RESUMO
Background During pregnancy, a physiological increase of molecular activation markers (MAM) of hemostasis such as prothrombin fragments 1 + 2, thrombin-antithrombin complex, and D-dimers (DD) occurs. Therefore, monitoring MAM levels during pregnancy to evaluate the risk of venous thromboembolism (VTE) may be unreliable; nevertheless, DD analysis in pregnancy is widely performed. In contrast to DD, fibrin monomer (FM) levels have been reported to remain stable during pregnancy. Objectives The main aim of this study was to define the expected range for FM levels in pregnant outpatients. In addition, we examined the impact of the individual VTE risk, as calculated by the pregnancy risk score of the Royal College of Obstetricians and Gynaecologists (RCOG), as well as that of antithrombotic treatment on FM levels. Methods A total of 342 pregnant women seen at our hemostasis unit were included throughout 350 pregnancies in 899 samples. Results Low-risk thrombophilia, but not the RCOG score itself, was found to influence all MAM levels, whereas antithrombotic treatment had only an impact on DD. For FM, a reference range could be calculated irrespective of the pregnancy term, in contrast to other MAMs, which fluctuated throughout pregnancy. Conclusions Our findings suggest a stronger impact of inherited thrombophilia on hemostasis activity during pregnancy as compared with acquired or other predisposing thrombophilic risk factors. FM levels showed a marginal increase during pregnancy in contrast to other MAM and remain a potential candidate to improve the laboratory assessment of VTE risk during pregnancy. Further prospective studies in pregnant patients with suspicion of VTE are needed.
RESUMO
Mild factor XIII deficiency is an underdiagnosed coagulation disorder. Considering the large number of coding and non-coding polymorphisms identified in the F13A1 gene, there is a possibility that some of these might result in alterations of plasma FXIII levels and cause mild FXIII deficiency. Recently, a homozygous F13A1 gene intron 1 variant (IVS1+12C>A) was found in a patient with FXIII deficiency. In vitro expression studies for this variant demonstrated its lowering effect on FXIII levels. In order to determine the impact of this variant on a population level, we analysed the prevalence of this variant in three clinically and genetically defined population cohorts: an apparently healthy control cohort C1 (n = 102), a mild FXIII deficiency cohort C2 with no detectable F13A1 or F13B gene mutations (n = 183) and a mild FXIII-A deficiency cohort C3 exhibiting heterozygous F13A1 mutations (n = 37). FXIII activity was determined using photometric assay on plasma samples. The F13A1 gene intron 1 variant was analysed by direct sequencing. The C1 cohort showed a normal distribution of FXIII activity (mean 114.1 ± 20.86%). Mean FXIII activity levels for the C2 and C3 cohorts were 54.45 ± 11.12% and 44.21 ± 10.16%, respectively. The frequencies of minor allele (A) were 0.07 in C1 cohort, 0.19 in C2 cohort and 0.11 in C3 cohort. The difference in minor allele frequencies for the C1 and C2 cohorts were highly significant (p < 0.001). The greater frequency of the IVS1+12(A) variant among C2 cohort patients suggests that this polymorphism is associated with mild FXIII deficiency.