Pharmacogenetics in Hemostasis: Friend or Foe?

Rumilla, Kandelaria M.; Chen, Dong; Baudhuin, Linnea M.

doi:10.1055/s-0029-1214147

Cited by 7 publications

(4 citation statements)

References 68 publications

(84 reference statements)

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“…Overall, sex differences in platelet function and aspirin effects are still to be fully elucidated, and more randomized controlled trials focused on women are needed to optimize gender-specific therapy and improve clinical outcomes in women with atherosclerosis. Hopefully, future studies will help to clarify whether pharmacogenomics 97 and laboratory monitoring of antiplatelet medications would be helpful in predicting individual responses in women.…”

Section: Resultsmentioning

confidence: 99%

Platelet Function and Response to Aspirin: Gender-Specific Features and Implications for Female Thrombotic Risk and Management

Zuern

Lindemann

Gawaz

2009

Semin Thromb Hemost

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This article reviews gender-specific differences in platelet function and response to aspirin. In contrast with men, women under 65 years of age do not benefit from aspirin therapy in primary prevention of coronary artery disease. Furthermore, the overall mortality after myocardial infarction is higher among women, which cannot simply be explained by age or individual treatment. Platelets play a central role in thrombo-ischemic events leading to myocardial infarction and ischemic stroke. Gender differences in platelet reactivity and "aspirin resistance" have been reported. Several studies using female platelets have shown increased platelet reactivity at baseline and a less effective inhibition of platelet aggregation by aspirin. The mechanisms underlying these differences are still to be elucidated, but influences of female sex hormones may play an important role. As a consequence, inhibition of platelet aggregation in women treated with aspirin may be insufficient, and female patients might benefit from higher maintenance dosages or the use of alternative antiplatelet medications. A potential future role of pharmacogenomics and laboratory monitoring of antiplatelet medications in predicting individual responsiveness is likely. Overall, primary prevention of myocardial infarction in women should be correlated with the individual risk score of the female patient. More studies focused on women are needed to optimize gender-specific therapy and, therefore, to improve clinical outcomes in women with atherosclerosis.

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Section: Resultsmentioning

confidence: 99%

Platelet Function and Response to Aspirin: Gender-Specific Features and Implications for Female Thrombotic Risk and Management

Zuern

Lindemann

Gawaz

2009

Semin Thromb Hemost

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“…Although there are some inherent limitations (82), pharmacogenetics is a burgeoning field that promises to revolutionize medicine by deciphering the genetic basis of variable drug responses in individuals. This has also found broad application in prevention and therapy of several thromboembolic disorders, with the most prominent Brought to you by | Purdue University Libraries Authenticated Download Date | 5/28/15 4:27 PM results from genetic testing of the pharmacological response to coumarin derivatives (4,83).…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics of vitamin K antagonists: useful or hype?

Lippi

Franchini

Favaloro

2009

Clinical Chemistry and Laboratory Medicine

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Oral anticoagulant therapy (OAT) based on vitamin K antagonists (VKAs; coumarin derivatives) is the current mainstay for the prevention and long-term treatment of a variety of thromboembolic disorders. Care of patients on OAT is challenging due to considerable variability in the response to a particular dose. This has been attributed to environmental, demographic, clinical and genetic variables. Individualized responses represent a major clinical challenge because patients may experience adverse health outcomes from bleeding or thrombosis as a result of over- or under-coagulation, respectively. Growing evidence indicates that up to 60% of the individual pharmacological response to coumarins might be due to genetic variables and affected by polymorphisms in the genes encoding two enzymes, namely, vitamin K epoxide reductase (VKOR) and cytochrome P450 CYP2C9. Genetic testing has been proposed as a useful tool for allowing prediction of the dose response during initial anticoagulation therapy, to assess variability in dose maintenance and to identify warfarin 'resistance'. However, genetic testing is not a panacea. Limitations include the optimal composition of test panels, still largely unknown, information concerning inter-individual variability, lack of analytical and quality specifications, lack of comprehensive outcome analyses to enable assessment of cost-effectiveness, lack of universal agreement related to reliable dosing algorithms and other ethical and social issues. The aim of this article is to provide a comprehensive overview of our current understanding of the pharmacogenetics of VKAs, as well as assessing potential advantages and limitations. Although it might be premature to recommend routine genetic testing, the future development and clinical validation of simple but comprehensive algorithms integrating the most informative gene polymorphisms (VKORC1 and CYP2C9) with some demographic information (age, race, body mass index) and clinical variables (comorbidities, drugs interference), and standardized dietary intake of vitamin K may provide a valuable tool in the care of patients on OAT with conventional VKAs. However, the ongoing development of new anticoagulant drugs targeting thrombin and factor X will introduce a paradigm shift in long-term anticoagulation therapy, so that consideration could be given to demise pharmacogenetics testing for VKAs.

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“…Although aspirin is efficacious in the secondary prevention of coronary artery disease, there is wide variability in the degree to which this drug attenuates platelet aggregation84–86. Aspirin-induced changes in platelet function are heritable86, and the genetic architecture underlying aspirin response has therefore been an intense focus of investigation84, 87–88. Clopidogrel is used to prevent stent restenosis following percutaneous intervention, and candidate genes contributing to its efficacy are rapidly coming into view89–91.…”

Section: Admixture In Pharmacogenomicsmentioning

confidence: 99%

Mapping genes that predict treatment outcome in admixed populations

Baye

Wilke

2010

Pharmacogenomics J

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There is great interest in characterizing the genetic architecture underlying drug response. For many drugs, gene-based dosing models explain a considerable amount of the overall variation in treatment outcome. As such, prescription drug labels are increasingly being modified to contain pharmacogenetic information. Genetic data must, however, be interpreted within the context of relevant clinical covariates. Even the most predictive models improve with the addition of data related to biogeographical ancestry. The current review explores analytical strategies that leverage population structure to more fully characterize genetic determinants of outcome in large clinical practice-based cohorts. The success of this approach will depend upon several key factors: (1) the availability of outcome data from groups of admixed individuals (i.e., populations recombined over multiple generations), (2) a measurable difference in treatment outcome (i.e., efficacy and toxicity endpoints), and (3) a measurable difference in allele frequency between the ancestral populations.

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Pharmacogenetics in Hemostasis: Friend or Foe?

Cited by 7 publications

References 68 publications

Platelet Function and Response to Aspirin: Gender-Specific Features and Implications for Female Thrombotic Risk and Management

Platelet Function and Response to Aspirin: Gender-Specific Features and Implications for Female Thrombotic Risk and Management

Pharmacogenetics of vitamin K antagonists: useful or hype?

Mapping genes that predict treatment outcome in admixed populations

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