Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal andheparin-treated antiphospholipid syndrome pregnancies

Lupus ◽  
2002 ◽  
Vol 11 (1) ◽  
pp. 11-20 ◽  
Author(s):  
S Donohoe ◽  
S Quenby ◽  
I Mackie ◽  
G Panal ◽  
R Farquharson ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Coagulation Activation ◽  
Activation Markers

Antibodies Against Platelet Glycoprotein Target Antigens in Antiphospholipid Syndrome (APS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3973-3973 ◽  
Author(s):  
Carlos J. Bidot ◽  
Wenche Jy ◽  
Carlos Bidot ◽  
Lawrence L. Horstman ◽  
Vincenzo Fontana ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Dominant Role ◽  
Endothelial Activation ◽  
Platelet Glycoprotein ◽  
Activation Markers ◽  
Positive Group ◽  
Platelet Antibodies ◽  
Platelet Microparticles

Abstract Introduction: Antiphospholipid syndrome (APS) is characterized clinically by thrombotic events and the presence of antiphospholipid antibodies (aPLA) and/or lupus anticoagulant (LA). It is frequently associated with thrombocytopenia and anti-platelet antibodies have been implicated by some. However the roles of anti-platelet antibodies in APS have not been elucidated. We previously reported that platelet activation, but not endothelial activation, was associated with thrombosis in aPLA+ patients [Blood, 104:143a, 2004] but the cause of platelet activation was not addressed. In the present study, we investigated the prevalence of anti-platelet antibodies in APS patients, as well as platelet and endothelial activation. Material and Methods: We evaluated 47 patients with primary APS. Anti-platelet antibodies against GP IIb/IIIa (CD41b), GP Ib/IX (CD 42b) and GP IV (CD36) for IgG and IgM class were measured by PAICA assay [Thromb Haemost76:1820, 1996]. We also measured platelet and endothelial activation markers by flow cytometry: CD62P on platelets, CD31+/CD42+ platelet microparticles (PMP), and CD31+/CD42- endothelial microparticles (EMP). Results: Of the 47 patients, 34 (72%) were positive for at least one anti-platelet antibody. Looking first at IgG, 18/34 (53%) were positive for GP IV; 17/34 (50%) for GP IIb/IIIa; and 16/34 (47%) for GP Ib/IX. IgM antibodies were 47% (14/30) for GP Ib/IX, 38%(13/34) for GP IIb/IIIa, and 24% (8/33) for GP IV. Platelet and endothelial markers were significantly more common in the anti-platelet antibodies positive group: 40% vs. 21% for CD62P, 40% vs. 28.5% for EMP, and 23% vs. 5% for PMP, respectively. We found that CD62P associated significantly with IgM anti-GP IIb/IIIa (p< 0.05), and PMP with IgM anti-GP IIb/IIIa (p< 0.05), and IgM anti-GP IV (p< 0.05). Conclusions: Anti-platelet antibodies are common in APS, confirming previous reports. We found that anti-platelet antibodies IgM anti-GP IIb/IIIa, and IgM anti-GP IV were often associated with platelet activation, suggesting that these antibodies may activate platelets to play an important role in the thrombogenesis of APS. These antibodies were also associated with endothelial activation. It remains to be determined which antibodies, APLA and/or anti-platelet antibodies, play a dominant role in the activation of platelet or endothelial cells and contibute most to the pathogenesis of thrombosis in APS.

The clinical relevance of isolated lupus anticoagulant positivity in patients with thrombotic antiphospholipid syndrome

2020 ◽  
Author(s):  
Dong-mei Yin ◽  
Philip de Groot ◽  
Marisa Ninivaggi ◽  
Katrien M.J. Devreese ◽  
Bas de Laat
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Relevance ◽  
Antiphospholipid Antibodies ◽  
Odds Ratio ◽  
Lupus Anticoagulant ◽  
Solid Phase ◽  
Control Group ◽  
Domain I ◽  
Normal Controls ◽  
Better Than

Background: Patients positive for three types of antiphospholipid antibodies (aPLs) (triple positivity) have been identified at a high risk for thrombotic events. However, the clinical significance of isolated lupus anticoagulant (LAC) positivity is debated. Objectives: To investigate the clinical relevance of isolated LAC. Patients/Methods 456 patients were enrolled in this study; 66 antiphospholipid syndrome patients and 390 control patients. The control group existed of autoimmune patients (n=91), patients with thrombosis but without aPLs (n=127) and normal controls (n=172). The criteria LAC, anti-cardiolipin (anti-CL) and anti-beta2glycoprotein I (anti-β2GPI) IgG and IgM and the non-criteria IgA anti-CL and anti-β2GPI, anti-domain I (anti-DI) of β2GPI IgG and anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG and IgM were detected according to the ISTH guidelines for solid phase assays. Results: 70 patients were positive for LAC, of which 44 were negative for both anti-β2GPI and anti-CL. We found that isolated LAC proved to be strongly associated with vascular thrombosis (Odds ratio (OR) (95% CI) 7.3 (3.3-16.1)), even better than triple positive samples (OR 4.3 (1.6-12.2)). The titers of the anti-PS/PT IgG and IgM were significantly higher in triple positivity samples compared to samples with isolated LAC positivity. The majority of single LAC positives were anti-PS/PT negative. We observed that LAC positivity was weaker in isolated LAC positive patients compared to LAC activity in triple positive patients. Conclusions: Isolated LAC was highly associated with thrombosis. The presence of anti-PS/PT could not explain LAC positivity in isolated LAC. Isolated LAC showed a weaker LAC activity compared to triple positive patients.

scholarly journals POS0712 “EXTRA”- CRITERIA ANTIPHOSPHOLIPID ANTIBODIES IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOSUS (PRELIMINARY DATA)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 605.2-606
Author(s):  
F. Cheldieva ◽  
T. Reshetnyak ◽  
M. Cherkasova ◽  
N. Seredavkina ◽  
A. Lila
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Preliminary Data ◽  
Antiphospholipid Antibodies ◽  
Disease Duration ◽  
Past History ◽  
Igg Antibodies ◽  
Systemic Lupus ◽  
Pregnancy Morbidity

Background:The study of antiphospholipid antibodies (aPL), not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood.Objectives:To determine the frequency of detection of IgA-aCL and IgA-aβ2GP1 and IgG antibodies to β2GP1 domain 1 (IgG-aβ2GP1-D1) in patients with APS with and without SLE.Methods:ELISA and chemiluminescence assays (CMA) were used to test 63 sera of patients: 22 (35%) with primary APS (pAPS) and 41 (65%) patients with APS and with SLE (secondary APS (sAPS)), with mean age 38,0 [33,0 – 43,0] years and disease duration 4,0 [0,1 – 9,9]. Both methods were used to test of IgG/IgM-aCL and IgG/IgM-aβ2GP1. CMA was used for research IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GPI and IgG-aβ2GP1-D1. Of them 49 (78%) (18 – with pAPS; 31 – with sAPS) displayed major thrombotic events and 18 of 22 pregnant women had pregnancy morbidity in past history. Lupus anticoagulant (LA) positivity was in 9 out of 12 patients who had it determined. LA was not investigated due to anticoagulant therapy in the remaining 52 patients.Results:IgG/IgM-aCL and IgG/IgM-aß2GP1 were recorded in 44/18 and 50/17 patients by ELISA and in 55/19 and 59/16 by CMA, respectively.IgA-aCL positivity was found in 35 (56%) of 63 patients. Thirty IgA-positive patients were positive for IgG-aCL by ELISA: 22 – IgG-aCL – highly positive, 6 – medium positive and 2 – low positive patients. IgM-aCL by ELISA was detected in 13 (37%) of 35 IgA-aCL positive patients: 11 – highly positive, 1 – medium positive and 1 – low positive. IgA-aCL was combined with IgG-aCL in 34 patients and with IgM-aCL in 16 patients in the CMA. IgG-aß2GP1 in ELISA was detected in 32 patients with IgA-aCL (24 –highly positive, 5 – medium positive and 3 – low positive) and in 34 – in CMA. IgM-aß2GP1 was combined with IgA-aß2GP1 with the same frequency in both methods (in 13 patients).IgA-aß2GP1 was detected in 30 (48%) of 63 patients. They were combined with both IgG-aCL and IgG-aß2GP1 in all cases in both methods. IgM-aCL and IgM-aß2GP1 were detected in 14 and 11 of 30 patients with IgA-aß2GP1, respectively. The combination of IgA-aß2GP1 with IgG-aCL by ELISA was in 27 (in most cases highly positive – 20) and with IgM-aCL – in 10 (highly positive - 8). IgG-aß2GP1 was detected in 28 patients with IgA-aß2GP1 (high positive – 21) and in 11 patients with IgM-aß2GP1 (high positive –7).IgG-aß2GP1-D1 was revealed in 48 (76%) patients. It was combined with IgG-aCL – in 38, with IgM-aCL – in 15 patients by the ELISA. The combination of IgG-aß2GP1-D1 by CMA was as follows: with IgG-aCL – in 46, with IgM-aCL – in 17, and with IgA-aCL – in 33 patients. In most cases, IgG-aß2gp1-D1 was combined with highly positive aCL levels. IgG-aß2GP1-D1 positivity was associated with IgG-aß2GP1 positivity in 42 – by ELISA and 47 – by CMA, IgМ-aβ2GP1 – in 13 and 14 patients by ELISA and CMA, respectively, and IgA-aß2GP1 – in 29. Isolated IgG-aß2GP1-D1 positivity was not observed.Conclusion:The frequency of IgA-aCL detection was 56% (35 patients out of 63), IgA-aβ2GP1 – 48% (30 patients out of 63), IgG-aβ2GP1-D1 – 76% (48 patients out of 63). There was not isolated positivity of this “extra” criterial antibodies. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with highly positivity of IgG/IgM-aCL and IgG/IgM- aβ2GP1.Disclosure of Interests:None declared

scholarly journals Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gunay Uludag ◽  
Neil Onghanseng ◽  
Anh N. T. Tran ◽  
Muhammad Hassan ◽  
Muhammad Sohail Halim ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Autoimmune Disorder ◽  
Ocular Involvement ◽  
Ocular Manifestations ◽  
Different Types ◽  
Thrombotic Complications ◽  
Specific Factors ◽  
Arteries And Veins

AbstractAntiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

scholarly journals Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome

Blood ◽  
2006 ◽  
Vol 107 (11) ◽  
pp. 4375-4382 ◽  
Author(s):  
Gabriela Cesarman-Maus ◽  
Nina P. Ríos-Luna ◽  
Arunkumar B. Deora ◽  
Bihui Huang ◽  
Rosario Villa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Cell Surface Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Antigen ◽  
Healthy Individuals ◽  
Annexin 2

AbstractThe association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and β2-glycoprotein I (β2GPI), the main antigen for antiphospholipid antibodies. Here, we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies. Anti-A2 antibodies (titer > 3 SDs) were significantly more prevalent in patients with APS (22.6%; venous, 17.5%; arterial, 34.3%; and mixed thrombosis, 40.4%) than in healthy individuals (2.1%, P < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001). Anti–A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold ± 0.13-fold SE), blocked A2-supported plasmin generation in a tPAdependent generation assay (19%-71%) independently of β2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%. We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome.

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