Cancer and venous thromboembolism

Paper IV is not available in Munin:Risk of cancer after venous thromboembolism - the Scandinavian Thrombosis and Cancer (STAC) Cohort. Jensvoll H, Severinsen MT, Hammerstrøm J, Brækkan SK, Kristensen SR, Cannegieter SC, Blix K, Tjønneland A, Rosendaal FR, Dziewiecka O, Overvad K, Næss IA, Hansen JB. (Manuscript)Venøs tromboembolisme (VTE) er et samlebegrep for lungeemboli og dyp venetrombose. VTE rammer ofte kreftpasienter og representerer en ledende dødsårsak i denne pasient gruppen. Dette understreker viktigheten av å kartlegge risikofaktorer for kreft-relatert VTE for å muliggjøre forebyggende behandling hos pasienter med høy risiko. En VTE hendelse kan også være det første symptomet på en bakenforliggende kreft som ennå ikke er påvist. Målet med denne avhandlingen var å undersøke om nivået av hvite blodceller og blodplater, målt før kreftutvikling, påvirket VTE risiko hos de med og uten kreft gjennom studieperioden. Videre ville vi undersøke risikoen for påfølgende kreft hos de med og uten VTE og kartlegge om forskjellige VTE kjennetegn hadde innvirkning på kreft risiko. I artikkel I og II er vår studiepopulasjon hentet fra den fjerde Tromsøundersøkelsen (Tromsø 4) gjennomført i 1994-1995, som inkluderte mer enn 27000 deltagere. Artikkel III og IV er basert på «the Scandiavian Thrombosis and Cancer (STAC) Cohort», som er en stor studie hvor Tromsø 4 studien, helseundersøkelsen i Nord-Trøndelag (HUNT 2) og den danske «Diet, Cancer and Health» studien er slått sammen, og inkluderer nesten 145000 deltagere. I alle fire artiklene er validerte VTE hendelser og kreft diagnoser registrert fra inklusjon (1993-1997) til studieslutt (2007-2012). Insidensraten av VTE i Tromsø 4 (1994-2009) var 13.5 per 1000 person-år blant kreftpasienter og 1.2 per 1000 person-år blant de uten kreft. Hos kreftpasientene var både nivået av hvite blodceller og blodplater over 80-persentilen målt før kreftutvikling forbundet med dobling i VTE risiko sammenlignet med 40-persentilen. Kombinasjonen av høye nivåer av begge parameterne ga en synergistisk effekt på VTE risikoen. Hos kreftfrie deltagere derimot, ble det ikke påvist en sammenheng mellom disse parameterne og VTE. Resultatene våre tyder på at nivået av hvite blodceller og blodplater bidrar til VTE hos kreftpasienter. I STAC kohorten studerte vi risikoen for kreft etter VTE. Insidensraten av kreft var 60.6 per 1000 person-år det første året etter VTE sammenlignet med 9.5 per 1000 person-år hos deltagere uten VTE. Pasienter med VTE hadde en firedoblet risiko for kreft sammenlignet med VTE-frie det første året etter VTE, og en 1.3 ganger høyere risiko de påfølgende år. Den anatomiske lokalisasjonen av blodproppen påvirket i liten grad kreftrisikoen, og det var også små forskjeller i kreftrisiko mellom pasienter med uprovosert og provosert VTE. Resultatene indikerer at fremtidige studier som kartlegger nytten av systematisk kreftutredning etter VTE ikke bør begrenses av disse faktorene

Platelet Count Measured Prior to Cancer Development Is a Risk Factor for Future Symptomatic Venous Thromboembolism: The Tromsø Study

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 personyears) and 377 in the non-cancer cohort (1.2 per 1000 person-years). In cancer patients, pre-cancer platelet count above the 80th percentile ($2956109/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 (,2356109/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

White blood cell count measured prior to cancer development is associated with future risk of venous thromboembolism - The Tromsø Study

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 cancerfree 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 (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

Platelet count and risk of symptomatic venous thromboembolism.

<p>Dose-response relationship between platelet count and risk of venous thromboembolism in cancer and non-cancer subjects obtained by generalized linear regression. The regression models are adjusted for age, sex, body mass index, smoking, leukocyte count and mean platelet volume. The solid lines show hazard ratios and the shaded areas represent 95% confidence intervals. Density plots show the distribution of platelet count, and white vertical lines indicate 2.5^th, 25^th, 50^th, 75^th and 97.5^th percentiles.</p

Characteristics across categories of platelet count at the time of cancer diagnosis; The Tromsø Study 1994–2009.

<p>*Includes es°phagus, stomach, small intestine, liver, gallbladder and biliary tract.</p><p>SD; standard deviation.</p

Incidence rates (IRs) and hazard ratios (HRs) for symptomatic venous thromboembolism by categories of platelet count and leukocyte count with 95% confidence intervals; The Tromsø Study 1994–2009.

<p>*10⁹/L.</p>†<p>Person years. Subjects who develop cancer during follow-up are treated as non-cancer subjects until one year prior to the cancer diagnosis.</p>‡<p>Incidence rate per 1000 person years.</p><p>Model 1: Adjusted for age and sex.</p><p>Model 2: Adjusted for age, sex, smoking, body mass index and mean platelet volume.</p><p>Model 3: Model 2+ cancer stage (defined as localized or disseminated disease).</p

Incidence rates (IRs) and hazard ratios (HRs) for symptomatic venous thromboembolism by increasing platelet count with 95% confidence intervals; The Tromsø Study 1994–2009.

<p>*10⁹/L.</p>†<p>Person years. Subjects who develop cancer during follow-up are treated as non-cancer subjects until one year prior to the cancer diagnosis.</p>‡<p>Incidence per 1000 person years.</p><p>Model 1: Adjusted for age and sex.</p><p>Model 2: Adjusted for age, sex, body mass index, smoking, leukocyte count and mean platelet volume.</p><p>Model 3: Model 2+ cancer stage (defined as localized or disseminated disease).</p

Thromboembolic Events During Treatment with Cisplatin-based Chemotherapy in Metastatic Testicular Germ-cell Cancer 2000–2014: A Population-based Cohort Study

Background - Cisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking. Objective - To evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding. Design, setting, and participants - In a population-based study, 506 men administered first-line CBCT during 2000–2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records. Outcome measurements and statistical analysis Patients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors. Results and limitations - Overall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01–3.91), central venous access (OR 2.84, 95% CI 1.46–5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12–5.07) as incident VTE risk factors. Thromboprophylaxis (n = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p  Conclusions - We found a high rate of thromboembolism incidence of 13.6%. Thromboprophylaxis did not decrease the risk of VTE but was associated with an increased risk of bleeding. Patient summary - We found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events

WBC count and risk of venous thromboembolism.

<p>Dose–response relationship between WBC count and risk of VTE in cancer and non-cancer subjects obtained by generalized linear regression. The regression models are adjusted for age, sex, BMI, smoking, self-reported diabetes, physical activity and self-reported CVD. The solid lines show HRs and the shaded areas show 95% CIs. Density plots show the distribution of WBC, and white vertical lines indicate 2.5^th, 25^th, 50^th, 75^th and 97.5^th percentiles.</p