Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis*,**,***
Section snippets
Patients and methods
We evaluated 29 consecutive nonsmoking patients with SSc, admitted to the Rheumatology Unit of University of Florence (13 patients) and to the Second University of Naples (16 patients) from January 1, 1998, to December 31, 1998.
No differences in clinical features were detected between patients enrolled in the 2 centers (Table 1; patients 1-5,12,19-25 from Florence Center, patients 6-11, 13-18, 26-29 from Naples Center). There were 12 patients who were classified as having diffuse cutaneous SSc
Results
The clinical characteristics of the patients and the results of the circulating parameters are reported in Tables 1 and 2, respectively.
Discussion
Our results show that the coagulative system is activated in patients with dSSc and lSSc , as shown by an increase of TAT and F1+2, which is in agreement with previous reports (8, 25, 26).
The coagulative abnormality is enhanced by the increase of Lp(a), mainly in lSSc. lSSc is characterized by a significant macrovascular involvement and atherosclerosis of the great vessels (27). Lp(a) is a low-density lipoprotein particle bound to apolipoprotein (a) that represents a risk factor of
Acknowledgements
The authors are indebted to the Association for Autoimmune Diseases (APAI) for their continuous support in this work.
References (74)
- et al.
Fibrin and fibrinogen related antigens in systemic sclerosis (scleroderma)
J Am Acad Dermatol
(1991) - et al.
Leiden fibrinolysis working party: blood collection and handling procedures for assessment of tissue-type plasminogen activator and plasminogen activator inhibitor 1
Fibrinolysis
(1990) - et al.
Blood sampling and determination of of tissue plasminogen activator activity with COA-SET t-PA
Fibrinolysis
(1990) - et al.
Plasma levels of molecular markers of blood coagulation and fibrinolysis in progressive systemic sclerosis
J Dermatol Sci
(1996) - et al.
Sulphated proteoglycans synthetized by vascular endothelial cells in culture
J Biol Chem
(1983) - et al.
Dermatansulphate, heparin cofactor II and F1+2 peptide in non-insulin-dependent diabetes mellitus
Thromb Res
(2000) - et al.
Fibrin-dependent platelet procoagulant activity requires GPIb receptors and von Willebrand factor
Blood
(1999) - et al.
Supranormal von Willebrand factor multimers in scleroderma
Blood
(1989) - et al.
Treatment with interferon gamma enhances fibrinolysis in systemic sclerosis
Thromb Res
(1998) - et al.
Vascular involvement: pathogenesis
Arterial thrombosis in scleroderma
Br J Dermatol
Venous blood fibrinolysis and fibrinolytic potential in primary Raynaud's phenomenon and systemic sclerosis associated with Raynaud's phenomenon
Cutaneous and plasma fibrinolytic activity in systemic sclerosis: evidence of a normal plasminogen activation
Int J Dermatol
Cutaneous fibrinolytic activity in scleroderma
Clin Exp Rheumatol
von Willebrand factor, thrombomodulin, thromboxane, thromboglobulin and markers of fibrinolysis in primary Raynaud's phenomenon and systemic sclerosis
Ann Rheum Dis
The coagulation/fibrinolysis balance in systemic sclerosis: evidence for a haematological stress sindrome
Br J Rheumatol
Scleroderma (systemic sclerosis): classification, subsets and pathogenesis
J Rheumatol
Detection of the prothrombotic state due to procoagulant imbalance
Eur J Haemost
Determination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay
Thromb Haemost
Determination of human prothrombin activation fragment 1+2 and TAT in plasma with antibody against a synthetic peptide
Thromb Haemost
Activation of heparin cofactor II by dermatan sulphate
J Biol Chem
A simple method to measure dermatan sulphate at sub-microgram conceentration in plasma
Thromb Haemost
Circulating thrombomodulin as a novel endothelial cell marker: comparison of its behaviour with von Willebrand factor and tissue type plasminogen activator
Am J Hematol
Increased factor VIII/von Willebrand factor antigen and von Willebrand factor activity in scleroderma and in Raynaud's phenomenon
Ann Int Med
von Willebrand Factor levels in hypertrophic osteoarthropathy
J Rheumatol
Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE)
J Clin Invest
A new adaptation of COA-SET PAI measurement of low inhibitor concentration in plasma
Fibrinolysis
Measurement of cross-linked fibrin derivatives in plasma: an immunoassay using monoclonal antibodies
J Clin Pathol
Anti-endothelial cell antibodies in systemic sclerosis: significant association with vascular involvement and alveolo-capillary impairment
Clin Exp Rheumatol
A modified scleroderma skin scoring method
Clin Exp Rheumatol
The clinical significance of coagulation abnormalities in systemic sclerosis (scleroderma)
J Rheumatol
Increased prevalence of symptomatic macrovascular disease in systemic sclerosis
Ann Rheum Dis
Detection and quantitation of lipoprotein (a) in the arterial wall of 107 coronary artery patients
Arteriosclerosis
Serum lipoprotein (a) and apolipoprotein (a) phenotypes in patients with rheumatoid arthritis
Arthritis Rheum
Lipoprotein (a) levels in systemic lupus erythematosus
J Rheumatol
Elevated plasma lipoprotein (a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome
J Rheumatol
Factors influencing the accumulation in fibrous plaques of lipid derived from low density lipoprotein (a)
Atherosclerosis
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Marco Matucci Cerinic, MD, PhD: Professor of Medicine; S Generini MD, PhD: Fellow in Rheumatology; A. Pignone, MD, PhD: Associate Professor of Medicine; S Guiducci, MD; A. Del Rosso, MD, PhD: Department of Medicine, Division of Rheumatology, University of Florence, Italy; G. Valentini, MD: Professor of Rheumatology; S. D'Angelo, MD: Fellow in Rheumatology; G. Cuomo, MD: Fellow in Rheumatology, Department of Clinical and Experimental Internal Medicine “F Magrassi,” Rheumatology Unit, II University of Naples, Italy; F. Marongiu, MD: Professor of Medicine; G. G. Sorano, MD: L. Fenu, MD: Institute of Internal Medicine, University of Cagliari, Italy; S. Cinotti, BsC; M. Morfini, MD: Department of Hematology and Hemophilia Center, University of Florence, Italy; D. Das, MD: Professor of Cardiology; R. Kalfin, PhD: Department of Cardiology, University Connecticut Health Center, Farmington, CT.
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Address reprint requests to Marco Matucci Cerinic, MD, PhD, Department of Medicine, Division of Rheumatology “Villa Monna Tessa,” viale Pieraccini 18, 50139 Italy. E-mail: [email protected]
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