Resistance to activated protein C due to factor V R506Q mutation as a cause of venous thrombosis

Department of Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden.
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion (Impact Factor: 0.48). 06/1997; 49 Suppl 1:3-5.
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    • "Similarly, coexistence of FVL and PC deficiency has 3 to 7-fold more risk of VTE than either of the two defects alone (Hallam et al, 1995; Zama et al, 1996; Koeleman et al, 1997, Jadaon & Dashti, 2005b). Moreover, more than half of patients with both APC-R and genetic PS deficiency were found to have thrombosis (Garcia de Frutos & Dahlbäck, 1995; Koeleman et al, 1997). It is interesting to mention here that a few isolated cases were reported to be double heterozygous for FVL and factor V deficiency, the mutations being present on opposite chromosomes. "

    Full-text · Chapter · Jan 2012
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    • "APCR produces a thrombophilic state [1,2]. The combination of inherited thrombophilia and pregnancy greatly increases the risk of venous thromboembolism (VTE), which remains the commonest cause of maternal death in the developing world [3]. "
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    ABSTRACT: Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women. Blood samples collected from 907 pregnant women were tested using the Coatest Classic and Modified functional haematological tests to establish the frequency of APCR. PCR-Restriction Enzyme Analysis (PCR-REA), PCR-DNA probe hybridisation analysis and DNA sequencing were used for molecular screening of known mutations in the factor V gene in subjects determined to have APCR based on the Coatest Classic and/or Modified functional haematological tests. Glycosylase Mediated Polymorphism Detection (GMPD), a SNP screening technique and DNA sequencing, were used to identify SNPs in the factor V gene of 5 APCR subjects. Sixteen percent of the study group had an APCR phenotype. Factor V Leiden (FVL), FV Cambridge, and haplotype (H) R2 alleles were identified in this group. Thirty-three SNPs; 9 silent SNPs and 24 missense SNPs, of which 20 SNPs were novel, were identified in the 5 APCR subjects. Adverse pregnancy outcomes were found at a frequency of 35% in the group with APCR based on Classic Coatest test only and at 45% in the group with APCR based on the Modified Coatest test. Forty-eight percent of subjects with FVL had adverse outcomes while in the group of subjects with no FVL, adverse outcomes occurred at a frequency of 37%. Known mutations and novel SNPs in the factor V gene were identified in the study cohort determined to have APCR in pregnancy. Further studies are required to investigate the contribution of these novel SNPs to the APCR phenotype. Adverse outcomes including early pregnancy loss (EPL), preeclampsia (PET) and intrauterine growth restriction (IGUR) were not significantly more frequent in subjects with APCR compared to normal pregnant women however Pregnancy induced hypertension (PIH) was found to be associated with FVL in our study group.
    Full-text · Article · Mar 2010 · BMC Pregnancy and Childbirth
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    ABSTRACT: This study was carried out to determine the prevalence of genetic thrombophilia in patients with retinal vascular occlusion. We investigated 116 consecutive patients with central retinal vein occlusion (CRVO, n = 48), branch retinal vein occlusion (BRVO, n = 33), central retinal artery occlusion (CRAO, n = 21), branch retinal artery occlusion (BRAO, n = 14). All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, prothrombin gene mutation (G20210A), resistance to activated protein C (APCR), and were screened for vascular disease risk factors. APC resistance was confirmed by a PCR method to detect the factor V R506Q mutation. A PCR method was also used to detect the G20210A mutation. For comparative purposes, we screened 209 consecutive patients with deep vein thrombosis (DVT) and 581 patients with coronary heart disease (control group) for APC resistance. 13 (27%) of 48 patients with CRVO had the factor V R506Q mutation. The factor V R506Q mutation was detected in six (18%) of 33 patients with BRVO, but in only one patient with CRAO and in two patients with BRAO. Other thrombophilic defects were not detected. The APCR prevalence within the CRVO group was significantly increased when compared to the control group (8%). There was no significant difference in the factor V R506Q mutation prevalence between the CRVO group and the DVT group (19%). The factor V R506Q mutation is the most common cause of genetic thrombophilia in patients with CRVO and has a similar prevalence as in DVT patients.
    No preview · Article · Feb 1999 · International Ophthalmology
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