Real-world Data on Treatment Patterns and Bleeding in Cancer-associated Thrombosis: Data from the TROLL Registry.

Background International guidelines are increasingly recommending direct oral anticoagulants (DOACs) as the first-line treatment for cancer-associated thrombosis (CAT). However, data regarding treatment patterns and adherence to guidelines in patients with CAT are scarce. Objectives This study aimed to explore anticoagulant treatment patterns in patients with CAT and to calculate the incidence rates of bleeding events. Methods Patients ≥18 years with active cancer and a first-time venous thromboembolism between 2005 and 2020 were identified through the Venous T hrombosis R egistry in Østf OL d Hospita L . Outcome measures were patterns of anticoagulant treatment during the study period and bleeding events. We calculated overall incidence rates per 100 person-years and 6- and 12-month cumulative incidence of major and clinically relevant nonmajor bleeding (CRNMB) during anticoagulant treatment. Results Median age of 842 CAT patients at the time of thrombosis was 69 years (interquartile range 61-77), and 443 (52.6%) were men. In total, 526 patients (62.5%) had pulmonary embolism and 255 (30.3%) had deep vein thrombosis. Low molecular weight heparin (LMWH) was prescribed to 713 (85.8%) patients, whereas 64 (7.7%) received DOACs and 54 (6.5%) received vitamin K antagonists as the initial anticoagulant treatment. Prescription of DOACs as initial treatment increased from 3.0% in 2013/2014 to 18.0% in 2019/2020. The incidence rate of major bleeding was 6.9 (95% confidence interval [CI] 5.2-9.2) and 10.1 (95% CI 8.0-12.9) in CRNMB. Conclusion Most patients were treated with LMWH. However, a gradual shift in treatment toward DOACs was observed. Overall, bleeding complications were rare and comparable to those reported in randomized trials.

Incidence of venous thromboembolism, recurrence, and bleeding after isolated superficial vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital.

BACKGROUND: There are limited data on the long-term risk of venous thromboembolism (VTE) after high-risk isolated superficial vein thrombosis (iSVT) treated with anticoagulants. OBJECTIVES: To determine the short- and long-term risk of VTE and iSVT recurrence after cessation of anticoagulant treatment and to calculate 45-day cumulative bleeding incidence in patients with iSVT. METHODS: Between January 2014 and December 2021, 229 patients with high-risk iSVT (ie, thrombus length ≥5cm), without active cancer, with no history of VTE or iSVT, and who had received anticoagulant treatment for the iSVT were identified through the Venous Thrombosis Registry in Østfold Hospital (TROLL registry), Norway. Cumulative incidences of VTE and iSVT recurrence, as well as cumulative incidences of major and clinically relevant nonmajor bleeding events, were assessed. RESULTS: Median age was 60 years (IQR, 48-71), and 125 (55%) were women. Most patients were treated with direct oral anticoagulants (74%), and of these, 79% received a dose of rivaroxaban 10 mg daily. Low-molecular-weight heparin was given to 26% of the patients. The 1- and 5-year cumulative incidences of VTE after iSVT were 4.6% (95% CI, 2.5-8.3) and 15.9% (95% CI, 10.8-22.9), respectively. Further, the 1- and 5-year cumulative incidences of iSVT recurrence were 6.5% (95% CI, 3.9-10.7) and 15.9% (95% CI, 10.8-23.1), respectively. The overall 45-day cumulative incidence of major and clinically relevant nonmajor bleeding events was 0.4% (95% CI, 0.06-3.06) and 1.8% (95% CI, 0.7-4.6), respectively. No major bleeding events were observed in patients treated with direct oral anticoagulants. CONCLUSION: Despite anticoagulant treatment, the risk of VTE after high-risk iSVT was substantial, while bleeding complications were low.

Incidence of bleeding and recurrence in isolated distal deep vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital.

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is a common presentation of deep vein thrombosis. There are limited data on the long-term risk of recurrence after IDDVT. OBJECTIVES: We aimed to determine the short- and long-term incidence of venous thrombosis (VTE) recurrence after cessation of anticoagulation and the 3-month incidence of bleeding during anticoagulant treatment in patients with IDDVT. METHODS: Between January 2005 and May 2020, 475 patients with IDDVT and without active cancer were identified from the Venous Thrombosis Registry in Østfold Hospital, which is an ongoing registry of consecutive patients with VTE at Østfold Hospital, Norway. Major and clinically relevant, nonmajor bleeding as well as recurrent VTE were registered, and the cumulative incidences of these events were assessed. RESULTS: The median age of the patients was 59 years (IQR, 48-72 years), 243 (51%) patients were women, and 175 events (36.8%) were classified as unprovoked. The 1-, 5-, and 10-year cumulative incidences of recurrent VTE were 5.6% (95% CI, 3.7-8.4), 14.7% (95% CI, 11.1-19.4), and 27.2% (95% CI, 21.1-34.5), respectively. The recurrence rates were higher for unprovoked IDDVT than for provoked IDDVT. Among the recurrent events, 18 (29%) were pulmonary embolisms and 21 (33%) were proximal deep vein thromboses. The 3-month cumulative incidence of major bleeding was 1.5% (95% CI, 0.7-3.1) overall and 0.8% (95% CI, 0.2-3.1) when restricted to patients treated with direct oral anticoagulants. CONCLUSION: Despite initial treatment, the long-term risk of VTE recurrence after first-time IDDVT is high. The bleeding rates during anticoagulation, particularly with direct oral anticoagulants, were acceptably low.

Diagnostic Blood Biomarkers for Acute Pulmonary Embolism: A Systematic Review.

(1) Background: The current diagnostic algorithm for acute pulmonary embolism (PE) is associated with the overuse of CT pulmonary angiography (CTPA). An additional highly specific blood test could potentially lower the proportion of patients with suspected PE that require CTPA. The aim was to summarize the literature on the diagnostic performance of biomarkers of patients admitted to an emergency department with suspected acute PE. (2) Methods: Medline and Embase databases were searched from 1995 to the present. The study selection process, data extraction, and risk of bias assessment were conducted by two reviewers. Eligibility criteria accepted all blood biomarkers except D-dimer, and CTPA was used as the reference standard. Qualitative data synthesis was performed. (3) Results: Of the 8448 identified records, only 6 were included. Eight blood biomarkers were identified, of which, three were investigated in two separate studies. Red distribution width and mean platelet volume were reported to have a specificity of ≥ 90% in one study, although these findings were not confirmed by other studies. The majority of the studies contained a high risk of selection bias. (4) Conclusions: The modest findings and the uncertain validity of the included studies suggest that none of the biomarkers identified in this systematic review have the potential to improve the current diagnostic algorithm for acute PE by reducing the overuse of CTPA.

The venous thrombosis registry in Østfold Hospital (TROLL registry) - design and cohort description.

Purpose: The incidence of venous thromboembolism (VTE) is expected to increase over the next decades, further increasing its substantial impact on patients and health care resources. Registries have the benefit of reporting real-world data without excluding clinically important subgroups. Our aim was to describe a Norwegian VTE registry and to provide descriptive data on the population and management. Registry Population: The Venous Thrombosis Registry in Østfold Hospital (TROLL) is an ongoing registry of consecutive patients diagnosed with, treated, and/or followed up for VTE at Østfold Hospital, Norway, since 2005. Baseline and follow-up data, including demographics, clinical features, risk factors, diagnostic procedures, classification of VTE, and treatment were collected during hospitalization, and at scheduled outpatient visits. Findings to Date: From January 2005 to June 2021, 5037 patients were eligible for research in TROLL. Median age was 67 years (interquartile range, 55-77), and 2622 (52.1%) were male. Of these, 2736 (54.3%) had pulmonary embolism (PE), 2034 (40.4%) had deep vein thrombosis (DVT), and 265 (5.3%) had upper-extremity DVT or splanchnic or cerebral sinus vein thrombosis. In total, 2330 (46.3%) were classified as unprovoked VTE, and 1131 (22.5%) had cancer. Direct oral anticoagulants were the most frequent therapeutic agents (39.3%) followed by low-molecular-weight heparins (30.4%) and vitamin K antagonists (30.3%). Outpatient treatment for PE increased from 4% in 2005 to 23% in 2019. Future Plans: TROLL is a population-based ongoing registry that represents a valuable source of real-world data that will be used for future research on the management and outcomes of VTE.

Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism.

The role of complement in the pathogenesis of venous thromboembolism (VTE) is unclear. We wanted to investigate (1) whether plasma complement component C5 (C5) levels are influenced by genetic variants or chronic inflammation and (2) the association between plasma C5 and risk of future VTE in a nested case-control study of 415 patients with VTE and 848 age- and sex-matched controls derived from the Tromsø Study. Plasma C5 levels were measured at inclusion. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for provoked and unprovoked VTE across tertiles of C5 concentrations were estimated by logistic regression. Adjustment for C-reactive protein (CRP) served as a proxy for general inflammation. Whole-exome sequencing and protein quantitative trait loci analyses were performed to assess genetic influence on C5 concentrations. There was no association between genome-wide or C5-related gene variants and C5 levels. The association between plasma C5 levels and VTE risk displayed a threshold effect, where subjects with C5 levels above the lowest tertile had increased risk of VTE. Subjects in tertile 3 (highest C5 levels) had an age- and sex-adjusted OR of 1.45 (95% CI, 1.07-1.96) compared with tertile 1 (lowest). These statistics were more pronounced for unprovoked VTE (OR, 1.70; 95% CI, 1.11-2.60). Adjustments for body mass index and CRP had minor impact on risk estimates. The OR increased substantially with shorter time between blood sampling and VTE event. In conclusion, plasma C5 was associated with risk of future VTE. C5 levels were not genetically regulated and were only slightly influenced by chronic inflammation.

C-reactive protein and risk of venous thromboembolism: results from a population-based case-crossover study.

Long-term, low-grade inflammation does not seem to be a risk factor for venous thromboembolism. The impact of acute inflammation, regardless of cause, on risk of venous thromboembolism is scarcely studied. We aimed to investigate the impact of acute inflammation, assessed by C-reactive protein, on short-term risk of venous thromboembolism. We conducted a case-crossover study of patients with venous thromboembolism (n=707) recruited from a general population. Information on triggers and C-reactive protein levels were retrieved from hospital records during the 90 days before the event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to obtain ß coefficients for change in natural log (ln) transformed C-reactive protein from control to hazard periods and to determine corresponding odds ratios for venous thromboembolism. Median C-reactive protein was 107 mg/L in the hazard period, and ranged from 7 mg/L to 16 mg/L in the control periods. The level of C-reactive protein was 58% (95% CI 39-77%) higher in the hazard period than in the control periods. A one-unit increase in ln-C-reactive protein was associated with increased risk of venous thromboembolism (OR 1.79, 95% CI 1.48-2.16). The risk estimates were only slightly attenuated after adjustment for immobilization and infection. In stratified analyses, ln-C-reactive protein was associated with increased risk of venous thromboembolism in cases with (OR 1.55, 95% CI 1.01-2.38) and without infection (OR 1.77, 95% CI 1.22-2.57). In conclusion, we found that acute inflammation, assessed by C-reactive protein, was a trigger for venous thromboembolism.

Impact of Venous Thromboembolism on the Formation and Progression of Carotid Atherosclerosis: The Tromsø Study.

Venous thromboembolism (VTE) is associated with increased risk of arterial cardiovascular diseases (CVD), and development of atherosclerosis secondary to VTE may be an intermediate between VTE and CVD. Therefore, we aimed to investigate whether incident VTE was associated with subsequent carotid atherosclerosis formation and progression in a population-based observational study. Subjects attending two or more ultrasound examinations of the right carotid artery, with measurement of total plaque area (TPA), in the Tromsø Study in 1994-1995, 2001-2002, and/or 2007-2008 were eligible. We identified 150 subjects diagnosed with first-lifetime VTE between the initial and follow-up visit, and randomly selected 600 age- and sex-matched subjects without VTE between the visits. Subjects with VTE and carotid plaque(s) at the first visit had 4.1 mm 2 (ß: 4.13, 95% CI: -1.72 to 9.98) larger change in TPA between the first and second visit compared with subjects without VTE after adjustment for change in high-sensitivity C-reactive protein (hs-CRP) and traditional atherosclerotic risk factors. The association remained after restricting the analyses to VTE events diagnosed in the first half of the time interval between the carotid ultrasounds (ß: 4.02, 95% CI: -3.66 to 11.70), supporting that the change in TPA occurred subsequent to the VTE. No association was found between VTE and novel carotid plaque formation. In conclusion, we found a possible association between VTE and atherosclerosis progression in those with already established carotid plaques, but not between VTE and novel plaque formation. The association between VTE and carotid plaque progression was not mediated by low-grade inflammation assessed by hs-CRP.