Abstract
After a first episode of pulmonary embolism (PE), two major problems need to be considered: risk of recurrence when anticoagulation is stopped, and risk of chronic thromboembolic pulmonary hypertension (CTPH). We followed prospectively consecutive patients who survived a first episode of PE, with or without deep vein thrombosis, to assess the incidence of venous thromboembolism (VTE) recurrences and of symptomatic and asymptomatic CTPH. After 3–6 months of oral anticoagulant therapy (OAT) patients underwent transthoracic echocardiography for measuring transtricuspid (rV-rA) gradient. When rV-rA gradient was >35 mmHg further evaluations were performed to rule in or out CTPH. During follow-up patients who developed persistent dyspnea were re-evaluated. In patients who underwent OAT withdrawal D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), and thrombophilia were evaluated one month after warfarin discontinuation. Overall, 239 patients, 118 males, median age 59(16–89) years, were followed up for a median time of 36(9–192) months. Nine patients had rV-rA gradient >30 mmHg and ≤35 mmHg, and one of 37 mmHg. Among patients with normal rV-rA gradient, one developed persistent dyspnea 55 months after the first event and CPTH was confirmed. Among 206 patients who stopped OAT, 23(11.2%) had VTE recurrence, 11 PE(48%). Elevated DD and F1 + 2 levels after stopping OAT were significantly associated with recurrence. None of patients with recurrent VTE had elevated rV-rA gradient. In our series the incidence of CTPH after a first episode of PE was 0.4%. VTE recurrence and elevated DD and F1 + 2 levels seemed not to be related to the development of CTPH.
Similar content being viewed by others
References
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd (1998) Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 158:585–593
Goldhaber SZ (1998) Pulmonary embolism. N Engl J Med 339:93–104
Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ, American College of Chest Physicians (2008) Antithrombotic therapy for venous thromboembolic disease: American College of chest physicians evidence-based clinical practice guidelines (8th edition). Chest 133:454S–545S
Agnelli G, Prandoni P, Becattini C, Silingardi M, Taliani MR, Miccio M, Imberti D, Poggio R, Ageno W, Pogliani E, Porro F, Zonzin P, Warfarin Optimal Duration Italian Trial Investigators (2003) Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 139:19–25
Kearon C (2007) Indefinite anticoagulation after a first episode of unprovoked venous thromboembolism: yes. J Thromb Haemost 5:2330–2335
Baglin T (2007) Unprovoked deep vein thrombosis should be treated with long-term anticoagulation––no. J Thromb Haemost 5:2336–2339
Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J, Hobbins, Spera MA, Alavi A, Terrin ML (1992) The clinical course of pulmonary embolism. N Engl J Med 326:1240–1245
Fedullo PF, Auger WR, Kerr KM, Rubin LJ (2001) Chronic thromboembolic pulmonary hypertension. N Engl J Med 345:1465–1472
Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P (2004) Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 350:2257–2264
Miniati M, Monti S, Bottai M, Scoscia E, Bauleo C, Tonelli L, Dainelli A, Giuntini C (2006) Survival and restoration of pulmonary perfusion in a long-term follow-up of patients after acute pulmonary embolism. Medicine 85:253–262
Becattini C, Agnelli G, Pesavento R, Silingardi M, Poggio R, Taliani MR, Ageno W (2006) Incidence of chronic thromboembolic pulmonary hypertension after a first episode of pulmonary embolism. Chest 130:172–175
Dentali F, Donadini M, Gianni M, Bertolini A, Squizzato A, Venco A, Ageno W (2009) Incidence of chronic pulmonary hypertension in patients with previous pulmonary embolism. Thromb Res 124:256–258
Klok F, van Kralingen K, van Dijk A, Heyning F, Vliegen H, Huisman M (2010) Prospective cardiopulmonary screening program to detect chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism. Haematologica. doi:10.3324/haematol.2009.018960
Galiè N, Torbicki A, Barst R, Dartevelle P, Haworth S, Higenbottam T, Olschewski H, Peacock A, Pietra G, Rubin LJ, Simonneau G, Priori SG, Garcia MA, Blanc JJ, Budaj A, Cowie M, Dean V, Deckers J, Burgos EF, Lekakis J, Lindahl B, Mazzotta G, McGregor K, Morais J, Oto A, Smiseth OA, Barbera JA, Gibbs S, Hoeper M, Humbert M, Naeije R, Pepke-Zaba J (2004) Task force. 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 25:2243–2278
Marcucci R, Sodi A, Giambene B, Alessandrello Liotta A, Poli D, Mannini L, Falciani M, Abbate R, Menchini U, Prisco D (2007) Cardiovascular and thrombophilic risk factors in patients with retinal artery occlusion. Blood Coagul Fibrinolysis 18:321–326
Poli D, Antonucci E, Ciuti G, Abbate R, Prisco D (2008) 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 6:708–710
Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RHWM, de Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306
Prandoni P, Cogo A, Bernardi E, Villalta S, Polistena P, Simioni P, Noventa F, Benedetti L, Girolami A (1993) A simple ultrasound approach for detection of recurrent proximal vein thrombosis. Circulation 88:1730–1735
Perrier A, Miron MJ, Desmarais S, De Moerloose P, Slosman D, Didier D, Unger PF, Junod A, Patenaude JV, Bounameaux H (2000) 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 160:512–516
Pengo V, Palareti G, Cosmi B, Legnani C, Tosetto A, Alatri A, Marzot F, Pegoraro C, Cucchini U, Iliceto S, PROLONG Investigators (2008) D-dimer testing and recurrent venous thromboembolism after unprovoked pulmonary embolism: a post-hoc analysis of the prolong extension study. Thromb Haemost 100:718–721
Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A, Pengo V, Ghirarduzzi A, Pattacini C, Testa S, Lensing AWA, Tripodi A, PROLONG Investigators (2006) D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 355:1780–1789
Verhovsek M, Douketis JD, Yi Q, Shrivastava S, Tait RC, Baglin T, Poli D, Lim W (2008) Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Ann Intern Med 149:481–490
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Poli, D., Grifoni, E., Antonucci, E. et al. Incidence of recurrent venous thromboembolism and of chronic thromboembolic pulmonary hypertension in patients after a first episode of pulmonary embolism. J Thromb Thrombolysis 30, 294–299 (2010). https://doi.org/10.1007/s11239-010-0452-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11239-010-0452-x