Activated protein C resistance (factor V Leiden) associated with thrombosis in pregnancy

Hallak, Mordechai; Senderowicz, Judith; Cassel, Aliza; Shapira, Chen; Aghai, E; Auslender, Ron; Abramovici, H

doi:10.1016/s0002-9378(97)70617-3

Cited by 78 publications

(41 citation statements)

References 20 publications

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“…Both FV Leiden and T MTHFR have been implicated in several pregnancy-related conditions, including thrombosis, [22][23][24] fetal loss, 25,26 and preeclampsia, 27,28 based on the frequency of the mutations in selected disease groups. However, estimates of gene frequency in diseased populations may be confounded by other factors, either environmental or genetic, so that the impact of a mutation may be overestimated.…”

Section: Discussionmentioning

confidence: 99%

Prospective Evaluation of the Risk Conferred by Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase Polymorphisms in Pregnancy

Murphy

Donoghue

Nallen

et al. 2000

ATVB

142

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Abstract-Factor V (FV) Leiden and thermolabile methylenetetrahydrofolate reductase (MTHFR) are 2 common polymorphisms that have been implicated in vascular thrombosis. We determined whether these mutations predicted an adverse outcome in pregnancy. Second, we looked for an interaction between these 2 mutations in patients with recurrent fetal loss or thrombosis in pregnancy. Primigravid subjects at their booking visit to the National Maternity Hospital (Holles Street, Dublin, Ireland) were screened for the polymorphisms. Thermolabile MTHFR and FV Leiden genotypes were detected by either restriction fragment length polymorphism or heteroduplex capillary chromatography. The carrier frequency of FV Leiden in the screened primigravid population was 2.7% (allele frequency 1.36%), all being heterozygous for the mutation. This value was lower than expected from previous studies in European populations. Forty-nine percent of the screened population (289 of 584) were heterozygous for thermolabile MTHFR, and 10.6% were homozygous (62 of 584). The frequency of the 2 polymorphisms was no higher in those who subsequently developed preeclampsia (nϭ12) or intrauterine growth retardation (nϭ9), and none of the screened population developed thrombosis. However, the frequency of FV Leiden was higher in patients who subsequently miscarried after the first trimester of pregnancy (allele frequency of 5.5%, Pϭ0.0356). Among those positive for FV Leiden, 3 of 27 miscarried, compared with 24 of 572 of FV Leiden-negative patients (11% versus 4.2%). No interaction was found between the 2 mutations in the control or patient populations. In patients with a prior history of venous thrombosis, the carrier rate of FV Leiden was increased (4 of 33, allele frequency of 7.6%, Pϭ0.0115). In contrast, the carrier frequency for thermolabile MTHFR was no higher, and there was no interaction between the 2 mutations. Neither mutation occurred at a significantly higher frequency in patients with a prior history of recurrent fetal loss. In conclusion, FV Leiden is a risk factor for thrombosis in pregnancy and possibly for second-trimester miscarriage independent of thermolabile MTHFR. However, prospective analysis suggests that the risk conferred by FV Leiden is low in a primigravid population. The thermolabile MTHFR genotype was not implicated in any adverse outcome. Key Words: factor V Leiden polymorphism Ⅲ thermolabile methylenetetrahydrofolate reductase polymorphism Ⅲ pregnancy Ⅲ venous thrombosis Ⅲ recurrent fetal loss Ⅲ genetic risk factors

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Section: Discussionmentioning

confidence: 99%

Prospective Evaluation of the Risk Conferred by Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase Polymorphisms in Pregnancy

Murphy

Donoghue

Nallen

et al. 2000

ATVB

142

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“…2,3 The presence of this mutation or its functional consequence, APC resistance, is associated with an increased risk of venous thromboembolic events (VTEs). 1,4 -6 Risk for VTE appears to be even higher in women with APC resistance or the factor V Leiden mutation who are also pregnant [7][8][9][10][11] or who use oral contraceptives. 7,[12][13][14][15] The effect of hormone replacement therapy (HRT) on the risk of VTE in women with APC resistance is not well established.…”

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confidence: 99%

Factor V Leiden, Hormone Replacement Therapy, and Risk of Venous Thromboembolic Events in Women With Coronary Disease

Herrington

Vittinghoff

Howard

et al. 2002

ATVB

144

100

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Abstract-Oral contraceptive use in women with factor V Leiden is associated with increased rates of venous thromboembolic events (VTEs). However, the effects of hormone replacement therapy (HRT) in postmenopausal women with factor V Leiden are not known. A nested case-control study was conducted among women with established coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio [OR] Leiden 3.3, 95% CI 1.1 to 9.8; Pϭ0.03). In women without the factor V Leiden mutation, risk associated with HRT use was significantly increased (OR HRT 3.7, 95% CI 1.4 to 9.4; PϽ0.01). On the other hand, in women with the factor V Leiden mutation, the estimated risk associated with HRT was increased nearly 6-fold, although the CIs were wide and included unity (OR HRT 5.7, 95% CI 0.6 to 53.9; Pϭ0.13). The OR for women with the Leiden mutation who were also assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95% CI 2.7 to 72.4, Pϭ0.0015). In women with the factor V Leiden mutation who were treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per year compared with 2.0 of 1000 per year in women without the mutation who were taking a placebo (Pϭ0.0015). On the basis of these data, in women with coronary disease, the estimated number needed to screen for factor V Leiden to avoid an HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease. Key Words: cardiology Ⅲ risk factors for stroke Ⅲ genetics Ⅲ thrombosis risk factors I n 1994, Bertina et al 1 described a single point mutation in the gene coding for factor V. This mutation, referred to as the factor V Leiden mutation, renders factor Va relatively resistant to degradation by the natural anticoagulant, activated protein C (APC). 2,3 The presence of this mutation or its functional consequence, APC resistance, is associated with an increased risk of venous thromboembolic events (VTEs). 1,4 -6 Risk for VTE appears to be even higher in women with APC resistance or the factor V Leiden mutation who are also pregnant 7-11 or who use oral contraceptives. 7,[12][13][14][15] The effect of hormone replacement therapy (HRT) on the risk of VTE in women with APC resistance is not well established. One observational study found a multiplicative relationship between the effects of HRT and APC resistance on VTE risk, 16 whereas a small randomized clinical trial of oral HRT in women with previously verified VTE failed to confirm such a relationship. 17 Determining the relative and absolute impact of HRT and factor V Leiden on VTE risk is especially important for older women or for women with coronary disease, whose baseline risk of VTE i...

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“…On the other hand, the factors that block coagulation are decreased. [1][2][3][4][5] As this patient was in the late puerperium, and might have been in a state of hypercoagulability, the occurrence of deep vein thrombosis can be explained.…”

Section: Discussionmentioning

confidence: 99%

Vena cava thrombosis associated with nephrotic syndrome in the puerperal gestational cycle

Araújo

Gonçalves

et al. 2001

Sao Paulo Med. J.

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CONTEXT:The puerperal gestational cycle is accompanied by a state of physiological hypercoagulability. Thromboembolic phenomena may occur at this time. OBJECTIVE:To report on a clinic case involving a patient that presented a family history of thromboembolism and developed deep vein thrombosis in a lower limb and vena cava thrombosis during the puerperal gestational cycle, displaying nephrotic syndrome as the main complication. DESIGN:Case report.

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Activated protein C resistance (factor V Leiden) associated with thrombosis in pregnancy

Cited by 78 publications

References 20 publications

Prospective Evaluation of the Risk Conferred by Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase Polymorphisms in Pregnancy

Prospective Evaluation of the Risk Conferred by Factor V Leiden and Thermolabile Methylenetetrahydrofolate Reductase Polymorphisms in Pregnancy

Factor V Leiden, Hormone Replacement Therapy, and Risk of Venous Thromboembolic Events in Women With Coronary Disease

Vena cava thrombosis associated with nephrotic syndrome in the puerperal gestational cycle

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