Comparative assessment of changes ADAMTS-13/von Willebrand factor axis in singleton and bichorial biamniotic pregnancy
https://doi.org/10.17749/2313-7347/ob.gyn.rep.2024.538
Abstract
Aim: to compare changes in the ADAMTS-13 metalloproteinase/von Willebrand factor (vWF) axis in pregnant women with spontaneous or following in vitro fertilization (IVF) singleton and bichorial biamniotic pregnancies.
Materials and Methods. A prospective observational randomized controlled trial was conducted. The examination data of pregnant women with singleton (group 1, n = 34) and multiple bichorial biamniotic spontaneous pregnancies (group 2, n = 17), and with singleton (group 3, n = 34) and multiple bichorial biamniotic pregnancies (group 4, n = 34) following reproductive technologies were analyzed. The studied parameters included quantitation of ADAMTS-13 antigen (ADAMTS-13:Ag), ADAMTS-13 activity (ADAMTS-13:Ac) and vWF antigen (vWF: Ag) by chromogenic enzyme immunoassay.
Results. A progressive increase in the vWF:Ag level has been revealed that was proportional to escalating gestational age and a decrease in ADAMTS-13:Ag level from the second trimester of physiological non-induced pregnancy, more profound during twin pregnancy (p < 0.001). In induced pregnancy, vWF:Ag level increased, ADAMTS-13:Ag - decreased starting from 6-7 weeks of gestation (p < 0.001), more prominent in twin pregnancy (p < 0.001). The ADAMTS-13 activity in induced single and multiple pregnancies did not differ significantly by trimester but was lower compared with non-induced pregnancies of matched timeframe. The most pronounced decrease in the ADAMTS-13:Ag/vWF:Ag ratio was observed in multiple induced pregnancies.
Conclusion. Stimulation of superovulation and subsequent embryo transfer into the uterine cavity is accompanied by higher procoagulant vascular endothelium properties, vWF release, which activates platelets and the coagulation cascade from the early stages of induced pregnancy. vWF hyperreactivity is compensated by the expenditure of ADAMTS-13, which level declines dramatically during twin pregnancy creating conditions for disruption of hemostasis gestational adaptation and increases a risk of thrombotic complications and obstetric pathology.
About the Authors
F. Е. YagubovaRussian Federation
Fidan E. Yagubova - MD.
8 bldg. 2, Trubetskaya Str., Moscow 119991
V. O. Bitsadze
Russian Federation
Victoria O. Bitsadze - MD, Dr Sci Med, Prof., Professor of RAS.
8 bldg. 2, Trubetskaya Str., Moscow 119991
Scopus Author ID 6506003478; WoS ResearcherID F-8409-2017
N. V. Samburova
Russian Federation
Natalia V. Samburova - MD, PhD.
8 bldg. 2, Trubetskaya Str., Moscow 119991
Scopus Author ID 57208129705
J. Kh. Khizroeva
Russian Federation
Jamilya Kh. Khizroeva - MD, Dr Sci Med, Prof.
8 bldg. 2, Trubetskaya Str., Moscow 119991
Scopus Author ID 57194547147; WoS ResearcherID F-8384-2017
A. D. Makatsariya
Russian Federation
Alexander D. Makatsariya - MD, Dr Sci Med, Prof., Academician of RAS.
8 bldg. 2, Trubetskaya Str., Moscow 119991
Scopus Author ID 57222220144; WoS ResearcherID M-5660-2016
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What is already known about this subject?
► Elevated level of von Willebrand factor (vWF) is an important thrombosis risk factor. ADAMTS-13 metalloproteinase cleaves ultralarge vWF molecules and lowers its thrombo-
genicity.
► During pregnancy, vWF level increases significantly in the second and third trimesters, ADAMTS-13 antigen (ADAMTS-13:Ag) level decreases starting from the second trimester, staying within the reference range even in the third trimester.
► During in vitro fertilization (IVF), hormonal stimulation increases vWF level and activity accompanied by decreased circulating ADAMTS-13:Ag level.
What are the new findings?
► The chronological sequence of hemostasis gestational adaptation is disrupted by using hormonal ovulation stimulation in IVF programs.
► In twin pregnancy after IVF, vWF level even in the first trimester was 2-fold higher than for non-pregnant women and was significantly higher than the corresponding values in patients with singleton pregnancy after IVF and spontaneous multiple pregnancy.
► A decline in ADAMTS-13:Ag level was observed also from early pregnancy; in bichorial biamniotic pregnancy, the parameter in the first trimester was up to 2-fold lower than that before the onset of ovulation stimulation.
How might it impact on clinical practice in the foreseeable future?
► Increase in vWF:Ag, decrease in ADAMTS-13:Ag and disturbance of ADAMTS-13/vWF axis can be used as predictors of gestational adaptation failure and development of gestational and thrombotic complications in multiple pregnancy resulting from applying assisted reproductive technologies (ART).
► Multiple pregnancy after IVF should be considered as a pregnancy with the top risk of gestational adaptation disruption, and discuss an issue of timing for using antithrombotic prophylactic agents.
Review
For citations:
Yagubova F.Е., Bitsadze V.O., Samburova N.V., Khizroeva J.Kh., Makatsariya A.D. Comparative assessment of changes ADAMTS-13/von Willebrand factor axis in singleton and bichorial biamniotic pregnancy. Obstetrics, Gynecology and Reproduction. 2024;18(4):514-524. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2024.538

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