The role of thrombosis in severe pulmonary hypertension.

Considering the important surface in pulmonary circulation where blood can interact with the endothelium, the maintenance of blood fluidity through the lung, by antithrombotic pathways and products of the endothelium, is essential. This function appears to be ineffective in primary pulmonary hypertension and in severe secondary pulmonary hypertension. Thrombotic lesions are frequently found in pulmonary arteries in these diseases. Thrombin activity appears to be increased in severe pulmonary hypertension. Antithrombotic pathway disorders may account for this abnormality, particularly in chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension. Injured endothelium, a constant feature in severe pulmonary hypertension, either primary or secondary, enhances thrombus formation in pulmonary vessels. This is probably related to thrombomodulin and tissue factor imbalance, impairment of prostacyclin and nitric oxide release, as well as inefficiency of fibrinolysis. Moreover, platelets appear to be activated in the pulmonary circulation of these patients. They release several mediators acting on vascular tone and as mitogenic agents, and may also contribute to thrombin and clot generation. Long-term oral anticoagulant and continuous infusion of prostacyclin, treatments which impede thrombosis, are known to improve the survival rate in patients with primary pulmonary hypertension. These are the strongest arguments, so far, in favour of the role of thrombosis in severe pulmonary hypertension. However, we do not know whether these abnormalities result from a previous vascular injury or represent the primary disturbance.

[1]  長尾 光修.  The Lung: Scientific Foundations , 1997 .

[2]  J. Launay,et al.  Increased plasma serotonin in primary pulmonary hypertension. , 1995, The American journal of medicine.

[3]  A. Lopes,et al.  Abnormal degradation of von Willebrand factor main subunit in pulmonary hypertension. , 1995, The European respiratory journal.

[4]  J. Golden,et al.  Do patients with primary pulmonary hypertension develop extensive central thrombi? , 1995, Circulation.

[5]  B. Dahlbäck.  The protein C anticoagulant system: inherited defects as basis for venous thrombosis. , 1995, Thrombosis research.

[6]  G. Escolar,et al.  Effect of Plasma from Patients with Primary Antiphospholipid Syndrome on Platelet Function in a Collagen Rich Perfusion System , 1995, Thrombosis and Haemostasis.

[7]  J. Francis,et al.  Hemostasis and Thrombosis: Basic Principles and Clinical Practice , 1988 .

[8]  K. Huber,et al.  Fibrinogen, t-PA, and PAI-1 plasma levels in patients with pulmonary hypertension. , 1994, American journal of respiratory and critical care medicine.

[9]  K. Horwitz,et al.  Platelet-induced vascular smooth muscle cell proliferation is modulated by the growth amplification factors serotonin and adenosine diphosphate. , 1994, Circulation.

[10]  R. Pakala,et al.  Mitogenic effect of serotonin on vascular endothelial cells. , 1994, Circulation.

[11]  R. Barst,et al.  Survival in Primary Pulmonary Hypertension with Long-Term Continuous Intravenous Prostacyclin , 1994, Annals of Internal Medicine.

[12]  Pieter H. Reitsma,et al.  Mutation in blood coagulation factor V associated with resistance to activated protein C , 1994, Nature.

[13]  D. Perry.  Antithrombin and its inherited deficiencies. , 1994, Blood reviews.

[14]  B. Dahlbäck,et al.  Resistance to activated protein C as a basis for venous thrombosis. , 1994, The New England journal of medicine.

[15]  R. Blakely,et al.  Serotonin increases DNA synthesis in rat proximal and distal pulmonary vascular smooth muscle cells in culture. , 1994, The American journal of physiology.

[16]  B. Fanburg,et al.  Serotonin produces both hyperplasia and hypertrophy of bovine pulmonary artery smooth muscle cells in culture. , 1994, The American journal of physiology.

[17]  L. Schulman,et al.  Platelet activation and fibrinopeptide formation in pulmonary hypertension. , 1993, Chest.

[18]  G. Simonneau,et al.  Primary pulmonary hypertension and fenfluramine use. , 1993, British heart journal.

[19]  A. Lopes,et al.  Abnormal multimeric and oligomeric composition is associated with enhanced endothelial expression of von Willebrand factor in pulmonary hypertension. , 1993, Chest.

[20]  V. Fuster,et al.  Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension. , 1993, British heart journal.

[21]  R. Roth,et al.  Procoagulant and fibrinolytic properties of bovine endothelial cells treated with monocrotaline pyrrole. , 1993, Toxicology and applied pharmacology.

[22]  N. Aikawa,et al.  Role of 5-hydroxytryptamine in the progression of monocrotaline induced pulmonary hypertension in rats. , 1993, Cardiovascular research.

[23]  J. Mlczoch,et al.  [Aminorex-induced, plexogenic pulmonary arteriopathy: 25 years later!]. , 1993, Zeitschrift fur Kardiologie.

[24]  G. Hughes.  The antiphospholipid syndrome: ten years on , 1993, The Lancet.

[25]  R. Roth,et al.  Fibrinolytic activity in blood and lungs of rats treated with monocrotaline pyrrole. , 1993, Toxicology and applied pharmacology.

[26]  T. McMahon,et al.  Analysis of responses to serotonin in the pulmonary vascular bed of the cat. , 1993, Journal of applied physiology.

[27]  D. Heistad,et al.  Seminars in medicine of the Beth Israel Hospital, Boston. Platelet-endothelium interactions. , 1993 .

[28]  K. Moser,et al.  Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. , 1993, Chest.

[29]  P. Mulder,et al.  Thrombotic lesions in primary plexogenic arteriopathy. Similar pathogenesis or complication? , 1993, Chest.

[30]  B. Dahlbäck,et al.  Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[31]  P. Reitsma,et al.  Protein C Deficiency: A Database of Mutations , 1993, Thrombosis and Haemostasis.

[32]  B. Binder,et al.  Endogenous Fibrinolytic System in Chronic Large‐Vessel Thromboembolic Pulmonary Hypertension , 1992, Circulation.

[33]  B. Groves,et al.  An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. , 1992, The New England journal of medicine.

[34]  S. Rich,et al.  The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. , 1992, The New England journal of medicine.

[35]  A. Parke,et al.  The thrombotic diathesis associated with the presence of phospholipid antibodies may be due to low levels of free protein S. , 1992, The American journal of medicine.

[36]  R. Lahita,et al.  Primary idiopathic pulmonary hypertension complicated by pulmonary arterial thrombosis. Association with antiphospholipid antibodies. , 1992, Arthritis and rheumatism.

[37]  S. Moncada,et al.  Nitric oxide: physiology, pathophysiology, and pharmacology. , 1991, Pharmacological reviews.

[38]  J. Wallwork,et al.  Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease. , 1991, The New England journal of medicine.

[39]  S. Rich,et al.  Familial pulmonary hypertension in association with an abnormal hemoglobin. Insights into the pathogenesis of primary pulmonary hypertension. , 1991, Chest.

[40]  R. Abbate,et al.  Pulmonary hypertension associated with long-standing thrombocytosis. , 1991, Chest.

[41]  R. Crystal,et al.  The Lung: Scientific Foundations , 1991 .

[42]  H. Büller,et al.  Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis. , 1990, The New England journal of medicine.

[43]  G. Hughes,et al.  Pulmonary hypertension in a lupus clinic: experience with twenty-four patients. , 1990, The Journal of rheumatology.

[44]  A. Jaffe,et al.  Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension. , 1990, Circulation.

[45]  J. Launay,et al.  Primary pulmonary hypertension in a patient with a familial platelet storage pool disease: role of serotonin. , 1990, The American journal of medicine.

[46]  B. Groves,et al.  Histopathology of primary pulmonary hypertension. A qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry. , 1989, Circulation.

[47]  G. Hughes,et al.  The “Primary” Antiphospholipid Syndrome: Major Clinical and Serological Features , 1989, Medicine.

[48]  D. Tsakiris,et al.  Impaired Fibrinolysis as an Essential Contribution to Thrombosis in Patients with Lupus Anticoagulant , 1989, Thrombosis and Haemostasis.

[49]  P. Callas,et al.  The clinical spectrum of heterozygous protein C deficiency in a large New England kindred. , 1989, Blood.

[50]  W. Konigsberg,et al.  Tumor necrosis factor enhances expression of tissue factor mRNA in endothelial cells. , 1989, Thrombosis research.

[51]  D. Tsakiris,et al.  Impaired fibrinolysis as an essential contribution to thrombosis in patients with lupus anticoagulant. , 1989, Thrombosis and haemostasis.

[52]  E. Romond,et al.  Impaired catalytic function of activated protein C: a new in vitro manifestation of lupus anticoagulant. , 1989, Blood.

[53]  R. Rosenberg,et al.  Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells , 1988, Molecular and cellular biology.

[54]  E. Bovill,et al.  The lupus anticoagulant stimulates the release of prostacyclin from human endothelial cells. , 1988, Thrombosis research.

[55]  Y. Sakata,et al.  Interaction of tissue-type plasminogen activator and plasminogen activator inhibitor 1 on the surface of endothelial cells. , 1988, The Journal of biological chemistry.

[56]  Triplett Da,et al.  Lupus anticoagulants: misnomer, paradox, riddle, epiphenomenon. , 1988 .

[57]  J. Brandt,et al.  Lupus anticoagulants: misnomer, paradox, riddle, epiphenomenon. , 1988, Hematologic pathology.

[58]  H. Prydz,et al.  Synthesis of thromboplastin (tissue factor) by endothelial cells. , 1988, Haemostasis.

[59]  D. Buff.  Primary pulmonary hypertension. , 1987, Annals of internal medicine.

[60]  W. Williams,et al.  Abnormal endothelial factor VIII associated with pulmonary hypertension and congenital heart defects. , 1987, Circulation.

[61]  J. Sixma,et al.  Structure-function relationship of human von Willebrand factor. , 1987, Blood.

[62]  C. Esmon.  The regulation of natural anticoagulant pathways , 1987, Science.

[63]  J. Heffner,et al.  The role of platelets in the adult respiratory distress syndrome. Culprits or bystanders? , 1987, The American review of respiratory disease.

[64]  L. Hoyer,et al.  von Willebrand factor abnormalities in primary pulmonary hypertension. , 1987, The American review of respiratory disease.

[65]  R. Colman,et al.  Hemostasis and Thrombosis: Basic Principles and Clinical Practice , 1988 .

[66]  B. Brundage,et al.  Primary pulmonary hypertension: radiographic and scintigraphic patterns of histologic subtypes. , 1986, Annals of internal medicine.

[67]  J. George,et al.  Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery. , 1986, The Journal of clinical investigation.

[68]  C. Soria,et al.  Inhibition of protein C activation by endothelial cells in the presence of lupus anticoagulant. , 1986, The New England journal of medicine.

[69]  B. Boneu,et al.  CONSTITUTIONAL HEPARIN CO-FACTOR II DEFICIENCY ASSOCIATED WITH RECURRENT THROMBOSIS , 1985, The Lancet.

[70]  G. Marbet,et al.  ASSOCIATION OF HEREDITARY HEPARIN CO-FACTOR II DEFICIENCY WITH THROMBOSIS , 1985, The Lancet.

[71]  W. Kisiel,et al.  The binding of factor IXa to cultured bovine aortic endothelial cells. Induction of a specific site in the presence of factors VIII and X. , 1985, The Journal of biological chemistry.

[72]  W. Edwards,et al.  Primary pulmonary hypertension: a histopathologic study of 80 cases. , 1985, Mayo Clinic proceedings.

[73]  V. Fuster,et al.  Primary pulmonary hypertension: natural history and the importance of thrombosis. , 1984, Circulation.

[74]  T. Higenbottam,et al.  LONG-TERM TREATMENT OF PRIMARY PULMONARY HYPERTENSION WITH CONTINUOUS INTRAVENOUS EPOPROSTENOL (PROSTACYCLIN) , 1984, The Lancet.

[75]  M. Gimbrone,et al.  Unidirectional transfer of prostaglandin endoperoxides between platelets and endothelial cells. , 1984, The Journal of clinical investigation.

[76]  J. Alpert,et al.  The clinical profile of unresolved pulmonary embolism. , 1983, Chest.

[77]  M. Shuman,et al.  Characterization of the effects of cultured vascular cells on the activation of blood coagulation. , 1983, Blood.

[78]  J. Vermylen,et al.  “Lupus” Anticoagulant and Thrombosis – Possible Role of Inhibition of Prostacyclin Formation , 1982, Thrombosis and Haemostasis.

[79]  C. Wagenvoort.  Lung biopsy specimens in the evaluation of pulmonary vascular disease. , 1980, Chest.

[80]  S Moncada,et al.  Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls. , 1979, The New England journal of medicine.

[81]  D. Loskutoff,et al.  Synthesis of a fibrinolytic activator and inhibitor by endothelial cells. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[82]  Y. Nemerson,et al.  The tissue factor pathway of blood coagulation. , 1992, Progress in hemostasis and thrombosis.

[83]  C. Wagenvoort,et al.  Primary Pulmonary Hypertension: A Pathologic Study of the Lung Vessels in 156 Clinically Diagnosed Cases , 1970 .

[84]  J. Kleinerman,et al.  An electron microscopic study of pulmonary vasculitis induced by monocrotaline. , 1966, Laboratory investigation; a journal of technical methods and pathology.