scholarly journals Lower limb ischemia in a thrombophilic woman during ovarian stimulation for assisted reproduction techniques

2013 ◽  
pp. 116-118
Author(s):  
Ida Strina ◽  
Giuseppe De Placido ◽  
Maristella D’Uva ◽  
Ilaria Jane Romano ◽  
Pierpaolo Di Micco
Keyword(s):  
Assisted Reproduction ◽  
Ovarian Stimulation ◽  
Factor V Leiden ◽  
Limb Ischemia ◽  
Factor V ◽  
Thrombotic Risk ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
Pharmacological Thromboprophylaxis

Introduction Women receiving hormone therapy as part of assisted reproduction protocols are at increased risk for thrombosis. Controlled ovarian stimulation may be a risk factor for thrombotic events, and thrombophilic subjects are more prone to develop thrombosis during hormone therapies. Materials and methods We report a case of arterial thrombosis of the iliacofemuropopliteal axis, which occurred in a young woman with Factor V Leiden-related thrombophilia, who was receiving recombinant follicle-stimulating hormone and leuprorelin in preparation for in vitro fertilization and embryo transfer, and pharmacological thromboprophylaxis with enoxaparin. Results The thrombosis resulted in critical limb ischemia whose clinical evolution is described. Discussion Further research is needed to identify the best strategy for reducing the thrombotic risk associated with assisted reproduction protocols and to determine whether these women should receive pharmacological thromboprophylaxis.

Polymorphisms in the protein C gene as risk factor for venous thrombosis

2009 ◽  
Vol 101 (01) ◽  
pp. 62-67 ◽  
Author(s):  
Carine Doggen ◽  
Hans Vos ◽  
Pieter Reitsma ◽  
Frits Rosendaal ◽  
Elisabeth Pomp
Keyword(s):  
Oral Contraceptive ◽  
Venous Thrombosis ◽  
Protein C ◽  
Contraceptive Use ◽  
Factor V Leiden ◽  
Factor V ◽  
Thrombotic Risk ◽  
Control Subjects ◽  
Oral Contraceptive Use ◽  
Increased Risk

SummaryProtein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype – a genotype associated with higher protein C levels – the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09–1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/ GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/ GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk.

Risk of Pregnancy-related Venous Thrombosis in Carriers of Severe Inherited Thrombophilia

2001 ◽  
Vol 86 (09) ◽  
pp. 800-803 ◽  
Author(s):  
Cristina Legnani ◽  
Paolo Bucciarelli ◽  
Elvira Grandone ◽  
Valerio De Stefano ◽  
Pier Mannuccio Mannucci ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Study Cohort ◽  
Factor V ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Prothrombin Gene ◽  
Heterozygous Carriers ◽  
Anticoagulant Prophylaxis

SummaryHomozygous carriers of factor V Leiden have an approximately 80-fold increased risk of venous thrombosis. Also double heterozygous carriers of both the factor V Leiden and the prothrombin gene mutations are at high thrombotic risk. The magnitude of the risk of venous thrombosis in pregnant women with the two severe thrombophilic conditions has not been estimated so far. We performed a multicenter retrospective family study in women with homozygous factor V Leiden, double heterozygous factor V Leiden and the prothrombin gene mutation, and women with normal coagulation. Only relatives of index patients with thrombosis formed the study cohort. Fifteen homozygous and 39 double heterozygous women were compared to 182 women with normal coagulation. Venous thrombosis occurred in 3 of 19, 2 of 50 and 1 of 221 pregnancies, respectively. One thrombotic episode occurred in the third trimester, the remaining 5 in the postpartum. The prevalence of venous thrombosis was 15.8% (95% CI 3.4-39.6) for homozygotes, 4.0% (95% CI 0.5-13.7) for double heterozygotes and 0.5% for women with normal coagulation. The relative risk of pregnancy-related venous thrombosis was 41.3 (95% CI 4.1-419.7) for homozygous and 9.2 (95% CI 0.8-103.2) for double heterozygous carriers. In conclusion, homozygous carriers of factor V Leiden and, to a lesser extent, double heterozygous carriers of factor V Leiden and of the prothrombin mutation have an increased risk of venous thrombosis during pregnancy, particularly high during the postpartum period. On the basis of these findings we recommend that these women receive anticoagulant prophylaxis at least in the postpartum, that should perhaps be extended to the whole pregnancy in homozygous carriers.

New Interactive Effects Involving Factor XIII Gene Polymorphisms in Venous Thrombotic Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2590-2590
Author(s):  
Maria C. Pintao ◽  
Dayse M. Lourenço ◽  
Francisco H.A. Maffei ◽  
Vania M. Morelli ◽  
Amelia G. Araujo ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Specific Activity ◽  
Interactive Effect ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Interactive Effects ◽  
Coagulation Cascade ◽  
Factor V ◽  
Thrombotic Risk ◽  
Increased Risk

Abstract Venous thrombosis (VT) is considered to be a multifactorial disorder in which several genetic and acquired risk factors interact dynamically. Coagulation factor XIII (FXIII) is an enzyme that participates in the final steps of the coagulation cascade. A number of gene variations have been described in both FXIII A and B subunits. FXIIIA Val34Leu, Tyr204Phe and Pro564Leu polymorphisms have been associated to increased specific activity of FXIII, and FXIIIA Val34Leu has been claimed to be protective against VT in several studies. In the FXIII B subunit, two common polymorphisms (His95Arg and G30899A) have been also reported, but its association with VT is uncertain. In addition, possible interactive effects between these polymorphisms and between these polymorphisms and the two most prevalent mutations associated with VT, factor V Leiden (FVL) and factor II (FII) G20210A mutations, have not been explored. In the present study, we determined the prevalence of the five above-mentioned FXIII polymorphisms in 418 consecutive patients with an objective diagnosis of VT and in 418 age-, gender- and race-matched controls in the BRATROS (Brazilian Thrombosis Study) case-control investigation. Genotyping for Val34Leu, Pro564Leu, His95Arg and G30899A was performed by PCR amplification followed by MseI, BstUI, NsiI and BspHI restriction digestion analysis, respectively. Genotyping for Tyr204Phe was performed by single-strand conformation polymorphism (SSCP) analysis followed by DNA sequencing of samples showing mobility shifts. Odds ratios (OR) as a measure of relative risks of VT, and 95% confidence intervals (CI95), were calculated. Stratified analyses were performed to search for interactions between the FXIII polymorphisms and between the FXIII polymorphisms, FVL and FII G20210A. Overall OR for VT linked to Val34Leu was 0,78 (CI95: 0,59–1,03); OR for heterozygotes (HT) was 0,85 (CI95: 0,64–1,13) and for homozygotes (HM) the OR was 0,33 (CI95: 0,15–0,71). Overall OR linked to G30899A was 1,06 (CI95: 0,81–1,39); OR for HT was 0,96 (CI95: 0,72–1,28) and for HM the OR was 1,58 (IC95: 1,00–2,49). No impacts over the risk of VT were observed, related to the other three polymorphisms investigated. When stratified analyses were performed to search for interactions, a trend towards increased risk of VT was detected when the Val34 allele was co-inherited with the Arg95 allele (OR 1,45; CI95: 0,97–2,18), and a trend towards decreased thrombotic risk was verified when the Leu34 and Leu564 alleles were co-inherited (OR 0,63; CI95: 0,40–1,00). Furthermore, increased risk for VT was observed when the mutant A30899 allele was co-inherited with FII G20210A, pointing to a notable interaction effect (OR 18,29; CI95: 2,41–138,87). The data confirm that homozygosity for FXIII Val34Leu is protective against the occurrence of VT in our population. In addition, the findings point to a previously unknown increased risk of VT related to homozygosity for FXIIIB G30899A of the order of 58%. Lastly, an impressive interactive effect (18-fold increased risk of VT) between FXIIIB G30899A and FII G20210A is reported for the first time. Taken together, the findings from the present investigation strengthen the clinical significance of FXIII in vascular thrombosis and reinforce the concept of VT as a multigenic disease.

scholarly journals Factor V Leiden and prothrombin gene G20210A mutation and in vitro fertilization: prospective cohort study

2011 ◽  
Vol 26 (11) ◽  
pp. 3068-3077 ◽  
Author(s):  
G. Ricci ◽  
P. Bogatti ◽  
L. Fischer-Tamaro ◽  
E. Giolo ◽  
S. Luppi ◽  
...  
Keyword(s):  
Cohort Study ◽  
In Vitro Fertilization ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Factor V Leiden ◽  
Factor V ◽  
Vitro Fertilization ◽  
G20210a Mutation ◽  
Prothrombin Gene

Danger of false negative (exclusion) or false positive (diagnosis) for ‘congenital thrombophilia’ in the age of anticoagulants

2019 ◽  
Vol 57 (6) ◽  
pp. 873-882 ◽  
Author(s):  
Emmanuel J. Favaloro
Keyword(s):  
False Positive ◽  
Ex Vivo ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
False Negative ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Increased Risk

Abstract Background Most guidelines and experts recommend against performance of thrombophilia testing in general, and specifically against testing patients on pharmacological anticoagulants, due to substantially increased risk of false positive identification. For example, vitamin K antagonist (VKA) therapy affects protein C (PC) and protein S (PS), as well as some clotting assays (e.g. as used to investigate activated PC resistance [APCR]). Although heparin may also affect clotting assays, most commercial methods contain neutralisers to make them ‘insensitive’ to therapeutic levels. Direct oral anticoagulants (DOACs) also affect a wide variety of thrombophilia assays, although most reported data has employed artificial in vitro spiked samples. Methods In the current report, data from our facility for the past 2.5 years has been assessed for all ‘congenital thrombophilia’ related tests, as evaluated against patient anticoagulant status. We processed 10,571 ‘thrombophilia’ related test requests, including antithrombin (AT; n=3470), PC (n=3569), PS (n=3585), APCR (n=2359), factor V Leiden (FVL; n=2659), and prothrombin gene mutation (PGM; n=2103). Results As expected, VKA therapy affected PC and PS, and despite manufacturer claims, also APCR. Most assays, as suggested by manufacturers, were largely resistant to heparin therapy. DOACs’ use was associated with falsely low APCR ratios (i.e. FVL-like effect) and somewhat unexpectedly, anti-Xa agents apixaban and rivaroxaban were also associated with lower AT and higher PS values. Conclusions It is concluded that ex-vivo data appears to confirm the potential for both false positive and false negative ‘thrombophilia’ events in patients on anticoagulant (including DOAC) treatment.

Venous Thrombotic Risk in Family Members of Unselected Individuals with Factor V Leiden

2000 ◽  
Vol 83 (06) ◽  
pp. 817-821 ◽  
Author(s):  
R. P. M. Lensen ◽  
R. M. Bertina ◽  
H. de Ronde ◽  
J. P. Vandenbroucke ◽  
F. R. Rosendaal
Keyword(s):  
Risk Factors ◽  
Positive Family History ◽  
Family Members ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Asymptomatic Carriers ◽  
Kaplan Meier ◽  
Increased Risk

SummaryThe factor V Leiden mutation (FVL) leads to a seven-fold increased risk of venous thromboembolism (VTE). In thrombophilic families, 25% of carriers have experienced thrombosis before the age of 40 years. Aim of our study was to assess the association of FVL with VTE in first-degree family members of unselected symptomatic and asymptomatic carriers of FVL.We tested 197 relatives of consecutive thrombosis patients with FVL and 36 relatives of asymptomatic carriers on the presence of FVL and the occurrence of VTE.The incidence of VTE in relatives with FVL of symptomatic carriers was 0.34%/year. This was similar to the incidence in relatives with FVL of asymptomatic carriers. Kaplan Meier analysis in relatives of symptomatic propositi showed that at the age of 58 years, thrombosisfree survival was reduced to 75% in carriers and 93% in non-carriers (P < 0.05). Carriers of FVL had a three times higher thrombotic risk than non-carriers. In combination with environmental risk factors, FVL clearly adds to the risk of VTE. The thrombotic incidence rate in these unselected relatives with FVL, however, is considerably lower than was seen in carriers of thrombophilic families (1.7%/year). Therefore, special care should be paid to individuals with a positive family history of venous thrombosis while exposed to these risk factors.

scholarly journals A Genetic study in assisted reproduction and the risk of congenital anomalies

2021 ◽  
Vol 4 (4) ◽  
pp. 096-100
Author(s):  
Chrysoula Kaparelioti ◽  
Eleni Koniari ◽  
Vasiliki Efthymiou ◽  
Dimitrios Loutradis ◽  
George Chrousos ◽  
...  
Keyword(s):  
Birth Weight ◽  
In Vitro Fertilization ◽  
Assisted Reproduction ◽  
Congenital Anomalies ◽  
Clinical Genetics ◽  
Genetic Syndromes ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
One Year

In vitro fertilization is one of the most common and effective procedure for thousands of couples worldwide who want to have a child and are unable to do so for various reasons. Diverse studies show that couples who conceive naturally after one year of trying had newborns with an increased risk of prematurity and low birth weight, compared with couples who conceived before completing one year of trying. Children from assisted reproduction (AR), have a 30% increased risk of prematurity and low birth weight, compared with children from infertile fathers. Regarding the conflicting results the present study aimed to record the frequency of genetic, congenital anomalies in children and adolescents who had examined in the last decade to the Clinical Genetics Clinic of the National and Kapodistrian University of Athens whose mothers had undergone assisted reproduction. The research process was conducted at the "Aghia Sofia" Children's Hospital based in Athens. However, the cases that were studied came from all over Greece. Initially, the researcher recorded the cases that came to the clinic of Clinical Genetics and whose conception occurred after technical assisted reproduction. After telephone communication and the consent of the parents, a live appointment was scheduled. In this meeting-interview all the provisions of the investigation and the protocol were asked and some elements of the medical history of the cases were confirmed. The total sample included 230 children and adolescents. The resulting data were recorded on a printed form/questionnaire. Then, they were registered electronically in the program SPSS 25.0 (Statistical Package for Social Sciences) with a specific unit code for each case/patient, followed by the processing and statistical analysis of the data as well as the recording of the results. The gender of the participants was male for 118 participants (51.3%) and 112 females (48.7%). Mean and standard deviation (SD) of maternal, paternal (at the time of delivery) age was equal to 36.38 (5.94) and 39.94 (6.58) respectively. The observed abdormalities were 35.53% psychomotor retardation, 23.68% facial abnormalities, 23.68% spinal cord abnormalities, 21.05% morphological abnormalities, 20.61% short stature, 19.74% developmental disorders, 19.30% heart disease, 16.67% neurological diseases, 14.47% genetic syndromes, 11.40% genital abnormalities, 8.33% limb abnormalities, 7.46% dermatological abnormalities, 6.14% eye abnormalities, 6.14% hypothyroidism, 5.70% endocrine disorders, 5.26%otolaryngology abnormalities, 2.63% disease of kidney, intestine, 2.19% vascular malformations. Regarding the karyotype chromosome analysis by G-banding technique, from the 230 children in: 24 (10.43%) a pathological result was found, in 158 children (68.70%) it was found normal (46, XX or 46, XY by case) without other findings, while in 48 children (20.87%) the test was not performed for various reasons. Regarding the results of molecular analysis (DNA) from the 230 children, in 50 (21.74%) a pathological finding was found, in 56 children (24.35%) no abnormalities were found and in 124 children (53.91%) no molecular analysis was performed for various reasons. In conclusion, the sample of this descriptive study is characterized as uniform in terms of the method of assisted reproduction since 96.24% had followed the classic IVF. Full-term pregnancy was associated with the appearance of malignancy and head morphological abnormalities (64.6%), normal pregnancy was associated with genetic syndromes (18.2%) and facial abnormalities (11.1%). It is recommended the screening oocyte and sperm donors in order to help protect the safety and health of donors, recipients, and future offspring. The present study confirms the association of the presence of congenital anomalies after in vitro fertilization (IVF). However, the absolute risk of developing severe dysplasias after an IVF procedure is limited.

Prevalence of Common Thrombophilia and Antiphospholipid Antibodies in Unexplained Infertility Women Undergoing in Vitro Fertilization (IVF)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 628-628
Author(s):  
Arie Steinvil ◽  
Raanan Raz ◽  
Shlomo A. Berliner ◽  
David M Steinberg ◽  
David Zeltser ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Success Rate ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Unexplained Infertility ◽  
Factor V ◽  
Vitro Fertilization ◽  
History Of ◽  
The Mean

Abstract Abstract 628 Assisted reproductive technology (ART) is extensively used as a tool for pregnancy achievement in subfertile couples. Congenital and acquired thrombophilia have been suggested by some investigators to play a role in abnormal embryos implantation and placentation. The objective of this study was to assess the role of common thrombophilia in women with unexplained infertility undergoing in vitro fertilization (IVF). We enrolled five hundred ninety-four women from a large healthcare maintenance organization going through IVF and who had a thrombophilia workup, and compared them for prevalence of thrombophilia to two reference groups consisting of 637 fertile women from previous work and 17,337 women members of the same healthcare organization with no history of venous thromboembolisms. The mean age of the women at the first cycle of IVF was 30.9 years (SD: ±4.1).The mean number of IVF cycles was 7.3 (SD: 5.0), and the mean fertility success rate per woman was 14.6% (SD: 19.0). None of the common thrombophilia tested was found to be significantly associated with the number of IVF cycles or with lower fertility success rate. Rather, women who had APCR and/or factor V Leiden and lupus anticoagulant had significantly higher live birth rates (12.25% and 12.64%, respectively) in comparison to women who were tested negative (8.98% and 9.7%, respectively). Thus, hypercoagulability is not associated with failure to achieve pregnancy. These data suggest that neither screening for thrombophilia nor anticoagulant treatment is indicated in cases with unexplained reproductive failure. Disclosures: No relevant conflicts of interest to declare.

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