Article information
Resumen
La hipertensión pulmonar tromboembólica crónica se caracteriza por la organización de material trombótico dentro de las arterias pulmonares. La falta de correlación entre la proporción de arterias pulmonares obliteradas y las cifras de hipertensión pulmonar sugiere que una teoría exclusivamente mecánica podría ser demasiado simplista. El embolismo pulmonar agudo podría ser el evento inicial, pero la progresión de la enfermedad resultaría del remodelado vascular progresivo de los pequeños vasos. Es posible que la trombosis arterial pulmonar no resuelta sea un factor decisivo para que células endoteliales vasculares inicien su transición mesenquimal. Se analizan los aspectos genéticos, mecanismos inflamatorios y condicionantes clínicos que influyen en el mosaico fisiopatológico de esta compleja entidad.
Palabras clave:
Hipertensión pulmonar postrombótica
Embolia pulmonar crónica
Fisiopatología
Enfermedad tromboembólica venosa
Etiopathogenesis and physiopathology
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the organization of thrombotic material within the pulmonary arteries. The lack of correlation between the proportion of obliterated pulmonary arteries and pulmonary hypertension values suggest that an exclusively mechanical theory could be too simplistic. Acute pulmonary embolism could be the initial event, but disease progression probably results from progressive vascular remodelling of the small vessels. Unresolved pulmonary arterial thrombosis may be a decisive factor in initiating endothelial-to-mesenchymal transition. The present article analyzes the genetic features, inflammatory mechanisms and clinical factors influencing the physiopathological mosaic of this complex entity.
Keywords:
Postthrombotic pulmonary hypertension
Chronic pulmonary embolism
Physiopathology
Venous thromboembolic disease
Full text is only aviable in PDF
Bibliografía
[1.]
I.M. Lang.
Chronic thromboembolic pulmonary hypertension – not so rare after all.
N Engl J Med, 350 (2004), pp. 2236-2238
[2.]
I.M. Lang, W. Klepetko.
Chronic thromboembolic pulmonary hypertension: an updated review.
Curr Opin Cardiol, 23 (2008), pp. 555-559
[3.]
I.M. Lang, W. Klepetko.
Actualización sobre la hipertensión pulmonar tromboembólica crónica, una enfermedad que a menudo no se detecta.
Rev Esp Cardiol, 62 (2009), pp. 120-125
[4.]
D. Bonderman, P.L. Turecek, J. Jakowitsch, A. Weltermann, C. Adlbrecht, B. Schneider, et al.
High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension.
Thromb Haemost, 90 (2003), pp. 372-376
[5.]
M. Wolf, C. Boyer-Neumann, F. Parent, Eschwege., H. Jaillet, D. Meyer, et al.
Thrombotic risk factors in pulmonary hypertension.
Eur Respir J, 15 (2000), pp. 395-399
[6.]
J.A. Barberá, P. Escribano, P. Morales, M.A. Gómez, M. Oribe, A. Martínez, et al.
Estándares asistenciales en hipertensión pulmonar. Documento de consenso elaborado por la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) y la Sociedad Española de Cardiología (SEC).
Rev Esp Cardiol, 61 (2008), pp. 170-184
[7.]
L. Rubin, M.M. Hoeper, W. Klepetko, N. Galie, I. Lang, G. Simonneau.
Current and future management of CTEPH: from diagnosis to treatment responses.
Proc Am Thorac Soc, 3 (2006), pp. 601-607
[8.]
A. Peacock, G. Simonneau, L. Rubin.
Controversies, uncertainties and future research on the treatment of chronic thromboembolic pulmonary hypertension.
Am Thorac Soc, 3 (2006), pp. 608-614
[9.]
P.F. Fedullo, K.M. Kerr, W.R. Auger, S.W. Jamieson, D.P. Kapelanski.
Chronic thromboembolic pulmonary hypertension.
Semin Respir Crit Care Med, 21 (2000), pp. 563-574
[10.]
K.M. Moser, W.R. Auger, P.F. Fedullo.
Chronic major-vessel thromboembolic pulmonary hypertension.
Circulation, 81 (1990), pp. 1735-1743
[11.]
P.F. Fedullo, W.R. Auger, K.M. Kerr, L.J. Rubin.
Chronic thromboembolic pulmonary hypertension.
N Engl J Med, 345 (2001), pp. 1465-1472
[12.]
J.E. Dalen, J.S. Alpert.
Natural history of pulmonary embolism.
Prog Cardiovasc Dis, 17 (1975), pp. 259-270
[13.]
P.F. Fedullo, W.R. Auger, K.M. Kerr, N.H. Kim.
Chronic thromboembolic pulmonary hypertension.
Semin Respir Crit Care Med, 24 (2003), pp. 273-286
[14.]
V. Pengo, A.W. Lensing, M.H. Prins, A. Marchiori, B.L. Davidson, F. Tiozzo, Thromboembolic Pulmonary Hypertension Study Group, et al.
Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism.
N Engl J Med, 350 (2004), pp. 2257-2264
[15.]
P. Egermayer, A.J. Peacock.
Is pulmonary embolism a common cause of chronic pulmonary hypertension? Limitations of the embolic hypothesis.
Eur Respir J, 15 (2000), pp. 440-448
[16.]
T. Kunieda, N. Nakanishi, T. Satoh, S. Kyotani, Y. Okano, N. Nagaya.
Prognoses of primary pulmonary hypertension and chronic major vessel thromboembolic pulmonary hypertension determined from cumulative survival curves.
Intern Med, 38 (1999), pp. 543-546
[17.]
M. Riedel, V. Stanek, J. Widimsky, I. Prerovsky.
Longterm follow- up of patients with pulmonary thromboembolism. Late prognosis and evolution of hemodynamic and respiratory data.
Chest, 81 (1982), pp. 151-158
[18.]
J. Lewczuk, P. Piszko, J. Jagas, A. Porada, S. Wojciak, B. Sobkowicz, et al.
Prognostic factors in medically treated patients with chronic pulmonary embolism.
Chest, 119 (2001), pp. 818-823
[19.]
M.M. Hoeper, E. Mayer, G. Simonneau, L.J. Rubin.
Chronic thromboembolic pulmonary hypertension.
Circulation, 113 (2006), pp. 2011-2020
[20.]
N. Galiè, N.H.S. Kim.
Pulmonary microvascular disease in chronic thromboembolic pulmonary hypertension.
Proc Am Thorac Soc, 3 (2006), pp. 571-576
[21.]
K.M. Moser, N.S. Braunwald.
Successful surgical intervention in severe chronic thromboembolic pulmonary hypertension.
Chest, 64 (1973), pp. 29-35
[22.]
R.P. Michel, T.S. Hakim.
Increased resistence in postobstructive pulmonary vasculopaty: structure-function relationship.
J Appl Physiol, 71 (1991), pp. 601-610
[23.]
E. Fadel, G.M. Mazmanian, B. Baudet, H. Detruit, J.P. Verhoye, J. Cron, et al.
Endothelial nitric oxide synthase function in pig lung after chronic pulmonary artery obstruction.
Am J Respir Crit Care Med, 162 (2000), pp. 1429-1434
[24.]
E.S. Yi, H. Kim, H. Ahn, J. Strother, T. Morris, E. Masliah, et al.
Distribution of obstructive intimal lesions and their cellular phenotypes in chronic pulmonary hypertension: a morphometric and immunohistochemical study.
Am J Respir Crit Care Med, 162 (2000), pp. 1577-1586
[25.]
K.M. Moser, C.M. Bloor.
Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension.
Chest, 103 (1993), pp. 685-692
[26.]
D. Heath, P. Smith, J. Gosney, D. Mulcahy, K. Fox, M. Yacoub, et al.
The pathology of the early and late stages of primary pulmonary hypertension.
Br Heart J, 58 (1987), pp. 204-213
[27.]
P. Smith, D. Heath, M. Yacoub, B. Madden, A. Caslin, J. Gosney.
The ultrastructure of plexogenic pulmonary arteriopathy.
J Pathol, 160 (1990), pp. 111-121
[28.]
G.G. Pietra, F. Capron, S. Stewart, O. Leone, M. Humbert, I.M. Robbins, et al.
Pathologic assessment of vasculopathies in pulmonary hypertension.
J Am Coll Cardiol, 43 (2004), pp. S25-S32
[29.]
C.A. Wagenvoort.
Lung biopsies and pulmonary vascular disease.
Pulmonary hypertension, pp. 393-438
[30.]
L.M. Reid.
Structure and function in pulmonary hypertension: new perceptions.
Chest, 89 (1986), pp. 279-288
[31.]
E. Arbustini, P. Morbini, A.M. D’Armini, A. Repetto, G. Minzioni, F. Piovella, et al.
Plaque composition in plexogenic and thromboembolic pulmonary hypertension: the critical role of thrombotic material in pultaceous core formation.
Heart, 88 (2002), pp. 177-182
[32.]
I.M. Lang, J.J. Marsh, M.A. Olman, K.M. Moser, R.R. Schleef.
Parallel analysis of tissuetype plasminogen activator and type 1 plasminogen activator inhibitor in plasma and endothelialcells derived from patients with chronic pulmonary thromboembolic.
Circulation, 90 (1994), pp. 706-712
[33.]
M.A. Olman, J.J. Marsh, I. Lang, K.M. Moser, B.R. Binder, R.R. Schleef.
Endogenous fibrinolytic system in chronic large-vessel thromboembolic pulmonary hypertension.
Circulation, 86 (1992), pp. 1241-1248
[34.]
T.M. Morris, J.J. Marsh, P.G. Chiles, W.R. Auger, P.F. Fedullo, V.L. Woods Jr.
Fibrin derived from patients with chronic thromboembolic pulmonary hypertension is resistant to lysis.
Am J Respir Crit Care Med, 173 (2006), pp. 1270-1275
[35.]
I.M. Lang, W. Klepetko, I. Pabinger.
No increased prevalence of the factor V Leiden mutation in chronic major vessel thromboembolic pulmonary hypertension (CTEPH).
Thromb Haemost, 76 (1996), pp. 476-477
[36.]
M. Wolf, C. Boyer-Neumann, F. Parent, V. Eschwege, H. Jaillet, D. Meyer, et al.
Thrombotic risk factors in pulmonary hypertension.
Eur Respir J, 15 (2000), pp. 395-399
[37.]
D. Bonderman, P.L. Turecek, J. Jakowitsch, A. Weltermann, C. Adlbrecht, B. Schneider, et al.
High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension.
Thromb Haemost, 90 (2003), pp. 372-376
[38.]
M.M. Hoeper, M. Sosada, H. Fabel.
Plasma coagulation profiles in patients with severe primary pulmonary hypertension.
Eur Respir J, 12 (1998), pp. 1446-1449
[39.]
W. Yao, A.L. Firth, R.S. Sacks, A. Ogawa, W.R. Auger, P.F. Fedullo, et al.
Identification of putative endothelial progenitor cells (CD34+CD133+Flk-1+) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension.
Am J Physiol Lung Cell Mol Physiol, 296 (2009), pp. 870-878
[40.]
E. Arciniegas, M.G. Frid, I.S. Douglas, K.R. Stenmark.
Perspectives on endothelial-tomesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension.
Am J Physiol Lung Cell Mol Physiol, 293 (2007), pp. 1-8
[41.]
L. Du, C.C. Sullivan, D. Chu, A.J. Cho, M. Kido, P.L. Wolf, et al.
Signaling molecules in non familial pulmonary hypertension.
N Engl J Med, 348 (2003), pp. 500-509
[42.]
R.A. Ariens, T.S. Lai, J.W. Weisel, C.S. Greenberg, P.J. Grant.
Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms.
Blood, 100 (2002), pp. 743-754
[43.]
J. Suntharalingam, K. Goldsmith, V. Van Marion, L. Long, C.M. Treacy, F. Dudbridge, et al.
Fibrinogen Aa Thr312Ala polymorphism is associated with chronic thromboembolic pulmonary hypertension.
Eur Respir J, 31 (2008), pp. 736-741
[44.]
K.F. Standeven, P.J. Grant, A.M. Carter, T. Scheiner, J.W. Weisel, R.A. Ariens.
Functional analysis of the fibrinogen Aa Thr312Ala polymorphism: effects on fibrin structure and function.
Circulation, 107 (2003), pp. 2326-2330
[45.]
J.M. Curran, K. Fatah-Ardalani, P. Tornvall, S.E. Humphries, F.R. Green.
A hypothesis to explain the reported association of the a-fibrinogen A312 allele with thromboembolic disease.
Thromb Haemost, 85 (2001), pp. 1122-1123
[46.]
P. Dorfmuller, F. Perros, K. Balabanian, M. Humbert.
Inflammation in pulmonary arterial hypertension.
Eur Respir J, 22 (2003), pp. 358-363
[47.]
P. Dorfmüller, V. Zarka, I. Durand-Gasselin, G. Monti, K. Balabanian, G. García, et al.
Chemokine RANTES in severe pulmonary arterial hypertension.
Am J Respir Crit Care Med, 165 (2002), pp. 534-539
[48.]
F. Perros, P. Dorfmuller, R. Souza, I. Durand-Gasselin, V. Godot, F. Capel, et al.
Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension.
Eur Respir J, 29 (2007), pp. 937-943
[49.]
H. Kimura, O. Okada, N. Tanabe, O. Tanaka, M. Terai, Y. Takiguchi, et al.
Plasma monocyte chemoattractant protein-1 and pulmonary vascular resistance in chronic thromboembolic pulmonary hypertension.
Am J Respir Crit Care Med, 164 (2001), pp. 319-324
[50.]
F. Langer, R. Schramm, M. Bauer, D. Tscholl, T. Kunihara, H.J. Schäfers.
Cytokine response to pulmonary thromboendarterectomy.
Chest, 126 (2004), pp. 135-141
[51.]
F. Sakamaki, S. Kyotani, N. Nagaya, N. Sato, H. Oya, N. Nakanishi.
Increase in thrombomodulin concentrations after pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension.
Chest, 124 (2003), pp. 1305-1311
[52.]
J. Lindner, P. Maruna, J. Kunstyr, P. Jansa, R. Gürlich, K. Kubzova, et al.
Hemodynamic instability after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension correlates with cytokine network hyperstimulation.
Eur Surg Res, 43 (2009), pp. 39-46
[53.]
M. Bauer, H. Wilkens, F. Langer, S.O. Schneider, H. Lausberg, H.J. Schafers.
Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension.
Circulation, 105 (2002), pp. 1034-1036
[54.]
H.J. Reesink, R.C. Meijer, R. Lutter, F. Boomsma, H.M. Jansen, J.J. Kloek, et al.
Hemodynamic and clinical correlates of endothelin-1 in chronic thromboembolic pulmonary hypertension.
Circ J, 70 (2006), pp. 1058-1063
[55.]
H. Kim, G.L. Yung, J.J. Marsh, R.G. Konopka, C.A. Pedersen, P.G. Chiles, et al.
Endothelin mediates pulmonary vascular remodelling in a canine model of chronic embolic pulmonary hypertension.
Eur Respir J, 15 (2000), pp. 640-648
[56.]
N. Skoro-Sajer, F. Mittermayer, A. Panzenboeck, D. Bonderman, R. Sadushi, R. Hitsch, et al.
Asymmetric dimethylarginine is increased in chronic thromboembolic pulmonary hypertension.
Am J Respir Crit Care Med, 176 (2007), pp. 1154-1160
[57.]
I. Lang, K. Kerr.
Risk factors for chronic tromboembolic pulmonary hypertension.
Proc Am Thorac Soc, 3 (2006), pp. 568-570
[58.]
D. Bonderman, N. Skoro-Sajer, J. Jakowitsch, C. Adlbrecht, D. Dunkler, S. Taghavi, et al.
Predictors of outcome in chronic thromboembolic pulmonary hypertension.
Circulation, 115 (2007), pp. 2153-2158
[59.]
D. Bonderman, J. Jakowitsch, C. Adlbrecht, M. Schemper, P.A. Kyrle, V. Schönauer, et al.
Medical conditions increasing the risk of chronic thromboembolic pulmonary hypertension.
Thromb Haemost, 93 (2005), pp. 512-516
[60.]
E.A. Fox, S.R. Kahn.
The relationship between inflammation and venous thrombosis: a systematic review of clinical studies.
Thromb Haemost, 94 (2005), pp. 362-365
[61.]
C.T. Esmon.
The impact of the inflammatory response on coagulation.
Thromb Res, 114 (2004), pp. 321-327
[62.]
X. Jais, V. Ioos, C. Jardim, O. Sitbon, F. Parent, A. Hamid, et al.
Splenectomy and chronic thromboembolic pulmonary hypertension.
Thorax, 60 (2005), pp. 1031-1034
[63.]
D. Bonderman, J. Jakowitsch, B. Redwan, H. Bergmeister, M.C. Renner, H. Panzenböck, et al.
Role for Staphylococci in misguided thrombus resolution of chronic thromboembolic pulmonary hypertension.
Arterioscler Thromb Vasc Biol, 28 (2008), pp. 678-684
[64.]
R.L. Bick.
Cancer-associated thrombosis.
N Engl J Med, 349 (2003), pp. 109-111
[65.]
D. Bonderman, H. Wilkens, S. Wakounig, H.J. Schafers, P. Jansa, J. Lindner, et al.
Risk factors for chronic thromboembolic pulmonary hypertension.
Eur Respir J, 33 (2009), pp. 325-331
Copyright © 2009. Sociedad Española de Neumología y Cirugía Torácica
