Thrombotic risk factors in pulmonary hypertension

Thrombotic lesions are consistently observed in chronic thromboembolic pulmonary hypertension (CTEPH) and frequently found in primary pulmonary hypertension (PPH). It remains unknown, however, whether thrombosis is related to defects of the antithrombotic pathway or to previous vascular injury. This study therefore analysed the frequency of both hereditary and acquired thrombotic risk factors in CTEPH and PPH. One hundred and forty-seven consecutive patients with CTEPH investigated in the author's institution were compared to 99 consecutive patients with PPH. In 116 CTEPH patients and 83 PPH patients, phospholipid-dependent antibodies (antiphospholipid antibodies and lupus anticoagulant) were analysed by both immunological and clotting assays. In patients enrolled since 1994 (46 CTEPH and 64 PPH), hereditary thrombotic risk factors were also determined. Antithrombin, protein C and protein S activities were measured by functional assays. Mutations of factor V and factor II were identified by polymerase chain reaction. The prevalence of hereditary thrombotic risk factors was not increased in patients with either PPH or CTEPH. In contrast, a high frequency of phospholipid-dependent antibodies was observed in PPH (10%) and more notably in CTEPH (20%). Moreover, in PPH, antibodies were present only in low titre whereas in CTEPH, half of the patients with antiphospholipid antibodies had high titres. In addition, in CTEPH all but one of the patients with lupus anticoagulant also had antiphospholipid antibodies. The most striking finding of this study was the high prevalence of phospholipid-dependent antibodies but their clinical relevance appears to be different in primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. In primary pulmonary hypertension, these antibodies in low titre probably reflect endothelial dysfunction. In contrast, in chronic thromboembolic pulmonary hypertension the presence of antibodies in high titre associated with lupus anticoagulant, underlines the role of thrombosis in the pathogenesis of this condition.

This article has been cited by other articles:

				D. Bonderman, H. Wilkens, S. Wakounig, H-J. Schafers, P. Jansa, J. Lindner, I. Simkova, A. M. Martischnig, J. Dudczak, R. Sadushi, et al. Risk factors for chronic thromboembolic pulmonary hypertension Eur. Respir. J., February 1, 2009; 33(2): 325 - 331. [Abstract] [Full Text] [PDF]

				J. Suntharalingam, K. Goldsmith, V. van Marion, L. Long, C. M. Treacy, F. Dudbridge, M. R. Toshner, J. Pepke-Zaba, J. C. J. Eikenboom, and N. W. Morrell Fibrinogen A{alpha} Thr312Ala polymorphism is associated with chronic thromboembolic pulmonary hypertension Eur. Respir. J., April 1, 2008; 31(4): 736 - 741. [Abstract] [Full Text] [PDF]

				D. Bonderman, J. Jakowitsch, B. Redwan, H. Bergmeister, M.-K. Renner, H. Panzenbock, C. Adlbrecht, A. Georgopoulos, W. Klepetko, M. Kneussl, et al. Role for Staphylococci in Misguided Thrombus Resolution of Chronic Thromboembolic Pulmonary Hypertension Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 678 - 684. [Abstract] [Full Text] [PDF]

				National Pulmonary Hypertension Centres of the UK Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland Heart, March 1, 2008; 94(Suppl_1): i1 - i41. [Full Text] [PDF]

				National Pulmonary Hypertension Centres of the UK Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland Thorax, March 1, 2008; 63(Suppl_2): ii1 - ii41. [Full Text] [PDF]

				B. G. Stevinson, J. Hernandez-Nino, G. Rose, and J. A. Kline Echocardiographic and functional cardiopulmonary problems 6 months after first-time pulmonary embolism in previously healthy patients Eur. Heart J., October 2, 2007; 28(20): 2517 - 2524. [Abstract] [Full Text] [PDF]

				D. Bonderman, N. Skoro-Sajer, J. Jakowitsch, C. Adlbrecht, D. Dunkler, S. Taghavi, W. Klepetko, M. Kneussl, and I. M. Lang Predictors of Outcome in Chronic Thromboembolic Pulmonary Hypertension Circulation, April 24, 2007; 115(16): 2153 - 2158. [Abstract] [Full Text] [PDF]

				S. Ulrich, M. Fischler, R. Speich, V. Popov, and M. Maggiorini Chronic thromboembolic and pulmonary arterial hypertension share acute vasoreactivity properties. Chest, September 1, 2006; 130(3): 841 - 846. [Abstract] [Full Text] [PDF]

				I. Lang and K. Kerr Risk Factors for Chronic Thromboembolic Pulmonary Hypertension Proceedings of the ATS, September 1, 2006; 3(7): 568 - 570. [Abstract] [Full Text] [PDF]

				N. Galie and N. H. S. Kim Pulmonary Microvascular Disease in Chronic Thromboembolic Pulmonary Hypertension Proceedings of the ATS, September 1, 2006; 3(7): 571 - 576. [Abstract] [Full Text] [PDF]

				S. R. Johnson, J. T. Granton, and S. Mehta Thrombotic Arteriopathy and Anticoagulation in Pulmonary Hypertension. Chest, August 1, 2006; 130(2): 545 - 552. [Abstract] [Full Text] [PDF]

				T. A. Morris, J. J. Marsh, P. G. Chiles, W. R. Auger, P. F. Fedullo, and V. L. Woods Jr. Fibrin Derived from Patients with Chronic Thromboembolic Pulmonary Hypertension Is Resistant to Lysis Am. J. Respir. Crit. Care Med., June 1, 2006; 173(11): 1270 - 1275. [Abstract] [Full Text] [PDF]

				M. M. Hoeper, E. Mayer, G. Simonneau, and L. J. Rubin Chronic Thromboembolic Pulmonary Hypertension Circulation, April 25, 2006; 113(16): 2011 - 2020. [Full Text] [PDF]

				X Jais, V Ioos, C Jardim, O Sitbon, F Parent, A Hamid, E Fadel, P Dartevelle, G Simonneau, and M Humbert Splenectomy and chronic thromboembolic pulmonary hypertension Thorax, December 1, 2005; 60(12): 1031 - 1034. [Abstract] [Full Text] [PDF]

				G. R. Manecke Jr, W. C. Wilson, W. R. Auger, and S. W. Jamieson Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Thromboendarterectomy Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2005; 9(3): 189 - 204. [Abstract] [PDF]

				L. Puis, E. Vandezande, L. Vercaemst, P. Janssens, Y. Taverniers, M. Foulon, R. Demeyere, M. Delcroix, and W. Daenen Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension Perfusion, March 1, 2005; 20(2): 101 - 108. [Abstract] [PDF]

				M. McGoon, D. Gutterman, V. Steen, R. Barst, D. C. McCrory, T. A. Fortin, and J. E. Loyd Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension: ACCP Evidence-Based Clinical Practice Guidelines Chest, July 1, 2004; 126(1_suppl): 14S - 34S. [Abstract] [Full Text] [PDF]

				V. Pengo, A. W.A. Lensing, M. H. Prins, A. Marchiori, B. L. Davidson, F. Tiozzo, P. Albanese, A. Biasiolo, C. Pegoraro, S. Iliceto, et al. Incidence of Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism N. Engl. J. Med., May 27, 2004; 350(22): 2257 - 2264. [Abstract] [Full Text] [PDF]

				P. Dartevelle, E. Fadel, S. Mussot, A. Chapelier, P. Herve, M. de Perrot, J. Cerrina, F.L. Ladurie, D. Lehouerou, M. Humbert, et al. Chronic thromboembolic pulmonary hypertension Eur. Respir. J., April 1, 2004; 23(4): 637 - 648. [Abstract] [Full Text] [PDF]

				F. Sakamaki, S. Kyotani, N. Nagaya, N. Sato, H. Oya, and N. Nakanishi Increase in Thrombomodulin Concentrations After Pulmonary Thromboendarterectomy in Chronic Thromboembolic Pulmonary Hypertension Chest, October 1, 2003; 124(4): 1305 - 1311. [Abstract] [Full Text] [PDF]

				G Espinosa, R Cervera, J Font, and R A Asherson The lung in the antiphospholipid syndrome Ann Rheum Dis, March 1, 2002; 61(3): 195 - 198. [Abstract] [Full Text] [PDF]

				K. Laczika, I. M. Lang, P. Quehenberger, C. Mannhalter, M. Muhm, W. Klepetko, and P. A. Kyrle Unilateral Chronic Thromboembolic Pulmonary Disease Associated With Combined Inherited Thrombophilia Chest, January 1, 2002; 121(1): 286 - 289. [Abstract] [Full Text] [PDF]

				P. F. Fedullo, W. R. Auger, K. M. Kerr, and L. J. Rubin Chronic Thromboembolic Pulmonary Hypertension N. Engl. J. Med., November 15, 2001; 345(20): 1465 - 1472. [Full Text] [PDF]