scholarly journals Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk

2021 ◽  
Vol 12 ◽  
Author(s):  
Laure Morimont ◽  
Hélène Haguet ◽  
Jean-Michel Dogné ◽  
Ulysse Gaspard ◽  
Jonathan Douxfils
Keyword(s):  
Venous Thromboembolism ◽  
Oral Contraceptives ◽  
Health Care Professionals ◽  
Contraceptive Method ◽  
Natural Form ◽  
Thrombotic Risk ◽  
Combined Oral Contraceptives ◽  
Hereditary Thrombophilia ◽  
Increased Risk ◽  
The Impact

Many factors must be considered and discussed with women when initiating a contraceptive method and the risk of venous thromboembolism (VTE) is one of them. In this review, we discuss the numerous strategies that have been implemented to reduce the thrombotic risk associated with combined oral contraceptives (COCs) from their arrival on the market until today. Evidences suggesting that COCs were associated with an increased risk of VTE appeared rapidly after their marketing. Identified as the main contributor of this risk, the dosage of the estrogen, i.e., ethinylestradiol (EE), was significantly reduced. New progestins were also synthetized (e.g., desogestrel or gestodene) but their weak androgenic activity did not permit to counterbalance the effect of EE as did the initial progestins such as levonorgestrel. Numerous studies assessed the impact of estroprogestative combinations on hemostasis and demonstrated that women under COC suffered from resistance towards activated protein C (APC). Subsequently, the European Medicines Agency updated its guidelines on clinical investigation of steroid contraceptives in which they recommended to assess this biological marker. In 2009, estradiol-containing COCs were marketed and the use of this natural form of estrogen was found to exert a weaker effect on the synthesis of hepatic proteins compared to EE. In this year 2021, a novel COC based on a native estrogen, i.e., estetrol, will be introduced on the market. Associated with drospirenone, this preparation demonstrated minor effects on coagulation proteins as compared with other drospirenone-containing COCs. At the present time, the standard of care when starting a contraception, consists of identifying the presence of hereditary thrombophilia solely on the basis of familial history of VTE. This strategy has however been reported as poorly predictive of hereditary thrombophilia. One rationale and affordable perspective which has already been considered in the past could be the implementation of a baseline screening of the prothrombotic state to provide health care professionals with objective data to support the prescription of the more appropriate contraceptive method. While this strategy was judged too expensive due to limited laboratory solutions, the endogenous thrombin potential-based APC resistance assay could now represent an interesting alternative.

scholarly journals American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate intensity anticoagulation in critically ill patients

2021 ◽  
Author(s):  
Adam Cuker ◽  
Eric K. Tseng ◽  
Robby Nieuwlaat ◽  
Pantep Angchaisuksiri ◽  
Clifton Blair ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Health Care Professionals ◽  
Conflicts Of Interest ◽  
Guideline Development ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
American Society ◽  
The Impact

Background: COVID-19 related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel, including three patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 5, 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. Results: The panel agreed on one additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19 related-critical illness who do not have confirmed or suspected VTE. Conclusions: This recommendation was based on low certainty in the evidence, underscoring the need for further high-quality, randomized controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence on predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of non-anticoagulant therapies (e.g., antiviral agents, corticosteroids) on thrombotic risk.

scholarly journals Venous thromboembolism and oral contraception

2010 ◽  
Vol 63 (5-6) ◽  
pp. 376-379 ◽  
Author(s):  
Milena Veljkovic ◽  
Jasmina Popovic
Keyword(s):  
Venous Thromboembolism ◽  
Oral Contraceptives ◽  
Absolute Risk ◽  
Oral Contraception ◽  
Dependent Manner ◽  
Substantial Impact ◽  
Combined Oral Contraceptives ◽  
Increased Risk ◽  
The Absolute ◽  
Dose Dependent

Introduction. Because of their safety and efficacy, oral contraceptives are available without prescription in many countries. Monophasic combined oral contraceptives are a combination of estrogen and progestin taken in constant amounts. Venous thromboembolism. Combined oral contraceptives slightly increase the risk of venous thromboemolism, but this event is very rare among non-pregnant women of reproductive age. The absolute risk rises with age, obesity, recent surgery and certain forms of thrombophilia. The estrogen component of combined oral contraceptives increases the synthesis of several coagulation factors in a dose-dependent manner. Changes of most of these parameters are very small and there is no evidence that they have any effect upon the clinical risk of developing venous thrombosis. If a woman has an inherited coagulation disorder that increases her risk of developing thrombosis, the risk is increased several fold if she ingests estrogen containing oral contraception. Conclusion. The increased risk of venous thromboembolism associated with combined oral contraceptives should have little impact on healthy women, but may have substantial impact on women with a history of thromboembolism. Combined oral contraceptive use increases the risk of venous thromboembolosm in a dose-dependent manner. The absolute risk of venous thromboembolism rises with age, obesity, recent surgery and certain forms of thrombophilia, as well.

Platelet Adhesiveness in Symptomatic Women Taking Oral Contraceptives

1971 ◽  
Vol 26 (03) ◽  
pp. 426-430 ◽  
Author(s):  
T. F Zuck ◽  
J. J Bergin ◽  
Jane M. Raymond ◽  
W. R Dwyre ◽  
D. G Corby
Keyword(s):  
Oral Contraceptives ◽  
Platelet Adhesiveness ◽  
Combined Oral Contraceptives ◽  
Increased Risk ◽  
Normal Women ◽  
Asymptomatic Women

SummaryPlatelet adhesiveness to glass was determined in several groups of women. Increases were found in women developing thrombovascular symptoms while taking combined oral contraceptives, compared to both normal women and asymptomatic users of oral contraceptives. Despite this increase, overlap of the groups did not permit discrimination between symptomatic and asymptomatic women. However, it is possible, that in concert with other coagulation changes, platelet adhesiveness to glass may prove adjunctive in defining women at increased risk of developing thrombovascular symptoms while taking oral contraceptives, and further define the mechanism of the increased risk.

Impact of Weight-Band Dosing of Tinzaparin for Venous Thromboembolism Prophylaxis on Persistent Wound Drainage in Adult Patients Undergoing Hip and Knee Arthroplasty

2021 ◽  
pp. 106002802110242
Author(s):  
Cassandra Cooper ◽  
Ouida Antle ◽  
Jennifer Lowerison ◽  
Deonne Dersch-Mills ◽  
Ashley Kenny
Keyword(s):  
Body Weight ◽  
Venous Thromboembolism ◽  
Knee Arthroplasty ◽  
Total Joint Arthroplasty ◽  
Joint Arthroplasty ◽  
Thromboembolism Prophylaxis ◽  
Wound Drainage ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact

Background: Persistent wound drainage and venous thromboembolism (VTE) are potential complications of total joint arthroplasty, and these risks can be challenging to balance in clinical practice. Anecdotal observation has suggested that following joint arthroplasty, persistent wound drainage occurs more frequently with higher body weight and higher doses of tinzaparin when compared with lower body weight and lower doses of tinzaparin. Objective: The overall purpose of this study was to describe the impact of a tinzaparin weight-band dosing table for VTE prophylaxis on wound healing, thrombosis, and bleeding outcomes in patients undergoing total joint arthroplasty. Methods: This retrospective chart review included patients who underwent total hip or knee arthroplasty and received tinzaparin for thromboprophylaxis per their weight-banding category. The primary outcome was the incidence of persistent wound drainage. Secondary outcomes include the occurrence of VTE and clinically important bleeding during hospital admission. Results: A total of 231 patients were included in the analysis. There was no significant difference in persistent wound drainage between the 3 weight categories, and there were no differences in rates of VTE or clinically important bleeding. Concurrent use of low-dose acetylsalicylic acid was associated with a 3-fold increased risk of persistent wound drainage (risk ratio = 3.35; 95% CI = 2.14-5.24; P = 0.00003). Conclusion and Relevance: In joint arthroplasty patients, we observed no significant difference in rates of persistent wound drainage between various weight categories receiving different weight-banded doses of tinzaparin. Our results do not suggest that the current weight-band dosing table for tinzaparin needs to be adjusted to optimize patient outcomes.

The use of oral contraceptives in women over age 35 years

1995 ◽  
Vol 4 (2) ◽  
pp. 115-120
Author(s):  
Robert F Casper ◽  
Selim Senoz ◽  
Avraham Ben-Chetrit
Keyword(s):  
Cardiovascular Disease ◽  
Oral Contraceptive ◽  
Oral Contraceptives ◽  
Contraceptive Use ◽  
Older Woman ◽  
Oral Contraceptive Use ◽  
Increased Risk ◽  
Potential Risks ◽  
Europe Today ◽  
The Impact

Oral contraceptives remain the most widely used form of contraception in North America and Europe today. In spite of the concerns of many women relating to the potential risks of these preparations, recent data have demonstrated that currently available oral contraceptives are safe, with no increased risk of cardiovascular disease or cancer in nonsmoking women. The present review will focus on the impact of oral contraceptive use in the older woman, including a discussion of the noncontraceptive health benefits of oral contraceptives.

Contribution of polymorphisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk

2004 ◽  
Vol 91 (05) ◽  
pp. 905-911 ◽  
Author(s):  
Pilar Medina ◽  
Silvia Navarro ◽  
Amparo Estellés ◽  
Amparo Vayá ◽  
Barry Woodhams ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Receptor Gene ◽  
Activated Protein C ◽  
Soluble Form ◽  
Cell Protein ◽  
Endothelial Protein C Receptor ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
The Relationship

SummaryEndothelial cell protein C receptor (EPCR) enhances the generation of activated protein C (APC) by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR), which is generated by metalloprotease activity, is present in plasma. The distribution of sEPCR levels in healthy populations is bimodal. Previously, we described two polymorphisms in exon 4 of the EPCR gene, 4600A/G that encodes the substitution of Ser219 by Gly in the transmembrane region of EPCR and 4678G/C in the 3’-UT region. The aim of this study was to investigate the relationship between these two polymorphisms and plasma sEPCR and APC levels and risk of venous thrombosis. We genotyped 401 healthy controls from the Spanish population and measured their plasma sEPCR and APC levels. Carriers of the 4600AG genotype had significantly higher sEPCR levels than those with the AA genotype, while the 4678CC genotype was associated, to a lesser extent, with elevated APC levels. To assess the effect of these polymorphisms on the risk of thrombosis, we genotyped 405 patients with venous thromboembolism. The frequency of the 4600AG genotype was very similar in patients and controls (p=0.975), whereas the 4678CC genotype was significantly more frequent in controls than in patients (p=0.008). In multivariate analysis, carriers of the 4678CC genotype had a decreased risk of thrombosis (OR=0.61, p=0.009). These data indicate that individuals carrying the 4600AG genotype have high sEPCR levels but do not have an increased risk of thrombosis, whereas individuals carrying the 4678CC genotype have higher APC levels and lower risk of venous thromboembolism.

Is prolonged immobilization a risk factor for symptomatic venous thromboembolism in elderly bedridden patients?

2004 ◽  
Vol 91 (03) ◽  
pp. 538-543 ◽  
Author(s):  
Ora Paltiel ◽  
Michael Bursztyn ◽  
Moshe Gatt
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Early Period ◽  
Thromboembolic Events ◽  
Historical Cohort ◽  
Increased Risk ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Prolonged Immobilization ◽  
The Impact

SummaryProlonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinically apparent VTE, we performed a historical-cohort study of nursing home residents during a ten-year period. Data concerning patient’s mobility and incidence of overt deep vein thrombosis or pulmonary embolism were registered. The mean resident age was 85 ± 8.4 years. Eighteen mobile and eight immobile patients were diagnosed with clinically significant thromboembolic events, during 1137 and 573 patient-years of follow up, respectively. The incidence of venous thromboembolic events was similar in both chronically immobilized and mobile patient groups, 13.9 and 15.8 per thousand patient years, respectively (p = 0.77). The rate ratio for having a VTE event in the immobilized patient group as compared with the mobile group was 0.88 (95% Confidence Interval (CI) 0.33 to 2.13). When taking into account baseline characteristics, risk factors and death rates by various causes, no differences were found between the two groups. In conclusion, chronically immobile bedridden patients are no more prone to clinically overt venous thromboembolic events than institutionalized mobile patients. Until further studies are performed concerning the impact of very prolonged immobilization on the risk of VTE, there is no evidence to support primary prevention after the first three months of immobilization. Evidence for efficacy or cost effectiveness beyond this early period is not available.

scholarly journals Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromsø study

2009 ◽  
Vol 160 (5) ◽  
pp. 833-838 ◽  
Author(s):  
Johan Svartberg ◽  
Sigrid K Brækkan ◽  
Gail A Laughlin ◽  
John-Bjarne Hansen
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Free Testosterone ◽  
Population Based ◽  
Sex Hormone ◽  
Population Based Study ◽  
Hormone Levels ◽  
Increased Risk ◽  
The Impact

ObjectivesLow testosterone levels in men have been associated with cardiovascular risk factors and atherosclerosis and lately also an increased risk of both cardiovascular disease (CVD) and all-cause mortality. As arterial CVDs and venous thromboembolism (VTE) have been shown to share common risk factors, the purpose of the present study was to determine the impact of endogenous sex hormone levels on the incidence of VTE in a cohort of men.DesignA prospective, population-based study.MethodsSex hormone measurements were available in 1350 men, aged 50–84, participating in the Tromsø study in 1994–1995. First, lifetime VTE-events during the follow-up were registered up to September 1 2007.ResultsThere were 63 incident VTE-events (4.5 per 1000 person-years) during a mean of 10.4 years of follow-up. Age was significantly associated with increased risk of VTE; men 70 years or older had a 2.5-fold higher risk of VTE (HR 2.47, 95% CI 1.19–5.12), compared with those between 50 and 60 years of age. In age-adjusted analyses, endogenous sex hormones levels were not associated with risk of VTE; for each s.d. increase, hazards ratios (95% CI) were 1.06 (0.83–1.35) for total testosterone, 1.02 (0.79–1.33) for free testosterone, and 1.27 (0.94–1.71) for ln-estradiol. In dichotomized analyses comparing men in the lowest total and free testosterone quartile with men in the higher quartiles, hypoandrogenemia was not associated with risk of VTE.ConclusionsIn this population-based study of middle-aged and older men, endogenous sex hormone levels were not associated with 10-year risk of VTE.

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