Fibrinolytic Potential and Antiphospholipid Antibodies in Systemic Lupus Erythematosus and Other Connective Tissue Disorders

Jurado, Manuel; Páramo, José A.; Gutiérrez-Pimentel, María José; Rocha, Eduardo

doi:10.1055/s-0038-1646310

Cited by 47 publications

(27 citation statements)

References 26 publications

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“…The same authors suggested that in these patients the occurrence of abortions might be linked to the PAI-1 increase. Also in patients without SLE, the presence of aPL was associated with hypofibrinolysis due to high PAL1 levels [34,49]. However, data on fibrinolytic parameters in patients with antiphospholipid antibodies have given contradictory results [33-351.…”

Section: Discussionmentioning

confidence: 97%

Fibrinolytic pattern in recurrent spontaneous abortions: No relationship between hypofibrinolysis and anti‐phospholipid antibodies

Gm¹,

Sartori²,

Ruffatti³

et al. 1994

American J Hematol

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Patients with antiphospholipid antibodies may suffer from thrombotic events and recurrent spontaneous abortions. A defective fibrinolytic potential has been described in women with recurrent fetal losses. We investigated the prevalence of anticardiolipin antibodies and of various fibrinolytic abnormalities in 64 females with a history of at least two abortions of unknown origin. Anticardiolipin antibodies were present in the serum of 31 patients (48.4%). The overall prevalence of fibrinolytic disorders was 67.2% (43 cases) and resulted significantly higher than that of aCL positivity (P = 0.03). In most of cases the impaired fibrinolytic potential after venous occlusion test was due to increased PAI-1 levels; only in a few instances a defective fibrinolytic response was due to reduced t-PA release, a combined defect or an intrinsic fibrinolytic deficiency. After division of patients in two groups on the basis of the aCL presence, the distribution of different fibrinolytic defects was similar in aCL positive and negative women, suggesting the lack of correlation between hypofibrinolysis and aCL antibodies. Plasminogen abnormalities resulted compatible with congenital hypoplasminogenemia in two aCL negative women, whereas in four aCL positive patients they were suggestive for acquired dysplasminogenemia. Our results indicate that patients with recurrent spontaneous abortions may present fibrinolytic disorders, which occur independently and more often than aCL positivity. An accurate investigation of the fibrinolytic potential, and, namely, of PAI-1 levels, should be included in the study of females suffering from repeated fetal losses.

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Section: Discussionmentioning

confidence: 97%

Fibrinolytic pattern in recurrent spontaneous abortions: No relationship between hypofibrinolysis and anti‐phospholipid antibodies

Gm¹,

Sartori²,

Ruffatti³

et al. 1994

American J Hematol

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“…IgG containing aCL bound to cultured endothelial cells in the presence of b 2 -GPI, and induced cell adhesion molecules such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) [56], which may lead to a procoagulant state. It is also known that aPL induce procoagulant substances such as tissue factor [57,58], plasminogen activator inhibitor-1 [59] and thromboxane A2 [60], in which processes aPL are likely to affect cells via b 2 -GPI or other phospholipid-binding proteins [61]. In terms of the binding mechanism of aPL, the binding of aCL to protein C with a combination of phospholipids and b 2 -GPI might be a similar phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Binding of anticardiolipin antibodies to protein C via β2-glycoprotein I (β2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system

Atsumi

Khamashta

Amengual

et al. 1998

Clinical and Experimental Immunology

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SUMMARYIt is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via b 2 -GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of b 2 -GPI by ELISA (anti-'protein C' antibody ELISA), and compared their binding with those obtained in the absence of b 2 -GPI. In the anti-'protein C' antibody ELISA system, 47% of 78 aPL þ patients had a positive titre in the presence of cardiolipin (CL) and b 2 -GPI, but binding was not found in the absence of b 2 -GPI. Highly significant correlations were found between the titre of anti-'protein C' antibody in the presence of b 2 -GPI and that of anti-b 2 -GPI antibody (r ¼ 0·802, P ¼ 0·0001). We further analysed the interaction between protein C, phospholipids, b 2 -GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of b 2 -GPI to protein C and its phospholipid dependency were investigated. b 2 -GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of b 2 -GPI (virtually anti-b 2 -GPI antibodies) was evaluated in the presence of cardiolipin and b 2 -GPI. All three human monoclonal aCL bound to protein C in the presence of CL and b 2 -GPI, whereas they did not in the absence of either b 2 -GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and b 2 -GPI, leading to protein C dysfunction.

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“…Whereas there is general consensus that plasminogen activator inhibitor-1 (PAI-1) [18,[21][22][23][24] and PAI-1/t-PA ratios [25] are increased, there is conflicting evidence on the plasma levels of other fibrinolysis proteins such as t-PA, which has been reported to be variable in SLE patients [20][21][22][26][27][28][29]. Furthermore, the role of TAFI in SLE has yet to be fully evaluated.…”

Section: Introductionmentioning

confidence: 98%

“…Indeed, impaired fibrinolytic activity has been suggested to be a contributing factor for increased thrombotic events in patients with SLE; however, the exact cause(s) remains unclear [17][18][19][20][21][22]. Whereas there is general consensus that plasminogen activator inhibitor-1 (PAI-1) [18,[21][22][23][24] and PAI-1/t-PA ratios [25] are increased, there is conflicting evidence on the plasma levels of other fibrinolysis proteins such as t-PA, which has been reported to be variable in SLE patients [20][21][22][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Changes to fibrinolysis in patients with systemic lupus erythematosus are associated with endothelial cell damage and inflammation, but not antiphospholipid antibodies

Dhillon

Khalafallah

Adams

2016

Blood Coagulation &Amp; Fibrinolysis

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We investigated whether changes to fibrinolysis were associated with other manifestations of systemic lupus erythematosus (SLE), including antiphospholipid (APL) antibody status, endothelial damage, and inflammation. Ninety-four patients (36 SLE patients, 58 healthy controls) were recruited from Tasmania, Australia. Circulating levels of plasminogen, α2-antiplasmin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured, as well as APL antibodies (including lupus anticoagulant, anticardiolipin, and antibeta-2 glycoprotein-1 antibodies), soluble E-selectin, and interleukin-6. Whereas there was a significant decrease in plasminogen (patient vs. control; median) (210 vs. 444 ng/ml; P < 0.0001) and increase in α2-antiplasmin (0.53 vs. 0.09 μg/ml; P = 0.0007), there was increased t-PA (0.65 vs. 0.40 ng/ml; P = 0.0001) and decreased TAFI (8.8 vs. 10.0 ng/ml; P = 0.002) in SLE patients compared to healthy controls. Plasminogen was significantly associated with α2-antiplasmin (rho = -0.563, P < 0.001); TAFI (rho = 0.410, P = 0.011); soluble E-selectin (rho = 0.531, P = 0.001); and interleukin-6 (rho = 0.489, P = 0.002) in SLE patients; however, APL antibody status was not associated with any of the markers measured. This study has demonstrated that fibrinolysis is significantly altered in patients with SLE compared to controls, and associated with endothelial cell damage and inflammation, but not APL antibody status.

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Fibrinolytic Potential and Antiphospholipid Antibodies in Systemic Lupus Erythematosus and Other Connective Tissue Disorders

Cited by 47 publications

References 26 publications

Fibrinolytic pattern in recurrent spontaneous abortions: No relationship between hypofibrinolysis and anti‐phospholipid antibodies

Fibrinolytic pattern in recurrent spontaneous abortions: No relationship between hypofibrinolysis and anti‐phospholipid antibodies

Binding of anticardiolipin antibodies to protein C via β2-glycoprotein I (β2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system

Changes to fibrinolysis in patients with systemic lupus erythematosus are associated with endothelial cell damage and inflammation, but not antiphospholipid antibodies

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