Risk of recurrence in patients with pulmonary embolism: Predictive role of D-dimer and of residual perfusion defects on lung scintigraphy

Summary

The stratification of recurrence risk after a first episode of venous thromboembolism (VTE) is an important topic of research, especially in patients with pulmonary embolism (PE). Elevated D-dimer levels and residual vein obstruction (RVO) at compression ultrasonography have been studied as predictors of recurrence after withdrawing oral anticoagulant treatment (OAT). It is still unknown if residual perfusion defects (PD) on lung scintigraphy are related to recurrent PE. In the present study, we evaluated the association of PD with PE recurrence. The relationship between PD, elevated D-dimer levels, and RVO was also investigated. We prospectively followed 236 consecutive patients who survived a first episode of objectively confirmed PE, with or without deep-vein thrombosis. After at least three months of OAT, treatment was withdrawn in 139 patients. D-dimer levels were evaluated at one month of OAT withdrawal, RVO was measured, and perfusion lung scan (P-scan) was performed to evaluate PD. During follow-up, 20 patients experienced a recurrent episode of VTE. Elevated D-dimer levels were significantly associated with VTE recurrence, (p=0.003). RVO was present in 22% of the patients with recurrence and in 7.5% of those without (p=0.07). No significant association was found between PD >10% and VTE recurrence, D-dimer, or RVO. In conclusion, we confirmed the positive predictive value of elevated D-dimer levels for recurrent VTE. Residual PD on lung scintigraphy are neither predictive of recurrence nor related to D-dimer levels or RVO.

Keywords

D-dimer - perfusion defects - pulmonary embolism - recurrence

• References

• 1 Douketis JD, Kearon C, Bates S. et al. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. J Am Med Assoc 1998; 279: 458-462.
• 2 Murin S, Romano PS, White RH. Comparison of outcomes after hospitalization for deep venous thrombosis or pulmonary embolism. Thromb Haemost 2002; 88: 407-414.
• 3 Kearon C, Akl EA, Comerota AJ. et al. American College of Chest Physicians. 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: e419S.-494S
• 4 Palareti G, Cosmi B, Legnani C. et al PROLONG Investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355: 1780-1789.
• 5 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: 481-490.
• 6 Prisco D, Grifoni E. The role of D-dimer testing in patients with suspected venous thromboembolism. Semin Thromb Hemost 2009; 35: 50-59.
• 7 Douketis J, Tosetto A, Marcucci M. et al. Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism. Ann Intern Med 2010; 153: 523-531.
• 8 Poli D, Antonucci E, Ciuti G. et al. Combination of D-dimer, F1+2 and residual vein obstruction as predictors of VTE recurrence in patients with first VTE episode after OAT withdrawal. J Thromb Haemost 2008; 06: 708-710.
• 9 Siragusa S, Malato A, Anastasio R. et al. Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study. Blood 2008; 112: 511-515.
• 10 Baglin T, Douketis J, Tosetto A. et al. Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence?. A patient-level meta-analysis J Thromb Haemost 2010; 08: 2436-2442.
• 11 Prandoni P, Prins MH, Lensing AW. et al. AESOPUS Investigators. Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis: a randomized trial. Ann Intern Med 2009; 150: 577-585.
• 12 Cosmi B, Legnani C, Iorio A. et al. Residual venous obstruction, alone and in combination with D-dimer, as a risk factor for recurrence after anticoagulation withdrawal following a first idiopathic deep vein thrombosis in the prolong study. Eur J Vasc Endovasc Surg 2010; 39: 356-365.
• 13 Carrier M, Rodger MA, Wells PS. et al. Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost 2011; 09: 1119-1125.
• 14 Miniati M, Monti S, Bottai M. et al. Survival and restoration of pulmonary perfusion in a long-term follow-up of patients after acute pulmonary embolism. Medicine 2006; 85: 253-262.
• 15 Miniati M, Pistolesi M, Marini C. et al. Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA- PED). Am J Respir Crit Care Med 1996; 154: 1387-1393.
• 16 Meyer G, Collignon MA, Guinet F. et al. Comparison of perfusion lung scanning and angiography in the estimation of vascular obstruction in acute pulmonary embolism. Eur J Nucl Med 1990; 17: 315-319.
• 17 Galie N, Torbicki A, Barst R. et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The task force on diagnosis and treatment of pulmonary arterial hypertension of the European society of cardiology. Eur Heart J 2004; 25: 2243-2278.
• 18 Marcucci R, Sodi A, Giambene B. et al. Cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion. Blood Coagul Fibrinolysis 2007; 18: 321-326.
• 19 Prandoni P, Cogo A, Bernardi E. et al. A simple ultrasound approach for detection of recurrent proximal vein thrombosis. Circulation 1993; 88: 1730-1735.
• 20 Perrier A, Miron MJ, Desmarais S. et al. Using clinical evaluation and lung scan to rule out suspected pulmonary embolism: is it a valid option in patients with normal results of lower limb venous compression ultrasonography?. Arch Intern Med 2000; 160: 512-516.
• 21 Pengo V, Lensing AW, Prins MH. et al. Incidenceof chronic thromboembolic pulmonary hypertension after pulmonaryembolism. N Engl J Med 2004; 350: 2257-2264.
• 22 Palareti G, Legnani C, Cosmi B. et al. Predictive value of D-dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and in carriers of congenital thrombophilia. Circulation 2003; 108: 313-318.
• 23 Cosmi B, Legnani C, Tosetto A. et al. Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study. Blood 2010; 115: 481-488.
• 24 Pengo V, Palareti G, Cosmi B. et al. D-dimer testing and recurrent venous thromboembolism after unprovoked pulmonary embolism: A post-hoc analysis of the prolong extension study. Thromb Haemost 2008; 100: 718-722.
• 25 Tan M, Mos IC, Klok FA. et al. Residual venous thrombosis as predictive factor for recurrent venous thromboembolim in patients with proximal deep vein thrombosis: a sytematic review. Br J Haematol 2011; 153: 168-178.