Multicenter Evaluation of a Kit for Activated Protein C Resistance on Various Coagulation Instruments Using Plasmas from Healthy Individuals

Rosén, S.; Johansson, Karin J; Lindberg, Kjell; Dahlbäck, Björn

doi:10.1055/s-0038-1648849

Cited by 82 publications

(50 citation statements)

References 18 publications

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“…We used 2 methods, a firstgeneration APC sensitivity ratio (APC-SR) 21 and a newer assay incorporating predilution with factor V-deficient plasma to improve detection of factor V-dependent APC (modified APC-SR). 22 Measurement was done on an ACL Futura Coagulation System (Instrumentation Laboratory). Laboratory interassay and intra-assay variation is about 7%.…”

Section: Laboratory Methodsmentioning

confidence: 99%

A prospective study of venous thromboembolism in relation to factor V Leiden and related factors

Folsom

Cushman

Tsai

et al. 2002

Blood

127

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The aim of this study was to examine the occurrence of venous thromboembolism (VTE) in relation to factor V-related risk factors. Using a nested case-control design combining 2 population-based prospective studies, we measured factor V Leiden, HR2 haplotype, activated protein C (APC) resistance, and plasma factor V antigen in 335 participants who developed VTE during 8 years of follow-up and 688 controls. The overall odds ratio (OR) of VTE was 3.67 (95% CI, 2.20-6.12) in participants carrying factor V Leiden compared with noncarriers. APC resistance measured after predilution with factor V-deficient plasma conferred an OR of 2.58 (95% CI, 1.62-4.10). All 3 participants homozygous for the HR2 haplotype had a VTE, and the OR of VTE for homozygosity was estimated to be 5.5 (95% CI, 2.45-12.5). Carriers of the HR2 haplotype otherwise were not at increased risk of VTE overall (OR ‫؍‬ 1.05; 95% CI, 0.64-1.72), but double heterozygotes for HR2 and factor V Leiden carried an OR of idiopathic VTE of 16.3 (95% CI, 1.7-159) compared with noncarriers. Factor V antigen also was not associated with VTE overall, but for participants with the combination of high factor V antigen plus factor V Leiden the OR of idiopathic VTE was 11.5 (95% CI, 4.2-31.4). In the general population, APC resistance and factor V Leiden were important VTE risk factors; homozygosity for the HR2 haplotype may be a risk factor but was rare; otherwise, HR2 haplotype and factor V antigen were not risk factors except in carriers of factor V Leiden. (Blood. 2002;99:2720-2725

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Section: Laboratory Methodsmentioning

confidence: 99%

A prospective study of venous thromboembolism in relation to factor V Leiden and related factors

Folsom

Cushman

Tsai

et al. 2002

Blood

127

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“…6 The activated protein C sensitivity ratio (APC-SR) was determined by the addition of APC to an activated partial thromboplastin time (APTT) assay using a Coatest APC resistance kit (Chromogenix AB, Molendal, Sweden). 7 The results were expressed as a ratio of the APTT level in the presence of APC to the APTT level in the absence of APC (APC-SR). All samples with an APC-SR of 2.4 or less were screened for the factor V Leiden mutation by polymerase chain reaction.…”

Section: Coagulation Markersmentioning

confidence: 99%

Venous Sonography for the Diagnosis of Asymptomatic Deep Vein Thrombosis in Patients With Cancer Undergoing Chemotherapy

Bernstein

Haim

Brenner

et al. 2004

Journal of Ultrasound in Medicine

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Objective. Early detection of asymptomatic deep vein thrombosis by venous sonography may identify patients who may benefit from anticoagulant therapy and thus may prevent morbidity and mortality associated with deep vein thrombosis. The aim of this study was to examine the prevalence of deep vein thrombosis by venous sonography in asymptomatic ambulatory patients with cancer undergoing chemotherapy and to evaluate the correlation between procoagulant activity and asymptomatic deep vein thrombosis. Methods. The study population included 62 patients (32 with lung cancer and 30 with lymphoma) receiving chemotherapy with an ambulatory performance status and without clinical evidence of deep vein thrombosis. Bilateral venous sonographic studies of the lower extremities were performed, covering the femoropopliteal venous system. The D‐dimer level and acquired activated protein C resistance were determined in the patients and in 30 healthy control subjects. Results. Sonographic evidence of deep vein thrombosis on the femoropopliteal axis was found in 0 (0%) of 62 patients (1‐sided 95% confidence interval, 0%–4.8%). Acquired activated protein C resistance prevalence and D‐dimer levels were increased in study patients compared with control subjects (34% versus 0%; P < .003; median, 0.72 versus 0.25 mg/L; P < .0001, respectively). Conclusions. Despite the procoagulant tendency, venous sonography did not detect asymptomatic deep vein thrombosis in patients with cancer undergoing chemotherapy. Thus, screening by venous sonography is not justified in this patient population.

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“…" 15 The most commonly used test for APC resistance is a partial thromboplastin time (PTT)-based test, reported as the ratio of a PTT performed in the presence of a standard quantity of APC divided by the PTT without APC added. It has been shown that most healthy individuals will have a ratio of >2, whereas those with APC resistance were defined as having a ratio < 2.…”

mentioning

confidence: 99%

Sensitivity and Specificity ofthe APC Resistance Assay in Detection of Individuals With Factor V Leiden

Zehnder

Benson

1996

Am J Clin Pathol

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Resistance to activated protein C (APC) is the most common cause of familial thrombophilia. The partial thromboplastin time (PTT)-based test for resistance to APC has been widely employed as a screening test for this disorder. However, the utility of this test for screening is not well characterized. More than 90% of patients with resistance to APC have the G1691A mutation in factor V (factor V Leiden). The authors studied the ability of a commercial APC resistance assay to correctly identify the factor V Leiden genotype in 130 individuals. At the recommended assay cut-off value of 2, the sensitivity of the APC resistance assay was 50%, with a specificity of 98%. Increasing the cut-off value increased the sensitivity but decreased the specificity of the test. ReActivated protein C (APC) limits the clotting process by proteolytic inactivation ofthe two clotting co-factors factor Va and factor Villa. '" 3 Resistance to activated protein C has been shown to be a common risk factor for venous thrombosis. 4,5 In >90% of cases, APC resistance is due to a mutation in the factor V gene, G1691A (factor V Leiden). "10 This mutation does not appear to alter the procoagulant activity of factor Va. However, the mutation occurs at one ofthe two APC cleavage sites, resulting in decreased inactivation of factor Va, and increases the risk of venous thrombosis in affected individuals. Horaozygotes for factor V Leiden have a relative risk of thrombosis of 50 to 100, whereas the risk in heterozygotes is 5-to 10-fold higher than healthy subjects." The factor V Leiden mutation appears to be relatively common with a prevalence of 5% to 10% in several populations studied, 46 although a recent report suggests that the incidence of this mutation in people of Japanese ancestry is much lower.12 This defect is the most common cause of familial thrombophilia yet identified. Testing for this syndrome can be performed by an in vitro assay of resistance to activated protein C, or by isolating genomic DNA of patients, amplifying and analyzing the area ofthe mutation by restriction enzyme digestion or by oligonucleotide hybridization. - 613" 15 The most commonly used test for APC resistance is a partial thromboplastin time (PTT)-based test, reported as the ratio of a PTT performed in the presence of a standard quantity of APC divided by the PTT without APC added. It has been shown that most healthy individuals will have a ratio of >2, whereas those with APC resistance were defined as having a ratio < 2. 4 Because of its simplicity this test has been widely employed as a screening test for APC resistance.The definitive test for this syndrome is molecular diagnosis of factor V Leiden.6 Determination of factor V genotype is performed by isolating genomic DNA from patient leukocytes. The DNA sequence flanking the mutation site in the factor V gene is then amplified using the polymerase chain reaction (PCR), and the resultant product analyzed by restriction enzyme digestion. 6 In this way, patients can be classified as wild type (two normal factor ...

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Multicenter Evaluation of a Kit for Activated Protein C Resistance on Various Coagulation Instruments Using Plasmas from Healthy Individuals

Cited by 82 publications

References 18 publications

A prospective study of venous thromboembolism in relation to factor V Leiden and related factors

A prospective study of venous thromboembolism in relation to factor V Leiden and related factors

Venous Sonography for the Diagnosis of Asymptomatic Deep Vein Thrombosis in Patients With Cancer Undergoing Chemotherapy

Sensitivity and Specificity ofthe APC Resistance Assay in Detection of Individuals With Factor V Leiden

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