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Study of an Argentinian cohort" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "249" "paginaFinal" => "254" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Silvia Perés Wingeyer, Federico Aranda, Sebastián Udry, José Latino, Gabriela de Larrañaga" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Silvia" "apellidos" => "Perés Wingeyer" "email" => array:1 [ 0 => "sdaperes@yahoo.com.ar" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Federico" "apellidos" => "Aranda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Sebastián" "apellidos" => "Udry" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "José" "apellidos" => "Latino" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Gabriela" "apellidos" => "de Larrañaga" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Laboratorio de Hemostasia y Trombosis, Hospital de Infecciosas “Dr. Francisco Javier Muñiz”, Buenos Aires, Argentina" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Sección de Enfermedades Autoinmunes, Trombofilia y Embarazo, Hospital General de Agudos “Dr. Carlos G. Durand”, Buenos Aires, Argentina" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trombofilia hereditaria y pérdidas de embarazo. Estudio de una cohorte de Argentina" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Among women of reproductive age, 1–3% of them suffer an obstetric pathology called recurrent pregnancy loss (RPL). RPL is defined as the consecutive loss of two or more clinical pregnancies.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> Among these losses, approximately only half have known aetiology while the rest are considered idiopathic. The main causes, whose association with RPL have been clearly established, include uterine malformations, chromosomal defects, infections, autoimmune diseases, haematological diseases and endocrinopathies such as thyroid disease and diabetes.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The haemostatic system relevantly intervenes in the reproductive process. During normal pregnancy, a state of physiological hypercoagulability occurs, as there is an increase in the levels of coagulation factors and a decrease in those of the coagulation cascade inhibitors, among other changes. A successful pregnancy depends, among other factors, on the balance of all the mechanisms involved in haemostasis in order to ensure adequate placental circulation.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">3</span></a> Consequently, it has been postulated that thrombophilia – defined as a hereditary or acquired abnormality of haemostasis that results in an increased risk of thrombosis – would increase the risk of obstetric complications by affecting normal vascular functioning of the placenta. In addition, thrombophilia could also affect the growth and differentiation of the trophoblast.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">An alteration of the foetus–maternal circulation would produce placental insufficiency, which is associated with loss of pregnancy (unprovoked spontaneous abortion or foetal death) or obstetric complications of vascular origin such as preeclampsia (PE), foetal growth retardation and placental abruption (PA), among others.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Antiphospholipid syndrome, considered an acquired thrombophilia, is the most common cause of PRE and obstetric complications of vascular origin.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> It has also been suggested that hereditary thrombophilia is another possible cause of these pathologies, however there is no concurrence in the literature regarding its causal role in PRE. Numerous studies have been carried out to determine whether there is an association between the presence of hereditary thrombophilia, either maternal and paternal, and an increased risk of pregnancy loss and other obstetric complications, but the results obtained have been contradictory.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">8–12</span></a> Some of these studies showed that certain risk factors would be more strongly associated with pregnancy losses at certain gestational times, mainly according to losses occurring before or after the tenth week of gestation. This could explain, at least in part, the discrepancies between the studies mentioned.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Hereditary thrombophilia is essentially caused by two different mechanisms: the loss of natural anticoagulant function or the gain of procoagulant factor function. Deficiencies or dysfunctions of antithrombin (AT), protein C (PC) or protein S (PS) are the most common alterations among those following the first mechanism, while the genetic variants factor V Leiden (FVL) and prothrombin G20210A (II20210A) stand out among those of the second. A third postulated mechanism corresponds to the inhibition of the fibrinolytic system, as would be the case of polymorphism −675 4G/5G of the plasminogen activator inhibitor type 1 (−675 4G/5G PAI-1), although its role as a classic isolated thrombophilia is controversial.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">14</span></a> On the other hand, there are two other genetic variants, related to the coagulation system, that have been associated with deep vein thrombosis but whose impact on pregnancy losses has not yet been studied: the variants gamma fibrinogen 10034C/T (FGG10034T) and 7872 C/T from the factor XI gene (FXI7872C).<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">15,16</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">On the basis of all the above, our objective was to study the frequencies of the deficiencies and/or dysfunctions of PC, AT and PS and the genotypic distributions of genetic variants associated with thrombosis (FVL, II20210A, −675 4G/5G PAI-1, FGG10034T and FXI7872C) in a group of Argentine women, who have experienced RPL, without apparent cause, and compare them with those corresponding to a strictly selected control group of post-fertile women and with those of a second reference group from the general Argentine population, respectively. Similarly, our secondary objective is to analyse the possible association between carrying these genetic variants and the gestational time of the losses and an increased risk of suffering other obstetric complications such as foetal growth retardation, PA and PE.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">A descriptive and cross-sectional study of cases and controls was carried out. The protocol was approved by the participating hospitals’ Research and Teaching Ethics Committee and carried out in accordance with the 1975 Declaration of Helsinki ethical standards and current national regulations. In all cases, each participant's informed consent was obtained before they were included in the study.</p><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 578 subjects participated: 247 women with a history of pregnancy loss (patient-cases), 107 women from a strictly selected control group (control group) and 224 subjects from the general population (reference group).</p><p id="par0045" class="elsevierStylePara elsevierViewall">All 247 participants were patients of the Dr. Carlos G. Durand General Hospital high-risk pregnancy clinic and were selected from a more extensive cohort of 1185 patients treated at that clinic during June 2010 and March 2016. The patients excluded from the study included: those with known causes for their pregnancy losses, anatomical and endocrinological alterations (diabetes mellitus, hypothyroidism, hyperthyroidism, polycystic ovarian syndrome, hyperprolactinemia), chromosomal alterations identified in parenteral karyotypes; those with other clinical pathologies such as liver, renal, cardiovascular and neurological diseases; those whose data were incomplete and those who refused to give their informed consent. Pregnancies were confirmed by ultrasound and a positive foetal heartbeat. Considering that the tenth week of gestation would mark the end of the embryonic period and the beginning of the foetal period, the patients were stratified according to the gestational time of the losses: (a) early RPL, defined as the consecutive and inexplicable loss of at least two confirmed pregnancies within the first 10 weeks and (b) late losses, defined as the loss of at least one pregnancy occurring at 10 or more weeks.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a> A subgroup of patients who suffered foetal losses was also analysed, defining foetus deaths as those that were miscarried at 20 or more weeks, when the gestational age was known, and when it was not, foetuses that weighed greater than 350<span class="elsevierStyleHsp" style=""></span>g, which corresponds to the 50th percentile of weight at 20 weeks’ gestation.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> Patients were also classified according to the following obstetric complications of vascular origin: PE, PA and/or foetal growth retardation. PE was defined as the presence of hypertension (systolic blood pressure<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>140<span class="elsevierStyleHsp" style=""></span>mmHg or diastolic pressure ≥90<span class="elsevierStyleHsp" style=""></span>mmHg) and proteinuria 24<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>0.3<span class="elsevierStyleHsp" style=""></span>g.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> PA was defined as bleeding associated with partial or total separation of the placenta from its normal insertion site, the uterine fundus, from the 20th week of gestation until before the birth of the foetus.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> Delayed foetal growth was defined as the presence of a foetus with more than 20 weeks of gestation with growth measurements below the 3rd percentile, or below the 10th percentile and Doppler alterations (ultrasound diagnosis).<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Obstetric antiphospholipid syndrome was diagnosed according to the international classification criteria established by the Sydney Consensus 2006.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">We also studied a strictly selected control group of 107 women with a history of at least two normal pregnancies, currently in menopause or in post-menopause, whose children were born healthy and within normal weight, and without any history of obstetric complications; and a general population reference group of 224 subjects, not selected, in order to estimate the genotypic frequencies of the genetic variants.</p><p id="par0060" class="elsevierStylePara elsevierViewall">All the subjects who participated in the study, whether as patients or in the control and reference groups, were Argentines of Argentine descent, of similar ethnic, geographical and social origins and were representative of the urban population of Buenos Aires, Argentina. This population is the result of genetic mixing processes that involved mainly Europeans, mostly Spaniards and Italians, and Native Americans.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">After fasting for eight hours, a blood sample was taken from all patients by venous puncture in plastic tubes with: (a) 3.2% sodium citrate (ratio 9:1) and (b) EDTA. From the sodium citrate samples, we obtained plasma by centrifugation at 3500<span class="elsevierStyleHsp" style=""></span>g for 15<span class="elsevierStyleHsp" style=""></span>min, from which aliquots were obtained and stored at −40<span class="elsevierStyleHsp" style=""></span>°C until analysis; the aliquots we used were thawed only once in a water bath at 37<span class="elsevierStyleHsp" style=""></span>°C before use. The blood collected in tubes with EDTA was stored at −40<span class="elsevierStyleHsp" style=""></span>°C for later use in the molecular biology techniques.</p><p id="par0070" class="elsevierStylePara elsevierViewall">They were quantified by chromogenic method using a Destiny Max coagulometer (Tcoag, Ireland): PC (Stachrom PC, Stago, France) and AT (AT Xa – Chromogenix, Mölndal, Sweden); and, by immunoturbidimetric method, the functionally active form of PS: Free PS (Liatest PSL, Stago, France). Those cases where patients had PC levels of less than 70%, AT of less than 80% and/or free PS of less than 60%, were defined as a deficit of the corresponding natural anticoagulant. Given that the levels of free PS vary in pregnancy, in the patients who were pregnant, we considered the cut-off point to be the values suggested by Szecsi et al.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a> adjusted to the week of gestation. PC and AT levels do not change during pregnancy. PC, AT and free PS deficits were confirmed with a second independent sample.</p><p id="par0075" class="elsevierStylePara elsevierViewall">The extraction of human DNA was carried out by a semi-automated method (High Pure PCR Template Preparation Kit, Roche Diagnostics, GmbH, Mannheim, Germany). Genotyping of the FVL and II20210A variants was performed through the real-time PCR technique using the factor V Leiden Kit and factor II (Prothrombin) G20210A Kit (LightCycler 2.0 – Roche Diagnostics) diagnostic kits, while the genotyping of the variants FGG10034T, FXI7872T and −675 4G/5G PAI-1 were carried out by PCR-RFLP techniques designed and tuned up in our laboratory.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Data analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The statistical analysis was performed using the statistical program SPSS<span class="elsevierStyleSup">®</span> version 21.0 for Windows (IBM SPSS Statistics 21, USA). The genotypic distributions of each variant in the case, control and general population groups were described as percentages. In order to evaluate the association of the genetic variants and the different clinical variables studied, a contingency table was constructed to test the hypothesis of association through a <span class="elsevierStyleItalic">χ</span> test.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a> The odds ratios and their corresponding 95% confidence intervals were estimated by binary logistic regression. A value of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 was considered statistically significant.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0085" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the clinical characteristics of the group of patients with pregnancy loss studied. We can see that 51 patients (20.1%) had antiphospholipid syndrome.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">When studying hereditary thrombophilias, in the group of women with RPL, PC deficit was found in 0.4% (1/247), AT deficit in 0.8% (2/247) and free PS deficit in 0.4% (1/247).</p><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the genotypic distributions of all the genetic variants studied in the group of patients with RPL, compared with the frequencies obtained in the control group and in the reference group of the general population, respectively. No significant differences (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05) were found in the genotypic distributions of any of the variants analysed between these groups. The heterozygous A/G genotype of II20210A was more frequent in patients with RPL than in the control group (5.3 vs. 0.9%), however this difference was not significant (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.10). Likewise, no significant differences were observed in the distributions of the variants when considering the different models of allelic dominance. The genotypic frequencies observed in the reference group for all the genetic variants studied were in Hardy–Weinberg equilibrium (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">We subsequently analysed the possible association between having any of these genetic variants with the gestational time the loss occurred. When comparing the groups of patients with early RPL (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>89), late losses (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>158) or dead foetus (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>107) individually compared to the control group, no significant differences (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05) were found in the genotypic distributions of those genetic variants, even considering the different models of allelic dominance. Finally, when considering clinical subgroups according to the obstetric complications suffered: foetal growth retardation (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>34), PA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16) or PE (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17) and comparing them with the control group, no significant differences of these genetic distributions were observed except for patients carrying the heterozygous genotype for FVL with a history of foetal growth retardation. 11.8% (4/34) of the patients with this complication were found to be heterozygous carriers of the FVL variant, while only 1.9% (2/107) of the women in the control group were found to be carriers (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04). Of the four patients with foetal growth retardation who were carriers of VLF, only one had another thrombophilia (AL) while among the other 30 patients with non-VLF foetal growth retardation, there was one heterozygous II20210A carrier and seven carriers of acquired thrombophilia. We performed a binary logistic regression analysis that included as independent variables the presence of FVL and II20210A (heterozygous genotype) and it was found that having the FVL allele turned out to be predictive of foetal growth retardation (OR: 7.11 [1.24–40.93], <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">The results obtained in this study indicate that there is no association between being a carrier of any of the genetic variants FVL, II20210A, −675 4G/5G PAI-1, FGG10034T and FXI7872C and an increase in the risk of suffering RPL, either generally or in a stratified manner according to the gestational time of the losses. As mentioned, the role of hereditary thrombophilia in pregnancy losses continues to be controversial worldwide and its causality is not clear. Earlier studies, mainly case–control studies and mostly retrospective, found a strong association between being a carrier of FVL, II20210A and PS deficiency and late pregnancy losses<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">.</span><a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> although in subsequent prospective cohort studies these associations were not confirmed.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">6,23</span></a> The results obtained in our study concurs with the latter. Likewise, we have not found a clear, if any, association between a predisposition to suffering RPL and the deficit of PC or AT or PS, although our cohort's sample size and the very low population prevalence is a limitation to the interpretation of the results.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Like other studies that have found that being a carrier of FVL is associated with an increased risk of PE and foetal growth retardation,<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">25,26</span></a> our results indicate that when the progenitor is heterozygous for FVL, it increases the chances of the foetus presenting such a complication by almost seven. In any case, we must recognise that the sample size of our patients with foetal growth retardation is a limiting factor when interpreting this result. However, we must also note that other studies have presented results that contradict these associations.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">6,27</span></a> Furthermore, part of these discrepancies could be due mainly to confounding factors such as differences in the ethnic origin of the populations studied and the use of different definitions for foetal growth retardation, among other factors.</p><p id="par0115" class="elsevierStylePara elsevierViewall">In our opinion, the finding obtained in our study is relevant for two reasons: firstly, because the delay of foetal growth is an important cause of perinatal morbidity and mortality that increases the risk of cardiovascular disease, hypertension, type 2 diabetes and other comorbidities in the adult life of the affected child<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a> and, secondly, because it reinforces the hypothesis that certain hereditary thrombophilias should be studied in vascular obstetric complications. This is a controversial issue that generates debates around the world: “who should we study and when?”. Updated recommendations from different scientific societies around the world agree that hereditary thrombophilias should not be studied in pregnancies losses occurring before ten weeks, but there is no unanimity regarding losses after the tenth week of gestation. While the <span class="elsevierStyleItalic">Royal College of Obstetricians and Gynecologists</span> recommends conducting FVL, II20210A and PS studies, both the <span class="elsevierStyleItalic">American College of Chest Physicians</span> and the <span class="elsevierStyleItalic">European Society of Human Reproduction and Embryology</span> recommend not carrying them out.<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">29–31</span></a> In Argentina, the latest consensus of the Argentine Federation of Gynecology and Obstetrics Societies recommends assessing each case on an individual basis and, if studies are to be carried out, analyses of PC, free PS, activated protein C/FVL resistance and II20210A should be requested.</p><p id="par0120" class="elsevierStylePara elsevierViewall">The variants FGG10034T and FXI7872C are two genetic polymorphisms that were recently described as being associated with an increased risk of suffering deep vein thrombosis,<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">15,16,32</span></a> probably due to an increase in the capacity of thrombin generation, so, theoretically, they could also be involved in obstetric complications with a physiopathological basis of thrombotic origin. The first national data of its distribution are presented in this study. As mentioned above, our results indicate that being a carrier of any of these two variants is not associated with the predisposition of suffering RPL, with gestational time of the losses or with other obstetric complications of vascular origin.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Regarding highly prevalent genetic variants such as −675 4G/5G PAI-1 and the thermolabile variant C667T of the enzyme methylenetetrahydrofolate reductase - whose implication in RPL has generated much debate around the world – we can today confirm, based on many studies,<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a> that there is no evidence to justify their role in pregnancy losses. The latest Argentine Federation of Gynecology and Obstetrics Societies consensus and the 2015 Argentine Haematology Society Guidelines concur with this. Additionally, the results this study obtained in the −675 4G/5G PAI-1, variant, coincide with this recommendation.</p><p id="par0130" class="elsevierStylePara elsevierViewall">It is important to note that the prevalences of hereditary thrombophilias in the population vary depending on the ethnic group used in the study. Furthermore, it is important to note that the incidence of thrombotic pathologies in individuals carrying these genetic variants is very variable; some individuals never develop complications, while others develop severe recurrent events at an early age. Being pathologies of multifactorial origin, they depend on a particular genotype, the coexistence of other genetic variants of risk and the influence of acquired risk factors. The interaction capacity of these factors is more important than the isolated power of each one individually. On this basis, future studies must analyse the complexity of different thrombophilias in defined patient subgroups in a larger sample, such as those formed by patients who present obstetric complications of vascular origin (foetal growth retardation and PE) or those who represent two different gestational pathologies but could share certain similar physiopathological mechanisms.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Finally, other possible causes of discrepancies in the results of studies on the role that thrombophilia could play in obstetric pathologies are those related to the heterogeneity of study designs, inclusion criteria, sample sizes, definitions and diagnostic criteria, as well as the selection of the control group. In this sense, our control group represents one of the greatest strengths of this study. As mentioned, it was strictly selected after a thorough medical examination, ruling out any possibility of lost pregnancies and gestational complications, and ensuring that the patient's complete obstetric history was considered, as we were considering women of post-fertile age.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In conclusion, the results drawn from this study represent unpublished data of hereditary thrombophilias in an Argentine cohort studied exhaustively; with classic thrombophilias and with other genetic variants associated with newer thrombophilia. As reported in other studies, FVL plays a significant role in certain obstetric complications of vascular origin such as foetal growth retardation, where the thrombotic imprint seems to have a leading role. Our future focus of study will be to expand this subgroup of patients and explore thrombophilic interactions, with the aim of trying to understand how to achieve successful pregnancies, which will hopefully lead to ensuring newborn babies are healthy.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Authorship/collaborators</span><p id="par0145" class="elsevierStylePara elsevierViewall">All the authors equally contributed to the study design, data analysis, writing process and approving the manuscript.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1172136" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1096376" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1172137" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1096375" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Data analysis" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Authorship/collaborators" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 11 => array:2 [ "identificador" => "xack400523" "titulo" => "Acknowledgements" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-09-29" "fechaAceptado" => "2017-12-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1096376" "palabras" => array:6 [ 0 => "Inherited thrombophilia" 1 => "Recurrent pregnancy loss" 2 => "Foetal growth retardation" 3 => "Factor V Leiden" 4 => "Fibrinogen gamma" 5 => "Factor XI" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1096375" "palabras" => array:6 [ 0 => "Trombofilia hereditaria" 1 => "Pérdidas recurrentes de embarazo" 2 => "Retraso del crecimiento fetal" 3 => "Factor V de Leiden" 4 => "Fibrinógeno gamma" 5 => "Factor XI" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Thrombophilia might increase the risk of suffering from obstetric complications by adversely affecting the normal placental vascular function. Our aim was to study the distributions of five thrombosis-associated genetic variants: factor V Leiden, prothrombin G20210A, −675 4G/5G PAI-1, 10034C/T gamma fibrinogen and 7872C/T factor XI and the frequencies of the deficiencies of protein C, S and antithrombin in Argentinian patients with recurrent pregnancy loss (RPL) and, therefore, to analyse their association with the risk and timing of RPL and the risk of suffering other vascular obstetric pathologies.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We performed a case–control study that included 247 patients with idiopathic RPL (cases), 107 fertile controls and 224 subjects from general population (reference group). Cases were stratified according to the gestational time of the losses (early RPL, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>89; late losses, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>158; foetal losses, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>107) and according to the type of vascular obstetric pathologies.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">No differences were found in the distribution of the genetic variants among RPL group vs. control/reference group (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.05). Similarly, no differences were observed in their distributions when analysing RPL patients stratified according to gestational times or vascular obstetric pathologies (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.05), except for the factor V Leiden carriage in patients with foetal growth retardation vs. controls (11.8%, 4/34 vs. 1.9%, 2/107; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.04) (OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7.11 [1.24–40.93], <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.03).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Factor V Leiden might have a significant impact on certain obstetric pathologies such as foetal growth retardation. The genetic variants, 10034C/T gamma fibrinogen and 7872C/T factor XI, associated with thromboembolic disease, would not have an impact on PRE.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La trombofilia aumentaría el riesgo de complicaciones obstétricas al afectar la función vascular normal a nivel placentario. Nuestro objetivo fue estudiar las distribuciones genotípicas de cinco variantes genéticas asociadas a trombosis: factor V Leiden, protrombina G20210A, −675 4G/5G PAI-1, 10034C/T fibrinógeno gamma y 7872C/T factor XI y las frecuencias de los déficits de proteína C/S/antitrombina en pacientes argentinas con pérdida recurrente de embarazo (PRE) y, así, analizar su asociación con PRE, el tiempo gestacional de las pérdidas y el riesgo a sufrir otras complicaciones obstétricas de origen vascular.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realizó un estudio de casos y controles, incluyendo 247 pacientes con PRE (casos), 107 mujeres fértiles (controles) y 224 individuos de población general (grupo de referencia). Los casos fueron estratificados de acuerdo con el tiempo gestacional de las pérdidas (PRE temprana, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>89; pérdidas tardías, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>158; pérdidas fetales, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>107) y según el tipo de complicación obstétrica.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">No se encontraron diferencias significativas (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0,05) en la distribuciones genotípicas de las variantes analizadas entre el grupo PRE comparados con controles/grupo referencia, respectivamente. Tampoco según tiempo gestacional de la pérdida o las complicaciones obstétricas, excepto para la portación factor V Leiden en pacientes con retraso del crecimiento fetal vs. controles (el 11,8%, 4/34 vs. el 1,9%, 2/107 <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,04) (OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7,11 [1,24-40,93], <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,03).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El factor V Leiden cumpliría un rol importante en ciertas patologías obstétricas como retraso del crecimiento fetal, donde la impronta trombótica parecería tener un papel importante. Las variantes genéticas 10034C/T fibrinógeno gamma y 7872C/T factor XI, con impacto reconocido en enfermedad tromboembólica, no estarían asociadas a PRE.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Perés Wingeyer S, Aranda F, Udry S, Latino J, de Larrañaga G. Trombofilia hereditaria y pérdidas de embarazo. Estudio de una cohorte de Argentina. Med Clin (Barc). 2019;152:249–254.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Results are expressed in medians and interquartile ranges or percentages as appropriate.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Clinical characteristics (n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">247)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32 (26–37) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Body mass index (kg/m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.9 (21.8–27.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Number of losses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (2–4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Early losses (<span class="elsevierStyleItalic">n</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Late losses (<span class="elsevierStyleItalic">n</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">158 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dead foetus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">107 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Vascular complications (n)</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Foetal growth retardation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Placental abruption \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Preeclampsia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2000442.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of patients with pregnancy loss.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables studied (%, <span class="elsevierStyleItalic">n</span>) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>247) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>107) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>247) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference group (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>224) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">FVL</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96.8 (239) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98.1 (105) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96.8 (239) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96.9 (217) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.94 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.2 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.2 (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.1 (7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">II20210A</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>G/G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94.7 (234) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99.1 (106) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94.7 (234) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97.8 (219) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>A/G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.3 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.3 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">−<span class="elsevierStyleItalic">675 4G/5G PAI-1</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>5G/5G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.4 (99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.8 (34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.4 (99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.8 (69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.36 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>4G/5G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45.6 (109) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.3 (57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45.6 (109) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46.3 (104) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>4G/4G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.6 (39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.9 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.6 (39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.9 (51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">10034C/T FGG</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C/C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.2 (163) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65.4 (70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.2 (163) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68.2 (153) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.83 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C/T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.4 (78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.7 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.4 (78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.0 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T/T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.4 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.4 (6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.8 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">7872C/T FXI</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C/C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.7 (73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.7 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.7 (73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.7 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C/T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.7 (118) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43.0 (46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.7 (118) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48.2 (108) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T/T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.6 (56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.3 (26) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.6 (56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.1 (45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2000443.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Genotypic distribution of genetic variants in recurrent pregnancy loss in relation to the control group and the general population reference group respectively.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib0170" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "ACOG Practice Bulletin No. 102: management of stillbirth" ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/AOG.0b013e31819e9ee2" "Revista" => array:6 [ "tituloSerie" => "Obstet Gynecol" "fecha" => "2009" "volumen" => "113" "paginaInicial" => "748" "paginaFinal" => "761" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19300347" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0175" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent pregnancy loss: etiology, diagnosis, and therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.B. Ford" 1 => "D.J. Schust" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Obstet Gynecol" "fecha" => "2009" "volumen" => "2" "paginaInicial" => "76" "paginaFinal" => "83" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19609401" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0180" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemostasis in normal pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B. Brenner" 1 => "A. Aharon" 2 => "N. Lanir" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Thromb Res" "fecha" => "2005" "volumen" => "115" "numero" => "Suppl. 1" "paginaInicial" => "6" "paginaFinal" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15790141" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0185" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Do thrombophilias cause placenta-mediated pregnancy complications?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.A. Rodger" 1 => "M. Paidas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-2007-985756" "Revista" => array:6 [ "tituloSerie" => "Semin Thromb Hemost" "fecha" => "2007" "volumen" => "33" "paginaInicial" => "597" "paginaFinal" => "603" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17768692" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0190" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The thrombomodulin-protein C system is essential for the maintenance of pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Isermann" 1 => "R. Sood" 2 => "R. Pawlinski" 3 => "M. Zogg" 4 => "S. Kalloway" 5 => "J.L. Degen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nm825" "Revista" => array:6 [ "tituloSerie" => "Nat Med" "fecha" => "2003" "volumen" => "9" "paginaInicial" => "331" "paginaFinal" => "337" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12579195" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0195" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association of factor V Leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Rodger" 1 => "M.T. Betancourt" 2 => "P. Clark" 3 => "P.G. Lindqvist" 4 => "D. Dizon-Townson" 5 => "J. Said" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pmed.1000292" "Revista" => array:5 [ "tituloSerie" => "PLoS Med" "fecha" => "2010" "volumen" => "7" "paginaInicial" => "e1000292" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20563311" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0200" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombophilia and fetal loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B. Brenner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-2003-38831" "Revista" => array:6 [ "tituloSerie" => "Semin Thromb Hemost" "fecha" => "2003" "volumen" => "29" "paginaInicial" => "165" "paginaFinal" => "170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12709919" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0205" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Z. Alfirevic" 1 => "D. Roberts" 2 => "V. Martlew" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Eur J Obstet Gynecol Reprod Biol" "fecha" => "2002" "volumen" => "101" "paginaInicial" => "6" "paginaFinal" => "14" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11803092" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022510X15020481" "estado" => "S300" "issn" => "0022510X" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0210" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombophilic disorders and fetal loss: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Rey" 1 => "S.R. Kahn" 2 => "M. David" 3 => "I. Shrier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(03)12771-7" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2003" "volumen" => "361" "paginaInicial" => "901" "paginaFinal" => "908" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12648968" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0215" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombophilia and pregnancy complications: cause or association?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. Middeldorp" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2007.02501.x" "Revista" => array:7 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2007" "volumen" => "5" "numero" => "Suppl. 1" "paginaInicial" => "276" "paginaFinal" => "282" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17635737" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0220" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hereditary thrombophilia and recurrent pregnancy loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.M. Pritchard" 1 => "P.W. Hendrix" 2 => "M.J. Paidas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/GRF.0000000000000226" "Revista" => array:6 [ "tituloSerie" => "Clin Obstet Gynecol" "fecha" => "2016" "volumen" => "59" "paginaInicial" => "487" "paginaFinal" => "497" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27427827" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0225" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Case–control study of the frequency of thrombophilic disorders in couples with late foetal loss and no thrombotic antecedent – the Nimes Obstetricians and Haematologists Study5 (NOHA5)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.C. Gris" 1 => "I. Quere" 2 => "F. Monpeyroux" 3 => "E. Mercier" 4 => "S. Ripart-Neveu" 5 => "M.L. Tailland" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "1999" "volumen" => "81" "paginaInicial" => "891" "paginaFinal" => "899" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10404763" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0230" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New insights into mechanisms behind miscarriage" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E.C. Larsen" 1 => "O.B. Christiansen" 2 => "A.M. Kolte" 3 => "N. Macklon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1741-7015-11-154" "Revista" => array:5 [ "tituloSerie" => "BMC Med" "fecha" => "2013" "volumen" => "11" "paginaInicial" => "154" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23803387" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0235" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and risk of venous thromboembolism: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Wang" 1 => "C. Wang" 2 => "N. Chen" 3 => "C. Shu" 4 => "X. Guo" 5 => "Y. He" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.thromres.2014.09.035" "Revista" => array:6 [ "tituloSerie" => "Thromb Res" "fecha" => "2014" "volumen" => "134" "paginaInicial" => "1241" "paginaFinal" => "1248" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25450536" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0240" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma’ levels" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Uitte de Willige" 1 => "M.C. de Visser" 2 => "J.J. Houwing-Duistermaat" 3 => "F.R. Rosendaal" 4 => "H.L. Vos" 5 => "R.M. Bertina" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2005-05-2180" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2005" "volumen" => "106" "paginaInicial" => "4176" "paginaFinal" => "4183" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16144795" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0245" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple SNP testing improves risk prediction of first venous thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.G. De Haan" 1 => "I.D. Bezemer" 2 => "C.J. Doggen" 3 => "S. Le Cessie" 4 => "P.H. Reitsma" 5 => "A.R. Arellano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2011-12-397752" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2012" "volumen" => "120" "paginaInicial" => "656" "paginaFinal" => "663" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22586183" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0250" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.M. Kolte" 1 => "L.A. Bernardi" 2 => "O.B. Christiansen" 3 => "S. Quenby" 4 => "R.G. Farquharson" 5 => "M. Goddijn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/humrep/deu299" "Revista" => array:6 [ "tituloSerie" => "Hum Reprod" "fecha" => "2015" "volumen" => "30" "paginaInicial" => "495" "paginaFinal" => "498" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25376455" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0255" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Task Force on Hypertension in Pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "American College of Obstetricians and Gynecologists" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.AOG.0000437382.03963.88" "Revista" => array:6 [ "tituloSerie" => "Obstet Gynecol" "fecha" => "2013" "volumen" => "122" "paginaInicial" => "1122" "paginaFinal" => "1131" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24150027" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0260" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "290e1–e6" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Unterscheider" 1 => "S. Daly" 2 => "M.P. Geary" 3 => "M.M. Kennelly" 4 => "F.M. McAuliffe" 5 => "K. O’Donoghue" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Am J Obstet Gynecol" "fecha" => "2013" "volumen" => "208" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0265" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Miyakis" 1 => "M.D. Lockshin" 2 => "T. Atsumi" 3 => "D.W. Branch" 4 => "R.L. Brey" 5 => "R. Cervera" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2006.01753.x" "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2006" "volumen" => "4" "paginaInicial" => "295" "paginaFinal" => "306" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16420554" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0270" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The impact of modern migrations on present-day multi-ethnic Argentina as recorded on the mitochondrial DNA genome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.L. Catelli" 1 => "V. Alvarez-Iglesias" 2 => "A. Gomez-Carballa" 3 => "A. Mosquera-Miguel" 4 => "C. Romanini" 5 => "A. Borosky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2156-12-77" "Revista" => array:5 [ "tituloSerie" => "BMC Genet" "fecha" => "2011" "volumen" => "12" "paginaInicial" => "77" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21878127" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0275" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Haemostatic reference intervals in pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P.B. Szecsi" 1 => "M. Jorgensen" 2 => "A. Klajnbard" 3 => "M.R. Andersen" 4 => "N.P. Colov" 5 => "S. Stender" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1160/TH09-10-0704" "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "2010" "volumen" => "103" "paginaInicial" => "718" "paginaFinal" => "727" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20174768" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0280" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is thrombophilia associated with placenta-mediated pregnancy complications? A prospective cohort study: reply" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.A. Rodger" 1 => "N.J. Langlois" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jth.12632" "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2014" "volumen" => "12" "paginaInicial" => "1378" "paginaFinal" => "1379" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24931062" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0285" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombophilia: an update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Middeldorp" 1 => "M. Levi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-2007-985752" "Revista" => array:7 [ "tituloSerie" => "Semin Thromb Hemost" "fecha" => "2007" "volumen" => "33" "paginaInicial" => "563" "paginaFinal" => "572" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17768688" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0920121116300894" "estado" => "S300" "issn" => "09201211" ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0290" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased frequency of genetic thrombophilia in women with complications of pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J. Kupferminc" 1 => "A. Eldor" 2 => "N. Steinman" 3 => "A. Many" 4 => "A. Bar-Am" 5 => "A. Jaffa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199901073400102" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1999" "volumen" => "340" "paginaInicial" => "9" "paginaFinal" => "13" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9878639" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0295" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[discussion 32-4]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiphospholipid antibodies in women at risk for preeclampsia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.W. Branch" 1 => "T.F. Porter" 2 => "L. Rittenhouse" 3 => "S. Caritis" 4 => "B. Sibai" 5 => "B. Hogg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1067/mob.2001.113846" "Revista" => array:6 [ "tituloSerie" => "Am J Obstet Gynecol" "fecha" => "2001" "volumen" => "184" "paginaInicial" => "825" "paginaFinal" => "832" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11303189" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0300" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombophilia and pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.J. Kupferminc" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1477-7827-1-111" "Revista" => array:5 [ "tituloSerie" => "Reprod Biol Endocrinol" "fecha" => "2003" "volumen" => "1" "paginaInicial" => "111" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14617365" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0305" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The developmental origins of chronic adult disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.J. Barker" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Paediatr Suppl" "fecha" => "2004" "volumen" => "93" "paginaInicial" => "26" "paginaFinal" => "33" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15702667" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0310" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.M. Bates" 1 => "I.A. Greer" 2 => "S. Middeldorp" 3 => "D.L. Veenstra" 4 => "A.M. Prabulos" 5 => "P.O. Vandvik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.11-2300" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2012" "volumen" => "141" "paginaInicial" => "e691S" "paginaFinal" => "e736S" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22315276" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0315" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriages" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. Regan" 1 => "M. Backos" 2 => "R. Rai" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "Royal College of Obstetricians and Gynaecologists Green-top guideline No. 17" "serieFecha" => "2011" ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0320" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Avaialble from: <a class="elsevierStyleInterRef" target="_blank" id="intr0010" href="https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Recurrent-pregnancy-loss.aspx">https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Recurrent-pregnancy-loss.aspx</a> [November 2017]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent pregnancy loss. Guideline of the European Society of Human Reproduction and Embryology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "ESHRE Early Pregnancy Guideline Development Group" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2017" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0325" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High levels of coagulation factor XI as a risk factor for venous thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.C. Meijers" 1 => "W.L. Tekelenburg" 2 => "B.N. Bouma" 3 => "R.M. Bertina" 4 => "F.R. Rosendaal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM200003093421004" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2000" "volumen" => "342" "paginaInicial" => "696" "paginaFinal" => "701" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10706899" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0330" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic association studies of ACE and PAI-1 genes in women with recurrent pregnancy loss: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.T. Su" 1 => "S.H. Lin" 2 => "Y.C. Chen" 3 => "P.L. Kuo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1160/TH12-08-0584" "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "2013" "volumen" => "109" "paginaInicial" => "8" "paginaFinal" => "15" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23179239" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack400523" "titulo" => "Acknowledgements" "texto" => "<p id="par0155" class="elsevierStylePara elsevierViewall">The authors would like thank Analía Lucero, Valentina Lara and Mauro Moiana's invaluable collaboration in the development of this work.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015200000007/v1_201903290642/S2387020619300749/v1_201903290642/en/main.assets" "Apartado" => array:4 [ "identificador" => "43310" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015200000007/v1_201903290642/S2387020619300749/v1_201903290642/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619300749?idApp=UINPBA00004N" ]
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