Risk factors and role of low molecular weight heparin in obstetric complications among women with inherited thrombophilia - a cohort study

ABSTRACT Introduction: Although there is a vast literature regarding the association between inherited thrombophilia, obstetric complications and the effect of low molecular weight heparin (LMWH), these are controversial and we have not found publications related to additional risk factors other than thrombophilia.Our objectives were to assess the prevalence of miscarriage, placenta-mediated pregnancy complications and fetal loss in pregnant women with IT, establishing associated risk factors and the effect of LMWH. Materials and methods: A retrospective cohort of pregnant women with IT was formed. Risk factors considered were: high-risk IT, age ≥35 years, body mass index ≥25 and ≥30, assisted reproductive technology, antiphospholipid antibodies, autoimmune disease, first-degree family history of obstetric complications and personal history of venous or arterial thromboembolic disease, the outcomes being M, FL and PMPC. Results and conclusions: Data from 250 pregnancies in 88 women were obtained.There were 112 (45%) Ms, 13 (5.2%) FLs and 25 (10%) PMPCs.High-risk IT was associated with FL (OR = 4.96; 95% CI, 1.42-17.3). Antiphospholipid antibodies and family history of obstetric complications were associated with PMPC (OR = 7.12; 95% CI, 1.89-26.74, OR = 3.88; 95% CI, 1.18-12.78, respectively). The LMWH presented a benefit in the combined outcome (any obstetric complication, OR = 0.25; 95% CI, 0.12-0.54) and M (OR = 0.41; 95% CI, 0.20-0.82).We conclude that obstetric complications are common in women with IT. Antiphospholipid antibodies, family history of obstetric complications and high-risk IT might be additional risk factors. The LMWH has an apparent protective effect against obstetric complications, which is consistent with some previous studies.

Risk factors and role of low molecular weight heparin in obstetric complications among women with inherited thrombophilia - a cohort study.

INTRODUCTION: Although there is a vast literature regarding the association between inherited thrombophilia, obstetric complications and the effect of low molecular weight heparin (LMWH), these are controversial and we have not found publications related to additional risk factors other than thrombophilia. Our objectives were to assess the prevalence of miscarriage, placenta-mediated pregnancy complications and fetal loss in pregnant women with IT, establishing associated risk factors and the effect of LMWH. MATERIALS AND METHODS: A retrospective cohort of pregnant women with IT was formed. Risk factors considered were: high-risk IT, age ≥35 years, body mass index ≥25 and ≥30, assisted reproductive technology, antiphospholipid antibodies, autoimmune disease, first-degree family history of obstetric complications and personal history of venous or arterial thromboembolic disease, the outcomes being M, FL and PMPC. RESULTS AND CONCLUSIONS: Data from 250 pregnancies in 88 women were obtained. There were 112 (45%) Ms, 13 (5.2%) FLs and 25 (10%) PMPCs. High-risk IT was associated with FL (OR=4.96; 95% CI, 1.42-17.3). Antiphospholipid antibodies and family history of obstetric complications were associated with PMPC (OR=7.12; 95% CI, 1.89-26.74, OR=3.88; 95% CI, 1.18-12.78, respectively). The LMWH presented a benefit in the combined outcome (any obstetric complication, OR=0.25; 95% CI, 0.12-0.54) and M (OR=0.41; 95% CI, 0.20-0.82). We conclude that obstetric complications are common in women with IT. Antiphospholipid antibodies, family history of obstetric complications and high-risk IT might be additional risk factors. The LMWH has an apparent protective effect against obstetric complications, which is consistent with some previous studies.

Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort. / Trombofilia hereditaria y pérdidas de embarazo. Estudio de una cohorte de Argentina.

BACKGROUND AND OBJECTIVES: 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. PATIENTS AND METHODS: 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, n = 89; late losses, n = 158; foetal losses, n = 107) and according to the type of vascular obstetric pathologies. RESULTS: No differences were found in the distribution of the genetic variants among RPL group vs. control/reference group (p >.05). Similarly, no differences were observed in their distributions when analysing RPL patients stratified according to gestational times or vascular obstetric pathologies (p >.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; p = .04) (OR = 7.11 [1.24-40.93], p = .03). CONCLUSIONS: 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.

Mutación g20210a del gen de la protrombina: presentación clínica en dos gestantes / G20210a mutation of the prothrombin gene: clinical presentation in two pregnant women

La trombofilia hereditaria es una enfermedad genética que resulta de dos o más mutaciones en genes involucrados en el sistema hemostático, con variabilidad en la penetrancia del fenotipo trombótico. Entre los genes mutados asociados al incremento del riesgo de trombosis venosa se encuentra la mutación G20210A del gen de la protrombina. Se presentan los casos de dos pacientes jóvenes embarazadas que acudieron a la consulta de Hemostasia del Instituto de Hematología e Inmunología. Una, con historia personal de enfermedad tromboembólica (ETE) asociada al uso de anticonceptivos orales; y la otra, con antecedentes familiares de ETE e historia personal de abortos recurrentes. A ambas pacientes se les realizó estudio de trombofilia en el que se detectó la mutación G20210A del gen de la protrombina en estado heterocigoto. Recibieron seguimiento médico multidisciplinario y tratamiento profiláctico con aspirina a bajas dosis hasta la semana 34 de la gestación; y heparina de bajo peso molecular durante la gestación y seis semanas después del parto. Se lograron dos nacimientos sin complicaciones obstétricas ni fetales. La expresión de gen de la protrombina G20210A es variable, incluso dentro de una misma familia, y puede estar influenciada por factores de riesgo adquiridos, como el uso de anticonceptivos orales, el embarazo y el puerperio(AU)

Hereditary thrombophilia is a genetic disease that results from two or more mutations in genes involved in the hemostatic system, with variable penetrance of the thrombotic phenotype. Among the mutated genes associated with increased risk of venous thrombosis is mutation G20210A prothrombin gene. We present two pregnant young patients who attended the Haemostasis outpatient service at the Institute of Hematology and Immunology. One of them, with personal history of thromboembolic disease (TED) associated with use of oral contraceptives; and the other one, with a family history of TED and personal history of recurrent abortions. In both patients´ thrombophilia studies the G20210A mutation in the prothrombin gene in heterozygous state was detected. The patients received multidisciplinary medical monitoring and prophylactic treatment with low-dose aspirin until week 34 of gestation, and low molecular weight heparin during pregnancy and six weeks after delivery. Two births without obstetric or fetal complications were achieved. The gene expression of prothrombin G20210A is variable, even within the same family and may be influenced by acquired risk factors such as the use of oral contraceptives, pregnancy and the postpartum period(AU)

Mutación g20210a del gen de la protrombina: presentación clínica en dos gestantes / G20210a mutation of the prothrombin gene: clinical presentation in two pregnant women

La trombofilia hereditaria es una enfermedad genética que resulta de dos o más mutaciones en genes involucrados en el sistema hemostático, con variabilidad en la penetrancia del fenotipo trombótico. Entre los genes mutados asociados al incremento del riesgo de trombosis venosa se encuentra la mutación G20210A del gen de la protrombina. Se presentan los casos de dos pacientes jóvenes embarazadas que acudieron a la consulta de Hemostasia del Instituto de Hematología e Inmunología. Una, con historia personal de enfermedad tromboembólica (ETE) asociada al uso de anticonceptivos orales; y la otra, con antecedentes familiares de ETE e historia personal de abortos recurrentes. A ambas pacientes se les realizó estudio de trombofilia en el que se detectó la mutación G20210A del gen de la protrombina en estado heterocigoto. Recibieron seguimiento médico multidisciplinario y tratamiento profiláctico con aspirina a bajas dosis hasta la semana 34 de la gestación; y heparina de bajo peso molecular durante la gestación y seis semanas después del parto. Se lograron dos nacimientos sin complicaciones obstétricas ni fetales. La expresión de gen de la protrombina G20210A es variable, incluso dentro de una misma familia, y puede estar influenciada por factores de riesgo adquiridos, como el uso de anticonceptivos orales, el embarazo y el puerperio(AU)

Hereditary thrombophilia is a genetic disease that results from two or more mutations in genes involved in the hemostatic system, with variable penetrance of the thrombotic phenotype. Among the mutated genes associated with increased risk of venous thrombosis is mutation G20210A prothrombin gene. We present two pregnant young patients who attended the Haemostasis outpatient service at the Institute of Hematology and Immunology. One of them, with personal history of thromboembolic disease (TED) associated with use of oral contraceptives; and the other one, with a family history of TED and personal history of recurrent abortions. In both patients´ thrombophilia studies the G20210A mutation in the prothrombin gene in heterozygous state was detected. The patients received multidisciplinary medical monitoring and prophylactic treatment with low-dose aspirin until week 34 of gestation, and low molecular weight heparin during pregnancy and six weeks after delivery. Two births without obstetric or fetal complications were achieved. The gene expression of prothrombin G20210A is variable, even within the same family and may be influenced by acquired risk factors such as the use of oral contraceptives, pregnancy and the postpartum period(AU)

Deficiencia congénita de Proteína C asociada a polimorfismo C677T del gen de la 5,10-metiltetrahidrofolato reductasa, a propósito de un caso / Congenital deficiency of protein C associated with C677T polymorphism of the gene from the 5,10-methyltetrahydrofolate reductase. Case report

Se presenta el caso clínico de un recién nacido con trombofilia hereditaria por deficiencia congénita de proteína C asociada a polimorfismo C677T del gen de la 5,10-metiltetrahidrofolato reductasa.

We present a clinical case of a newborn with inherited thrombophilia by congenital deficiency of protein C associated with the gene from the 5, 10-methyltetrahydrofolate reductase C677T polymorphism.