Abstract
ObjectivesTo investigate the incidence of inherited thrombophilias in patients with adverse obstetric outcomes and to compare detection rates of thrombophilias between standard blood tests and a novel genetic test.MethodsThis is a case-control prospective study performed in Hospital Sant Joan de Déu in Barcelona, Spain. Cases had a history of intrauterine growth restriction requiring delivery before 34 weeks gestation, placental abruption before 34 weeks gestation, or severe preeclampsia. Controls had at least two normal, spontaneously conceived pregnancies at term, without complications or no underlying medical disease. At least 3 months after delivery, all case and control women underwent blood collection for standard blood tests for thrombophilias and saliva collection for the genetic test, which enables the diagnosis of 12 hereditary thrombophilias by analyzing genetic variants affecting different points of the blood coagulation cascade.ResultsThe study included 33 cases and 41 controls. There were no statistically significant differences between cases and controls in the standard blood tests for thrombophilias in plasma or the TiC test for genetic variables. One clinical-genetic model was generated using variables with the lowest P values: ABO, body mass index, C_rs5985, C_rs6025, and protein S. This model exhibited good prediction capacity, with an area under the curve of almost 0.7 (P <0.05), sensitivity of almost 67%, and specificity of 70%.ConclusionAlthough some association may exist between hypercoagulability and pregnancy outcomes, no significant direct correlation was observed between adverse obstetric outcomes and inherited thrombophilias when analyzed using either standard blood tests or the genetic test. Future studies with a larger sample size are required to create a clinical-genetic model that better discriminates women with a history of adverse pregnancy outcomes and an increased risk of poor outcomes in subsequent pregnancies.
Highlights
Thrombophilia describes a tendency to develop thromboses because of inherited or acquired disorders of blood coagulation or fibrinolysis, which lead to a prothrombotic state [1, 2]
Development of the placental circulation is ensured by structural modifications of the spiral arteries and a pregnancy-induced hypercoagulable state resulting from an increase in procoagulant factors and a decrease in anticoagulant factors and fibrinolysis [2,3, 4]
A number of authors suggest that the presence of any thrombophilic condition may cause venous or arterial thrombosis and placental circulation abnormalities, leading to a higher rate of certain obstetrical complications, such as fetal loss, severe preeclampsia, severe fetal growth restriction, or placental abruption [2, 5, 8]
Summary
Thrombophilia describes a tendency to develop thromboses because of inherited or acquired disorders of blood coagulation or fibrinolysis, which lead to a prothrombotic state [1, 2]. Padmashree et al.[9] reported that inherited and acquired thrombophilias can be found in 49% to 65% of women with pregnancy complications, in contrast to 28% to 22% of women with normal pregnancies, suggesting a three- to eight-fold increased risk of thrombophilia in women with complications These authors recommended antenatal screening for congenital and acquired thrombophilias among women with prior adverse pregnancy outcomes, with the intention of offering treatment with anticoagulants or antiplatelet agents. Most studies supporting this approach hypothesize that microthrombi, thrombosis, and infarction of the placenta contribute to pregnancy complications or loss [10,11]. There is evidence that women with any type of thromboembolic defect have a higher prevalence of pregnancy complications [12,13]
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