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
Protein C (PC) deficiency is associated with an increased risk for venous thromboembolism (VTE). In daily practice, exclusion of a hereditary PC deficiency is often based on a single determination of PC activity, by either clotting time-based or mostly chromogenic assay. However, diagnosis of hereditary PC deficiency is challenging due to several laboratory and clinical limitations. We compared the potential of PC activity values measured by either chromogenic or clotting time-based assay to predict a variation in the PROC gene. One hundred one (35%) of 287 patients carried variations within the PROC gene, including 2 previously not published variations. In 20 (20%) patients with identified variation, PC activity, determined by chromogenic assay, was within the reference range. For prediction of an underlying genetic defect determined by chromogenic and clotting time-based assay, sensitivity was 80% versus 99%, specificity 75% versus 18%, positive predictive value 64% versus 39%, and negative predictive value (NPV) 88% versus 97%. The lower NPV of chromogenic versus clotting time-based PC assay can be mainly explained by the presence of PC deficiency type IIb. Following our proposed diagnostic algorithm, additional measurement of PC activity by clotting time-based assay in case of a positive VTE history improves detection of this subtype of PC deficiency. Considering potential therapeutic consequences for primary and especially for secondary VTE prophylaxis, genetic analysis is required not only for confirmation but also for clarification of PC deficiency.