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      Hereditary thrombophilia and low -molecular -weight heparin in women: useful determinants, including thyroid dysfunction, incorporating the management of treatment and outcomes of the entity

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          SUMMARY

          OBJECTIVE:

          Our study purposed to examine the complex relationship between low-molecular-weight heparin therapy, multiple pregnancy determinants, and adverse pregnancy outcomes during the third trimester in women with inherited thrombophilia.

          METHODS:

          Patients were selected from a prospective cohort of 358 pregnant patients recruited between 2016 and 2018 at the Clinic for Obstetrics and Gynecology, University Clinical Centre of Serbia, Belgrade.

          RESULTS:

          Gestational age at delivery (β=-0.081, p=0.014), resistance index of the umbilical artery (β=0.601, p=0.039), and D-dimer (β=0.245, p<0.001) between 36th and 38th weeks of gestation presented the direct predictors for adverse pregnancy outcomes. The model fit was examined using the root mean square error of approximation 0.00 (95%CI 0.00–0.18), the goodness-of-fit index was 0.998, and the adjusted goodness-of-fit index was 0.966.

          CONCLUSION:

          There is a need for the introduction of more precise protocols for the assessment of hereditary thrombophilias and the need for the introduction of low-molecular-weight heparin.

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          Most cited references23

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          Uteroplacental vascular development and placental function: an update.

          The importance of the placenta and its vascular development to fetal growth and development has been appreciated since ancient times. Based on numerous studies in humans and animal model organisms in the last 2-3 decades, normal placental angiogenesis is critically important to ensure adequate blood flow to the placenta and therefore to provide the substrates that support normal fetal growth. Placental angiogenesis is abnormal at term in compromised pregnancies (those in which fetal growth is altered), including those resulting from maternal nutritional or environmental stress, maternal age, increased numbers of fetuses, maternal or fetal genotype, or the use of assisted reproductive technologies (e.g., cloning by somatic cell nuclear transfer). We and others have recently shown that these defects in placental vascular development occur quite early in pregnancy and may therefore presage compromised fetal growth and development. The challenges will be to find biomarkers of abnormal placental angiogenesis and to develop therapeutic strategies to "rescue" placental vascular development and thus fetal growth in compromised pregnancies. Animal models will be essential in meeting these challenges.
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            ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy.

            (2018)
            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.
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              D-dimer during pregnancy: establishing trimester-specific reference intervals

              Pregnancy is associated with an increased risk of venous thromboembolism (VTE). D-dimer is a biomarker used as an exclusion criterion of VTE disease, but its usefulness during pregnancy shows limitations because D-dimer levels physiologically increase through pregnancy. The aim of our study was to follow the changes of D-dimer levels and to establish trimester-specific reference intervals during normal pregnancy. This is a longitudinal prospective study in which the reference population finally included 102 healthy pregnant women. Plasma D-dimer levels were measured during the three trimesters of pregnancy, using a latex-based immunoturbidimetric assay. Reference intervals were calculated according to the Clinical and Laboratory Standards Institute recommendations. D-dimer levels increased progressively and significantly through pregnancy and peaked in the third trimester, in which D-dimer levels were above the conventional cut-off point (500 µg/L) in 99% of pregnant women. The following reference intervals were defined: first trimester: 169-1202 µg/L, second trimester: 393-3258 µg/L and third trimester: 551-3333 µg/L. The study provides reference intervals of D-dimer during the pregnancy using latex-based immunoturbidimetry on the ACL 300 TOP automated coagulation analyser. Further prospective studies of pregnant women with clinical suspicion of VTE are needed to validate these results.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal AnalysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: InvestigationRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Formal AnalysisRole: InvestigationRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal AnalysisRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Formal AnalysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Formal AnalysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Journal
                Rev Assoc Med Bras (1992)
                Rev Assoc Med Bras (1992)
                ramb
                Revista da Associação Médica Brasileira
                Associação Médica Brasileira
                0104-4230
                1806-9282
                03 March 2023
                2023
                : 69
                : 2
                : 335-340
                Affiliations
                [1 ]University Clinical Center of Serbia, Clinic for Gynecology and Obstetrics – Belgrade, Serbia.
                [2 ]Univerzitet u Beogradu, Faculty of Medicine, Department of Gynecology and Obstetrics – Belgrade, Serbia.
                [3 ]Giresun Üniversitesi, Faculty of Medicine, Department of Pathology – Giresun, Turkey.
                [4 ]General Hospital Novi Pazar, Department of Ophthalmology – Novi Pazar, Serbia.
                [5 ]Giresun Üniversitesi, Faculty of Medicine, Division of Endocrine Surgery – Giresun, Turkey.
                [6 ]Giresun Üniversitesi, Faculty of Medicine, Department of General Surgery – Giresun, Turkey.
                [7 ]Universidade de São Paulo, Faculty of Medicine of Ribeirão Preto, Department of Gynecology and Obstetrics – São Paulo (SP), Brazil.
                [8 ]Univerzitet u Beogradu, Institute of Social Medicine, Faculty of Medicine – Belgrade, Serbia.
                Author notes
                [* ]Corresponding author: jovana.todorovic@ 123456med.bg.ac.rs

                Conflicts of interest: the authors declare there is no conflicts of interest.

                Author information
                http://orcid.org/0000-0001-5292-0595
                http://orcid.org/0000-0003-1183-7386
                http://orcid.org/0000-0002-0416-0621
                http://orcid.org/0000-0001-9225-6879
                http://orcid.org/0000-0001-5217-0755
                http://orcid.org/0000-0002-0167-861X
                http://orcid.org/0000-0003-1663-3972
                http://orcid.org/0000-0002-5924-9199
                http://orcid.org/0000-0001-9741-6317
                http://orcid.org/0000-0002-7926-3916
                Article
                1806-9282.20221445
                10.1590/1806-9282.20221445
                9983488
                36888774
                3a4a0961-c884-4641-b9ed-f9c03ae2841f

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 October 2022
                : 04 November 2022
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 19, Pages: 6
                Categories
                Original Article

                thrombophilia, hereditary,pregnancy,thyroid gland,heparin, low-molecular-weight

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