The Influence of Antiphospholipid Antibodies on the Protein C Pathway

2000 ◽  
pp. 307-316 ◽  
Author(s):  
P. G. de Groot ◽  
R. H. W. M. Derksen
Keyword(s):  
Antiphospholipid Antibodies ◽  
Protein C

Activated protein C resistance phenotype in patients with antiphospholipid antibodies

1997 ◽  
Vol 130 (2) ◽  
pp. 202-208 ◽  
Author(s):  
Justo Aznar ◽  
Piedad Villa ◽  
Francisco España ◽  
Amparo Estellés ◽  
Salvador Grancha ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Protein C ◽  
Activated Protein C ◽  
Activated Protein C Resistance ◽  
Resistance Phenotype

Resistance to activated protein C in systemic lupus erythematosus patients with antiphospholipid antibodies

2009 ◽  
Vol 53 (3) ◽  
pp. 188-189 ◽  
Author(s):  
Juzo Matsuda ◽  
Kengo Gohchi ◽  
Miyo Tsukamoto ◽  
Moritaka Gotoh ◽  
Noriko Saitoh ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Protein C ◽  
Activated Protein C ◽  
Systemic Lupus

scholarly journals Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis

2004 ◽  
Vol 92 (12) ◽  
pp. 1312-1319 ◽  
Author(s):  
Jeannine Kassis ◽  
Carolyn Neville ◽  
Joyce Rauch ◽  
Lambert Busque ◽  
Erika Chang ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Complete Blood Count ◽  
Tertiary Care ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Activated Protein C Resistance ◽  
Increased Risk

SummaryAlthough antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-β2-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.

Protein C resistance and antiphospholipid antibodies

Lupus ◽  
1996 ◽  
Vol 5 (6) ◽  
pp. 633-633 ◽  
Author(s):  
GJ Ruiz-Argüelles
Keyword(s):  
Antiphospholipid Antibodies ◽  
Protein C

Antiphospholipid Antibodies with LAC Activity That Bind beta2-Glycoprotein I Cause Increased Resistance Against Activated Protein C.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3622-3622
Author(s):  
Bas de Laat ◽  
Sander B. Meijer ◽  
Carel M. Eckmann ◽  
M. van Schagen ◽  
Koen Mertens ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Protein C ◽  
Activated Protein C ◽  
Plasma Samples ◽  
Surface Plasmon Resonance Analysis ◽  
Resonance Analysis ◽  
Igm Antibodies ◽  
Apc Resistance ◽  
Glycoprotein I ◽  
Direct Binding

Abstract Background: The antiphospholipid syndrome is characterized by the occurrence of vascular thrombosis combined with the presence of antiphospholipid antibodies (aPL) in plasma of patients. Recently it was published that aPL with lupus anticoagulant activity (LAC), caused by anti-beta2-glycoprotein I (beta2GPI) antibodies, highly correlate with a history of thrombosis. aPL-related resistance against activated protein C (APC) is one of the proposed mechanism responsible for thrombosis. We investigated a possible correlation between a beta2GPI-dependent LAC and increased APC-resistance in a population of 22 plasma samples with LAC activity. Methods: Twenty-two LAC-positive plasma samples were tested for beta2GPI-dependence (titration of cardiolipin into an APTT-based assay), increased APC-resistance, anti-beta2GPI IgG/IgM antibodies, anti-prothrombin IgG/IgM antibodies and anti-protein C IgG/IgM antibodies. In addition, a monoclonal anti-beta2GPI antibody and patient-purified IgG (both with LAC activity) were diluted in plasma with/without protein C and tested for occurrence of a beta2GPI-dependent LAC (normalization of clotting time by the addition of cardiolipin). To study aPL-induced APC-resistance in more detail, surface plasmon resonance analysis was used to investigate binding between APC and beta2GPI in the presence/absence of a mouse-derived monoclonal anti-beta2GPI antibody. Results: Eleven plasma samples that displayed a beta2GPI-dependent LAC also showed increased APC resistance. In contrast, only 1 of the 11 plasma samples with a beta2GPI-independent LAC displayed increased APC-resistance. None of the other serological parameters (antibodies against beta2-glycoprotein I, prothrombin or protein C) displayed the same association with increased APC resistance as a beta2-glycoprotein I dependent LAC. Furthermore, we found a linear correlation between the potency of a beta2GPI-dependent LAC and the level of APC-resistance. When a monoclonal anti-beta2GPI antibody and a patient-purified IgG were tested for a beta2GPI-dependent LAC, both antibodies did not display a beta2GPI-dependent LAC when diluted in protein C deficient plasma. In literature it has been proposed that direct binding of beta2GPI to APC results in a decreased activity of APC. By using surface plasmon resonance analysis, we found that beta2GPI displayed a higher affinity for coated APC in the presence of the monoclonal anti-beta2GPI antibody (4 nM) compared to beta2GPI alone (400 nM). Conclusion: The results of this study indicate that by adding cardiolipin into an APTT-based clotting assay, one can detect beta2GPI-dependent LAC based on increased resistance against APC. Increased resistance against activated protein C might result from direct binding of beta2GPI to activated protein C. In conclusion, our observations indicate a direct correlation between a major clinical symptom of APS (thrombosis), a diagnostic assay (beta2GPI-dependent LAC) and a potential mechanism responsible for thrombosis in the antiphospholipid syndrome (increased APC-resistance).

scholarly journals Antiphospholipid antibodies impact the protein C (PC) pathway behavior

2002 ◽  
Vol 71 (2) ◽  
pp. 128-130 ◽  
Author(s):  
Laura C. Gennari ◽  
Alicia N. Blanco ◽  
Mar�a Fabiana Alberto ◽  
Silvia H. Grosso ◽  
Andrea A. Peirano ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Protein C

scholarly journals Letter to the editor: Spurious protein C deficiency due to antiphospholipid antibodies

1991 ◽  
Vol 36 (4) ◽  
pp. 299-300 ◽  
Author(s):  
Paolo Simioni ◽  
Annarosa Lazzaro ◽  
Sandra Zanardi ◽  
Antonio Girolami
Keyword(s):  
Antiphospholipid Antibodies ◽  
Protein C ◽  
Protein C Deficiency ◽  
Letter To The Editor

Early Pathophysiology of Osteonecrosis

1998 ◽  
Vol 8 (2) ◽  
pp. 71-79
Author(s):  
J.P. Jones
Keyword(s):  
Antiphospholipid Antibodies ◽  
Protein C ◽  
Viral Infections ◽  
Proteolytic Enzymes ◽  
Arterial Occlusion ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Disc Disease ◽  
Organ Rejection ◽  
Intravascular Coagulation

Current concepts regarding the early pathophysiology of osteonecrosis (ON) are reviewed. Traumatic ON appears to result from arterial severance, an acute ischaemic event. Intravascular coagulation of the intraosseous microcirculation (capillaries and venous sinusoids) progressing to generalized venous thrombosis, and less commonly retrograde arterial occlusion, now appears to be the genesis of nontraumatic ON. However, a coagulopathy is only an intermediary event, which is always activated by some underlying aetiological risk factor(s). Conditions capable of triggering intravascular coagulation include familial thrombophilia (resistance to activated protein C, decreased protein C, protein S, or antithrombin III), hyperlipaemia and embolic lipid (alcoholism and hypercortisonism), hypersensitivy reactions (allograft organ rejection, immune complexes, and antiphospholipid antibodies), bacterial endotoxic (Shwartzman) reactions and various viral infections, proteolytic enzymes (pancreatitis), tissue factor release (inflammatory bowel disease, malignancies, neurotrauma, and pregnancy), and other prethrombotic and hypofibrinolytic conditions. In order to exceed the ischaemic threshold and produce ON, significant residual fibrin-platelet microthrombi must remain within the intraosseous vasculature for a minimum of two to six hours, and not be immediately removed by endogenous fibrinolysis. Hypofibrinolysis with increased plasminogen activator inhibitor has been found in patients with ON. The thrombotic threshold may be decreased in those hypercoagulable patients with hereditary thrombophilia, antiphospholipid antibodies, or hyperlipaemia. Subsequent exposure to an additional factor should facilitate intraosseous thrombosis and ON. It is also conceivable that fractional subchondral ON can cause both degenerative disc disease and “primary” osteoarthritis of aging and obesity.

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