The effect of different hormonal contraceptives on plasma levels of free protein S and free TFPI

Raps, Marjolein; Helmerhorst, Frans M.; Fleischer, Kathrin; Dahm, Anders Erik Astrup; Rosendaal, Frits R.; Rosing, Jan; Reitsma, Pieter H.; Sandset, Per Morten; Vliet, Huib A.A.M. van

doi:10.1160/th12-10-0771

Cited by 22 publications

(7 citation statements)

References 43 publications

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“…Use of combined oral contraceptives is associated with a three-to six-fold increased risk of venous thrombosis. This increased risk depends on the estrogen dose as well as the progestogen type of oral contraceptives [22]. These changes tend to me more pronounced in women taking third generation combined oral contraceptives than on second generation [21].…”

Section: Methodsmentioning

confidence: 99%

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Pre-analytical issues in the haemostasis laboratory: guidance for the clinical laboratories

Magnette¹,

Chatelain²,

Châtelain³

et al. 2016

Thrombosis J

101

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Ensuring quality has become a daily requirement in laboratories. In haemostasis, even more than in other disciplines of biology, quality is determined by a pre-analytical step that encompasses all procedures, starting with the formulation of the medical question, and includes patient preparation, sample collection, handling, transportation, processing, and storage until time of analysis. This step, based on a variety of manual activities, is the most vulnerable part of the total testing process and is a major component of the reliability and validity of results in haemostasis and constitutes the most important source of erroneous or un-interpretable results.Pre-analytical errors may occur throughout the testing process and arise from unsuitable, inappropriate or wrongly handled procedures. Problems may arise during the collection of blood specimens such as misidentification of the sample, use of inadequate devices or needles, incorrect order of draw, prolonged tourniquet placing, unsuccessful attempts to locate the vein, incorrect use of additive tubes, collection of unsuitable samples for quality or quantity, inappropriate mixing of a sample, etc. Some factors can alter the result of a sample constituent after collection during transportation, preparation and storage.Laboratory errors can often have serious adverse consequences. Lack of standardized procedures for sample collection accounts for most of the errors encountered within the total testing process. They can also have clinical consequences as well as a significant impact on patient care, especially those related to specialized tests as these are often considered as “diagnostic”. Controlling pre-analytical variables is critical since this has a direct influence on the quality of results and on their clinical reliability. The accurate standardization of the pre-analytical phase is of pivotal importance for achieving reliable results of coagulation tests and should reduce the side effects of the influence factors. This review is a summary of the most important recommendations regarding the importance of pre-analytical factors for coagulation testing and should be a tool to increase awareness about the importance of pre-analytical factors for coagulation testing.

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Section: Methodsmentioning

confidence: 99%

“…containing desogestrel, cyproterone acetate or drospirenone), have lower levels of PS and TFPI than women using the combined oral contraceptive with the lowest risk of venous thrombosis (i.e. contraceptives containing levonorgestrel) [22, 23]. …”

Section: Methodsmentioning

confidence: 99%

Pre-analytical issues in the haemostasis laboratory: guidance for the clinical laboratories

Magnette¹,

Chatelain²,

Châtelain³

et al. 2016

Thrombosis J

101

View full text Add to dashboard Cite

show abstract

“…It has recently been reported that patients receiving such drugs have increased levels of free protein S and free tissue factor pathway inhibitor (TFPI), which are the two main determinants acquired resistance to activated protein C (APC), suggesting that VTE can be caused via this pathway [53] .…”

Section: Discussionmentioning

confidence: 99%

Hormonal contraceptives and venous thromboembolism: Are inflammatory bowel disease patients at increased risk? A retrospective study on a prospective database

Pellino

Sciaudone

Caprio

et al. 2015

Annals of Medicine &Amp; Surgery

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Recent studies showed an increased risk of venous thromboembolism (VTE) in patients receiving oral hormonal contraceptives. Inflammatory bowel diseases (IBD) often affect young patients and represent a pro-coagulant condition. This could result from active inflammation, but a potential role for genetic and molecular factors has been suggested. Hormonal contraceptives have also been associated with increased risk of VTE and the risk may be greater in IBD patients that already are in a pro-coagulant status, but no definitive data are available in this population. The purpose of our study was to seek for differences of the risk of VTE in IBD patients receiving hormonal contraceptives compared with controls.This is a retrospective study. We interrogated a prospectively maintained database of IBD patients observed at our outpatient clinic between 2000 and 2014. All female patients managed conservatively, with no active disease, who were taking oral hormone contraceptives in the study period, were included. Patients observed for other-than-IBD conditions at our Unit and at the Unit of Gynaecology and Obstetrics, receiving contraceptives, served as controls (ratio 1:2). Patients with cancer, those receiving hormonal therapy, and those with known genetic predisposition to VTE were excluded.We included 146 six IBD patients and 290 controls. One patient in each group developed VTE. Overall, the incidence of VTE associated with oral contraceptives was 0.5%. IBD was associated with increased risk of VTE (OR 1.9, 95% CI 0.12–32.12, p > 0.99). Active smokers since 10 years (17.2%) had higher risks of VTE (OR 8.6, 95% CI 1.16–19.25, p = 0.03).Our data show that patients with IBD in remission are not at higher risk of VTE due to oral oestrogen-containing contraceptives compared with non-IBD controls. Smokers are at increased risk, irrespective of the baseline disease.

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“…Women have lower levels of plasma full length TFPI compared with men and in women the use of oral contraceptives is associated with a further reduction in full length TFPI by 25–45 [ 16 – 19 ]. The minimum sample size to detect a difference of 20% in platelet TFPI between at least two groups with a confidence level of 95% and a power of 0.80 is 9 for each group.…”

Section: Methodsmentioning

confidence: 99%

Platelet full length TFPI-α in healthy volunteers is not affected by sex or hormonal use

et al. 2017

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BackgroundOnly 10% of plasma TFPIα (TFPI) exists in the full length form, the rest circulates as a C-terminally truncated form. However, blood platelets exclusively contain full length TFPI, which is released at the site of injury upon platelet activation, and which could play an important local regulatory role in thrombin generation and prevention of thrombosis.MethodsThe anticoagulant activities of full length and truncated TFPI were investigated using thrombin generation assays. Blood samples were obtained from 30 healthy volunteers (10 male subjects, 10 female subjects, and 10 females using oral contraceptives). Platelet TFPI was released in platelet rich plasma and in platelet isolates using convulxin or thrombin, and measured by free TFPI ELISA and thrombin generation assays.ResultsFull length TFPI and platelet TFPI were much more potent inhibitors of thrombin generation than truncated TFPI, which was virtually inactive. Although mean plasma TFPI antigen levels decreased from men (0.30 nM) to women (0.20 nM) to women using oral contraceptives (0.11 nM), no relevant differences were found in platelet TFPI among those subgroups.ConclusionsPlatelets release similar amounts of TFPI regardless of plasma TFPI concentrations and is unaffected by sex or oral contraceptive use. We speculate that platelet TFPI is important to prevent systemic coagulation and thrombosis and restrict thrombus formation to the site of the growing platelet plug. The stable contribution of platelet TFPI to the anticoagulant potential in plasma is likely to become particularly relevant under conditions of low plasma TFPI levels in combination of oral contraceptives use.

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The effect of different hormonal contraceptives on plasma levels of free protein S and free TFPI

Cited by 22 publications

References 43 publications

Pre-analytical issues in the haemostasis laboratory: guidance for the clinical laboratories

Pre-analytical issues in the haemostasis laboratory: guidance for the clinical laboratories

Hormonal contraceptives and venous thromboembolism: Are inflammatory bowel disease patients at increased risk? A retrospective study on a prospective database

Platelet full length TFPI-α in healthy volunteers is not affected by sex or hormonal use

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