Renal vein thrombosis in a newborn with prothrombotic genetic risk factors

Environmental and genetic risk factors interact to cause venous thromboembolism. Renal vein thrombosis in the newborn has been frequently associated with "risk factors" as catheters, surgery or trauma, but it has also been demonstrated a pathogenetic role of genetic prothrombotic risk factors, i.e. activated protein C resistance and FV Leiden. The treatment of neonatal venous thrombosis varies worldwide and different approaches have been proposed. We present a case of renal vein thrombosis in a female newborn with normal plasma levels of protein C, protein S and antithrombin III, but with her genotype characterized by the presence of three prothrombotic risk factors: factor V Leiden, methylentetrahydrofolate reductase and platelet glycoprotein IIIa polymorphisms. The treatment with recombinant tissue plasminogen determined complete thrombus dissolution.     

妊娠期及产褥期静脉血栓12例临床分析

目的 探讨妊娠期和产褥期静脉血栓的发生率,病因诊断,预防和治疗。方法 回顾性分析１９８４年１月至１９９７年１２月间,我院住院诊治的１２例妊娠期及产褥期深静脉血栓栓塞患者的临床资料,并对４例患者进行蛋白Ｃ、蛋白Ｓ、抗凝血酶Ⅲ活性和活化蛋白Ｃ抵抗（ＡＰＣ－Ｒ）的测定,同时进行凝血因子Ｖ（ＦＶ）１６９１位核苷酸基因变异（ＦＶ Ｌｅｉｄｅｎ变异）筛选。结果 ４例血栓发生在妊娠期,８例发生在产褥期;２例合并     

Screening for pre-eclampsia in a low-risk population at 24 weeks: uterine artery Doppler flow velocimetry and genetic variants of factor V, prothrombin and methylenetetrahydrofolate reductase

AIM: Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. The aim of this study was to evaluate the clinical usefulness of screening of genetic thrombophilic mutations and uterine artery Doppler flow velocimetry at 24 weeks of gestation in the prediction of pre-eclampsia in low risk pregnant women. METHODS: We performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 24 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the Leiden FV was 17.4% in women with pre-eclampsia and abnormal artery Doppler flow velocimetry compared with 3.12% in patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of PT gene was 1.5% vs 4.3% between women with normal pregnancies and with pre-eclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among patients with pre-eclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic genes variants were found in women with pre-eclampsia and normal uterine artery Doppler flow velocimetry. CONCLUSION: We demonstrated the important association between FV Leiden mutation, abnormal uterine artery Doppler flow velocimetry at 24 weeks and pre-eclampsia in our low-risk population.     

Factor V Leiden in pregnancies complicated by placental abruption

Objective Recent studies suggest an increased prevalence of obstetric complications in female carriers of hereditary or acquired thrombophilias. The aim of the study was to determine if carriership of the factor V (FV) Leiden mutation (activated protein C [APC] resistance) is higher in women who have had of placental abruption during pregnancy.
Design A retrospective case–control study.
Setting University Hospital MAS, Malmö, Sweden.
Methods A comparison of 102 women with placental abruption with 2371 prospectively collected controls. Carriership of FV Leiden was determined and the women were interviewed.
Main outcome measures Proportion of FV Leiden carriership, first degree heritage of thrombosis and previous placental abruption in cases and controls.
Results Carriage of FV Leiden was found in 15.7% of women who have had placental abruption as compared with 10.8% of controls (   P = 0.12, odds ratio [OR] = 1.5, 95% confidence interval [CI] = 0.9–2.7  ). Around 20% of women with placental abruption reported first degree heritage for venous thrombosis, as compared with 6.7% of controls (   P ≤ 0.001  ).
Conclusions FV Leiden carriership was not significantly different in women with placental abruption. However, there was an increased prevalence of first degree heritage for venous thrombosis in women with placental abruption, indicating a higher prevalence of thrombophilia among women with placental abruption.     

Factor V Leiden and contraception

Factor V Leiden is the most common genetic cause of primary and recurrent venous thromboembolism in women. It is an inherited thrombophilia that results from a genetic mutation. A college-aged woman who presented for care and had a positive family history of venous thrombosis tested positive for Factor V Leiden. Laboratory tests and plans for continuing care are discussed.     

The factor V leiden mutation and the risk of venous thromboembolism in gynecologic oncology patients1

OBJECTIVE: To measure the strength of the association between the factor V Leiden mutation and venous thromboembolism in gynecologic oncology patients. METHODS: We conducted a case-control study of gynecologic cancer patients in a referral center who were group matched for demographics, tumor type, and treatment. The prevalence of the factor V Leiden mutation was determined in both cases and controls, and an odds ratio was calculated. The factor V Leiden mutation was detected using polymerase chain reaction amplification and nucleic acid restriction digest of deoxyribonucleic acid extracted from leukocytes. RESULTS: Seventy-five patients were enrolled in the study. Seventy-four samples were available for analysis. There were no differences between the cases and controls with respect to age, race, body mass index, smoking, cancer type, high stage (III or IV) of cancer, or treatment modality. The odds ratio for having the factor V Leiden mutation in patients with venous thromboembolism was 0.3 (95% confidence interval 0.1, 1.7). CONCLUSION: This study suggests that the factor V Leiden mutation is not associated with an increased risk of venous thromboembolism in gynecologic oncology patients. This contrasts with other studies showing a strong association between the factor V Leiden mutation and venous thromboembolism in cases of previously unexplained venous thromboembolism, and venous thromboembolism associated with other hypercoagulable states, such as pregnancy and oral contraceptive use. The risk of venous thromboembolism due to cancer outweighs the contribution of the factor V Leiden mutation.     

Factor V Leiden mutation. Successful outcome of a pregnancy after heparin therapy

Several reports have highlighted the significant correlation between maternal thromboembolism pathologies, such as factor V Leiden mutation, and the occurrence of gestational pathologies. The main causes of thromboembolism pathologies are the inherited coagulopathies. The most common genetic predispositions include autosomal dominant inheritance coagulative factors deficiencies, such as antithrombin III (AT III), C protein (CP), S protein (SP), G20210A mutation, hyperomocystinemia and the activated C protein resistance, caused by factor V Leiden mutation. Maternal thromboembolism as an inherited coagulopathy expression, may be associated with high fetal-maternal morbidity and mortality rate. Nowadays, a wide screening is not possible, but the patients with previous or familiar deep venous thrombosis episodes should at least undergo very careful examinations. In the present case the patient's knowledge of her own status as a factor V Leiden mutation carrier , the prophylactic therapy performed, and the frequent fetal and maternal monitoring allowed us to avoid the recurrence of the dramatic events occurring during her first pregnancy.     

Hypercoagulable state mutation analysis in white patients with early first-trimester recurrent pregnancy loss

Objective: Antiphospholipid antibodies (APA) and other coagulation abnormalities have been associated with an increased risk of venous, arterial, and placental thrombosis and recurrent pregnancy loss (RPL). Factor V Leiden (a point mutation [1691G→A] in the factor V gene), the prothrombin 20210G→A mutation, and homozygosity for a common polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene (677C→T) have been associated with arterial and venous thrombosis and arterial occlusive disease. We explored an association between these markers of thrombophilic states and RPL.

Design: Prospective case-control evaluation.

Setting: University-associated private practice.

Patient(s): Fifty nonpregnant women with three or more pregnancy losses and 50 healthy, nonpregnant controls.

Intervention(s): None.

Main Outcome Measure(s): Anticardiolipin and antiphosphatidylserine antibodies were detected in serum by ELISA. Polymerase chain reaction was performed to identify the factor V Leiden (1691G→A) mutation, the thermobile MTHFR (677C→T) mutation, and the prothrombin 20210G→A mutation.

Result(s): The following were identified by restriction fragment-linked polymorphism analyses: 1 (2%) factor V Leiden heterozygosity; 1 (2%) prothrombin 20210G→A heterozygosity; and 4 (8%) thermolabile MTHFR homozygosity. None of these mutation frequencies in women with RPL were statistically significantly different from controls.

Conclusion(s): These data suggest that factor V Leiden, thermolabile MTHFR (677C→T), and prothrombin 20210G→A are not found at an increased frequency in women with a history of early RPL.     

Factor V leiden and venous thromboembolism in a woman taking second generation oral contraceptives: a case report]

The most common cause of thrombophilia is a point mutation in factor V gene (G1691A), leading to factor V Leiden synthesis, which is resistant to the inhibition by activated protein C. Administration of oral contraceptives is associated with an increased risk of venous thromboembolism in carriers of factor V Leiden mutation. We describe here a case of 44-year-old woman who developed right popliteal and superficial deep vein thrombosis after a 2-month use of a contraceptive which consists of 0.15 mg levonorgestrel and 0.03 mg ethynylestradiol. The mutation G1691A of factor V gene was detected with the polymerase chain reaction. No other inherited or acquired risk factors for thrombosis was found in this patient. Treatment with low molecular weight heparin and subsequently, oral anticoagulation was effective. Women with factor V Leiden should be discouraged from taking oral contraceptives. Screening for factor V Leiden in these women appears to be useful and contribute to the prevention of thrombosis in risk situations.     

Genetic thrombophilias and uterine artery Doppler velocimetry and preeclampsia.

OBJECTIVE: The aim of this study was to evaluate the correlation between genetic thrombophilic mutations, uterine artery Doppler at 24 weeks of gestation and preeclampsia. METHODS: In a case control study we performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 20 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the factor V Leiden was 17.4% in the women with preeclampsia and abnormal artery Doppler compared with 3.12% in the patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of prothrombin gene was 1.5 vs. 4.3% between women with normal pregnancies and with preeclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among the patients with preeclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic gene variants were found in women with preeclampsia and normal uterine artery Doppler. CONCLUSION: We demonstrated the important association between factor V Leiden mutation, abnormal uterine Doppler at 24 weeks and preeclampsia in our population.     

Factor V Leiden G1691A and factor II G20210A point mutations and pregnancy in North-West of Iran

Purpose  

The roles of several hereditary predispositions for venous thromboembolism have been evaluated in women with habitual abortion. We studied the prevalence of FV Leiden G1691A and FII G20210A mutations in women with habitual abortion and healthy controls.     

Obstetric implications of activated protein C resistance and factor V Leiden mutation

An increasing number of reports have focused on activated protein C resistance (APCR) as it has been shown not only to be the most common genetic factor predisposing patients to thromboembolic disease but the most common identifiable cause overall. More than 90 percent of the cases of APCR are caused by the factor V Leiden mutation, in which a guanine to adenine substitution in the factor V gene at nucleotide position 1691 results in a glutamine to arginine switch at position 506. Recent studies have also pointed to evidence of an association between APCR/factor V Leiden mutation and hypertensive disorders of pregnancy, first and second trimester miscarriage, placental infarction, and placental abruption.     

Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism?

BACKGROUND: Major concern was raised by an earlier study regarding oral contraceptive use in women with the factor V Leiden mutation. A more than 30-fold increase in relative risk for venous thromboembolism was reported; for homozygotes, the relative risk was as much as 100-fold or more. OBJECTIVE: To replicate the reported risk estimates with a new population-based case-control study. METHODS: Eighty women with a diagnosis of venous thromboembolism were consecutively identified and compared with population-based controls (n = 406). Factor V Leiden mutation was identified by genotype analysis. The evaluation was performed with conditional logistic regression (matched for 5-year age group). RESULTS: Matched, adjusted odds ratios (OR) for idiopathic venous thromboembolism in women without and with the factor V Leiden mutation who used oral contraceptives were 4.1 (95% confidence interval (CI) 2.1-7.8) and 10.2 (95% CI 1.2-88.4), respectively. The adjusted OR for factor V Leiden carriers was 2.0 (95% CI 1.0-4.4). The OR for women with the factor V Leiden mutation and oral contraceptive use versus no factor V Leiden mutation and no oral contraceptive use was 10.2 (95% CI 3.8-27.6). CONCLUSION: The results confirm the increased relative risk of idiopathic venous thromboembolism for users of oral contraceptives and factor V Leiden carriers. However, we suspect that the true risk for women who are factor V Leiden carriers may be increased two- to four-fold rather than seven-fold or more, and that the risk for the combination of factor V Leiden and oral contraceptive use may be increased in the order often- to 15-fold rather than over 30-fold.     

Occurrence of plasmic and platelet prothrombotic polymorphisms in women in childbirth

DESIGN: Plasmic pro-thrombotic factors as well as pro-thrombotic platelet glycoprotein mutations have been shown to play an important role in the mechanism of the thrombo-embolic disease. However, there is no published study evaluating the role of above mentioned genetic factors in the thrombo-embolic episodes in women in childbirth. OBJECTIVE: The aim of the study was to evaluate the role of selected genetic factors in appearance of thrombo-embolic complications in the women in childbirth, and to determine if there is the coexistence of selected platelet glycoprotein polymorphisms and factor V Leiden mutations. MATERIAL AND METHODS: 71 cases of women in child birth with thrombo-embolic disease were analyzed. Selected demographic characteristics, and genetic pro-thrombotic factors like factor V Leiden mutation, and pro-thrombotic platelet glycoprotein GP Ia, and GP IIIa polymorphisms were examined. RESULTS: Amongst pro-thrombotic platelet glycoprotein polymorphisms moderately pro-thrombotic heterozygous A1/A2, and heterozygous C/T were most prevalent. The least common were strongly pro-thrombotic homozygous A2/A2, and T/T. Analysis of the factor V Leiden mutation revealed statistically significant difference in the presence of allele A, which determines the prothrombotic tendencies in its carrier. CONCLUSIONS: Our study shows that factor V Leiden mutation, and investigated platelet GP Ia, and GP IIIa polymorphisms frequently coexist. Moreover, presence of factor V Leiden mutation is a risk factor for thrombo-embolic disease in the women in childbirth.     

Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions

BACKGROUND: Several etiological factors have been proposed as a cause for recurrent fetal abortions. Changes in blood coagulation during pregnancy may play an important role in the occurrence of recurrent abortions (RA). METHODS: The aim of this study was to investigate the prevalence of factor V Leiden, factor II prothrombin, and methylenetetrahydrofolate reductase (MTHFR) mutations in women with recurrent abortions (> or =2 abortions) in the German population. The mean number of abortions was 3 (range 2-8). RESULTS: Frequencies of the factor V Leiden mutation and the prothrombin G20210A mutation were equally high in the patient group compared with our control group (for factor V Leiden: 11/101 vs. 9/122; p-value: 0.348; for prothrombin G20210A: 2/101 vs. 3/122; p-value: 0.81). Moreover, in both the patient and control groups, 15 of the women were homozygous for the MTHFR C677T allele (15/101 vs. 15/122; p-value: 0.635). The occurrence of FV Leiden, FII and MTHFR mutations was not significantly increased in the patient group compared with our control group. CONCLUSION: The results of the present study reveal no relationship between these common three thrombophilic mutations and recurrent abortions for the German population, and further studies are essentially recommended on whether a thrombophilia evaluation should be performed in patients with recurrent abortions.     

Factor V Leiden mutation in pregnancy

Normal maternal adaptation to pregnancy significantly increases the risk for thrombus formation. Inherited thrombophilias further increase risk for deep venous thrombosis and adverse outcome in pregnancy. Factor V Leiden mutation is the most common inherited thrombophilia, occurring in approximately 5% of the White and 1% of the Black populations. Nurses should be knowledgeable about screening for and diagnosis of factor V Leiden mutation, risk reduction counseling, recommended care of the affected patient, and implications of anticoagulant therapy during the perinatal period.     

Factor V Leiden mutation and the risk of thrombo-embolic disease in pregnancy: a case report

Factor V Leiden mutation is a risk factor for the development of thrombo-embolic episodes in pregnancy. A case is presented of a pregnant woman with repeated episodes of venous thrombosis with a complicated clinical course.     

High frequency of thrombophilic disorders in women with recurrent fetal miscarriage

OBJECTIVES: Our purpose was to examine whether genetic thrombophilias are etiological factors for recurrent fetal miscarriage or not. STUDY DESIGN: We compared the rate of thrombophilic anomalies in women with unexplained recurrent fetal miscarriages to the rate of age-matched women with successful pregnancies as a case-control study. RESULTS: A total of 101 consecutive patients with 102 age-matched controls were included in the study. The rate of Factor V (FV) Leiden mutation, Factor (F) II mutation, protein S, protein C, antithrombin III deficiencies and overall thrombophilia in patients with recurrent fetal loss was significantly higher than the frequencies in control patients. CONCLUSION: Women with recurrent fetal miscarriages have an increased incidence of thrombophilia. Genetic thrombophilias may be one of the major etiological factors for recurrent abortion and fetal demise.     

Screening for factor V Leiden mutation before prescribing combination oral contraceptives.

OBJECTIVE: To evaluate the cost-effectiveness of screening for factor V Leiden mutation in women in the United States who use combination oral contraceptives. DESIGN: Cost-effectiveness analysis. SETTING: A national research reference laboratory, a university medical center, and an academic health center managed care organization. PATIENT(S): Women of reproductive age in the United States. INTERVENTION(S): Baseline risk estimates of venous thromboembolic disease in the general population and in carriers of factor V Leiden mutation were calculated using available data. MAIN OUTCOME MEASURE(S): The number of women who would require factor V Leiden testing and the cost of identifying this cohort to prevent one death caused by venous thromboembolic disease before prescribing combination oral contraceptives. RESULT(S): To prevent one venous thromboembolic death attributable to the use of oral contraceptives in women with factor V Leiden mutation, >92,000 carriers would need to be identified and stopped from using these pills. The estimated charge to prevent this one death would exceed $300 million. If the price of testing were discounted to 34.5% of current charges, the cost still would be between $105 million and $130 million. CONCLUSION(S): Screening for factor V Leiden mutation before prescribing combination oral contraceptives is not a cost-effective use of U.S. health care dollars. The best and most cost-effective screening tool we have is taking a thorough personal and family history related to venous thromboembolic events.