Genetic Modulation of Oral Anticoagulation with Warfarin

2000 ◽  
Vol 84 (11) ◽  
pp. 775-778 ◽  
Author(s):  
Donatella Colaizzo ◽  
Giovanna D’Andrea ◽  
Vincenzo Brancaccio ◽  
Antonio Ciampa ◽  
Elvira Grandone ◽  
...  

SummaryCytochrome P450 CYP2C9 gene variants have been associated with hyperresponsiveness to small doses of warfarin and a higher bleeding complication rate. The aim of this study was to investigate whether CYP2C9 gene variants affect doses of drug prescribed to acquire the target anticoagulation intensity and the occurence of bleeding complications. In a cohort of 180 patients followed up at one specialized clinic from the start of the anticoagulation with warfarin, we have investigated whether CYP2C9 gene variants have affected doses of drug prescribed to acquire the target anticoagulation intensity and the incidence of bleeding complications.The adjusted dose required of warfarin was higher among patients with the CYP2C9*1 haplotype (5.6 mg) than those of patients carrying the CYP2C9*2 (4.7 mg; p = 0.007, Scheffé’s test) or the CYP2C9*3 haplotype (4.0 mg; p <0.001, Scheffé’s test). The occurrence of bleeding complications was more frequent among patients with the CYP2C9*2 and/or the CYP2C9*3 haplotype than in carriers of the CYP2C9*1 haplotype (OR: 2.57; 95% CI: 1.16–5.73). An interaction between the presence of local bleeding sources and the CYP2C9*2 and/or the CYP2C9*3 haplotype was observed (p <0.001). Patients with both local sites of potential bleeding and CYP2C9*2 and/or the CYP2C9*3 haplotype had the higher estimated risk of bleeding (OR: 12.81; 95% CI: 2.86–57.26).CYP2C9 gene variants modulate the anticoagulant effect of the dose of warfarin prescribed. The incidence of bleeding complications in CYP2C9*2 and CYP2C9*3 carriers was significantly higher than that in noncarriers and interacted with the presence of local bleeding sources.

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Gaurav Verma

Cardiac patients on aspirin therapy may require extractions for their diseased teeth. It is a common practice among physicians and treating surgeons to stop aspirin prior to tooth extraction because of fear of bleeding complications. This practice often predisposes the patient to adverse thromboembolic events. This practice is based on theoretical risk of bleeding and on isolated case reports of excessive bleeding with aspirin therapy. The current consensus and recommendations are in favor of continuing aspirin therapy during simple tooth extraction as the bleeding complication incidence is very less and if it occurs can be controlled efficiently with local hemostasis measures.


1979 ◽  
Author(s):  
J.J.F. Belch ◽  
G.D.O. Lowe ◽  
J.G. Pollock ◽  
C.D. Forbes ◽  
C.R.M. Prentice

In a randomised double-blind controlled trial 24 patients undergoing elective aortic bifurcation graft surgery received subcutaneous calcium heparin (2, 500 u preoperatively then 5,000 u 12 hourly or 7 days) and 25 control patients received saline injections. All patients received the routine dose of intravenous sodium heparin intraoperatively. The trial was terminated because of excess bleeding complications in patients on subcutaneous heparin (8 vs. 1, p<0.05). Deep venous thrombosis was diagnosed by 125I-fibrinogen scanning in 8 control patients and 3 patients on heparin (p>0.05). In this group of patients the risk of bleeding due to subcutaneous heparin appeared to outweigh the benefit of thrombotic prophylaxis.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
L. Testa ◽  
G. G. L. Biondi Zoccai ◽  
M. Valgimigli ◽  
R. A. Latini ◽  
S. Pizzocri ◽  
...  

Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice.


Author(s):  
Christine Oryhan ◽  
Kevin Vorenkamp ◽  
Daniel Warren

With the aging population and new anticoagulant medications, such as direct oral anticoagulants, being marketed in the United States, it is very important for pain physicians to be aware of the anticoagulants available and how they affect the safety of interventional pain procedures. In addition to anticoagulant and antiplatelet medications, other medications commonly used in the chronic pain population may put patients at increased risk of bleeding complications. Certain patient characteristics, particularly in the chronic pain population, may also increase a patient’s risk of bleeding. The chapter reviews common and emerging anticoagulant and antiplatelet medications and the ideal holding time before or after interventional pain procedures, particularly in the spine. The chapter also discusses the diagnosis, treatment, and outcomes of spinal epidural hematomas.


1981 ◽  
Author(s):  
H Kösteriag ◽  
K L Neuhaus ◽  
U Kasten ◽  
J Schrader ◽  
U Artmann ◽  
...  

Streptokinase, aplicated by intracoronary infusion in pat. with acute myocardial infarction has proven to be successfull in recanalisation of occluded coronary arteries. The good clinical, angiographic, chemical and EKG results suggests that jeopardized myocardium was salvaged by acute recanalisation. Till now, we infused Streptokinase (about 2000 U/min) in 78 pat. into the ischemia related occluded coronary artery. In this presentation we intend to demonstrate the results of these pat. and of a study, done before starting intracoronary Streptokinase infusion to be safe for bleeding complication. Neither after the infusion of 50 000 U.(n = 24) of 100 000 U. (n = 15) nor in 20 pat. who received SK equal to their ASTK-titres plus 50 000 U. SK whe found severe alterations of the blood-coagulation system. Only in the last group there was a small decrease of Fibrinogen of about 100 mg% and of Plasminogen 4 mg%. In none of the 78 pat., treated by intracoronary SK aplication, we resulted bleeding complication and the mean values of blood coagulation test remained within the normal range. On the other hand, we infused SK by veins and controlled the thrombolytic effect by coronarangiography. In 5 of 6 pat. we succeded in recanalisation of occluded coronary arteries within 45 Used very high dosages of SK, (about 2 Mill U) there was only a small decrease of 210 mg of Fibrinogen and no bleeding complications.


2005 ◽  
Vol 44 (05) ◽  
pp. 697-703 ◽  
Author(s):  
J. Westendorf ◽  
R. Diebow ◽  
M. Kieser ◽  
W. Gaus

Summary Objective: Information about adverse drug reactions plays an important role when assessing the benefit/risk profile of a drug. Identifying rare adverse drug reactions, however, is a difficult task. This paper illustrates the advantages of using a prescription database for this purpose. Methods: The mediplus® database used in our analysis covered data from 320,644 outpatients observed between July 1999 and June 2002. The example of bleeding complications during intake of antidementia drugs is used to illustrate this approach. The comparison of cohorts and subgroups is nearly always a problem in surveys. For our analyses we considered a set of patients who had taken a selected medication for a certain period of time and compared the frequency of adverse events with those occurring when the same patients did not take this medication. Hence, the comparison with versus without a certain medication is based on the same set of patients as in a cross-over study. Results: Our evaluations indicate that the rate of bleeding complications is low when taking any of the widely used antidementia drugs, glutamate modulators, cholinesterase inhibitors, calcium antagonists or the phytomedicine Ginkgo biloba. Conclusion: Basing the comparison of the rates of complications during periods with and without intake of a certain drug on the same set of patients may be a useful tool for assessing adverse drug reactions from data reported in prescription databases.


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