A case-control study on factor V Leiden: an independent, gender-dependent risk factor for venous thromboembolism

Abstract Background Activated protein C resistance (APCR) due to factor V Leiden (FVL) mutation (R506Q) is a major risk factor in patients with venous thromboembolism (VTE). The present study investigated the clinical manifestations and the risk of venous thromboembolism regarding multiple clinical, laboratory, and demographic properties in FVL patients. Material and methods A retrospective cross-sectional analysis was conducted on a total of 288 FVL patients with VTE according to APCR. In addition, 288 VET control samples, without FVL mutation, were also randomly selected. Demographic information, clinical manifestations, family and treatment history were recorded, and specific tests including t-test, chi-square and uni- and multi-variable regression tests applied. Results APCR was found to be 2.3 times significantly more likely in men (OR: 2.1, p < 0.05) than women. The risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in APCR patients was 4.5 and 3.2 times more than the control group, respectively (p < 0.05). However, APCR could not be an independent risk factor for arterial thrombosis (AT) and pregnancy complications. Moreover, patients were evaluated for thrombophilia panel tests and showed significantly lower protein C and S than the control group and patients without DVT (p < 0.0001). Conclusion FVL mutation and APCR abnormality are noticeable risk factors for VTE. Screening strategies for FVL mutation in patients undergoing surgery, oral contraceptive medication, and pregnancy cannot be recommended, but a phenotypic test for activated protein C resistance should be endorsed in patients with VTE.

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A Retrospective Cross-sectional Study on Activated Protein C Resistance (Factor V Leiden): an Independent, Gender-dependent Risk Factor for Venous Thromboembolism

10.21203/rs.3.rs-249037/v1 ◽

2021 ◽

Author(s):

Vahideh Takhviji ◽

Kazem Zibara ◽

Asma Maleki ◽

Ebrahim Azizi ◽

Sanaz Hommayoun ◽

...

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Control Group ◽

Factor V ◽

Activated Protein C Resistance ◽

Cross Sectional ◽

Factor V Leiden Mutation

Abstract Background: Activated protein C resistance (APCR) due to factor V R506Q (Leiden) mutation is a major risk factor in patients with venous thromboembolism. The present study investigated the symptoms patterns and the risk for venous thromboembolism regarding multiple clinical, laboratory, and demographic properties in APCR patients.Material and Methods: A retrospective cross-sectional analysis was conducted on a total of 288 APCR patients with age interval ranging between 1 to 80 years. In addition, 288 control samples, reported healthy after confirmatory tests, were also randomly selected. Demographic information, clinical manifestations, family and treatment history were recorded, and specific tests applied.Results: APCR was found to be 2.3 times significantly more likely in men (OR: 2.1, p < 0.05) than women. The risk of DVT and PE in APCR patients was 4.5 and 3.2 times more than the normal group, respectively (p < 0.05). However, APCR could not be an independent risk factor for arterial thrombosis and pregnancy complications. Moreover, patients were evaluated for thrombophilia panel tests and showed significantly lower protein C and S than the control group and patients without DVT (p<0.0001).Conclusion: Factor V Leiden mutation and APCR abnormality are noticeable independent risk factors for venous thromboembolism. Screening strategies for factor V Leiden mutation in patients undergoing surgery, oral contraceptive medication, and pregnancy cannot be recommended, but a phenotypic test for activated protein C resistance should be endorsed in patients with venous thromboembolism.

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The Diagnosis and Clinical Manifestations of Activated Protein C Resistance: A Case Report and Review of the Literature

Vascular Medicine ◽

10.1177/1358863x9600100406 ◽

1996 ◽

Vol 1 (4) ◽

pp. 275-280 ◽

Cited By ~ 5

Author(s):

Howard Daniel Hoerl ◽

Aldo Tabares ◽

Kandice Kottke-Marchant

Keyword(s):

Case Report ◽

Protein C ◽

Activated Protein C ◽

Clinical Manifestations ◽

Factor V Leiden ◽

Laboratory Diagnosis ◽

Factor V ◽

Review Of The Literature ◽

Activated Protein C Resistance ◽

Genetic Anomaly

Activated protein C resistance (APCR) is a recently discovered, medically important cause of venous thrombosis. More than 95% of cases are due to factor V Leiden (FVL), a mutated form of factor V that is resistant to degradation by activated protein C. The prevalence of this disorder, which is inherited in an autosomal dominant fashion, is approximately 5% among asymptomatic people of European heritage. In addition, 20 to 60% of patient cohorts with previous thrombosis demonstrate APCR, making it the most common known genetic cause of abnormal thrombophilia. Current laboratory techniques available for diagnosis include functional assays, such as the APC ratio, as well as DNA-based tests that detect the specific genetic anomaly responsible for FVL. A case report is presented, along with a review of the literature highlighting epidemiology, pathogenesis, clinical features and methods for laboratory diagnosis.

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Influence of factor VIII/von Willebrand complex on the activated protein C-resistance phenotype and on the risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation

Blood Coagulation & Fibrinolysis ◽

10.1097/00001721-199910000-00002 ◽

1999 ◽

Vol 10 (7) ◽

pp. 416 ◽

Cited By ~ 11

Author(s):

V. De Mitrio ◽

R. Marino ◽

F. A. Scaraggi ◽

L. Di Bari ◽

F. Giannoccaro ◽

...

Keyword(s):

Venous Thromboembolism ◽

Factor Viii ◽

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Factor V ◽

Activated Protein C Resistance ◽

Factor V Leiden Mutation ◽

Heterozygous Carriers ◽

Von Willebrand

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Prevalence of Factor V Leiden Is Not Increased in Women with Recurrent Miscarriage

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602969700300213 ◽

1997 ◽

Vol 3 (2) ◽

pp. 137-140 ◽

Cited By ~ 11

Author(s):

Jack Metz ◽

Michael Kloss ◽

Cindy J. O'Malley ◽

Steven P. Rockman ◽

Lidia DeRosa ◽

...

Keyword(s):

Protein C ◽

Recurrent Miscarriage ◽

Activated Protein C ◽

Factor V Leiden ◽

Subsequent Pregnancy ◽

Control Group ◽

Therapeutic Trial ◽

Factor V ◽

Activated Protein C Resistance ◽

Antithrombotic Prophylaxis

The purpose of this study was to determine if there is an increased prevalence of the thrombophilic genetic mutant factor V Leiden in patients with recurrent miscarriage. Functional assays were conducted for activated protein C resistance and genetic detection of factor V Leiden in 100 women with recurrent miscarriage compared with a control group. The prevalence of factor V Leiden in patients was 6/100 (6%) compared with 3/85 (3.5%) in controls. The difference was not statistically significant. Antithrombotic prophylaxis with heparin and/ or aspirin in a subsequent pregnancy in five of the six patients with factor V Leiden was associated with maintenance of pregnancy and delivery of a live, healthy, full-term infant in four. We have been unable to demonstrate a statistically significant increased prevalence of factor V Leiden in women with recurrent miscarriage. If antithrombotic prophylaxis in pregnancy can be shown by controlled therapeutic trial to prevent miscarriage in these patients, identification of this subgroup would be important. Key Words: Recurrent miscarriage—Factor V Leiden—Activated protein C resistance.

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Activated Protein C Resistance and Factor V Leiden Mutation Are Independent Risk Factors for Venous Thromboembolism

Annals of Internal Medicine ◽

10.7326/0003-4819-130-8-199904200-00004 ◽

1999 ◽

Vol 130 (8) ◽

pp. 643 ◽

Cited By ~ 152

Author(s):

Francesco Rodeghiero

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Factor V ◽

Activated Protein C Resistance ◽

Factor V Leiden Mutation ◽

Independent Risk Factors

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

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613291 ◽

2002 ◽

Vol 88 (11) ◽

pp. 716-722 ◽

Cited By ~ 15

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.

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