Skip to main content
Top
Published in: Rheumatology International 9/2013

01-09-2013 | Original Article

Elevated plasminogen activator inhibitor type-1 (PAI-1) as contributing factor in pathogenesis of hypercoagulable state in antiphospholipid syndrome

Authors: N. K. Singh, A. Gupta, Dibya R. Behera, D. Dash

Published in: Rheumatology International | Issue 9/2013

Login to get access

Abstract

The aim of this study is to explore the role of plasminogen activator inhibitor type 1 (PAI-1) in primary and secondary antiphospholipid syndrome (APS). Thirty patients of APS (24 primary and 6 secondary) were recruited in the study who fulfilled the revised Sapporo criteria. Control groups comprised of age- and sex-matched 10 healthy volunteers and 10 patients each of systemic lupus erythematosus and rheumatoid arthritis without any antecedent thrombotic event and/or APS-related pregnancy morbidity. Serum samples were tested for PAI-1 antigen levels measured by quantitative ELISA. Positivity rate of PAI-1 in patients of primary, secondary as well as total APS patients was significantly higher in relation to age- and sex-matched healthy volunteers (p = 0.010, p = 0.003 and p < 0.001, respectively). Mean ± SEM levels of PAI-1 in primary and secondary as well as total APS patients were significantly higher (p = 0.006, p < 0.001 and p < 0.001) in relation to healthy controls. Correlation of PAI-1 levels (mean ± SEM) with clinical characteristics, that is, thrombosis and pregnancy morbidity, revealed significantly higher levels of PAI-1 (p < 0.001) in patients having thrombosis and APS-related pregnancy morbidity. Elevated PAI-1 level leading to impaired fibrinolysis plays a significant role in producing hypercoagulable state in primary and secondary APS.
Literature
1.
go back to reference Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 42:1309–1311PubMedCrossRef Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 42:1309–1311PubMedCrossRef
2.
go back to reference Hughes GR (1983) Thrombosis, abortion, cerebral disease and the lupus anticoagulant. Br Med J 287:1088–1089CrossRef Hughes GR (1983) Thrombosis, abortion, cerebral disease and the lupus anticoagulant. Br Med J 287:1088–1089CrossRef
3.
go back to reference Alarcon-Segovia D, Deleze M, Oria CV et al (1989) Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus: a prospective analysis of 500 consecutive patients. Medicine (Baltimore) 68:353–365 Alarcon-Segovia D, Deleze M, Oria CV et al (1989) Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus: a prospective analysis of 500 consecutive patients. Medicine (Baltimore) 68:353–365
4.
go back to reference Arnold J, Holmes Z, Pickering W, Farmer C, Regan L, Cohen H (2001) Anti-beta 2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent miscarriage. Br J Haematol 113:911–914PubMedCrossRef Arnold J, Holmes Z, Pickering W, Farmer C, Regan L, Cohen H (2001) Anti-beta 2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent miscarriage. Br J Haematol 113:911–914PubMedCrossRef
5.
go back to reference Rand JH, Wu XX, Andree HA, Lockwood CJ, Guller S, Scher J et al (1997) Pregnancy loss in the antiphospholipid antibody syndrome—a possible thrombogenic mechanism. New Engl J Med 17:154–160CrossRef Rand JH, Wu XX, Andree HA, Lockwood CJ, Guller S, Scher J et al (1997) Pregnancy loss in the antiphospholipid antibody syndrome—a possible thrombogenic mechanism. New Engl J Med 17:154–160CrossRef
6.
go back to reference Ruiz-Arguelles G, Ruiz-Arguelles A, Alarcon-Segovia D, Drenkar C, Villa A, Cabiedes J et al (1991) Natural anticoagulants in systemic lupus erythematosus: deficiency of protein S bound to C4 bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome. J Rheumatol 18:552–558PubMed Ruiz-Arguelles G, Ruiz-Arguelles A, Alarcon-Segovia D, Drenkar C, Villa A, Cabiedes J et al (1991) Natural anticoagulants in systemic lupus erythematosus: deficiency of protein S bound to C4 bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome. J Rheumatol 18:552–558PubMed
7.
go back to reference Cosgriff PM, Martin BA (1981) Low functional and high antigenic antithrombin III level in a patient with the lupus anticoagulant and recurrent thrombosis. Arthritis Rheum 24:94–96PubMedCrossRef Cosgriff PM, Martin BA (1981) Low functional and high antigenic antithrombin III level in a patient with the lupus anticoagulant and recurrent thrombosis. Arthritis Rheum 24:94–96PubMedCrossRef
8.
go back to reference Rand JH, Wu XX, Andree HA, Ross JB, Rusinova E, Gascon-Lema MG et al (1998) Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a lupus “procoagulant” phenomenon. Blood 92:165260 Rand JH, Wu XX, Andree HA, Ross JB, Rusinova E, Gascon-Lema MG et al (1998) Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a lupus “procoagulant” phenomenon. Blood 92:165260
9.
go back to reference Arnout J, Vermylen J (1998) Mechanisms of action of β-2-glycoprotein I-dependent lupus anticoagulants. Lupus 7(suppl. 2):23–28CrossRef Arnout J, Vermylen J (1998) Mechanisms of action of β-2-glycoprotein I-dependent lupus anticoagulants. Lupus 7(suppl. 2):23–28CrossRef
10.
go back to reference Kornberg A, Renadineau Y, Blank M, Youinou P, Shoenfeld Y (2000) Anti-beta 2-glycoprotein I antibodies and anti-endothelial cell antibodies induce tissue factor in endothelial cells. Isr Med Assoc J 2(Suppl 2):27–31PubMed Kornberg A, Renadineau Y, Blank M, Youinou P, Shoenfeld Y (2000) Anti-beta 2-glycoprotein I antibodies and anti-endothelial cell antibodies induce tissue factor in endothelial cells. Isr Med Assoc J 2(Suppl 2):27–31PubMed
11.
go back to reference Carreras LO, de Freyn G, Machin SJ, Vermylen JG, Deman R, Spitz B et al (1981) Arterial thrombosis, intrauterine death and ‘lupus’ anticoagulant: detection of immunoglobulin interfering with prostacyclin formation. Lancet 1:244–246PubMedCrossRef Carreras LO, de Freyn G, Machin SJ, Vermylen JG, Deman R, Spitz B et al (1981) Arterial thrombosis, intrauterine death and ‘lupus’ anticoagulant: detection of immunoglobulin interfering with prostacyclin formation. Lancet 1:244–246PubMedCrossRef
12.
go back to reference Forastiero R, Martinuzzo M, Carreras LO, Maclouf J (1998) Anti-beta2 glycoprotein I antibodies and platelet activation in patients with antiphospholipid antibodies: association with increased excretion of platelet-derived thromboxane urinary metabolites. Thromb Haemost 79:42–45PubMed Forastiero R, Martinuzzo M, Carreras LO, Maclouf J (1998) Anti-beta2 glycoprotein I antibodies and platelet activation in patients with antiphospholipid antibodies: association with increased excretion of platelet-derived thromboxane urinary metabolites. Thromb Haemost 79:42–45PubMed
13.
go back to reference Urbanus RT, Derksen RH, de Groot PG (2008) Platelets and the antiphospholipid syndrome. Lupus 17:888PubMedCrossRef Urbanus RT, Derksen RH, de Groot PG (2008) Platelets and the antiphospholipid syndrome. Lupus 17:888PubMedCrossRef
14.
go back to reference Zorio E, Gilabert-Estelles J, Espana F et al (2008) Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem 15:923–929PubMedCrossRef Zorio E, Gilabert-Estelles J, Espana F et al (2008) Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem 15:923–929PubMedCrossRef
15.
go back to reference Castellino FJ, Ploplis VA (2005) Structure and function of plasminogen/plasmin system. Thromb Haemost 93:647–654PubMed Castellino FJ, Ploplis VA (2005) Structure and function of plasminogen/plasmin system. Thromb Haemost 93:647–654PubMed
16.
go back to reference Huber K (2001) Plasminogen activator inhibitor type-1 (part one): basic mechanisms, regulation, and role of thromboembolic diseases. J Thromb Thrombolysis 11:183–193PubMedCrossRef Huber K (2001) Plasminogen activator inhibitor type-1 (part one): basic mechanisms, regulation, and role of thromboembolic diseases. J Thromb Thrombolysis 11:183–193PubMedCrossRef
17.
go back to reference Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4(2):295–306PubMedCrossRef Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4(2):295–306PubMedCrossRef
18.
go back to reference Ames PR, Tommasino C, Iannaccone L et al (1996) Coagulation activation and fibrinolytic imbalance in subjects with idiopathic antiphospholipid antibodies—a crucial role for acquired free protein S deficiency. Thromb Haemost 76:190–194PubMed Ames PR, Tommasino C, Iannaccone L et al (1996) Coagulation activation and fibrinolytic imbalance in subjects with idiopathic antiphospholipid antibodies—a crucial role for acquired free protein S deficiency. Thromb Haemost 76:190–194PubMed
19.
go back to reference Juardo M, Paramo JA, Gutierrez-Pimentel M, Rocha E (1992) Fibrinolytic potential and antiphospholipid antibodies in systemic lupus erythematosus and other connective tissue disorders. Thromb Haemost 68:516–520 Juardo M, Paramo JA, Gutierrez-Pimentel M, Rocha E (1992) Fibrinolytic potential and antiphospholipid antibodies in systemic lupus erythematosus and other connective tissue disorders. Thromb Haemost 68:516–520
20.
go back to reference Coulam CB, Wallis D, Weinstein J, DasGupta DS, Jeyendran RS (2008) Comparison of thrombophilia gene mutations among patients experiencing recurrent miscarriages and deep vein thrombosis. Am J Reprod Immunol 60(5):426–431PubMedCrossRef Coulam CB, Wallis D, Weinstein J, DasGupta DS, Jeyendran RS (2008) Comparison of thrombophilia gene mutations among patients experiencing recurrent miscarriages and deep vein thrombosis. Am J Reprod Immunol 60(5):426–431PubMedCrossRef
21.
go back to reference Landin K, Tengborn L, Smith V (1990) Elevated fibrinogen and plasminogen activator (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. J Intern Med 227:273–278PubMedCrossRef Landin K, Tengborn L, Smith V (1990) Elevated fibrinogen and plasminogen activator (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. J Intern Med 227:273–278PubMedCrossRef
22.
go back to reference Juhan-Vague I, Alessi MC, Vague P (1991) Increased plasma plasminogen activator inhibitor levels: a possible link between insulin resistance and atherothrombosis. Diabetologia 34:457–462PubMedCrossRef Juhan-Vague I, Alessi MC, Vague P (1991) Increased plasma plasminogen activator inhibitor levels: a possible link between insulin resistance and atherothrombosis. Diabetologia 34:457–462PubMedCrossRef
23.
go back to reference Sobel BE, Woodcock-Mitchell J, Schneider DJ (1998) Increased plasminogen activator inhibitor type 1 in coronary artery atherectomy specimens from type 2 diabetic compared with nondiabetic patients. Circulation 97:2213–2221PubMedCrossRef Sobel BE, Woodcock-Mitchell J, Schneider DJ (1998) Increased plasminogen activator inhibitor type 1 in coronary artery atherectomy specimens from type 2 diabetic compared with nondiabetic patients. Circulation 97:2213–2221PubMedCrossRef
24.
go back to reference Hendrinks HFJ, Veenstgra J, Velthuis-teWierik EJM et al (1994) Effect of moderate dose of alcohol with evening meal on brinolytic factors. Br Med J 308:1003–1005CrossRef Hendrinks HFJ, Veenstgra J, Velthuis-teWierik EJM et al (1994) Effect of moderate dose of alcohol with evening meal on brinolytic factors. Br Med J 308:1003–1005CrossRef
25.
go back to reference Pralong G, Calandra T, Glauser MP et al (1989) Plasminogen activator inhibitor-1: a new prognostic marker in septic shock. Thromb Haemost 61:459–462PubMed Pralong G, Calandra T, Glauser MP et al (1989) Plasminogen activator inhibitor-1: a new prognostic marker in septic shock. Thromb Haemost 61:459–462PubMed
26.
go back to reference Sartori MT, Winman B, Veltore S et al (1998) 4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients with deep venous thrombosis. Thromb Haemost 80:956–960PubMed Sartori MT, Winman B, Veltore S et al (1998) 4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients with deep venous thrombosis. Thromb Haemost 80:956–960PubMed
27.
go back to reference Glueck CJ, Fontaine RN, Gupta A et al (1997) Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity and resistance to activated protein C. Metabolism 46:1470–1472PubMedCrossRef Glueck CJ, Fontaine RN, Gupta A et al (1997) Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity and resistance to activated protein C. Metabolism 46:1470–1472PubMedCrossRef
28.
go back to reference Margaglione M, Cappusi G, d’Addedda M et al (1998) PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environment and genetic determinants. Arterioscler Thromb Vasc Biol 18:562–567PubMedCrossRef Margaglione M, Cappusi G, d’Addedda M et al (1998) PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environment and genetic determinants. Arterioscler Thromb Vasc Biol 18:562–567PubMedCrossRef
29.
go back to reference Tsantes AE, Nikolopoulos GK, Bagos PG, Bonovas S, Kopterides P, Vaiopoulos G (2008) The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk. Thromb Res 122:736–742PubMedCrossRef Tsantes AE, Nikolopoulos GK, Bagos PG, Bonovas S, Kopterides P, Vaiopoulos G (2008) The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk. Thromb Res 122:736–742PubMedCrossRef
30.
go back to reference Yasuda S, Tsutsumi A, Atsumi T, Bertolaccini ML, Ichikawa K, Khamashta MA, Hughes GR, Koike T (2002) Gene polymorphisms of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with antiphospholipid antibodies. J Rheumatol 29(6):1192–1197PubMed Yasuda S, Tsutsumi A, Atsumi T, Bertolaccini ML, Ichikawa K, Khamashta MA, Hughes GR, Koike T (2002) Gene polymorphisms of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with antiphospholipid antibodies. J Rheumatol 29(6):1192–1197PubMed
Metadata
Title
Elevated plasminogen activator inhibitor type-1 (PAI-1) as contributing factor in pathogenesis of hypercoagulable state in antiphospholipid syndrome
Authors
N. K. Singh
A. Gupta
Dibya R. Behera
D. Dash
Publication date
01-09-2013
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 9/2013
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-013-2717-0

Other articles of this Issue 9/2013

Rheumatology International 9/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.