Comparison of factor XII levels in gestational diabetes, fetal macrosomia, and healthy pregnancies

Esra Ozbasli, Ozguc Takmaz, Emine Karabuk, Mete Gungor, Esra Ozbasli, Ozguc Takmaz, Emine Karabuk, Mete Gungor

Abstract

Background: If not detected and treated, gestational diabetes mellitus (GDM) can cause serious pregnancy complications such as macrosomia, preeclampsia, and fetal/neonatal mortality. Many studies have examined underlying contributing factors for GDM, including hypercoagulation. Factor XII (FXII) is a coagulation factor that increases throughout normal pregnancies, and we evaluated the relationship of GDM with FXII, FXIIa (activated FXII), and other coagulation parameter levels. GDM and macrosomia are closely related, but it is not known whether FXII could be an independent causal factor for macrosomia.

Methods: In this prospective study, blood samples were taken from 69 pregnant women at the time of term delivery to determine levels of FXII, FXIIa, and other coagulation parameters. Based on the results, pregnancies fell into GDM, non-diabetic with macrosomia (M), or healthy (C [control]).

Results: FXII concentration levels were significantly higher in GDM patients compared with the M and C groups. There were no significant differences when comparing FXIIa, activated partial thromboplastin time, prothrombin time (PT), and international normalized ratio. The GDM group saw a significant negative correlation between FXII concentrations and maternal pregestational body mass index (BMI) and BMI before delivery. In the M group, a positive correlation was observed between FXII concentrations and newborn weight and newborn weight percentile.

Conclusions: An increase in FXII levels was observed in patients with gestational diabetes. Associations between coagulation parameters and GDM should be further analyzed to define the mechanisms of GDM and possible treatment modalities.

Trial registration: Our study has been registered at clinicaltrials.gov ( NCT03583216 ). Registered on July 11, 2018.

Keywords: factor XII; gestational diabetes; pregnancy.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patient flow chart from recruitment to study completion
Fig. 2
Fig. 2
ROC Curve of gestational diabetes mellitus for prediction of high/low levels of FXII

References

    1. Coustan DR. Gestational diabetes mellitus. Clin Chem. 2013;59:1310–21. doi: 10.1373/clinchem.2013.203331.
    1. Deputy NP, Kim SY, Conrey EJ, Bullard KM. Prevalence and changes in preexisting diabetes and gestational diabetes among women who had a live birth - United States, 2012–2016. MMWR Morb Mortal Wkly Rep. 2018;67:1201–7. doi: 10.15585/mmwr.mm6743a2.
    1. Zhu Y, Zhang C. Prevalence of gestational diabetes and risk of progression to Type 2 diabetes: a global perspective. Curr Diab Rep. 2016;16:7. doi: 10.1007/s11892-015-0699-x.
    1. Hussain SA, Smith AM, Cross JA. Diabetes, fetal demise, and shoulder dystocia: the importance of glucose screening to prevent catastrophic obstetric outcomes. Case Rep Obstet Gynecol. 2020;2020:8142109.
    1. Gallimore MJ, Harris SL, Jones DW, Winter M. Plasma levels of factor XII, prekallikrein and high molecular weight kininogen in normal blood donors and patients having suffered venous thrombosis. Thromb Res. 2004;114:91–6. doi: 10.1016/j.thromres.2004.05.005.
    1. Teliga-Czajkowska J, Sienko J, Zareba-Szczudlik J, Malinowska-polubiec A, Romejko-Wolniewicz E, Czajkowski K. Influence of glycemic control on coagulation and lipid metabolism in pregnancies complicated by pregestational and gestational diabetes mellitus. Adv Exp Med Biol. 2019;1176:81–8. doi: 10.1007/5584_2019_382.
    1. Barillari G, Fabbro E, Pasca S, Bigotto E. Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population. Blood Coagul Fibrinolysis. 2009;20:290–6. doi: 10.1097/MBC.0b013e328329e49b.
    1. Carr ME. Diabetes mellitus. J Diabetes Complications. 2001;15:44–54. doi: 10.1016/S1056-8727(00)00132-X.
    1. O’Riordan MN, Higgins JR. Haemostasis in normal and abnormal pregnancy. Best Pract Res Clin Obstet Gynaecol. 2003;17:385–96. doi: 10.1016/S1521-6934(03)00019-1.
    1. Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol. 1982;144:768–73. doi: 10.1016/0002-9378(82)90349-0.
    1. Renné T, Schmaier AH, Nickel KF, Blombäck M, Maas C. In vivo roles of factor XII. Blood. 2012;120:4296–303. doi: 10.1182/blood-2012-07-292094.
    1. Kenne E, Nickel KF, Long AT, Fuchs TA, Stavrou EX, Stahl FR, et al. Factor XII: a novel target for safe prevention of thrombosis and inflammation. J Intern Med. 2015;278:571–85. doi: 10.1111/joim.12430.
    1. Patrassi GM, Vettor R, Padovan D, Girolami A. Contact phase of blood coagulation in diabetes mellitus. Eur J Clin Invest. 1982;12:307–11. doi: 10.1111/j.1365-2362.1982.tb02237.x.
    1. Cool DE, Edgell CJS, Louie GV, Zoller MJ, Brayer GD, MacGillivray RT. Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of β-factor XIIa. J Biol Chem. 1985;260:13666–76.
    1. Schmeidler-Sapiro KT, Ratnoff OD, Gordon EM. Mitogenic effects of coagulation factor XII and factor XIIa on HepG2 cells. Proc Natl Acad Sci U S A. 1991;88:4382–5. doi: 10.1073/pnas.88.10.4382.
    1. Xu Y, Cai TQ, Castriota G, Zhou Y, Hoos L, Jochnowitz N, et al. Factor XIIa inhibition by Infestin-4: in vitro mode of action and in vivo antithrombotic benefit. Thromb Haemost. 2014;111:694–704. doi: 10.1160/TH13-08-0668.
    1. Kolyadko VN, Lushchekina SV, Vuimo TA, Surov SS, Ovsepyan RA, Korneeva VA, et al. New Infestin-4 mutants with increased selectivity against Factor XIIa. PLOS ONE. 2015;10:e0144940. doi: 10.1371/journal.pone.0144940.
    1. Duryea EL, Hawkins JS, McIntire DD, Casey BM, Leveno KJ. A revised birth weight reference for the United States. Obstet Gynecol. 2014;124:16–22. doi: 10.1097/AOG.0000000000000345.
    1. Lemkes BA, Hermanides J, Devries JH, Holleman F, Meijers JCM, Hoekstra JBL. Hyperglycemia: A prothrombotic factor? J Thromb Haemost. 2010;8:1663–9. doi: 10.1111/j.1538-7836.2010.03910.x.
    1. Briseid K, Hoem N-O, Johannesen S, Fossum S. Contact activation factors in plasma from pregnant women–increased level of an association between factor XII and kallikrein. Thromb Res. 1991;61:123–33. doi: 10.1016/0049-3848(91)90239-S.
    1. Hron G, Eichinger S, Weltermann A, Quehenberger P, Halbmayer WM, Kyrle PA. Prediction of recurrent venous thromboembolism by the activated partial thromboplastin time. J Thromb Haemost. 2006;4:752–6. doi: 10.1111/j.1538-7836.2006.01868.x.
    1. Lippi G, Franchini M, Targher G, Montagnana M, Salvagno GL, Guidi GC, et al. Epidemiological Association between fasting plasma glucose and shortened APTT. Clin Biochem. 2009;42:118–20. doi: 10.1016/j.clinbiochem.2008.10.012.
    1. Gorar S, Alioglu B, Ademoglu E, Uyar S, Bekdemir H, Candan Z, et al. Is there a tendency for thrombosis in gestational diabetes mellitus? J Lab Phys. 2016;8:101–5.
    1. Weitz JI. Factor XI and factor XII as targets for new Anticoagulants. Thromb Res. 2016;141:40-5. doi: 10.1016/S0049-3848(16)30363-2.

Source: PubMed

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