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Author(s): Jasmijn F. Timp, Sigrid K. Braekkan, Willem M. Lijfering, Astrid van Hylckama Vlieg, John-Bjarne Hansen, Frits R. Rosendaal, Saskia le Cessie, Suzanne C. Cannegieter In Table 2, the coefficients [...]

Background Recurrent venous thromboembolism (VTE) is common. Current guidelines suggest that patients with unprovoked VTE should continue anticoagulants unless they have a high bleeding risk, whereas all others can stop. Prediction models may refine this dichotomous distinction, but existing models apply only to patients with unprovoked first thrombosis. We aimed to develop a prediction model for all patients with first VTE, either provoked or unprovoked. Methods and findings Data were used from two population-based cohorts of patients with first VTE from the Netherlands (Multiple Environment and Genetic Assessment of Risk Factors for Venous Thrombosis [MEGA] follow-up study, performed from 1994 to 2009; model derivation; n = 3,750) and from Norway (Tromsø study, performed from 1999 to 2016; model validation; n = 663). Four versions of a VTE prediction model were developed: model A (clinical, laboratory, and genetic variables), model B (clinical variables and fewer laboratory markers), model C (clinical and genetic factors), and model D (clinical variables only). The outcome measure was recurrent VTE. To determine the discriminatory power, Harrell's C-statistic was calculated. A prognostic score was assessed for each patient. Kaplan-Meier plots for the observed recurrence risks were created in quintiles of the prognostic scores. For each patient, the 2-year predicted recurrence risk was calculated. Models C and D were validated in the Tromsø study. During 19,201 person-years of follow-up (median duration 5.7 years) in the MEGA study, 507 recurrences occurred. Model A had the highest predictive capability, with a C-statistic of 0.73 (95% CI 0.71-0.76). The discriminative performance was somewhat lower in the other models, with C-statistics of 0.72 for model B, 0.70 for model C, and 0.69 for model D. Internal validation showed a minimal degree of optimism bias. Models C and D were externally validated, with C-statistics of 0.64 (95% CI 0.62-0.66) and 0.65 (95% CI 0.63-0.66), respectively. According to model C, in 2,592 patients with provoked first events, 367 (15%) patients had a predicted 2-year risk of >10%, whereas in 1,082 patients whose first event was unprovoked, 484 (45%) had a predicted 2-year risk of Conclusions The prediction model we propose applies to patients with provoked or unprovoked first VTE-except for patients with (a history of) cancer-allows refined risk stratification, and is easily usable. For optimal individualized treatment, a management study in which bleeding risks are also taken into account is necessary., Author(s): Jasmijn F. Timp 1, Sigrid K. Braekkan 2,3, Willem M. Lijfering 1, Astrid van Hylckama Vlieg 1, John-Bjarne Hansen 2,3, Frits R. Rosendaal 1, Saskia le Cessie 4, Suzanne [...]

Background: Obesity is a major risk factor for venous thromboembolism (VTE), but it is unknown to what extent weight change over time affects VTE risk. Aims: To investigate the association between weight change and risk of incident VTE in a population-based cohort with repeated measurements. Methods: Participant data were collected from the Tromsø 3 (1986–87), 4 (1994–95), 5 (2000–01) and 6 (2007–08) surveys. Subjects who attended two subsequent or more surveys were included (n = 17802), and weight change between the surveys was calculated. Person-time at risk was accrued from the second of two subsequent vists until the next survey, the date of an incident VTE, migration, death or study end (December 31st 2012), whichever came first. Cox regression models were used to calculate risk of VTE according to change in body weight. Results: There were 302 incident VTE events during a median of 6.0 years of follow-up. Subjects who gained most weight (7.5–40.0 kg weight gain) had a 1.9-fold higher risk of VTE compared to those with no or a moderate (0–7.4 kg) weight gain (HR 1.92; 95% CI 1.38–2.68). The VTE risk by ≥7.5 kgs over no or moderate (0–7.4 kg) weight gain was highest (HR 3.75; 95% 1.83–7.68) in subjects with baseline body mass index (BMI) ≥30 kg/m2. There was a joint effect of weight gain and baseline BMI on VTE risk. Those with BMI ≥30 who gained ≥7.5 kgs had a 6.6-fold increased risk (HR 6.64; 95% CI 3.61–12.22) compared to subjects with BMI <25 and no or moderate (0–7.4 kg) weight gain. Conclusions: Our findings imply that further weight gain is a considerable risk factor for VTE, particularly in obese individuals. [ABSTRACT FROM AUTHOR]

Background: Elevated platelet count is associated with risk of venous thromboembolism in cancer patients initiating chemotherapy. It is not known whether this risk by platelet count is causal or merely reflects the malignant disease. We investigated whether pre-cancer platelet count alone or together with high leukocyte count was associated with risk of venous thromboembolism in subjects who did and did not develop cancer during follow-up in a population-based cohort study. Methods: Platelet count and other baseline characteristics were measured in 25160 initially cancer-free subjects who participated in the Tromsø Study in 1994–1995. Incident cancer and symptomatic venous thromboembolism events were registered up to December 31st, 2009. Multivariable Cox regression models were used to calculate hazard ratio for venous thromboembolism across categories of platelet count (<40th, 40–80th, and >80th percentile) with 95% confidence interval. Results: During follow-up, 2082 subjects were diagnosed with cancer. Platelet count was measured on average 8.3 years before the cancer diagnosis. There were 129 venous thromboembolism events in the cancer cohort (13.5 per 1000 person-years) and 377 in the non-cancer cohort (1.2 per 1000 person-years). In cancer patients, pre-cancer platelet count above the 80th percentile (≥295×109/L) was associated with a 2-fold higher risk of venous thromboembolism (Hazard ratio: 1.98, 95% confidence interval 1.21–3.23) compared to platelet count below the 40th percentile (<235×109/L). Concomitant high platelet and leukocyte counts showed a synergistic effect on the VTE risk. In cancer-free subjects, no association was found. Comment: In conclusion, pre-cancer platelet count was associated with risk of symptomatic venous thromboembolism in cancer patients, but not in cancer-free subjects. Our findings suggest that platelet count and platelet-leukocyte interactions may play a role in the pathogenesis of cancer-related venous thromboembolism. [ABSTRACT FROM AUTHOR]

Background:Elevated white blood cell (WBC) count is associated with risk of venous thromboembolism (VTE) in cancer patients initiating chemotherapy. It is not known whether the risk of VTE by WBC count in cancer patients is causal or merely a consequence of the malignant disease. To address this question, we studied the association between WBC count, measured prior to cancer development, and risk of VTE in subjects who did and did not develop cancer during follow-up in a prospective population-based study. Methods:Baseline characteristics, including WBC and neutrophil counts, were measured in 24304 initially cancer-free subjects who participated in the Tromsø Study in 1994-1995. Incident cancer diagnosis and VTE events were registered up to September 1, 2007. In the cancer cohort, WBC and neutrophil counts were measured in average 7.1 years before cancer development. Cox-regression models were used to calculate hazard ratios (HRs) for VTE by WBC and neutrophil counts as categorized variables (<40th, 40-80th, and >80th percentile) with 95% confidence intervals (CIs). Results:During follow-up, 1720 subjects developed cancer and there were 388 VTE events, of which 116 occurred in the cancer-group (6.9 per 1000 person-years) and 272 in the cancer-free group (1.1 per 1000 person-years). In those who developed cancer, WBC count above the 80th percentile (≥8.6x109 cells/L) was associated with a 2.4-fold higher risk (HR 2.36, 95% CI: 1.44-3.87) of VTE compared to WBC count below the 40th percentile (<6.4x109 cells/L). No association was found between WBC count and VTE in those who stayed cancer-free (HR 0.94, 95% CI 0.65-1.36). Similar findings were observed for neutrophils. Comment:Pre-cancer WBC count was associated with risk of VTE in cancer patients, but not in cancer-free subjects. Our findings suggest that leukocytes may play a causal role in cancer-related VTE rather than only reflecting the low-grade inflammation associated with cancer. [ABSTRACT FROM AUTHOR]