Response to activated protein C during normal menstrual cycle and ovarian stimulation

SummaryIncreased serum levels of endogenous as well as exogenous estrogen are regarded to be responsible for acquired activated protein C (APC) resistance. It was the objective of this study to evaluate whether the physiological increase in serum estradiol concentration during the normal menstrual cycle affects the individual’s sensitivity to APC. Seventy-two women with normal menstrual cycles were included in the study. Blood samples for analysis of estradiol (E2), progesterone (P4) and APC resistance were drawn at two time points of the menstrual cycle (day 3–5 and day 22–25). Two methods of measuring APC resistance were used: the activated partial thromboplastin time (aPTT)-based assay and the endogenous thrombin potential (ETP)-based APC resistance test. Independent of the method used, no changes in APC resistance were found, even though the E2 concentration increased significantly between the two menstrual phases. No correlations between E2 levels and APC resistance, P4 levels and APC resistance or changes in E2 concentrations and changes in APC resistance were detected. Ten women were carriers of the factor VLeiden mutation. Their baseline APC resistance was increased, but their response to elevated E2 during the menstrual cycle did not differ from that of non-carriers. In conclusion, our observations suggest that physiological differences in serum levels of estradiol and progesterone between the early follicular and the luteal phase in a normal menstrual cycle do not have any significant impact on the individual’s sensitivity to APC.

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EVALUATION OF ACTIVATED PROTEIN C RESISTANCE IN WOMEN UNDERGOING OVARIAN STIMULATION PRIOR IN-VITRO FERTILIZATION.

10.26226/morressier.615c7f2662ba8657678b0a2b ◽

2021 ◽

Author(s):

Morimont Laure

Keyword(s):

In Vitro Fertilization ◽

Ovarian Stimulation ◽

Protein C ◽

Activated Protein C ◽

Activated Protein C Resistance ◽

Vitro Fertilization

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Sensitivity to activated protein C during the menstrual cycle in women with and without factor VLeiden

Thrombosis Research ◽

10.1016/j.thromres.2007.08.010 ◽

2008 ◽

Vol 121 (6) ◽

pp. 757-761 ◽

Cited By ~ 6

Author(s):

Huib A.A.M. van Vliet ◽

Sharon P. Rodrigues ◽

Marieke N.E. Snieders ◽

Felix J.M. van der Meer ◽

Marijke Frolich ◽

...

Keyword(s):

Menstrual Cycle ◽

Protein C ◽

Activated Protein C

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Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation

Frontiers in Endocrinology ◽

10.3389/fendo.2021.613048 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sophie Fischer ◽

Rainald Ehrig ◽

Stefan Schäfer ◽

Enrico Tronci ◽

Toni Mancini ◽

...

Keyword(s):

Mathematical Modeling ◽

Menstrual Cycle ◽

Ovarian Stimulation ◽

Time Course ◽

Scientific Evidence ◽

Coupled Model ◽

Continuous Growth ◽

Time Points ◽

Follicular Waves ◽

Normal Menstrual Cycle

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts (“waves”) of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.

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Measurement of Activated Protein C Resistance during Menstrual Cycle in Women with and without the Leiden Mutation

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615642 ◽

2001 ◽

Vol 85 (04) ◽

pp. 614-618 ◽

Cited By ~ 1

Author(s):

K. Bremme ◽

M. Blombäck ◽

M. L. Wramsby

Keyword(s):

Menstrual Cycle ◽

Luteal Phase ◽

Protein C ◽

Activated Protein C ◽

Factor V ◽

Activated Protein C Resistance ◽

Blood Samples ◽

Plasma Methods

SummaryVariations in the APC ratio during the menstrual cycle were assessed in 25 women without the Leiden mutation, and 10 women who were carrier of the mutation. Blood samples were collected at four occasions during one menstrual cycle. APC ratios were measured with two APTT based plasma methods with and without factor V depleted plasma.None of the methods were able to accurately discriminate between mutated and non mutated women in all samples. Although a normalized method with factor V depleted plasma was favorable.The levels of estradiol and progesterone did not differ between mutated and non mutated women.Our findings suggest that the level of estradiol at estimated time of ovulation is of importance for the response to APC during luteal phase, since the women exhibiting the highest levels of estradiol at time for ovulation had the lowest response to APC.

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Activated protein C: the cure for sepsis - again?

Anaesthesia ◽

10.1046/j.1365-2044.2001.02441.x ◽

2001 ◽

Vol 56 (12) ◽

pp. 1133-1135 ◽

Cited By ~ 1

Author(s):

Tariq Hoth ◽

Timothy W. Evans

Keyword(s):

Protein C ◽

Activated Protein C

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Coagulation Factor V Leiden Mutation Was Detected in the Patients with Activated Protein C Resistance in Thailand

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615201 ◽

1998 ◽

Vol 80 (08) ◽

pp. 344-345 ◽

Cited By ~ 2

Author(s):

Pasra Arnutti ◽

Motofumi Hiyoshi ◽

Wichai Prayoonwiwat ◽

Oytip Nathalang ◽

Chamaiporn Suwanasophon ◽

...

Keyword(s):

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Coagulation Factor ◽

Factor V ◽

Activated Protein C Resistance ◽

Factor V Leiden Mutation ◽

Coagulation Factor V

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APC Resistance and other Haemostatic Variables during Pregnancy and Puerperium

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614518 ◽

1999 ◽

Vol 81 (04) ◽

pp. 527-531 ◽

Cited By ~ 114

Author(s):

U. Kjellberg ◽

N.-E. Andersson ◽

S. Rosén ◽

L. Tengborn ◽

M. Hellgren

Keyword(s):

Factor Viii ◽

Plasminogen Activator ◽

Protein C ◽

Activated Protein C ◽

Plasminogen Activator Inhibitor ◽

Protein S ◽

Reference Level ◽

Soluble Fibrin ◽

Prothrombin Fragment ◽

D Dimer

SummaryForty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type 1 and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

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Dermatan Sulfate and LMW Heparin Enhance the Anticoagulant Action of Activated Protein C

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614856 ◽

1999 ◽

Vol 82 (11) ◽

pp. 1462-1468 ◽

Cited By ~ 22

Author(s):

José Fernández ◽

Jari Petäjä ◽

John Griffin

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Protein C ◽

Dermatan Sulfate ◽

Anticoagulant Activity ◽

Activated Protein C ◽

Factor V ◽

Factor Va ◽

Anticoagulant Action

SummaryUnfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

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