Factor V Leiden: Is it the chief contributor to activated protein C resistance in Asian-Indian patients with deep vein thrombosis?

AbstractThrombophilia may be anticipated by single or combined hereditary defects in encoding genes factor V, Prothrombin, and MTHFR. The aim of this study was to determine the prevalence and associated risks of V Leiden (G1691A), Prothrombin (G20210A), and MTHFR (C677T) mutations in Saudi women with Deep Vein Thrombosis (DVT) and women with recurrent pregnancy loss (RPL). Protein C and protein S activity were measured to determine combined effects, if any. We examined 60 women with a history of DVT and 60 with RPL, extracted DNA from EDTA blood and determined three mutations by using multiplex PCR reactions followed by Strip Assay KIT. Pro C Global assay was used to determine the cutoff value [PCATNR = 0.80]. Protein C/S chromogenic assay was used to estimate protein C and S percentages. Frequency of Factor V Leiden G/A genotype in patients with DVT 7 (11.6%) had a significant association for DVT χ2 (OR = 5.1, P = 0.03). In women with RPL the three mutations did not show any significant association, levels of Protein C, protein S and PCAT-NR in patient groups not different from controls (P > 0.05). In conclusion, we recommend expanding on these data to provide larger-scale studies.

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The HR2 Haplotype of Factor V: Effects on Factor V Levels, Normalized Activated Protein C Sensitivity Ratios and the Risk of Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613866 ◽

2000 ◽

Vol 83 (04) ◽

pp. 577-582 ◽

Cited By ~ 48

Author(s):

Joan Guasch ◽

Pieter Kamphuisen ◽

Hans Vos ◽

Frits Rosendaal ◽

Rogier Bertina ◽

...

Keyword(s):

Venous Thrombosis ◽

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Compound Heterozygous ◽

Factor V ◽

Vein Thrombosis ◽

Increased Risk ◽

V Antigen ◽

Deep Vein

SummaryWe studied the HR2 haplotype of the factor V gene in a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched healthy controls (Leiden Thrombophilia Study, LETS). We investigated both the original His1299Arg (A4070G) polymorphism and the Met385Thr (T1328C) polymorphism. This latter polymorphism, located in exon 8 (heavy chain), is always present in the HR2 haplotype, but also occurs on its own in a His1299 (wt) background. The HR2 haplotype was not associated with an increased risk of venous thrombosis (OR = 1.2, 95% confidence interval: 0.8-2.0). We did not find an association between the HR2 haplotype and a reduced sensitivity for activated protein C (APC) in non-carriers of factor V Leiden (FVL). However, in compound heterozygous FVL/HR2 carriers the sensitivity for APC was reduced. The HR2 haplotype was also associated with reduced factor V antigen levels in both patients and controls. Sequence analysis of the promoter region of factor V in HR2 homozygotes did not reveal any sequence variations that could explain the reduced FV levels. Our results show that the HR2 haplotype is not associated with an increased risk of venous thrombosis or with a reduced sensitivity for APC in non-FVL carriers. However, the HR2 haplotype is associated with a reduced sensitivity for APC in carriers of FVL and with reduced factor V antigen levels.

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Activated protein C resistance in deep-vein thrombosis

The Lancet ◽

10.1016/s0140-6736(94)91494-x ◽

1994 ◽

Vol 343 (8896) ◽

pp. 541-542 ◽

Cited By ~ 14

Author(s):

C LEGNANI

Keyword(s):

Deep Vein Thrombosis ◽

Protein C ◽

Activated Protein C ◽

Activated Protein C Resistance ◽

Vein Thrombosis ◽

Deep Vein

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The incidence of activated protein C resistance among patients with deep vein thrombosis and healthy subjects in Osaka

Thrombosis Research ◽

10.1016/0049-3848(95)91527-r ◽

1995 ◽

Vol 79 (2) ◽

pp. 227-229 ◽

Cited By ~ 5

Author(s):

J. Kambayashi ◽

H. Fujimura ◽

T. Kawasaki ◽

M. Sakon ◽

M. Monden ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Healthy Subjects ◽

Protein C ◽

Activated Protein C ◽

Activated Protein C Resistance ◽

Vein Thrombosis ◽

Deep Vein

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Liver transplant acquired activated protein C resistance presenting with deep vein thrombosis 4 years after transplant

Blood Coagulation & Fibrinolysis ◽

10.1097/00001721-200106000-00014 ◽

2001 ◽

Vol 12 (4) ◽

pp. 325-326 ◽

Cited By ~ 5

Author(s):

C. Solano ◽

M. J. Self ◽

R. G. Cobcroft

Keyword(s):

Deep Vein Thrombosis ◽

Liver Transplant ◽

Protein C ◽

Activated Protein C ◽

Activated Protein C Resistance ◽

Vein Thrombosis ◽

Deep Vein

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FV HR2 Haplotype as Additional Inherited Risk Factor for Deep Vein Thrombosis in Individuals with a High-Risk Profile

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612939 ◽

2002 ◽

Vol 87 (01) ◽

pp. 32-36 ◽

Cited By ~ 21

Author(s):

Anna Bossone ◽

Donatella Coalizzo ◽

Giovanna D’Andrea ◽

Vincenzo Brancaccio ◽

Antonio Ciampa ◽

...

Keyword(s):

Risk Factor ◽

Deep Vein Thrombosis ◽

Protein C ◽

Activated Protein C ◽

Factor V ◽

Vein Thrombosis ◽

Estimated Risk ◽

Factor V Gene ◽

Fv Leiden ◽

Deep Vein

SummaryA number of strongly linked polymorphisms within the Factor V gene (FV HR2 haplotype) has been identified as a cause of resistance to activated protein C, and has suggested a modest risk factor for vein thrombosis. We investigated the frequency of the HR2 haplotype in 433 consecutive patients with confirmed deep vein thrombosis and 326 controls. The HR2 haplotype was more frequent in patients (15.2%) than in controls (10.1%). The risk of thrombosis among carriers of this haplotype was significantly increased (odds ratio: 1.6 [95% CI: 1.0-2.5]). The estimated risk associated with the HR2 haplotype was 1.8 (95% CI: 1.1-2.9) in subjects with (n = 255), and 1.4 (95% CI: 0.8-2.4) in those without (n = 178) acquired risk factors for vein thrombosis. After adjustment for sex, FV Leiden and FII A20210 mutations, the estimated risk of vein thrombosis among carriers of the HR2 haplotype was 1.8 (95% CI: 1.1-2.8). Present data indicate that the HR2 haplotype is independently associated with vein thrombosis among individuals with a highrisk profile.

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