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

 

 Buy Article Permissions and Reprints

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 After at least three months of OAT, treatment was withdrawn in 139 patients.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.

• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  Article in Thieme ConnectPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 6 Prisco D, Grifoni E. The role of D-dimer testing in patients with suspected venous thromboembolism. Semin Thromb Hemost 2009; 35: 50-59.
  Article in Thieme ConnectPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  PubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 21 Pengo V, Lensing AW, Prins MH. et al. Incidenceof chronic thromboembolic pulmonary hypertension after pulmonaryembolism. N Engl J Med 2004; 350: 2257-2264.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar
• 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.
  Article in Thieme ConnectPubMedGoogle Scholar
• 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.
  CrossrefPubMedGoogle Scholar