**Author details**

*New Insights into Metabolic Syndrome*

pregnancy and the puerperium [87].

the risk of pregnancy-related VTE.

**3. Conclusions**

**Conflict of interest**

The authors declare no conflicts of interest.

*vivo* samples [89].

In aPTT- and PT-based methods, by measuring the time to fibrin clot formation, these reactions terminate at the time of clot formation; however, thrombin continues to be formed after the termination of clot formation and the activity is maintained in the fibrin clot as the trapped form in α-2 macroglobulin. Compared with the thrombin activity measured by the PT-based method, the activity by the ETP-based method can reveal the approximate value of coagulation ability in *ex* 

An animal experiment has shown that thrombin generation is upregulated in high estrogenic conditions [86]. The ETP-based assay detected changes in thrombin generation in non-pregnant rats treated with exogenous estrogen compared to controls to examine the direct effect of estrogen on the thrombin generation. A peak of ETP was observed on day 21 of administration compared to the control group. ETP in the administration group showed a significant increase as compared to that of the control group and returned to a similar level as the control group. By contrast, the conventional method did not show a difference in coagulation ability between the rats treated with estrogen and control. This animal experiment may

Other studies have demonstrated changes in thrombin generation, which is measured by an ETP-based method because the conventional method detects a small difference between thrombin generation in pregnant and non-pregnant women. Those studies showed that thrombin generation is significantly enhanced in late pregnancy and on day 1 postpartum compared to non-pregnancy. This observation indicates more directly that the hypercoagulable state can be induced during

The prothrombotic state is regulated by the balance between coagulation and inhibitory factors. This concept has focused on the resistance to the inhibitory regulation of thrombin generation by activated protein C (APC) in studies of OC users [77, 90] because the reduced activity of APC can be associated with an increase in

Like the COC studies, a clinical case report [91] and previous research have shown a significant decrease in sensitivity to APC [87] during the postpartum period. Decreased sensitivity to APC during pregnancy in clinical samples is partially dependent on reduced protein S levels; however, it is difficult to conclude that resistance to APC in pregnancy and the puerperium is associated with the development of pregnancy-related VTE. Although the phenomena of APC resistance may be relevant [87], the sample size measured in the study is too small to judge the impact of the mechanisms in VTE during pregnancy and the puerperium.

Epidemiologic observations have demonstrated that prepregnant obese women

with underlying mechanisms of metabolic syndrome are at increased risk of pregnancy-related adverse outcomes of VTE, HDP, and GDM. Above all, maternal death by pregnancy-related VTE has an impact of great magnitude in the childbearing population. The mechanisms underlying the pathogenesis of VTE remain poorly understood although the overlapping connections among obesity, high estrogen levels, and prothrombotic status are essential keys for expanding knowledge.

simply indicate that estrogen induces a hypercoagulable state [86].

**146**

Motoi Sugimura Department of Obstetrics, Gynecology and Family Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

\*Address all correspondence to: msugimu@hama-med.ac.jp

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