Venous thromboembolism laboratory testing (factor V Leiden andfactor II c.*97G&gt;A), 2018 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Zhang, Shulin; Taylor, Annette K.; Huang, Xuan; Luo, Biao; Spector, Elaine; Fang, Ping; Richards, C. Sue

doi:10.1038/s41436-018-0322-z

Cited by 24 publications

(15 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At present, there is no clear indication that the acute management of patients with venous thrombosis should be different in those with or without FVL. However, some guidelines 86 have mentioned that evaluation of FVL could be advantageous in people with an increased risk of recurrent thrombotic events. These high-risk patients could benefit from lifespan antithrombotic therapy or temporarily aggressive thromboprophylaxis.…”

Section: Recommendations About Factor V Leiden Testingmentioning

confidence: 99%

See 1 more Smart Citation

Laboratory Diagnosis of Activated Protein C Resistance and Factor V Leiden

Bahraini

Fazeli

Dorgalaleh

2023

Semin Thromb Hemost

View full text Add to dashboard Cite

The factor V Leiden (FVL) polymorphism is known as the most common inherited risk factor for venous thrombosis. In turn, FVL is the leading cause of an activated protein C resistance (APCR) phenotype, in which the addition of exogenous activated protein C to plasma does not result in the expected anticoagulant effect. In the routine laboratory approach to the formal diagnosis of FVL, an initial positive screening plasma-based method for APCR is often performed, and only if needed, this is followed by a confirmatory DNA-based assay for FVL. Multiple methods with accepted sensitivity and specificity for determining an APCR/FVL phenotype are commonly categorized into two separate groups: (1) screening plasma-based assays, including qualitative functional clot-based assays, for APCR, and (2) confirmatory DNA-based molecular assays, entailing several tests and platforms, including polymerase chain reaction-based and non-PCR-based techniques, for FVL. This review will describe the methodological aspects of each laboratory test and prepare suggestions on the indication of APCR and FVL testing and method selection.

show abstract

Section: Recommendations About Factor V Leiden Testingmentioning

confidence: 99%

“…Recommendations of the last update (2018) by the American College of Medical Genetics Consensus testing on who should be tested for FVL are summarized in Table 5 . 86 87 88…”

Section: Recommendations About Factor V Leiden Testingmentioning

confidence: 99%

Laboratory Diagnosis of Activated Protein C Resistance and Factor V Leiden

Bahraini

Fazeli

Dorgalaleh

2023

Semin Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…Whether knowledge of a sex chromosome aneuploidy would affect clinical management of VTE is unclear. At this time, the American College of Medical Genetics does not provide a consensus regarding the role of genotype-guided treatment of VTE . As VTE is a major public health concern, more research into benefits and harms of genetic thrombophilia testing for management and prevention of VTE is needed .…”

Section: Discussionmentioning

confidence: 99%

Association of Supernumerary Sex Chromosome Aneuploidies With Venous Thromboembolism

Berry

Finucane

Myers

et al. 2023

JAMA

View full text Add to dashboard Cite

ImportanceAn increased risk of venous thromboembolism (VTE) has been reported in men with an additional sex chromosome. The association between other sex chromosome aneuploidies and VTE is not well characterized.ObjectiveTo determine if sex chromosome aneuploidy is associated with VTE.Design, Setting, and ParticipantsRetrospective cohort study of sex chromosome aneuploidy and VTE, performed by analyzing X- and Y-chromosome dosage and VTE incidence in 642 544 individuals from 2 population-scale biobanks: the US Geisinger MyCode Community Health Initiative (N = 154 519) and the UK Biobank (N = 488 025); analysis was limited to participants self-identified as White because of inadequate sample sizes for other race and ethnicity groups. A total of 108 461 unrelated MyCode participants with electronic health record follow-up ranging from September 1996 to December 2020 and 418 725 unrelated British and Irish UK Biobank participants who attended the baseline assessment between March 2006 and October 2010, with follow-up extending to November 2020, were included in analyses of VTE.ExposuresSex chromosome aneuploidies.Main Outcomes and MeasuresIndividuals with 1 primary inpatient VTE diagnosis, 2 primary outpatient VTE diagnoses, or a self-reported VTE diagnosis were defined as VTE cases. P values were adjusted for multiple comparisons.ResultsIdentification of sex chromosome aneuploidy was undertaken among 642 544 individuals aged 18 to 90 years. Identification of a diagnosis of VTE was undertaken among 108 461 unrelated MyCode participants (65 565 [60.5%] female; mean age at last visit, 58.0 [SD, 17.6] years; median follow-up, 15.3 [IQR, 9.7] years) and among 418 725 unrelated UK Biobank participants (224 695 [53.7%] female; mean age at baseline interview, 56.9 [SD, 8.0] years; median follow-up, 12.0 [IQR, 1.6] years). Among MyCode participants, during 10 years of follow-up, 17 incident VTE events per 1353 person-years were detected among those with supernumerary sex chromosome aneuploidy (1.3% per person-year) compared with 2060 per 816 682 person-years among those with 46,XX or 46,XY (0.25% per person-year) (hazard ratio, 5.4 [95% CI, 3.4-8.7]; 10-year risk difference, 8.8% [95% CI, 4.2%-14.0%]; P &lt; .001). Among UK Biobank participants, during 10 years of follow-up, 16 incident VTE events per 3803 person-years were detected among those with supernumerary sex chromosome aneuploidy (0.42% per person-year) compared with 4491 per 3 970 467 person-years among those with 46,XX or 46,XY (0.11% per person-year) (hazard ratio, 4.1 [95% CI, 2.5-6.7]; 10-year risk difference, 3.7% [95% CI, 1.4%-5.9%]; P &lt; .001).Conclusions and RelevanceAdults with supernumerary sex chromosome aneuploidies compared with 2 sex chromosomes had a small but statistically significant increased risk of VTE. Further research is needed to understand the clinical implications of this association.

show abstract

“…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 …”

Section: Preanalytic 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

View full text Add to dashboard Cite

| 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...

show abstract

Venous thromboembolism laboratory testing (factor V Leiden andfactor II c.*97G>A), 2018 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Cited by 24 publications

References 104 publications

Laboratory Diagnosis of Activated Protein C Resistance and Factor V Leiden

Laboratory Diagnosis of Activated Protein C Resistance and Factor V Leiden

Association of Supernumerary Sex Chromosome Aneuploidies With Venous Thromboembolism

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

Contact Info

Product

Resources

About