Tissue factor–dependent thrombin generation across pregnancy

Abstract

Objectives Normal pregnancy results in a pro-thrombotic state. Studies investigating the capacity of pregnant women to generate thrombin are limited. Our aim was to longitudinally evaluate thrombin generation from the pre-conception period, through pregnancy, and post-pregnancy. Study Design We evaluated young, healthy nulligravid women, n= 20, at 4 time points and compared them to 10 control women at 2 time points. Coagulation was initiated in contact pathway inhibited plasma, and thrombin generation was determined in the presence of a fluorogenic substrate. Results The maximum level and rate of thrombin generation increased during pregnancy, with the highest level and rate occurring in late pregnancy compared to pre-pregnancy (p<0.001). Subsequently, thrombin generation decreased in the post-pregnancy samples, including maximum level, rate, and area under the curve (AUC) (p<0.001). Conclusions Our data provide evidence for an increase in tissue factor-dependent thrombin generation with pregnancy progression, followed by a return to pre-pregnancy thrombin levels.

The Dynamics of the Hemo- static Parameters in Physio- logical Pregnancy and After Delivery

“…In this regard, our data do not contradict to previously published results by other authors devoted to the assessment of peculiarities of thrombin generation test during pregnancy [8,48,49]. The test for the assessment of disposable thrombography records the final result of the complex interaction of enzymes involving in blood coagulation.…”

“…As a strong initiator of coagulation TF, predominantly of placental origin [43,44], leads to thrombosis of vessels quickly to stop bleeding in women during delivery. It is very important since massive bleeding might occur in placental bloodstream 700 ml/min -1 because of coagulation system failure [8]. At the same time, the reasonability of the significant increase of the parameter as well as Factor VIIa level from 12-13 weeks of pregnancy compared to nonpregnant women is not clear in our study since delivery and consequently limitation of the extent of blood loss in the first half of pregnancy are not programmed by nature.…”

“…In the study the following equipment was used: Hematology Analyzer MEK-7222 J/K [1] (Nihon Kohden); оptical aggregometer AggRAM [2] (Helena Laboratories); semi-automated coagulometers Helena C-1 [3] (Helena Laboratories) and Start 4 [4] (Stago); automated coagulometers-STA Compact [5] (Stago) and Sysmex CA-1500 [6] (Sysmex Corporation); microplate fluorometer Fluoroskan Ascent [7] (Thermo Fisher SCIENTIFIC) with software «Thrombinoscope 3.0.0.26»; immunochemical analyzer-IMMULITE 2000 [8] (Siemens Healthcare Diagnostics); photometers-spectrophotometer Photometr 5010 v5+ [9] (Robert Riele GmbH & Co KG) and microplate reader Bio-Rad 680 [10] (Bio-Rad Laboratories); express analyzer (reflectometer) NycoCard Rider II [11] (Axis Shield).…”

Integrated laboratory coagulation tests in hypercoagulation diagnosis and thrombosis risk assessment. Part II. The sensitivity of integral tests to hypercoagulable states

“…ЭТП повышен практически при любых видах тромбофилии, включая полиморфизм G20210A [32], дефицит антитромбина [33], V Leiden [34] (с добавле-нием aPC), дефицит протеина S [35] (с добавлением aPC), а также при приеме оральных контрацептивов (с добавлением aPC) [36] и онкологических заболева-ниях [37]. В работах [38,39] ЭТП был повышен при бе-ременности, но в [40] ЭТП возрастал в I триместре относительно нормы и далее держался постоянным в течение всего срока беременности, в то время как маркеры активации свертывания D-димеры, F1 + 2 и TAT возрастали. Корреляция между параме-трами ЭТП и D-димерами, F1 + 2, TAT, РФМК отсут-ствовала.…”

The Dynamics of the Hemostatic Parameters in Physiological Pregnancy and After Delivery

“…Despite a large number of scientific publications devoted to the peculiarities of changes in hemocoagulation during pregnancy [6][7][8][9], there are unsolved problems today. The problems are that in practice the laboratory parameters of the hemostatic system in pregnant women are generally related to the intervals of allowed values of the panel of hemostatic parameters determined for nonpregnant women that do not allow making grounded clinical decisions [9].…”