Stable Anticoagulant Effect Research Articles

Preliminary Observations on the Antihypertension Action of Dabigatran Etexilate in Patients With Nonvalvular Atrial Fibrillation: A Prospective Multicenter Single-Arm Interventional Study.

BackgroundIn Japan, the number of patients with atrial fibrillation continues to grow with the aging of the population. Prevention of cardiogenic cerebral embolism is extremely important in patients with atrial fibrillation. While warfarin has long played a major role for this purpose, a new oral anticoagulant, dabigatran etexilate (dabigatran), has demonstrated superior efficacy and safety in recent years. We conducted a multicenter prospective interventional study to examine whether dabigatran could demonstrate superiority over warfarin in practical clinical situation.MethodsAmong outpatients attending Fukuoka University Chikushi Hospital or clinics registered with the Chikushi Cardiovascular Disease Clinical Research Network (Chikushi-JRN), 143 patients with nonvalvular atrial fibrillation (NVAF) were enrolled in this study and followed up for 12 months after initiation of dabigatran therapy. The primary endpoint was occurrence of cerebral embolism or systemic embolism, while secondary endpoints were: 1) Bleeding events; 2) Changes in the activated partial thromboplastin time (aPTT); 3) Adverse events; and 4) Changes in blood pressure and pulse rate.ResultsDuring the follow-up period, none of the patients developed cerebral or systemic embolism (the primary endpoint). In addition, there were no bleeding events or other adverse events (the secondary endpoints). aPTT remained stable throughout the 12-month observation period. A significant decrease in systolic blood pressure was observed at 1 month after initiation of dabigatran therapy, and blood pressure was reduced up to 12 months. Blood pressure showed a significant decrease in patients with paroxysmal atrial fibrillation, but not in patients with chronic atrial fibrillation.ConclusionsDabigatran showed a stable anticoagulant effect, and its safety was confirmed. Dabigatran also reduced blood pressure, which may help to explain why it causes fewer major bleeding events than warfarin.

Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute Stroke

Patients with certain types of stroke need urgent anticoagulation and it is extremely important for them to achieve fast and stable anticoagulant effect and receive individualized treatment during the initiation of warfarin therapy. We conducted a prospective study among 210 acute stroke patients who had an indication for anticoagulation and compared the impact of CYP2C9 and VKORC1 genotype-guided warfarin dosing (PhG) with fixed dosing (NPhG) on anticoagulation control and clinical outcome between groups. PhG achieved target INR values earlier, i.e., on average in 4.2 (4.1-4.7, 95% CI) days compared to NPhG (5.2 days [4.7-6.4, 95% CI]) (p = 0.0009), spent a higher percentage of time in the therapeutic INR range (76.3% [74.7-78.5, 95% CI] vs. 67.1% [64.5-69.6, 95% CI] in NPhG), and spent less time overdosed (INR > 3.1) (PhG 0.4 [0.1-0.7, 95% CI], NPhG 1.7 [1.1-2.3, 95% CI] days; p >0.000). PhG reached stable maintenance dose faster (10 [9.9-10.7, 95% CI] vs. 13.9 [13.3-14.7, 95% CI] days in controls; p = 0.0049) and had a better clinical outcome in relation to neurological deficit on admission as compared to NPhG. We confirmed that warfarin therapy with genotype-guided dosing instead of fixed dosing reduces the time required for stabilization and improves anticoagulant control with better clinical outcome in early stages of warfarin therapy introduction among acute stroke patients, which is essential for clinical practice.

Antimicrobial and anticoagulation activity of silver nanoparticles synthesized from the culture supernatant of Pseudomonas aeruginosa

Here, we describe biosynthesis of silver nanoparticles by reduction of aqueous Ag+ ions with the culture supernatant of Pseudomonas aeruginosa. The morphological, physiological, biochemical and molecular level identification of the strain GS1 resembles P. aeruginosa. The nanoparticles synthesized by P. aeruginosa were characterized by UV–vis spectroscopy, dynamic light scattering (DLS) and scanning electron microscopy (SEM). The size-distribution of nanoparticles was determined using a particle-size analyzer and the average particle-size was found to be 80nm. The biological activities of the synthesized silver nanoparticles like antimicrobial activity were confirmed against Escherichia coli and Staphylococcus aureus and it have stable anti-coagulant effect.

Relationship between aging and dosage of warfarin: The current status of warfarin anticoagulant therapy for Japanese outpatients in a department of cardiovascular medicine

Oral anticoagulant therapy with warfarin is essential for the optimal prophylaxis of thrombosis and embolism in many vascular disorders whose prevalence is high among elderly patients. Elderly Caucasians show increased sensitivity to oral anticoagulants. Although the Japanese are more sensitive to warfarin therapy than Caucasians, the relationship between age and warfarin dosage in the Japanese has not been investigated in detail. Here, we investigated this relationship in Japanese patients. The subjects comprised 102 outpatients (28-87 years) who showed a stable anticoagulant effect (prothrombin time expressed in terms of the international normalized ratio [PT-INR] between 1.6 and 2.6) following long-term warfarin therapy at the Department of Cardiovascular Medicine, National Hospital Organization Hakodate Hospital. The relationship between age, PT-INR, and daily warfarin dose was retrospectively investigated. The mean values of the characteristics of all the patients were as follows: age, 70.7 (+/-10.5) years; daily dose of warfarin, 2.68 (+/-0.95)mg; PT-INR, 1.99 (+/-0.24). The PT-INR was not correlated with increasing age. The daily dosage of warfarin and the dosage adjusted according to the PT-INR (dose/PT-INR), wherein the lower values indicate a higher sensitivity to warfarin therapy, were significantly inversely correlated with age. In the high PT-INR (PT-INR>2.1) group, no significant difference was observed between the older and younger patients with regard to any characteristics. Conversely, in the low PT-INR (1.6 ≤ PT-INR ≤ 2.1) group, the dose/PT-INR was significantly reduced in the older patients (≥ 65 years); however, no significant difference was observed in the PT-INR value. Both age and the controlled PT-INR value are factors responsible for the increasing sensitivity to warfarin in Japanese patients under optimal anticoagulant therapy. Since elderly Japanese patients with low PT-INR values are especially sensitive to warfarin, greater caution should be exercised while determining the dosage schedule in such patients.

Subcutaneous Low Molecular Weight Heparin for Management of Anticoagulation in Infants on Excor Ventricular Assist Device

Anticoagulation in infants and children on a ventricular assist device presents particular challenges. Unfractionated heparin has poor bioavailability; it can be difficult to achieve a stable anticoagulant effect; and, in the long-term, there is a risk of osteopenia. Long-term warfarin can be difficult to manage in infants on formula milk with vitamin K supplementation. We review our recent experience with subcutaneous low molecular weight heparin. Two patients received a left ventricular assist device (Excor, Berlin Heart AG) as a bridge to transplantation. Initial anticoagulation consisted of unfractionated heparin infusion beginning 6 hours after implantation to maintain an activated partial thromboplastin time of 70 seconds, checked every 4 to 6 hours. Platelet count (aim >80,000/microl) and thromboelastography were assessed daily. Antithrombin required substitution to maintain levels >70 IU/dl. To optimize anticoagulation, both infants were switched to subcutaneous low molecular weight heparin twice daily aiming for an anti-Xa activity between 0.5 and 1.0 IU/ml. Aspirin was added on day 4, checking platelet aggregation every 2 to 4 days, aiming at arachidonic acid stimulated aggregation 10% to 30% of baseline, collagen 100% of baseline. Dipyridamole was added once stability was reached if platelets count exceeded 150,000/microl. There were no clinical thromboembolic or bleeding events. Both patients had successful transplantation.

The Association of Age with Dosage Requirement for Warfarin

Two groups of patients have been studied in order to investigate the relationship between age and the effect of oral anticoagulant therapy. The first group comprised 364 patients aged 23-89 years who showed a stable anticoagulant effect on medium- or long-term warfarin therapy; in this group the elderly subjects were found to require, on average, a lower drug dose to maintain the same degree of anticoagulation. The second group comprised 130 patients aged 15-83 years who had received an initial standard oral dose of 10 mg of warfarin. No significant difference was found in the degree of anticoagulation achieved by 16 hours. Although the maintenance dose in elderly patients is somewhat lower than in younger, the same protocols can be used for the introduction of therapy.