Serum complement activation on heterologous platelets is associated with arterial thrombosis in patients with systemic lupus erythematosus and antiphospholipid antibodies

Objective.Antiphospholipid syndrome (APS) is characterized by thrombosis (venous and arterial) and pregnancy loss in conjunction with the lupus anticoagulant, IgG or IgM anticardiolipin, or IgG or IgM anti-ß2-glycoprotein I. In most series, only a minority of patients with antiphospholipid antibodies develop a clinical manifestation.Methods.A cross-sectional study of consecutive patients in the Hopkins Lupus Center was performed. Interviews were done and records were reviewed for the following variables: gender, ethnicity, hypertension, triglycerides, cholesterol, smoking, diabetes mellitus, homocysteine, cancer, hepatitis C, hormone replacement therapy/oral contraceptives, hereditary thrombophilia, anticardiolipin antibodies IgG, IgM and IgA, and lupus anticoagulant (LAC). Our aim was to identify risk factors associated with thrombosis and pregnancy loss in patients with antiphospholipid antibodies.Results.A total of 122 patients (84% female, 74% Caucasian) were studied. Patients were divided into 3 groups: primary APS, APS associated with systemic lupus erythematosus, and patients with systemic lupus erythematosus (SLE) with antiphospholipid antibodies but no thrombosis or pregnancy loss. Venous thrombosis was associated with high triglycerides (p = 0.001), hereditary thrombophilia (p = 0.02), anticardiolipin antibodies IgG > 40 (p = 0.04), and LAC (p = 0.012). Hypertriglyceridemia was associated with a 6.4-fold increase, hereditary thrombophilia with a 7.3-fold increase, and anticardiolipin IgG > 40 GPL with a 2.8-fold increase in the risk of venous thrombosis. Arterial thrombosis was associated with hypertension (p = 0.008) and elevated homocysteine (p = 0.044). Hypertension was associated with a 2.4-fold increase in the risk of arterial thrombosis. No correlations were found for pregnancy loss.Conclusion.The frequency of thrombosis and pregnancy loss is greater in APS associated with SLE than in primary APS. Risk factors differ for venous and arterial thrombosis in APS. Treatment of hypertension may be the most important intervention to reduce arterial thrombosis. Elevated triglycerides are a major associate of venous thrombosis, but the benefit of treatment is not known. Hereditary thrombophilia is an associate of venous but not arterial thrombosis, making it cost-effective to investigate only in venous thrombosis.

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Cell‐Bound Complement Activation Products Are Superior to Serum Complement C3 and C4 Levels to Detect Complement Activation in Systemic Lupus Erythematosus: Comment on the Article by Aringer et al

Arthritis & Rheumatology ◽

10.1002/art.41227 ◽

2020 ◽

Vol 72 (5) ◽

pp. 860-860

Author(s):

Arthur Weinstein

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Complement Activation ◽

Complement C3 ◽

Serum Complement ◽

Systemic Lupus ◽

Activation Products

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No Thrombotic Risk in Patients with Asymptomatic Antiphospholipid Antibodies

Blood ◽

10.1182/blood.v118.21.5254.5254 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5254-5254

Author(s):

Krystyna M Zawilska ◽

Agata M Kopydlowska

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Arterial Thrombosis ◽

Study Group ◽

Hemorrhagic Diathesis ◽

Thromboembolic Events ◽

Systemic Lupus ◽

Thrombotic Risk ◽

Abnormal Results

Abstract Abstract 5254 Aim of the study. Antiphospholipid antibodies (APA) are well known risk factor for thromboembolic events and/or obstetric complications. They may be found incidentally in patients without thrombotic complications (asymptomatic APA), and they often lead to an incorrect suspicion of hemorrhagic diathesis, as well as to an unnecessary disqualification from surgical procedures or withdrawal from a proper antithrombotic prophylaxis during these procedures. The aim of the study was to register venous and/or thrombotic events in a group of patients with asymptomatic APA, diagnosed according to the international guidelines (Myakis et all. 2006). Material and methods. The study group consisted of 25 patients (18 women and 7 men) of the mean age of 46 years (20 – 75 years). Concomitantly 9 of them had other autoimmune disorders (no systemic lupus erythematosus) and 4 had neoplasms. Among risk factors for arterial thrombosis 5 patients had hypercholesterolemia, 5 – hypertension, 4 were smokers and 4 were obese (BMI >30 kg/m2). None of the patients had hereditary thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A mutation, increased activity of factor VIII). Family history of venous thromboembolic disease has been noticed in 4 patients and of arterial thrombosis in 6 patients. The observation lasted for 3 to 127 months (mean 35 months). Results. The number and percent of patients (n = 25) with abnormal results 997337of different laboratory diagnostic assays for APA: aPTT-activated partial thromboplastin time; dRVVT - diluted Russell viper venom time; ACA-anticardiolipin antibodies; β2-GPI – anti-β2–glycoprotein I antibodies Abnormal results of more than one assay in any combination were found in 16 patients, lupus anticoagulant alone in 9 patients. Only 4 out of 25 patients have taken aspirin - 75mg daily, in the other 4 a prophylactic dose of low molecular weight heparin was administered temporarily because of surgery. During observation time no venous or arterial thrombotic events occurred in the study group. On a basis of a limited number of previous studies that predominantly included systemic lupus erythematosus patients, aPL-positive patients without previous thrombosis have a 0% to 3.8% annual incident thrombosis risk (Barbhaiya M, Erksan D. Curr Rheumatol Rep. 2011; 13: 59–69). In two patients asymptomatic APA disappeared. Conclusion: independently of the type and quantity of asymptomatic antiphospholipid antibodies, there were no venous or arterial thromboembolic events in the group of patients observed for meanly 35 months. Disclosures: No relevant conflicts of interest to declare.

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Factor V Leiden, Antiphospholipid Antibodies and Thrombosis in Systemic Lupus Erythematosus

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650614 ◽

1996 ◽

Vol 76 (04) ◽

pp. 514-517 ◽

Cited By ~ 36

Author(s):

R Fijnheer ◽

D A Horbach ◽

R C J M Donders ◽

H Vilé ◽

E v Oort ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Venous Thrombosis ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Odds Ratio ◽

Arterial Thrombosis ◽

Lupus Anticoagulant ◽

Factor V Leiden ◽

Factor V ◽

Systemic Lupus

SummaryThromboembolic complications are frequently observed in patients with systemic lupus erythematosus (SLE). Significant associations have been reported between these complications and the presence of antiphospholipid antibodies, notably the lupus anticoagulant and anti-cardiolipin antibodies. Factor V Leiden is a genetic disorder associated with an increased risk of venous thrombosis. We studied these factors in 173 patients with SLE in relation to both arterial and venous thrombosis. The frequency of factor V Leiden in SLE patients is comparable to that in the Dutch population (5%) and a risk factor for venous thrombosis (odds ratio 4.9; Cl 1.2-19.6), but not for arterial thrombosis. The lupus anticoagulant is a risk factor for both arterial thrombosis (odds ratio 7.1; Cl 2.9-17.4) and venous thrombosis (odds ratio 6.4; Cl 2.7-15.4). From multivariate analysis, both the lupus anticoagulant and factor V Leiden appeared independent risk factors for venous thrombosis.

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HETEROGENEOUS REACTIVITY OF HUMAN MONOCLONAL ANTIPHOSPHOLIPID ANTIBODIES (HMA) WITH ENDOTHELIAL CELLS (EC), PLATELETS AND DNA

10.1055/s-0038-1643659 ◽

1987 ◽

Author(s):

C A IZAGUIRRE ◽

S DUFF ◽

S HASHMENT ◽

C D SMITH ◽

Q H MENG ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Endothelial Cells ◽

Western Blot ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Arterial Thrombosis ◽

Antiphospholipid Antibody ◽

Systemic Lupus ◽

Fetal Wastage ◽

Heterogeneous Reactivity

Antibodies that react with cardiolipin (ACL) and/or have lupus anticoagulant (LA) properties are implicated in the thrombotic diathesis of patients with the antiphospholipid antibody syndromes: recurrent venousand arterial thrombosis, fetal wastage, thrombocytopenia and CNS disease, often associated with systemic lupus erythematosus. We studied a panel of 16 HMA with LA and/or ACL properties (J Biol Chem 261:9672 1986) for their reactivity with platelets (ELISA),DNA (ELISA), with surface antigensonEC (EC-ELISA) and with whole cell EC extracts as detected by western blot and immunoperoxidase (EC-WB). Three control HMA werenonreactive in all assays.Five HMA with LA activity alone did not react with EC. Five of 6 HMA-ACL reacted with EC both on ELISA and WB. All of the HMA-ACL also reacted with DNA and platelets but 4 did not react as LA. Our findings indicate that HMA antiphospholipid antibodies(LA and ACL) appear to be heterogeneous in terms of their spectrum of reactivities, thus, the ACL and LA tests may in some cases recognize antibodies with different properties and perhaps different pathogeneticmechanisms.xs

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Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: A systematic review and meta-analysis

Autoimmunity Reviews ◽

10.1016/j.autrev.2013.11.004 ◽

2014 ◽

Vol 13 (6) ◽

pp. 595-608 ◽

Cited By ~ 103

Author(s):

Quitterie Reynaud ◽

Jean-Christophe Lega ◽

Patrick Mismetti ◽

Céline Chapelle ◽

Denis Wahl ◽

...

Keyword(s):

Systematic Review ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Arterial Thrombosis ◽

Meta Analysis ◽

Systemic Lupus

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Profiling of non-criteria antiphospholipid antibodies in patients with SLE: differentiation of thrombotic SLE patients and risk of recurrence of thrombosis

Lupus ◽

10.1177/0961203320909952 ◽

2020 ◽

Vol 29 (5) ◽

pp. 490-498

Author(s):

O Tkachenko ◽

S Lapin ◽

A Mazing ◽

V Emanuel ◽

E Belolipetskaia ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Deep Vein Thrombosis ◽

Confidence Interval ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Odds Ratio ◽

Arterial Thrombosis ◽

Systemic Lupus ◽

Vein Thrombosis ◽

Deep Vein

To reveal the clinical significance of criteria and non-criteria antiphospholipid antibodies detected by line immunoassay in comparison with ELISA, systemic lupus erythematosus patients with and without thrombotic events were investigated. Thus, 107 systemic lupus erythematosus patients (48% with deep vein thrombosis or/and arterial thrombosis) and 120 healthy donors were enrolled. Serum antiphospholipid antibodies were detected by ELISA (Orgentec Diagnostika, Germany) and line immunoassay (GA Generic Assays, Germany). Lupus anticoagulant and IgG to cardiolipin and β2GPI but not IgM as well as triple positivity by ELISA and line immunoassay were linked with thrombosis in systemic lupus erythematosus. IgG to phosphatidylinositol and phosphatidylserine by line immunoassay showed significantly higher levels in systemic lupus erythematosus with deep vein thrombosis/arterial thrombosis than without and were independent risk factors for deep vein thrombosis (odds ratio 3.9, 95% confidence interval 1.1, 13.2) and arterial thrombosis (odds ratio 5.1, 95% confidence interval 1.3, 19.8) as well as thrombosis (odds ratio 3.6, 95% confidence interval 1.1, 11.3) and recurrence thereof (odds ratio 6.9, 95% confidence interval 2.1, 22.6), respectively. The occurrence of >4 IgG antiphospholipid antibodies by line immunoassay was an independent risk factor for thrombosis (odds ratio 10.9, 95% confidence interval 1.2, 101.5), arterial thrombosis (odds ratio 14.6, 95% confidence interval 2.5, 86.3), deep vein thrombosis (odds ratio 5.8, 95% confidence interval 1.0, 32.4) and recurrence of thrombosis (odds ratio 35.9, 95% confidence interval 3.8, 342.8). Line immunoassay is a promising multiplex test for the simultaneous detection of criteria and non-criteria antiphospholipid antibodies. Profiling of antiphospholipid antibodies by line immunoassay can differentiate systemic lupus erythematosus patients with thrombosis from systemic lupus erythematosus patients without and assess the risk for thrombosis and recurrence thereof.

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