Research Article: Genetic risk assessment of thrombophilia in patients with adverse obstetric outcomes

Date Published: February 27, 2019

Publisher: Public Library of Science

Author(s): M. Fernández Arias, E. Mazarico, A. Gonzalez, M. Muniesa, C. Molinet, L. Almeida, M. D. Gómez Roig, Dermot Cox.


To 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.

This 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.

The 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%. Although 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.

Partial Text

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]. Causes of hereditary thrombophilia include factor V Leiden mutation (activated protein C [PC] resistance); prothrombin 20210A mutation; PC, protein S (PS), and antithrombin III (AT III) deficiencies; lupus anticoagulant; anticardiolipin antibodies; methylenetetrahydrofolate (MTHFR) gene mutation; and hyperhomocysteinemia[1].

This is a case-control prospective study performed in Hospital Sant Joan de Deú in Barcelona, Spain. The study protocol was approved by the Institutional Review Board of Sant Joan de Déu University Hospital. Written informed consent was obtained from each participant.

A total of 33 patients were identified as cases and 41 as controls. Table 1 shows the baseline characteristics of each group. There were no significant differences between groups. Cases had a higher body mass index (BMI), but the difference between groups did not reach statistical significance (p = 0.064).

Over the past years, there has been much debate regarding the association between inherited thrombophilias and the risk of placenta-related adverse obstetric outcomes. Many case-control studies and systematic reviews [24–27] have suggested an association. Moreover, an increased risk of recurrent severe pregnancy complications has been reported in women with inherited thrombophilias [28–29]. However, our results did not show a high incidence of inherited thrombophilias in patients with adverse obstetric outcomes (severe fetal growth restriction, placental abruption, or severe preeclampsia). Furthermore, we found that analysis of inherited thrombophilias using the genetic test did not increase detection rates compared with the standard blood tests in patients with adverse obstetric outcomes.




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