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Pregnancy predisposes to thrombotic hemostasis, reflected in the laboratory as, e.g., increased levels of D-Dimers and fibrinogen, but in physiological pregnancy, the risk of venous thrombosis does not increase. Risk may increase if gestational diabetes mellitus (GDM) or nicotinism coexists. Study aims were to determine reference values for D-Dimers and fibrinogen concentrations in each trimester of pregnancy, corrected for GDM and nicotinism. Subjects and Methods . The study involved 71 pregnant women aged 25-44 y. Venous blood was collected three times: in the first (11-14 weeks), second (20-22 weeks), and third (30-31 weeks) trimesters. D-Dimer concentrations were determined by an enzyme-linked fluorescence assay, fibrinogen concentrations by a coagulation method according to Clauss. Results . Significant increases in D-Dimers and fibrinogen concentrations were observed, increasing with successive trimesters ( p  ANOVA < 0.0001). Furthermore, a positive correlation between D-Dimers and fibrinogen was detected in the second trimester of pregnancy ( r = 0.475; p < 0.0001). In addition, a significantly higher fibrinogen concentration was found in women with GDM compared to without GDM ( p = 0.0449). Reference ranges for D-Dimers were established, in trimester order, as follows: 167-721 ng/mL, 298-1653 ng/mL, and 483-2256 ng/mL. After adjusting for risk factors, significantly higher D-Dimer values (mainly second and third trimesters) were obtained: 165-638 ng/mL, 282-3474 ng/mL, and 483-4486 ng/mL, respectively. Reference ranges for fibrinogen were, in trimester order, 2.60-6.56 g/L, 3.40-8.53 g/L, and 3.63-9.14 g/L and, after adjustment for risk factors, 3.34-6.73 g/L, 3.40-8.84 g/L, and 3.12-9.91 g/L. Conclusions . We conclude that the increase in D-Dimers and fibrinogen levels in women with physiological pregnancy was compounded by gestational diabetes (GDM) and nicotinism. Therefore, D-Dimers and fibrinogen pregnancy reference values require correction for these risk factors., Competing Interests: The authors declare no conflicts of interest with respect to this research., (Copyright © 2020 Aldona Siennicka et al.)