Comparison of three activated protein C resistance tests in the risk assessment of venous thrombosis in non-carriers of the factor V Leiden mutation

2006 ◽  
Vol 95 (04) ◽  
pp. 728-734 ◽  
Author(s):  
Felipe Guerrero ◽  
Catherine Arnaud ◽  
Francoise Nguyen ◽  
Bernard Boneu ◽  
Pierre Sié
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Significant Risk ◽  
Factor V Leiden ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Risk Increase ◽  
Increased Risk

SummaryActivated protein C resistance (APCR), measured using the original assay described by Dahlbäck, is a risk factor for venous thrombosis independent of the factor V Leiden (FVL) mutation. This assay is based on the activated partial thromboplastin time (APTT) after plasma exposure to activated protein C (APC).As this assay was sensitive to numerous interferences, new assays have been developed for FVL screening. The objectives of the study were to investigate the association of second generation assays for APCR with venous thrombosis in FVL non-carriers. One hundred ninety-seven subjects with a history of venous thrombosis and 211 controls were explored using 3 APCR assays, the original APTT-based assay (test A), an APTT-based assay with factorV depleted plasma pre-dilution (test B) and a direct factorX activation-based assay with the same pre-dilution (test C).We found that subjects with results in the lowest quartile of the APTT-based assays are at increased risk, compared to those in the highest quartile (test A Odds Ratio = 6.39; 95%CI 3.23–12.63; test B OR=2.72; 95%CI 1.50–4.94). There was no significant risk increase associated with test C results. After adjusting for FVIII levels, the ORs of tests A and B were similar (test A OR=3.22; 95%CI 1.47–7.08; test B OR=3.10; 95%CI 1.54–6.21). In conclusion, APTT-based assays, but not direct factor X activation-based assays, effectively detect the risk for venous thrombosis independent of FVL. Pre-dilution in factor V depleted plasma is an effective way to directly assess the risk independent of FVIII levels.

A Reduced Sensitivity for Activated Protein C in the Absence of Factor V Leiden Increases the Risk of Venous Thrombosis

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1271-1276 ◽  
Author(s):  
Marieke C.H. de Visser ◽  
Frits R. Rosendaal ◽  
Rogier M. Bertina
Keyword(s):  
Risk Factor ◽  
Confidence Interval ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Apc Resistance ◽  
Increased Risk

Abstract Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis. We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis. For this analysis, we used the Leiden Thrombophilia Study (LETS), a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched controls. All carriers of the factor V Leiden mutation were excluded. A dose-response relationship was observed between the sensitivity for APC and the risk of thrombosis: the lower the normalized APC sensitivity ratio, the higher the associated risk. The risk for the lowest quartile of normalized APC-SR (<0.92), which included 16.5% of the healthy controls, compared with the highest quartile (normalized APC-SR > 1.05) was greater than fourfold increased (OR = 4.4; 95% confidence interval, 2.9 to 6.6). We adjusted for VIII:C levels, which appeared to affect our APC resistance test. The adjusted (age, sex, FVIII:C) odds ratio for the lowest quartile was 2.5 (95% confidence interval, 1.5 to 4.2). So, after adjustment for factor VIII levels, a reduced response to APC remained a risk factor. Our results show that a reduced sensitivity for APC, not caused by the factor V Leiden mutation, is a risk factor for venous thrombosis.

A Reduced Sensitivity for Activated Protein C in the Absence of Factor V Leiden Increases the Risk of Venous Thrombosis

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1271-1276 ◽  
Author(s):  
Marieke C.H. de Visser ◽  
Frits R. Rosendaal ◽  
Rogier M. Bertina
Keyword(s):  
Risk Factor ◽  
Confidence Interval ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Apc Resistance ◽  
Increased Risk

Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis. We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis. For this analysis, we used the Leiden Thrombophilia Study (LETS), a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched controls. All carriers of the factor V Leiden mutation were excluded. A dose-response relationship was observed between the sensitivity for APC and the risk of thrombosis: the lower the normalized APC sensitivity ratio, the higher the associated risk. The risk for the lowest quartile of normalized APC-SR (<0.92), which included 16.5% of the healthy controls, compared with the highest quartile (normalized APC-SR > 1.05) was greater than fourfold increased (OR = 4.4; 95% confidence interval, 2.9 to 6.6). We adjusted for VIII:C levels, which appeared to affect our APC resistance test. The adjusted (age, sex, FVIII:C) odds ratio for the lowest quartile was 2.5 (95% confidence interval, 1.5 to 4.2). So, after adjustment for factor VIII levels, a reduced response to APC remained a risk factor. Our results show that a reduced sensitivity for APC, not caused by the factor V Leiden mutation, is a risk factor for venous thrombosis.

Acquired Activated Protein C Resistance Associated with Anti-Protein S Antibody as a Strong Risk Factor for DVT in Non-SLE Patients

2002 ◽  
Vol 88 (11) ◽  
pp. 716-722 ◽  
Author(s):  
Hirohiko Kuratsune ◽  
Etsuji Suehisa ◽  
Tomio Kawasaki ◽  
Takashi Machii ◽  
Teruo Kitani ◽  
...  
Keyword(s):  
Risk Factor ◽  
Protein C ◽  
Activated Protein C ◽  
Significant Risk ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Strong Risk Factor

SummaryAnti-phospholipid (aPL) antibodies (Abs) are well known to be associated with thromboembolic events in patients with systemic lupus erythematosus (SLE). However, the clinical relevance of aPL Abs in patients without SLE (non-SLE) who have venous thromboembolism remains unclear. We evaluated 143 non-SLE patients with a first episode of clinically suspected deep vein thrombosis (DVT) by using objective tests for diagnosing DVT and laboratory tests including the activated protein C resistance (APC-R) test, the factor V Leiden test, and various aPL Abs. The prevalence of acquired APC-R, in which case there was no factor V Leiden mutation, was significantly higher in patients with DVT (15/58 cases, 25.9%, p <0.0001) than in those without DVT (3/80 cases, 3.7%), and confirmed that acquired APC-R was a strong risk factor for DVT (odds ratio [OR], 8.95; 95% confidence intervals [CI], 2.45-32.7; p <0.001). Multivariate logistic analysis revealed that the presence of LA, aCL, anti- β2-glycoprotein I, anti-prothrombin and anti-protein C Abs was not reliable as a risk factor for DVT in non-SLE patients, and that the presence of anti-protein S Abs was the most significant risk factor for DVT (OR, 5.88; 95% CI, 1.96-17.7; p <0.002). Furthermore, the presence of anti-protein S Abs was strongly associated with acquired APC-R (OR, 57.8; 95% CI, 8.53-391; p <0.0001). These results suggest that acquired APC-R may reflect functional interference by anti-protein S Abs of the protein C pathway, which action may represent an important mechanism for the development DVT in non-SLE patients.

Activated Protein C Resistance, the Factor V Leiden Mutation, and a Laboratory Testing Algorithm

2002 ◽  
Vol 126 (5) ◽  
pp. 577-582 ◽  
Author(s):  
Elizabeth M. Van Cott ◽  
Britt L. Soderberg ◽  
Michael Laposata
Keyword(s):  
Laboratory Testing ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Increased Risk ◽  
Testing Algorithm

Abstract Objectives.—To present the current understanding of factor V Leiden and activated protein C resistance, and to propose a laboratory testing algorithm. Data Sources.—Publications on MEDLINE with the terms factor V Leiden or activated protein C resistance through mid 2001, as well as publications in the authors' files, were screened for inclusion in this report. Study Selection.—Original studies that report a novel finding on testing or clinical features of activated protein C resistance or factor V Leiden are included. Data Extraction.—The novel or key findings from the selected studies are analyzed. Data Synthesis.—Protein C and protein S are the integral components of an anticoagulation pathway that limits fibrinogen conversion to fibrin through the degradation of factors Va and VIIIa. When factor Va is resistant to degradation by activated protein C, this anticoagulation pathway does not operate properly, and patients have an increased risk for thrombosis. This report describes the protein C/protein S pathway, the significance of activated protein C resistance and the factor V Leiden mutation, and the clinical testing used to detect activated protein C resistance and the factor V Leiden mutation. A proposed laboratory testing algorithm is also provided. Conclusions.—Factor V Leiden is a risk factor for venous thrombosis and it is particularly common in white populations. A laboratory testing algorithm is proposed.

Coagulation Factor V Leiden Mutation Was Detected in the Patients with Activated Protein C Resistance in Thailand

1998 ◽  
Vol 80 (08) ◽  
pp. 344-345 ◽  
Author(s):  
Pasra Arnutti ◽  
Motofumi Hiyoshi ◽  
Wichai Prayoonwiwat ◽  
Oytip Nathalang ◽  
Chamaiporn Suwanasophon ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Coagulation Factor V

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.

scholarly journals Activated Protein C Resistance and Factor V Leiden in Mexico

2007 ◽  
Vol 14 (4) ◽  
pp. 428-437 ◽  
Author(s):  
Abraham Majluf-Cruz ◽  
Manuel Moreno-Hernández ◽  
Adriana Ruiz-de-Chávez-Ochoa ◽  
Rosario Monroy-García ◽  
Karim Majluf-Cruz ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Common Cause ◽  
Factor V Gene ◽  
V Gene ◽  
Low Prevalence

A common cause of hereditary thrombophilia is activated protein C resistance (APCR), and most cases result from factor V Leiden mutation. An APCR phenotype without association with factor V Leiden has been described. This transversal, observational, nonrandomized study evaluated these 2 phenomena in healthy indigenous and mestizo Mexican subjects (n = 4345), including 600 Mexican natives. No indigenous subjects had APCR, but 82 mestizo subjects did. After retesting, 50 subjects had a negative test. The remaining 32 subjects had factor V Leiden, giving a 0.85% prevalence of factor V Leiden in the mestizo Mexican population. Only 31% of APCR carriers had factor V Leiden. These results show a very low prevalence of APCR and factor V Leiden in Mexico. Except for factor V Leiden, there are no other mutations in the factor V gene responsible for the APCR phenotype. Acquired APCR is nearly twice as prevalent as the inherited variant.

Sign in / Sign up

Export Citation Format

Share Document