Evaluation of a highly specific functional test for the detection of factor V Leiden

Quehenberger, Peter; Handler, Sylvia; Mannhalter, Christine; Pabinger‐Fasching, Ingrid; Speiser, Wolfgang

doi:10.1007/s005990070009

Cited by 13 publications

(6 citation statements)

References 19 publications

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“…Interestingly, no interference of low PS level has been found with the Staclot APC-R assay. 49 There might be other causes of APC-R, such as still unknown genetic polymorphisms (single nucleotide polymorphisms) especially in the Chinese population in which FV Hong Kong has been discovered.…”

Section: Discussionmentioning

confidence: 99%

Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group

Zhu¹,

Ding²,

Bai³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundInherited deficiency of antithrombin, protein C and protein S, three important, naturally occurring coagulation inhibitors, might play a major role in the occurrence of venous thromboembolism in Chinese. The establishment of age-and gender-related normal ranges of these inhibitors is crucial for an accurate diagnosis of these deficiencies. Design and MethodsWe designed a prospective cross-sectional study recruiting healthy adults from four universityaffiliated hospitals in China. Antithrombin, protein C and protein S were studied by measuring their activity. Gene analysis was performed when natural anticoagulant deficiency was suspected. Polymorphisms of the factor V gene were searched for among subjects who were positive for activated protein C resistance. ResultsIn 3493 healthy Chinese adults (1734 men, 1759 women; age 17-83 years), we found higher age-adjusted activities for protein C and protein S in men than in women but no sex difference for antithrombin. In women, mean protein C and protein S activities increased with age. In men, mean protein C levels increased with age up to the age of 49 but decreased after 50 years old; mean protein S levels decreased after 50 years of age. Antithrombin levels remained stable over time in women but decreased significantly after 50 years of age in men. Reference values according to age and sex allowed the identification of 15 genetic variants (protein C: 10, antithrombin: 3, protein S: 2) in subjects with protein activity below the 1 st percentile. ConclusionsThis is the largest survey ever conducted in the healthy general Chinese population. These normal ranges provide the essential basis for the diagnosis and treatment of thrombosis in Chinese.Key words: antithrombin, protein C, protein S, normal ranges, genetics, Chinese. Citation: Zhu T, Ding

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Section: Discussionmentioning

confidence: 99%

Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group

Zhu¹,

Ding²,

Bai³

et al. 2011

Haematologica

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“…Dilution in normal pooled plasma (NPP) can be used in place of FVDP . Alternatively, FX activator from Southern Pacific rattlesnake ( Crotalus viridis helleri ) venom is added to a mixture of test plasma diluted in buffer and FVDP enriched with phospholipid, and coagulation is initiated with a reagent containing calcium ions and exogenous APC . Reduced clotting times indicate APC‐R.…”

Section: Analytic Issuesmentioning

confidence: 99%

Recommendations for clinical laboratory testing of activated protein C resistance; communication from the SSC of the ISTH

Moore

Cott

Cutler

et al. 2019

Journal of Thrombosis and Haemostasis

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| INTRODUC TI ONRegulation of fibrin formation through activated protein C (APC) degradation of activated factor V (FVa) and activated FVIII is a major anticoagulant process of hemostasis. In 1993, Dahlbäck et al 1 identified thrombophilic individuals whose plasma showed a poor response to APC in a coagulation assay based on activated partial thromboplastin time (APTT). This was found to be related to an arginine 506 to glutamine substitution in F5 rendering FV resistant to APC inactivation, and called FV Leiden (FVL). 2 Mutations in F5 other than FVL that confer APC resistance (APC-R) with various degrees of clinical severity have been described, although they appear to be very rare. 3 As the original assay was based on APTTs performed on undiluted plasma, it was prone to numerous interferences, so a modification was subsequently proposed that improved sensitivity and specificity by diluting test plasma in FV-deficient plasma, and remains in widespread use. 4-6 Acquired APC-R may occur in the absence of F5 mutations, and represents an independent risk factor for venous thrombosis. 7 APC-R detection has evolved since the original assay and its modification, and this is the first guideline to address clinical laboratory testing recommendations for the wider set of commonly available phenotypic assays. | PRE ANALY TIC ISSUE S | Patient selectionIndiscriminate testing for APC-R is not recommended in unselected patients with venous thromboembolism (VTE). Targeted testing is recommended for those situations in which the results may give an indication of risk of recurrence and influence treatment, as is the case for any patient undergoing evaluation for thrombophilia involving VTE. More detail is available in recent clinical guidelines. 8-10 | Sample handlingVenous blood should be collected into a one-tenth volume of 3.2% (0.105-0.109 mol/L) trisodium citrate, and double-centrifuged to ensure a residual platelet count of <10.0 × 10 9 /L. 4,11,12 As some other thrombophilia assays also require similarly effective platelet removal, this permits running of multiple assays with the same, suitably prepared, plasma sample. The white cells remaining after plasma removal can be stored for DNA extraction should molecular analysis be required, or cells from an EDTA-anticoagulated sample can be used.Plasma for APC-R assays should be tested within 4 hours of collection or frozen (at -20°C if stored for ≤2 weeks, and at −70°C or below if stored for >2 weeks) if testing is postponed. Frozen samples should be rapidly thawed in a waterbath at 37°C, and thoroughly mixed by multiple, gentle inversions prior to testing. Icterus, hemolysis and lipemia can interfere, especially in assays performed on undiluted plasma. Plasma predilution assays are less affected by platelet contamination. 3 Preliminary coagulation screening is useful to detect previously unknown factor deficiencies and anticoagulation, and, if a suitably sensitive APTT reagent is employed, lupus anticoagulants (LAs) may also be detected. | InterferencesAssay design and reag...

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“…Thus, clotting tests can reveal a general increased risk of clotting, but does not prove the presence of the FVL mutation. Diagnostica Stago (Asnieres, France; http://www.stago.com), American Diagnostica (Stamford, CT; http://www.americandiagnostica.com), DiaPharma (West Chester, OH; http://www.diapharma.com), and Centerchem, Inc. (Norwalk, CT; http://www.centerchem.com/) are a few of the many companies marketing Food and Drug Administration (FDA)‐approved kits 23.…”

Section: Protein Detectionmentioning

confidence: 99%

Evolving methods for single nucleotide polymorphism detection: Factor V Leiden mutation detection

Oh¹,

Smith²

2011

Clinical Laboratory Analysis

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Evaluation of a highly specific functional test for the detection of factor V Leiden

Cited by 13 publications

References 19 publications

Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group

Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group

Recommendations for clinical laboratory testing of activated protein C resistance; communication from the SSC of the ISTH

Evolving methods for single nucleotide polymorphism detection: Factor V Leiden mutation detection

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