Thrombophilia In Pregnancy Research Articles

Thrombophilia and newborn

Introduction: The term thrombophilia (TF) describes disorders associated with an increased predisposition of developing venous thromboembolism. Thrombotic accidents during pregnancy are now widely recognized as a cause of morbidity and mortality. Objectives: To compare maternal and term newborn (NB) characteristics between healthy and thrombophilic pregnancies. Methods: The study included 31 full-term newborns whose mothers were diagnosed with TF before the current pregnancy and treatment was carried out through it. In the control group were included 37 full-term NBs. NB indicators which were used are gender, gestation age, birth weight, Apgar score, morbidity during the early neonatal period, hospital stay, treatment during the early neonatal period. The indicators for the mothers are the type of TF, mechanism of childbirth, sequence of pregnancy and sequence of childbirth. Results: In the observed groups of patients, we found that mothers with TF have an average higher age and have a higher number of unsuccessful pregnancies. Тhey more often give birth by operation. The higher the number of maternal TF mutations, the more unsuccessful pregnancies. The NB of mothers with TF have a lower Apgar score, develop RDS more often during the early neonatal period and need a larger volume of therapeutic manipulations and have a significantly longer hospital stay. Conclusions: TF in pregnant women, even when adequate treatment is administered during pregnancy, is associated with increased morbidity in their full-term NBs during the early neonatal period. This requires additional therapeutic measures in full-term newborns and is associated with a prolonged hospital stay.

Maternal and Newborn Characteristics-A Comparison between Healthy and Thrombophilic Pregnancy.

A thrombophilic woman is more likely to experience difficulties during pregnancy, difficulties that will also affect the development of the newborn. This study aims to compare maternal and newborn characteristics between healthy and thrombophilic pregnancy. The following characteristics were analysed: maternal characteristics (BMI- body mass index, haemostasis parameters, thrombophilia-specific treatment) and newborn characteristics (gestational period, birth weight, the Apgar score). This follow-up study spanning five years, from 2018 to 2022, focuses on a cohort of 500 women who underwent delivery hospitalization in the western region of Romania. The maternal characteristics influence the newborn: the greater the weight of the mother with thrombophilia, the more the chances that the fetus will have a lower birth weight; increasing the dose of LMWH (low molecular weight heparin), connected with the necessity to control the homeostasis parameters, the more likely the fetus will be born with a lower birth weight. A pregnant woman with thrombophilia, treated appropriately, having a normal weight, and not presenting other risk factors independent of thrombophilia, will have a newborn with characteristics similar to a healthy pregnant woman.

Pathophysiological, immunogenetic, anatomopathological profile of thrombophilia in pregnancy.

Thrombophilic states have been associated with early and/or late pregnancy loss and possibly other severe obstetrical complications. Pregnancy-induced hypercoagulability, increased stasis, and the consequences of inherited and acquired thrombophilia are just a few of the factors that contribute to the development of thrombosis in pregnancy. In this review, we illustrate the impact that these factors have on the development of thrombophilia during pregnancy. We also explore how thrombophilia impact pregnancy outcomes. Next, we discuss how human leukocyte antigen G plays a part in thrombophilia during pregnancy by regulating cytokine release to prevent trophoblastic cell invasion and maintain local immunotolerance constant. Human leukocyte antigen class E is briefly explored with thrombophilia in pregnancy. Regarding the anatomopathologic aspect, we describe the different histopathological lesions of the placenta found in women with thrombophilia.

Predicting Thrombophilia using Neural Networks and Decision Trees

The occurrence of thrombophilia during pregnancy results from a complex interaction of inherited and acquired factors, followed by an increase in blood coagulation and subsequent placental ischemic conditions. In this paper, a novel method is presented, whose aim is early identification of the risk of developing thrombophilia in pregnancy. The proposed method is based on machine learning algorithms: decision trees and neural networks. The research uses a dataset consisting of demographic, lifestyle, and clinical information from 35 pregnant women (22 healthy and 13 with thrombophilia). The results show the effectiveness of decision trees and neural networks in accurately predicting the risk of developing thrombophilia in pregnancy. The implications of this research are significant for clinical practice and it provides a valuable tool for early identifying women with high risk of thrombophilia in pregnancy that can enable improvement of preventive measures, such as lifestyle modifications and the use of therapeutic prophylaxis. In conclusion, this paper demonstrates the potential of machine learning algorithms for the prediction of thrombophilia in pregnancy. By combining advanced computational techniques with comprehensive datasets, we can enhance our understanding of thrombophilia in pregnancy risk factors and improve patient outcomes through personalized preventive measures.

Approach to Thrombophilia in Pregnancy-A Narrative Review.

Thrombophilia is a genetic predisposition to hypercoagulable states caused by acquired haemostasis conditions; pregnancy causes the haemostatic system to become hypercoagulable, which grows throughout the pregnancy and peaks around delivery. Genetic testing for thrombophilic gene mutations is evaluated using different methodologies of real-time polymerase chain reaction and DNA microarrays of specific genes. Adapting the general care of the pregnant woman to the particularities caused by thrombophilia is an important component, so screening is preferred to assess the degree of genetic damage that manifests itself as a risk of thrombosis. The major goal of this narrative review was to quantitatively evaluate the literature data on the specific care of pregnant women with thrombophilia that are at risk of developing unplanned miscarriages.

Referral for Thrombophilia Testing in an Obstetric Patient Population: A Tertiary Centre Experience

Introduction:Thrombophilias augment the risk of pregnancy related morbidity, increasing the likelihood of adverse events such as fetal loss [1,2]. Current guidelines recommend women be tested for antiphospholipid antibodies when they present with recurrent miscarriage (3 or more consecutive pregnancy losses before 24 weeks) or with a late miscarriage (loss between 12-24 weeks) [1]. Inherited thrombophilia testing (including factor V Leiden, prothrombin gene mutation and protein S) is also recommended for women with 2nd trimester miscarriage [1]. Controversy exists around the benefit of universal thrombophilia screening given the low relative increase in risk of pregnancy events and the lack of evidence surrounding interventions such as low molecular weight heparin (LMWH) and aspirin in most thrombophilias [2,3].Our aim was to evaluate our own testing for thrombophilia in pregnancy related events. We aimed to assess the frequency of positive results and evaluate whether testing resulted in a change in management for our cohort of women.Methods:Data was collected retrospectively on 151 thrombophilia screens requested for obstetric reasons from July 2016 to July 2017 at Waikato Hospital. The tests comprised antiphospholipid antibodies (APL) including lupus anticoagulant (LA), factor V Leiden (FVL), protein C and S levels, antithrombin III (ATIII) and prothrombin (PT) gene mutations. Data pertaining to request information, outcome of current and previous results were included. Cost analysis was done using NZ $300 (US $223) for a full thrombophilia screen and NZ $30 (US $22) for protein S alone. GraphPad Prism 7 software was used for all data interpretation.Results:The mean patient age was 31 years (range 18-48 years). The commonest reason for referral for testing was recurrent miscarriage (49/151) (Figure 1) and the majority of requests were from the obstetrics department (79/151) (Figure 2).83% (126/151) of tests requested were for a full thrombophilia screen; the remainder (25/151) were for single tests or a combination. The majority were being tested for the first time; 16.5% (25/151) had previous testing done. Of those with previous tests 52% (13/25) had no abnormality found; the others had low protein S levels or ATIII deficiency, or both.With the current test, almost two thirds of patients (62%, 94/151) had no abnormality found. Of the others, low protein S levels made up the majority of positive tests (26/57) (Figure 3). Of these 4/26 tests were repeated with 1 ongoing low result representing a likely true protein S deficiency. The laboratory cost of negative tests was estimated to be NZ $28,200 (US $20,992); while the cost of testing for protein S, including repeat testing due to low levels likely associated with pregnancy, was estimated at NZ $879 (US $648).Results that could potentially change management (APL antibodies, presence of VTE with positive inherited thrombophilia result) were few (6/151).Conclusion:In our tertiary centre, the majority of thrombophilia testing done for obstetric reasons over a 12 month period was negative. Most positive results (low protein S) were likely attributable to recent pregnancy, with a lack of repeat testing undertaken. There was a potential change in management for only 6 patients. Our results are in line with the literature which shows a scarcity of evidence supporting thrombophilia screens in pregnancy related morbidity. These tests are not only costly but for the majority provide no clinical benefit. Our next step is to disseminate these results locally and we aim to educate our colleagues on the utility of thrombophilia testing in pregnancy related events and when it is clinically helpful. We await with interest the results of ongoing randomised controlled trials assessing the role of LMWH and aspirin in thrombophilia in pregnancy.[1] Royal College of Obstetricians and Gynaecologists (RCOG) Green-top guideline No 7. The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. April 2011.[2] Baglin T, Gray E, Graves M, et al . Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010; 149(2): 209-20[3] de Jong PG, Kaandorp S, Di NM, et al . Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev . 2014;7:CD004734 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Redox status of pregnant women with thrombophilia

Background/Aim. Since the role of oxidative stress in the pathogenesis of thrombophilia in pregnancy has still not been clarified, the aim of the study was to assess the redox status of pregnant women with thrombophilia. Methods. The study involved 120 pregnant women divided into two groups: pregnant women with thrombophilia (n = 60) and women with normal pregnancy (n = 60). Blood samples for biochemical analysis were collected at the end of the first, second, and third trimester of pregnancy. Concentrations of hydrogen peroxide (H2O2), nitrites (NO2-), and the index of lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) were measured in plasma. Levels of reduced glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT) were measured in erythrocytes. Results. In women with thrombophilia, NO2- values were increased in the first and third trimester compared to healthy pregnant women (p < 0.05). The higher levels of TBARS and H2O2 were noticed in women with thrombophilia in the first trimester compared to healthy pregnant women (p < 0.05). The values of SOD and CAT were lower in women with thrombophilia in the third and GSH in the first trimester compared to the control group (p < 0.05). Conclusion. Our results suggest an increased generation of prooxidants in thrombophilia at the beginning of gestation, which declines as gestation progresses and reaches similar values as in normal pregnancy at the end of pregnancy. Generally viewed, pregnant women with thrombophilia was associated with impaired antioxidant capacity ? activities of SOD and CAT were lower in the third and GSH in the first trimester compared to their values in healthy pregnant women.

Prevention of Thromboembolic Disease and Thrombophilias in Pregnancy

Prevention of Thromboembolic Disease and Thrombophilias in Pregnancy

Inherited thrombophilia in pregnancy. Study by questionnaire method in a group of pregnant women

Inherited thrombophilia in pregnancy. Study by questionnaire method in a group of pregnant women

Acquired thrombophilia in pregnancy. Study by questionnaire method in a group of pregnant women

Acquired thrombophilia in pregnancy. Study by questionnaire method in a group of pregnant women

Тромботические события при редких формах генетических тромбофилий

Цель исследования: изучить лабораторный фенотип редких мутаций Лейдена [FVL А(1961)A] и гена протромбина [FII А(20210)A] при их клинической реализации в виде тромбозов. Материалы и методы. Проведено многоцентровое проспективное наблюдательное исследование, включающее 80 носителей редких генетических форм тромбофилий: FVL А(1961)A (n = 31), FII А(20210)A (n = 10) и компаунд FII G(20210)A + FVL G(1691)A (n = 39). У всех пациентов исследована резистентность фактора Va к активированному протеину С (APC-R) по нормализованному отношению (НО) и уровень активности протромбина в плазме крови в состоянии физического здоровья и в случае эпизода тромботического события. Результаты. Определена ассоциативная связь развития тромботических событий со снижением НО при оценке APC-R как у гомозиготных носителей мутации Лейден (Ме = 0,35; 95% ДИ = 0,31–0,37 по НО), так и гетерозиготных компаундов (Ме = 0,43; 95% ДИ = 0,42–0,45 по НО). Заключение. Лабораторный мониторинг пациентов с редкими формами генетических тромбофилий позволяет выделить группу высокого тромбогенного риска, нуждающуюся в пролонгированной тромбопрофилактике. Objectives: to study the laboratory phenotype of rare Leiden mutation [FVL A(1961)A] and the prothrombin gene mutation [FII А(20210)A] implementating clinically as thrombosis. Patients / Methods. A multicenter prospective observational study included 80 carriers of rare genetic kinds of thrombophilia: FVL A(1961)A (n = 31), prothrombin FII А(20210)A (n = 10) and the compound FII G(20210)A + FVL G(1691)A (n = 39). All patients were tested for the factor Va resistance to activated protein C (APC-R), normalized ratio (NR), and the plasma prothrombin activity (%) in healthy conditions and in the case of thrombotic event. Results. An associative relation between the development of thrombotic events and a decrease in NR was determined when assessing APC-R, both in homozygous carriers of the Leiden mutation (Me = 0.35; 95% CI = 0.31–0.37 in NR) and heterozygous compounds (Me = 0.43; 95% СI = 0.42–0.45 in NR). Conclusions. Laboratory follow up for patients with rare kinds of genetic thrombophilias allows to identify a group at high thrombogenic risk requiring prolonged thromboprophylaxis.

Oxidative status of maternal blood in pregnancies burdened by inherited thrombophilias.

Oxidative status of maternal blood represents an important parameter of pregnancy that is involved in both, regulation of physiological processes and (if significantly altered) development of different pregnancy complications. Inherited thrombophilias represent genetic disorders that increase the risk of thromboembolism in pregnancy. Little is known about the impact of thrombophilia on the oxidative status of maternal blood. In this study, we analyzed oxidative status of blood of 56 women with pregnancies burdened by inherited thrombophilias. The status was established at three different trimesters using biochemical assays and electrochemical measurements, and it was compared to 10 age- and trimester-matching controls. Activities of superoxide dismutase, catalase, and glutathione reductase in the 1st and the 2nd trimester of thrombophilic pregnancy were lower than controls. Also, there was less oxidation in the plasma, according to higher concentration of reduced thiols and lower oxidation-reduction potential. Therefore, it appears that thrombophilic mothers do not experience oxidative stress in the circulation in the first two trimesters. However, the rise in GPx, GR and SOD activities in the 3rd trimester of thrombophilic pregnancy implies that the risk of oxidative stress is increased during the late pregnancy. These results are important for developing antioxidative treatment that could tackle thrombophilia-related pregnancy complications.

POSTPARTUM CEREBRAL VENOUS THROMBOSIS ASSOCIATED WITH PROTEIN S DEFICIENCY: A CASE REPORT

There is a decline in the levels of protein S during pregnancy due to an increase in its binding protein. Thus, protein S deficiency increases the risk of thrombosis and may lead to poor pregnancy outcomes. In the setting of a hypercoagulable state during pregnancy, it is difficult to interpret protein S levels when measured with other tests of thrombophilia in pregnancy. The rate of developing thrombotic events is higher in those pregnant females with a deficiency of any natural anticoagulant like protein S. We report the case of a recently delivered female with multiple intracranial hemorrhages and cerebral venous thrombosis associated with protein S deficiency. This case highlights the need to extensively identify all risk factors of thrombosis in newly delivered females for the early and effective management of postpartum thrombosis.

Therapeutic Implications of Inherited Thrombophilia in Pregnancy.

Inherited (hereditary) thrombophilia is a genetic disorder that affects coagulation, being responsible for more than 60% of idiopathic (spontaneous or unprovoked) thromboembolic events. Association of inherited thrombophilia with pregnancy increases the risk of thromboembolic disease, and it may be related to many complications, such as preeclampsia, recurrent miscarriage intrauterine growth restriction, early detachment of placenta, and prematurity. Interpretation of a positive test for thrombophilia in pregnant women is difficult because they have many natural changes in the coagulation system. Genetic diagnosis of thrombophilia, after a thrombotic event or during a pregnancy complication, has a major importance, not only to define its etiology but also to determine the duration of anticoagulant treatment and risk stratification for prophylaxis treatment. Literature search was performed using electronic database (PubMed) between April 1981 and November 2018. We used different keywords and MeSH terms to generate the most relevant results related to the inherited thrombophilia and its impact on pregnancy. Screening for inherited thrombophilia in young women is recommended in case of personal history of venous thromboembolism, first-degree relatives with a history of high-risk thrombophilia, or personal history of second-trimester miscarriage. Decision to recommend thromboprophylaxis with anticoagulant treatment in pregnant women with inherited thrombophilia is determined by history of venous thromboembolism, type and associated risk of inherited thrombophilia, and presence of additional risk factors. Low-molecular-weight heparins are the preferred agents for prophylaxis in pregnancy, while the doses vary depending on thrombophilia type, personal history, and associated risk factors. Association between 2 procoagulant conditions, inherited thrombophilia and pregnancy, has an important impact for the mother and fetus. This review will summarize the impact of each inherited prothrombotic factor on cardiovascular and pregnancy outcomes and will discuss the role of anticoagulation treatment for women diagnosed with inherited thrombophilia.

Thrombophilia in Pregnancy and Puerperium

Abstract not available
 Bangladesh Journal of Medical Science Vol.18(2) 2019 p.178-183

Thrombophilia in Pregnancy

Pregnancy represents a physiologic hypercoagulable state. The presence of inherited thrombophilias (factor V Leiden, prothrombin G20210A mutation, deficiencies of protein C, protein S and antithrombin) or acquired thrombophilias (antiphospholipid syndrome) increases the risk for venous thromboembolism, which represents one of the most common causes of direct maternal death. The clinical diagnosis of thrombosis can be difficult because of the overlap of symptoms with pregnancy-related manifestations. Antiphospholipid syndrome is correlated with early and late pregnancy complications whereas the association between the inherited thrombophilias and adverse pregnancy outcomes is still controversial. The psychological impact of thrombophilia in pregnancy should be also taken into consideration to prevent the negative effects of anxiety and stress on mother’s health and on birth outcomes. Thrombophilia testing in pregnancy is recommended only in cases in which the result is likely to influence the therapeutic decision. Low-molecular-weight heparins are the preferred anticoagulant for prophylaxis and therapy of thromboembolic events in pregnancy, presenting a low incidence of side effects. Future research is required to establish the optimal therapeutic strategy in pregnant women with thrombophilia, based upon a better stratification, in order to prevent thromboembolism and to improve pregnancy outcomes.

Maternal-Fetal Management in Trombophilia Related and Placenta-Mediated Pregnancy Complications

It is widely accepted that thrombophilia in pregnancy greatly increases the risk of venous thromboembolism. Pregnancy complications arise, at least partly, from placental insufficiency. Any change in the functioning of the gestational transient biological system, such as inherited or acquired thrombophilia, might lead to placental insufficiency. In this research we included 64 pregnant women with trombophilia and 70 cases non-trombophilic pregnant women, with or without PMPC, over a two-year period. The purpose of this multicenter case-control study is to analyze the maternal-fetal management options in obstetric thrombophilia, the impact of this pathology on the placental structure and possible correlations with placenta-mediated pregnancy complications. Maternal-fetal management in obstetric thrombophilia means preconceptional or early diagnosis, prevention of pregnancy morbidity, specific therapy as quickly as possible and fetal systematic surveilance to identify the possible occurrence of placenta-mediated pregnancy complications.

ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy.

Inherited thrombophilias are associated with an increased risk of venous thromboembolism and have been linked to adverse outcomes in pregnancy. However, there is limited evidence to guide screening for and management of these conditions in pregnancy. The purpose of this document is to review common thrombophilias and their association with maternal venous thromboembolism risk and adverse pregnancy outcomes, indications for screening to detect these conditions, and management options in pregnancy. This Practice Bulletin has been revised to provide additional information on recommendations for candidates for thrombophilia evaluation, updated consensus guidelines regarding the need for prophylaxis in women with an inherited thrombophilia during pregnancy and the postpartum period, and discussion of new published consensus guidelines from the Society for Obstetric Anesthesia and Perinatology addressing thromboprophylaxis and neuraxial anesthetic considerations in the obstetric population.

Association Between Inherited Thrombophilia in Pregnancy and Micronucleus Frequency in Peripheral Blood Lymphocytes.

The aim of this study was to determine possible predictors of an increased frequency of micronucleus (MN) and the impact of thrombophilia on the chromosomal instability in peripheral blood lymphocytes (PBL) of pregnant women in their first trimester. This study was designed as a case-control study on 74 pregnant women. It was performed in the gestational age of 11 to 14 weeks, when blood samples were collected and incubated for 72 hours. The individual MN frequency in PBL was measured by cytokinesis-block micronucleus (CBMN) assay. Women were grouped in control group [≤4 MN/1000 binucleated (BN) cells] and case group (>4 MN/1000 BN cells). Potential mutagenic effects of exogenous/endogenous factors in pregnant women were analyzed. By analyzing the given results, it can be concluded that pregnant women with thrombophilia have 26.69-times more chance of having a frequency of >4 MN/1000 BN than pregnant women with no thrombophilia. Our research was primarily aimed at showing that the presence of thrombophilia was a statistically important predictor of an increased MN frequency in pregnant women and it can predict about one-third of the total variance in MN frequency in the studied population.

Screening for inherited thrombophilia in pregnancy in Bucharest Emergency University Hospital

Screening for inherited thrombophilia in pregnancy in Bucharest Emergency University Hospital