Background Previous reports on recurrence and mortality rates after a first episode of venous thromboembolism (VTE) vary considerably. Advances in the management and treatment of VTE during the last 15 years may have influenced the rates of clinical outcomes. Aim To estimate the rates of recurrence and mortality after a first VTE in patients recruited from a large population-based cohort. Method From the Tromsø study, patients (n = 710) with a first, symptomatic, objectively confirmed VTE were included and followed in the period 1994-2012. Recurrent episodes of VTE were identified from multiple sources and carefully validated by review of medical records. Incidence rates and cumulative incidence rates with 95% confidence intervals (CIs) of VTE recurrence and mortality were calculated. Results The mean age of the patients was 68 years (range 28-102 years), and 166 (23.4%) had cancer at the time of first VTE. There were 114 VTE recurrences and 333 deaths during a median study period of 7.7 years (range 0.04-18.2 years). The risk of recurrence was highest during the first year. The overall 1-year recurrence rate was 7.8 (95% CI 5.8-10.6) per 100 person-years (PY), whereas the recurrence rate in the remaining follow-up period (1-18 years) was 3.0 (95% CI 2.4-3.8) per 100 PY. The overall 1-year all-cause mortality rate was 29.9 (95% CI 25.7-34.8) per 100 PY, and in those without cancer the corresponding rate was 23.6 (95% CI 17.8-31.3) per 100 PY. Conclusion Despite advances in VTE management, the rates of adverse events remained fairly high, particularly in the first year following a first VTE.

Telephone: +47 99274024Highlights • Studies on the impact of hospitalization as a trigger factor for VTE are limited.• We explored this association in a case-crossover study of cancer-free VTE patients.• Hospitalization without concurrent immobilization was a major trigger for VTE.• Immobilization augmented the VTE-risk substantially in hospitalized patients. AbstractBackground: Previous studies have reported that around 50% of patients with venous thromboembolism (VTE) has undergone recent hospitalization. However, studies on the impact of hospitalization as a trigger factor for VTE are limited. Objectives:To investigate the impact of hospitalization with and without concurrent immobilization as a trigger factor for VTE. Methods:We conducted a case-crossover study of 530 cancer-free VTE patients. Hospitalizations were registered during the 90-day period preceding the VTE diagnosis (hazard period), and in four preceding 90-day control periods. A 90-day washout period between the control-and hazard periods was implemented to avoid potential carry-over effects. Conditional logistic regression was used to calculate odds ratios (OR) of VTE according to hospitalization. Results:In total, 159 (30%) of the VTE-patients had been hospitalized in the hazard period, and the OR of hospitalization was 9.4 (95% CI: 6.8-12.8). The risk increased slightly with the total number of days spent in hospital (OR per day: 1.11, 95% CI: 1.04-1.18), and with the number of hospitalizations (OR 8.9, 95% CI: 6.4-12.4 for 1 hospitalization and OR 12.3, 95% CI 6.4-23.6 for ≥2 hospitalizations).Hospitalization without immobilization was 6-times (OR: 6.3, 95% CI: 4.4-9.2) more common, whereas hospitalization with immobilization was near 20-times (OR: 19.8, 95% CI: 11.5-34.0) more common in the 90-days prior to a VTE compared to the control periods. Conclusions:Hospitalization is a major trigger factor for VTE also in the absence of immobilization.However, immobilization contributes substantially to the risk of VTE among hospitalized patients.

Essentials Whether D-dimer at incident venous thromboembolism (VTE) can predict recurrence-risk is unknown. We explored this association in 454 cancer-free patients with a first lifetime VTE. A low D-dimer at first VTE diagnosis was associated with a low recurrence risk. The association was predominant in patients with deep vein thrombosis and unprovoked VTE. Click to hear Dr Cannegieter's presentation on venous thrombosis: prediction of recurrence SUMMARY: Background Venous thromboembolism (VTE) is a common disease with a high recurrence rate. D-dimer measured after cessation of anticoagulant therapy predicts recurrence, and is used to decide on treatment prolongation. However, whether D-dimer measured at first VTE diagnosis can be used to assess recurrence-risk is unknown. Aims To investigate the association between D-dimer, measured at first VTE diagnosis and risk of recurrent VTE. Methods Information on clinical risk factors and laboratory markers were collected in 454 cancer-free patients with a first VTE. Recurrent VTEs and deaths during follow-up (1994-2012) were recorded. Results During a median follow-up of 3.9 years, 84 patients experienced a recurrent VTE. The crude recurrence rate was 1.7 (95% confidence interval [CI], 1.0-2.9) per 100 person-years in the lower quartile of D-dimer (≤ 1500 ng mL ), and 4.9 (95% CI, 3.9-6.1) per 100 person-years in the upper three quartiles combined, yielding an absolute risk difference of 3.2 per 100 person-years. Patients with D-dimer ≤ 1500 ng mL had 54% lower recurrence-risk than patients with D-dimer > 1500 ng mL (HR, 0.46; 95% CI, 0.25-0.82). The association was particularly pronounced among patients with unprovoked events and deep vein thrombosis, showing a 66% (HR, 0.34; 95% CI, 0.15-0.74) and 68% (HR, 0.32; 95% CI, 0.14-0.71) lower recurrence risk among patients with D-dimer ≤ 1500 ng mL , respectively. Conclusions A low D-dimer (≤ 1500 ng mL ) measured at first VTE diagnosis was associated with a low recurrence risk, particularly among patients with DVT and unprovoked events. Our findings suggest that a clinical decision to avoid prolonged anticoagulant treatment could be considered based on low D-dimer at the time of VTE diagnosis.

Identification of patients at risk of major bleeding is pivotal for optimal management of anticoagulant therapy in venous thromboembolism (VTE). Studies have suggested that D-dimer may predict major bleeding during anticoagulation; however, this is scarcely investigated in VTE patients. We aimed to investigate the role of D-dimer, measured at VTE diagnosis, as a predictive biomarker of major bleeding. The study population comprised 555 patients with a first community-acquired VTE (1994–2016), who were identified among participants from the Tromsø study. Major bleeding events were recorded during the first year after VTE and defined according to the criteria of the International Society on Thrombosis and Haemostasis. Cox-regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, and duration of anticoagulant therapy. In total, 29 patients experienced major bleeding (incidence rate: 5.7/100 person-years, 95% CI: 4.0–8.2). The major bleeding risk was highest during the first 3 months, especially in patients with D-dimer ≥8.3 µg/mL (upper 20th percentile), with 28.8 major bleedings/100 person-years (95% CI: 13.7–60.4). Patients with D-dimer ≥8.3 µg/mL had a 2.6-fold (95% CI: 1.1–6.6) higher risk of major bleeding than patients with D-dimer ≤2.3 µg/mL (lower 40th percentile). Major bleeding risk according to D-dimer ≥8.3 versus ≤2.3 µg/mL was particularly pronounced among those with deep vein thrombosis (HR: 4.6, 95% CI: 1.3–16.2) and provoked events (HR: 4.2, 95% CI: 1.0–16.8). In conclusion, our results suggest that D-dimer measured at diagnosis may serve as a predictive biomarker of major bleeding after VTE, especially within the initial 3 months.

Background Hospitalization is a well-established risk factor for first venous thromboembolism (VTE), but the risk of recurrence, particularly in patients hospitalized for conditions other than cancer or surgery, has scarcely been investigated. The cumulative incidence of recurrence in hospital-related VTE may be influenced by the competing risk of death. Objectives To investigate the risk of recurrence and mortality among patients with a first hospital-related VTE in models with and without death as a competing event. Methods Information on hospital-related risk factors was collected in 822 patients with a first-lifetime VTE derived from the Tromsø study. Recurrent VTEs and deaths were recorded during follow-up (1994-2012). Results During a median of 2.79 years of follow-up, 132 patients experienced a recurrent VTE. Stratification on hospital-related factors revealed considerable differences in recurrence risk. The 5-year cumulative incidence of recurrence was 27.4%, 11.0% and 20.1% in patients with incident VTEs related to cancer, surgery or other medical illness, respectively, and 18.4% in patients with a non-hospital-related first VTE. The mortality rates were high for all subgroups of hospital-related VTE, except for surgery-related events. Consequently, the cumulative incidence of recurrence dropped in the competing risk analyses, showing a 5-year cumulative incidence of 14.4%, 11.7% and 9.7% in patients with a first VTE related to hospitalization for other medical illness, cancer or surgery, respectively. Conclusions Our findings suggest that patients with incident VTEs related to hospitalization for medical illness other than cancer or surgery have a high recurrence-risk, even in the presence of competing risk of death.