High Mortality After Venous Thromboembolism: A Population-Based Cohort Study

AimTo analyze the incidence and characteristics of venous thromboembolism (VTE) in Croatia.MethodsThe Croatian Cooperative Group for Hematologic Diseases conducted an observational non-interventional study in 2011. Medical records of patients with newly diagnosed VTE hospitalized in general hospitals in 4 Croatian counties (Šibenik-Knin, Koprivnica-Križevci, Brod-Posavina, and Varaždin County) were reviewed. According to 2011 Census, the population of these counties comprises 13.1% of the Croatian population.ResultsThere were 663 patients with VTE; 408 (61.54%) had deep vein thrombosis, 219 (33.03%) had pulmonary embolism, and 36 (5.43%) had both conditions. Median age was 71 years, 290 (43.7%) were men and 373 (56.3%) women. Secondary VTE was found in 57.3% of participants, idiopathic VTE in 42.7%, and recurrent VTE in 11.9%. There were no differences between patients with secondary VTE and patients with idiopathic VTE in disease recurrence and sex. The most frequent causes of secondary VTE were cancer (40.8%), and trauma, surgery, and immobilization (38.2%), while 42.9% patients with secondary VTE had ≥2 causes. There were 8.9% patients ≤45 years; 3.3% with idiopathic or recurrent VTE. Seventy patients (10.6%) died, more of whom had secondary (81.4%) than idiopathic (18.6%) VTE (P < 0.001), and in 50.0% VTE was the main cause of death. Estimated incidence of VTE in Croatia was 1.185 per 1000 people.ConclusionCharacteristics of VTE in Croatia are similar to those reported in large international studies. Improved thromboprophylaxis during the presence of risk factors for secondary VTE might substantially lower the VTE burden.

Treatment patterns of venous thromboembolism in a real-world population: The Q-VTE study cohort

D-dimer and Factor VIII are Independent Risk Factors for Recurrence After Anticoagulation Withdrawal for a First Idiopathic Deep Vein Thrombosis

Venous thromboembolism (VTE) has been traditionally considered a transient acute disorder requiring a limited duration of anticoagulant therapy. Patients who suffer deep vein thrombosis (DVT) or pulmonary embolism (PE) following major surgery, major trauma, or periods of immobility are generally treated with anticoagulation for 3–6 months. After completion of anticoagulation for the initial event, the risk of VTE recurrence is believed to return to that of the general population. However, epidemiological studies suggest that VTE may be better characterized as a chronic disorder with periodic relapses. While patients who suffer unprovoked (idiopathic) VTE bear the highest risk of recurrent events, exceeding 50% over 10 years if not treated with extended duration anticoagulation, those who suffer VTE in the setting of identifiable provoking factors have an enduring risk of recurrence that exceeds 20% over 10 years. 1 Randomized controlled trials of extended duration anticoagulation for prevention of recurrent unprovoked VTE have demonstrated that the rate of recurrence increases abruptly if anticoagulation is discontinued. 2 An analysis of the Danish National Registry of Patients demonstrated that patients with VTE have increased mortality over 30 years of follow-up and that recurrent PE is an important cause of death throughout this period. 3 The efficacy of extended duration anticoagulation for prevention of recurrent events after an initial unprovoked DVT or PE further supports the classification of VTE as a chronic relapsing disease. Prolonged anticoagulation with a low- (international normalized ratio (INR) target 1.5–2.0) 4 or conventional-intensity (INR target 2.0–3.0) 5 or a non-vitamin K-dependent oral anticoagulant such as rivaroxaban, 6 dabigatran, 2 or apixaban 7 provides a 60–90% reduction in recurrent events in patients who suffer an initial unprovoked VTE. Evidence-based practice guidelines recognize the increased risk of recurrence among patients with idiopathic VTE and recommend extended duration anticoagulation in those with a low bleeding risk. Virchow’s Triad of stasis, hypercoagulability, and endothelial dysfunction and injury does not fully explain the increased risk of recurrent VTE and the need for extended duration anticoagulation. Immobility resulting in stasis is only a transient risk factor in the majority of patients with VTE. Although frequently sought as an explanation for VTE, thrombophilia is detected in only a minority of patients. 8 Furthermore, common thrombophilias such as the factor V Leiden and prothrombin gene mutations do not appear to increase the risk of recurrence. 8 Endothelial dysfunction and injury may play an important role in a subset of patients with VTE, but the underlying mechanism leading to recurrence remains unclear. Advances in our understanding of the pathophysiology of atherothrombosis may shed light on critical mechanisms for VTE recurrence. Traditionally, the burden of recurrent atherothrombotic events has been largely ascribed to dyslipidemia. However, even with intensive lipid-lowering therapy for secondary prevention, a significant burden of recurrent atherothrombotic events remains. A growing body of literature suggests that cardiovascular inflammation is a key pathophysiologic factor in recurrent atherothrombotic events. 9,10 Traditionally considered distinct and unrelated disorders, atherothrombosis and VTE are linked both epidemiologically and pathophysiologically. In fact, a reciprocal relationship exists: patients with VTE have an increased risk of myocardial infarction and stroke, and vice versa. Proven cardiovascular risk factors such as obesity, tobacco use, diabetes, stress, and diet increase the risk of atherothrombotic events and VTE. These particular risk factors share a common pathophysiological mechanism of promoting cardiovascular inflammation. In epidemiologic studies, systemic inflammation has been closely associated with an increased risk of VTE. The increased frequency of DVT and PE in patients with chronic inflammatory disorders such as inflammatory bowel disease and systemic vasculitis highlights the role of inflammation in VTE. Furthermore, increased levels of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of VTE. In an analysis of 10,505 participants in

Value of D-dimer testing to decide duration of anticoagulation after deep vein thrombosis: not yet.

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and its complication, pulmonary embolism (PE), is a multifactorial disease, involving complex interactions between environmental exposures and patients, including their hemostatic system and genetic predispositions. VTE is relatively common, with an overall average ageand sex-adjusted incidence of about 1.04–1.9 per 1000 person-years that rises dramatically with increasing age [1–4]. Active malignancy accounts for almost 20% of incident VTE events occurring in the community [5], and imparts a 4to 6.5-fold higher VTE risk compared to non-cancer patients, depending on concurrent use of anti-cancer therapy [6]. The risk of VTE also varies by cancer type and stage [7–10]. The association between VTE and malignancy has been recognized since 1861 when Trousseau, in a lecture, described thrombophlebitis as the presenting sign of visceral malignancy [11]. In fact, idiopathic VTE may be a harbinger for an occult malignancy. Patients who present with an acute episode of idiopathic VTE have an approximately threeto fourfold increased likelihood of being diagnosed with a malignancy within a year of the VTE event [12–16], leading to a debate on whether cancer screening should be conducted in all individuals presenting with idiopathic VTE [17, 18]. While a clinical trial comparing extensive malignancy screening vs usual care for incident idiopathic VTE identified earlier stage malignancies in the extensive screening group and reduced the mean delay to cancer diagnosis from about 1 year to 1 month, 2-year cancerrelated mortality did not differ between the two groups [19], thus making it challenging to justify aggressive screening. VTE in cancer patients is associated with numerous negative implications, including significant morbidity and mortality. These patients may have their

Venous Thromboembolism Incidence In The Cooperative Study Of Sickle Cell Disease: The Untold Story

Risk of Pregnancy-Associated Venous Thromboembolism in Sickle Cell Trait

The Risk of Malignancy Following Idiopathic Venous Thromboembolism: A Population-Based Cohort Study

The Seasonal Incidence of Venous Thromboembolism (VTE): A Population-Based Cohort Study.

A Negative D-dimer Excludes Recurrent Deep Vein Thrombosis: Results of a Multicentre Management Study.

Estimated Annual Number of Incident and Recurrent, Non-Fatal and Fatal Venous Thromboembolism (VTE) Events in the US.

Coagulation factors play important roles in the pathophysiology of venous thromboembolism (VTE), and most of them are glycoproteins, that is, proteins containing glycans attached. Although the connection between glycosylation and coagulation factors seems obvious, the association between glycosylation and VTE risk remains unexplored. We aimed to elucidate the association between N-glycans in plasma and VTE risk in the MEGA study (Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis), a case-control study aiming to identify risk factors for VTE. The total plasma N-glycomes of 491 VTE cases with a first idiopathic VTE and 472 controls were analyzed using a robust mass spectrometry platform. In total, 91 N-glycans were measured. The association between each N-glycan and the risk of a first VTE was analyzed with logistic regression models, adjusted for potential confounders. In addition, we also examined the associations between VTE-associated N-glycans as well as glycosylation features and VTE-associated coagulation factors with linear regression models. In the analysis, 466 idiopathic VTE cases and 454 controls were included. We found that fucosylation of complex-type glycans and the presence of more antennae in glycan structures were associated with an increased risk of VTE. Conversely, monoantennary and diantennary complex-type glycans, as well as oligomannose-type glycans, were associated with a reduced risk of VTE. The associations between glycan features and VTE risk were partially supported by their relationships with procoagulant factors. We demonstrated the relevance of plasma N-glycan signatures in the risk of a first VTE. Plasma N-glycome holds a strong potential for VTE risk stratification.

Influence of Preceding Length of Anticoagulant Treatment and Initial Presentation of Venous Thromboembolism on Risk of Recurrence After Stopping Treatment: Analysis of Individual Participants' Data From Seven Trials

The aim of this study was to evaluate the relationship between factor VIII (FVIII) levels, measured by chromogenic and clotting assays, and risk of venous thromboembolism (VTE) recurrence. A total of 564 patients underwent clinical follow-up after oral anticoagulant withdrawal (total follow-up = 924.4 years). Recurrent VTE developed in 39 of 309 (12.6%) patients with a first idiopathic VTE and in 14 of 255 (5.5%) patients whose first event was secondary. In patients with a first idiopathic VTE, the risk of recurrence was more than fivefold higher in patients with FVIII levels exceeding the 90th percentile [chromogenic FVIII: relative risk (RR) 5.43 (95% CI 1.76-16.8); clotting FVIII: RR 6.21 (95% CI 1.57-24.5)] after adjustment for all possible confounding variables. In patients with a first secondary VTE, the risk of recurrence was slightly higher in patients with high FVIII levels [chromogenic FVIII: RR 2.62 (95% CI 0.34-19.9); clotting FVIII: RR 1.74 (95% CI 0.25-12.1)], but, given the low number of recurrences, the 95% CI were very large. In conclusion, this study shows that high FVIII levels are associated with increased risk of VTE recurrence in patients with a first idiopathic VTE. Although the measurement of FVIII levels by a specific chromogenic assay might, in principle, be preferred to avoid the risk of aspecific clotting effects, no significant differences in results obtained by chromogenic or clotting methods were found.