FACTORS ASSOCIATED WITH D-DIMER ELEVATION IN PATIENTS WITH VENOUS THROMBOEMBOLIC EVENTS

Aim. To study the factors associated with elevated D-dimer levels in patients with acute venous thromboembolic events (VTEE).
material and methods. The study included 111 patients (76 men and 35 women aged 18–76 years) with a first or repeat episode of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in the last 2 months. The majority of the patients (n=80) received unfractionated heparin (UFH) for at least 5 days, followed by warfarin (international normalized ratio (INR) control at least once a month; target INR 2,0–3,0). Some patients (n=31) received therapeutic doses of enoxaparin (1 mg/kg subcutaneously, every 12 hours) for at least 30 days, followed by warfarin treatment. D-dimer levels (norm <0,5 mkg/ml) were measured by the latex agglutination method, with the use of “STA LIATEST >® D-DI” reagents (Diagnostica Stago). Results. D-dimer levels varied from 0,02 to 9,96 mkg/ml (median 1,05 mkg/ml, interquartile range 0,49–1,99 mkg/ml) and exceeded the upper norm limit in 74% of the patients. There was a positive association between D-dimer levels and thrombus “size” (r=0,304; p<0,001), and a negative association between D-dimer levels and >< 0,001), and a negative association between D-dimer levels and thrombus “age” (r=-0,418; p<0,001). Predictors of D-dimer elevation were identified among 150 demographic, anthropometric, anamnestic, clinical, laboratory, genetic, or ultrasound parameters and VTEE risk factors. The results of the multivariate stepwise regression analysis demonstrated that female gender, chronic heart failure (CHF), VTEE symptom duration ><28 days, and thrombus “size” >< 0,001). Predictors of D-dimer elevation were identified among 150 demographic, anthropometric, anamnestic, clinical, laboratory, genetic, or ultrasound parameters and VTEE risk factors. The results of the multivariate stepwise regression analysis demonstrated that female gender, chronic heart failure (CHF), VTEE symptom duration <28 days, and thrombus “size” >< 28 days, and thrombus “size” < 6 points were independent predictors of D-dimer elevation in the acute period of DVT/PE. Conclusion. D-dimer levels, measured 32 (23–44) days after the development of DVT/PE symptoms, were elevated in 74% of the patients. D-dimer elevation in the acute period of VTEE was associated with female gender, CHF, “age” and “size” of the thrombus.

1. Di Nisio M., Squizzato A., Rutjes A. W. et al. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost 2007; 5: 296–304.

2. Tita-Nwa F., Bos A., Adjei A. et al. Correlates of D-dimer in older persons. Aging Clin Exp Res 2010; 22: 20–23.

3. Goldhaber S. Z., Tapson V. F. A prospective registry of 5451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004; 93: 259–262.

4. de Bastos M., de Bastos M. R. D., Bogutchi T. et al. Duration of symptoms and D-dimer testing in the ruling-out of venous thromboembolism. J Thromb Haemost 2006; 4: 2079–2080.

5. de Monye W., Sanson B. J., Buller H. R. et al.; ANTELOPE Study Group. The performance of two rapid quantitative D-dimer assays in 287 patients with clinically suspected pulmonary embolism. Thromb Res 2002; 107: 283–286.

6. Wells P. S. Integrated strategies for the diagnosis of venous thromboembolism. J Thromb Haemost 2007; 5 (Suppl. 1): 41–50.

7. Jug B., Vene N., Salobir B. G. et al. Procoagulant state in heart failure with preserved left ventricular ejection fraction. Int Heart J 2009; 50: 591–600.

8. Marcucci R., Gori A. M., Giannotti F. et al. Markers of hypercoagulability and inflammation predict mortality in patients with heart failure. J Thromb Haemost 2006; 4: 1017–1022.

9. Jug B., Vene N., Salobir B. G. et al. Prognostic impact of haemostatic derangements in chronic heart failure. Thromb Haemost 2009; 102: 185–187.

10. Vorobjeva N. M., Dobrovolskiy A. B., Titaeva E. V. et al. D-dimer as marker of chronic heart failure decompensation. Heart Failure 2011; 12: 36–41. Russian (Н. М. Воробьёва, А. Б. Добровольский, Е. В. Титаева и др. Значимость Д-димера как маркёра декомпенсации хронической сердечной недостаточности. Сердечная недостаточность 2011; 12: 36–41).

11. Russian clinical recommendations about diagnostics, treatment and prevention of venous thromboembolic complications. Phlebology 2010; 4: 4–37. Russian (Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений. Флебология 2010; 4: 4–37).

12. Kearon C., Akl E. A., Comerota A. J. et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (Suppl): e419S-e494S.