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DOI: 10.1055/s-0038-1673694
Role of Routine Laboratory Tests in Assessing Risk of Recurrent Venous Thrombosis: Results from the MEGA Follow-Up Study
Funding This work was supported by the Netherlands Heart Foundation (grants NHS98.113, NHS2010B167, NHS208B086 and NHS2011T012), the Dutch Cancer Foundation (grant RUL 99/1992) and the Netherlands Organization for Scientific Research (grant 912–03–033|2003).Publikationsverlauf
04. Mai 2018
11. August 2018
Publikationsdatum:
24. Oktober 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201811/lookinside/thumbnails/10-1055-s-0038-1673694_180327-1.jpg)
Abstract
Background Kidney function, measured as estimated glomerular filtration rate (eGFR), glucose levels and haematologic variables (blood cell count) are easily obtainable tests, and have been associated with increased risk of first venous thrombosis (VT). Whether these routine tests can identify patients at risk of recurrence is unclear.
Aim Our aim was to investigate the predictive value of serum glucose levels, eGFR and haematologic variables in patients at risk of recurrent VT.
Methods Patients with a first VT were followed from discontinuation of anticoagulant treatment. Percentile categories of eGFR, glucose levels and haematologic variables were established. Crude incidence rates with 95% confidence intervals (CIs) of recurrence were estimated in each percentile category. Cox regression models were used to compare groups, adjusted for age and sex.
Results Of 2,106 patients followed for a median of 6.9 years, 326 developed recurrence (incidence rate, 2.7/100 patient-years; 95% CI, 2.5–3.1). The adjusted hazard ratio for recurrence was 1.5 (95% CI, 0.9–2.4) in the lowest eGFR percentile category (< 59 mL/min/1.73 m2) versus the reference (≥86 mL/min/1.73 m2). Stratification by unprovoked or provoked first events yielded similar results. The combination of a first unprovoked VT with renal dysfunction was associated with a threefold increased risk of recurrence compared with those with first provoked VT and normal kidney function (hazard ratio, 3.1, 95% CI, 1.6–5.9). Glucose levels and haematologic variables were not associated with increased recurrence risk.
Conclusion Testing glucose levels and haematologic variables did not identify patients at increased risk of recurrent VT. Renal dysfunction tests may have some predictive value, particularly in combination with other variables.
Authors' Contributions
V.M. Morelli had full access to the database, performed the statistical analysis, interpreted the data and drafted the manuscript. W.M. Lijfering designed the analysis, had full access to the database, supervised the statistical analysis, interpreted the data and revised the manuscript. S.M. Rezende interpreted the data and revised the manuscript. A. van Hylckama Vlieg interpreted the data and revised the manuscript. F.R. Rosendaal was responsible for the MEGA study concept and design, interpreted the data and revised the manuscript. S.C. Cannegieter designed the analysis, interpreted the data and revised the manuscript. All authors read and approved the final version of the manuscript.
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References
- 1 Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 05 (04) 692-699
- 2 Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293 (19) 2352-2361
- 3 Prandoni P, Noventa F, Ghirarduzzi A. , et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92 (02) 199-205
- 4 Arshad N, Bjøri E, Hindberg K, Isaksen T, Hansen JB, Braekkan SK. Recurrence and mortality after first venous thromboembolism in a large population-based cohort. J Thromb Haemost 2017; 15 (02) 295-303
- 5 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149 (02) 315-352
- 6 Lijfering WM, Biedermann JS, Kruip MJ, Leebeek FW, Rosendaal FR, Cannegieter SC. Can we prevent venous thrombosis with statins: an epidemiologic review into mechanism and clinical utility. Expert Rev Hematol 2016; 9 (11) 1023-1030
- 7 Kearon C, Gent M, Hirsh J. , et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340 (12) 901-907
- 8 Veeger NJ, Piersma-Wichers M, Tijssen JG, Hillege HL, van der Meer J. Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism. Br J Haematol 2005; 128 (04) 513-519
- 9 Verhovsek M, Douketis JD, Yi Q. , et al. Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Ann Intern Med 2008; 149 (07) 481-490
- 10 Kyrle PA, Minar E, Hirschl M. , et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343 (07) 457-462
- 11 Timp JF, Lijfering WM, Flinterman LE. , et al. Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study. J Thromb Haemost 2015; 13 (10) 1823-1832
- 12 Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296 (04) 397-402
- 13 Tichelaar V, de Jong H, Nijland H, Kluin-Nelemans H, Meijer K, Mulder A. Interference of rivaroxaban in one-stage and chromogenic factor VIII:C assays. Thromb Haemost 2011; 106 (05) 990-992
- 14 Adcock DM, Gosselin R, Kitchen S, Dwyre DM. The effect of dabigatran on select specialty coagulation assays. Am J Clin Pathol 2013; 139 (01) 102-109
- 15 Levey AS, Coresh J, Greene T. , et al; Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the Modification of Diet in Renal Disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145 (04) 247-254
- 16 Ocak G, Vossen CY, Lijfering WM. , et al. Role of hemostatic factors on the risk of venous thrombosis in people with impaired kidney function. Circulation 2014; 129 (06) 683-691
- 17 Mahmoodi BK, Gansevoort RT, Næss IA. , et al. Association of mild to moderate chronic kidney disease with venous thromboembolism: pooled analysis of five prospective general population cohorts. Circulation 2012; 126 (16) 1964-1971
- 18 Cheung KL, Zakai NA, Folsom AR. , et al. Measures of kidney disease and the risk of venous thromboembolism in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study. Am J Kidney Dis 2017; 70 (02) 182-190
- 19 Dekkers IA, de Mutsert R, de Vries APJ. , et al. Determinants of impaired renal and vascular function are associated with elevated levels of procoagulant factors in the general population. J Thromb Haemost 2018; 16 (03) 519-528
- 20 Cheung KL, Zakai NA, Callas PW. , et al. Mechanisms and mitigating factors for venous thromboembolism in chronic kidney disease: the REGARDS study. J Thromb Haemost 2018; 16 (09) 1743-1752
- 21 Hermanides J, Cohn DM, Devries JH. , et al. Venous thrombosis is associated with hyperglycemia at diagnosis: a case-control study. J Thromb Haemost 2009; 7 (06) 945-949
- 22 Tichelaar YIGV, Lijfering WM, ter Maaten JC, Kluin-Nelemans JC, Meijer K. High levels of glucose at time of diagnosing venous thrombosis: a case-control study. J Thromb Haemost 2011; 9 (04) 883-885
- 23 Heit JA, Leibson CL, Ashrani AA, Petterson TM, Bailey KR, Melton III LJ. Is diabetes mellitus an independent risk factor for venous thromboembolism?: a population-based case-control study. Arterioscler Thromb Vasc Biol 2009; 29 (09) 1399-1405
- 24 Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Hansen JB. Hematocrit and risk of venous thromboembolism in a general population. The Tromsø Study. Haematologica 2010; 95 (02) 270-275
- 25 Basavaraj MG, Brækkan SK, Brodin E, Østerud B, Hansen JB. Monocyte count and procoagulant functions are associated with risk of venous thromboembolism: the Tromsø Study. J Thromb Haemost 2011; 9 (08) 1673-1676
- 26 Zöller B, Melander O, Svensson P, Engström G. Red cell distribution width and risk for venous thromboembolism: a population-based cohort study. Thromb Res 2014; 133 (03) 334-339
- 27 Ellingsen TS, Lappegård J, Skjelbakken T, Brækkan SK, Hansen JB. Red cell distribution width is associated with incident venous thromboembolism (VTE) and case-fatality after VTE in a general population. Thromb Haemost 2015; 113 (01) 193-200
- 28 Bucciarelli P, Maino A, Felicetta I. , et al. Association between red cell distribution width and risk of venous thromboembolism. Thromb Res 2015; 136 (03) 590-594
- 29 Rezende SM, Lijfering WM, Rosendaal FR, Cannegieter SC. Hematologic variables and venous thrombosis: red cell distribution width and blood monocyte count are associated with an increased risk. Haematologica 2014; 99 (01) 194-200
- 30 Eischer L, Tscholl V, Heinze G, Traby L, Kyrle PA, Eichinger S. Hematocrit and the risk of recurrent venous thrombosis: a prospective cohort study. PLoS One 2012; 7 (06) e38705
- 31 Parikh AM, Spencer FA, Lessard D. , et al. Venous thromboembolism in patients with reduced estimated GFR: a population-based perspective. Am J Kidney Dis 2011; 58 (05) 746-755
- 32 van Stralen KJ, Rosendaal FR, Doggen CJ. Minor injuries as a risk factor for venous thrombosis. Arch Intern Med 2008; 168 (01) 21-26
- 33 Morelli VM, Lijfering WM, Rosendaal FR, Cannegieter SC. Lipid levels and risk of recurrent venous thrombosis: results from the MEGA follow-up study. J Thromb Haemost 2017; 15 (04) 695-701
- 34 Flinterman LE, van Hylckama Vlieg A, Cannegieter SC, Rosendaal FR. Long-term survival in a large cohort of patients with venous thrombosis: incidence and predictors. PLoS Med 2012; 9 (01) e1001155
- 35 World Health Organization. 2006 Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Available at: http://www.who.int/diabetes/publications/diagnosis_diabetes2006/en/ . Accessed August 2, 2018
- 36 Levey AS, Coresh J, Balk E. , et al; National Kidney Foundation. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139 (02) 137-147
- 37 Murphy WG. The sex difference in haemoglobin levels in adults - mechanisms, causes, and consequences. Blood Rev 2014; 28 (02) 41-47
- 38 Verduijn M, Grootendorst DC, Dekker FW, Jager KJ, le Cessie S. The analysis of competing events like cause-specific mortality--beware of the Kaplan-Meier method. Nephrol Dial Transplant 2011; 26 (01) 56-61
- 39 van Schouwenburg IM, Mahmoodi BK, Veeger NJ, Kluin-Nelemans HC, Gansevoort RT, Meijer K. Elevated albuminuria associated with increased risk of recurrent venous thromboembolism: results of a population-based cohort study. Br J Haematol 2012; 156 (05) 667-671
- 40 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160 (06) 809-815
- 41 Rogers MA, Levine DA, Blumberg N, Flanders SA, Chopra V, Langa KM. Triggers of hospitalization for venous thromboembolism. Circulation 2012; 125 (17) 2092-2099
- 42 Harnish MJ, Lange T, Dimitrov S, Born J, Fehm HL. Differential regulation of human blood glucose level by interleukin-2 and -6. Exp Clin Endocrinol Diabetes 2005; 113 (01) 43-48
- 43 Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol 2011; 11 (11) 762-774
- 44 O'Donnell J, Mumford AD, Manning RA, Laffan M. Elevation of FVIII: C in venous thromboembolism is persistent and independent of the acute phase response. Thromb Haemost 2000; 83 (01) 10-13
- 45 Tichelaar V, Mulder A, Kluin-Nelemans H, Meijer K. The acute phase reaction explains only a part of initially elevated factor VIII:C levels: a prospective cohort study in patients with venous thrombosis. Thromb Res 2012; 129 (02) 183-186