of cancer-associated VTE, but remains constant over time in patients without VTE. This study represents proof-of-concept that longitudinal trajectories of D-Dimer may advance the personalized assessment of VTE risk in the oncologic setting.