Poller, L; Roberts, C; Ibrahim, S;
Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate non......-inferiority to the manual dosage at the experienced centers in the EAA study. With the use of a cluster sampling procedure, a minimum number of centers and a minimum total of patients required to establish non-inferiority were determined. At least four centers, each recruiting 50 patients over a period of 6...... months, were shown to be required (excluding the results from the first 3 weeks of treatment). To achieve non-inferiority, the lower 95% confidence interval of the 'time in target International Normalized Ratio range' (TIR) of a marketed program must be above the TIR limit set by the manual dosage group...
Full Text Available In Japan, low-dose rivaroxaban [15 mg QD/10 mg QD for creatinine clearance of 30-49 mL/min] was approved for clinical use in NVAF patients partly because of its unique pharmacokinetics in Japanese subjects. The aim of the study was to determine the anticoagulation intensity of rivaroxaban and its determinant factors in Japanese stroke patients.Consecutive stroke patients with NVAF admitted between July 2012 and December 2013 were studied. Prothrombin time (PT, activated partial thromboplastin time (aPTT, and estimated plasma concentration of rivaroxaban (Criv based on an anti-factor Xa chromogenic assay were measured just before and 4 and 9 h after administration at the steady state level of rivaroxaban. Determinant factors for Criv were explored using a linear mixed-model approach.Of 110 patients (37 women, 75±9 years old, 59 took 15 mg QD of rivaroxaban and 51 took 10 mg QD. Criv at 4 h was 186 ng/mL for patients taking 15 mg QD and 147 ng/mL for those taking 10 mg QD. Both PT and aPTT were positively correlated with Criv. Criv was 72% lower at 4 h in 15 patients receiving crushed tablets than in the other patients, and tablet crushing was significantly associated with lower Criv (adjusted estimate -0.43, 95% CI -0.60 to -0.26 after multivariate-adjustment.The anticoagulation effects of rivaroxaban in the acute stroke setting for Japanese NVAF patients were relatively low as compared with those in the ROCKET-AF and J-ROCKET AF trials. Tablet crushing, common in dysphagic patients, decreased Criv.
Watt, Barbara E; Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister
Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as 'superwarfarins', 'single dose' or 'long-acting'. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K(1)-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K(1)-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation. Substantial ingestion produces epistaxis, gingival bleeding, widespread bruising, haematomas, haematuria with flank pain, menorrhagia, gastrointestinal bleeding, rectal bleeding and haemorrhage into any internal organ; anaemia may result. Spontaneous haemoperitoneum has been described. Severe blood loss may result in hypovolaemic shock, coma and death. The first clinical signs of bleeding may be delayed and patients may remain anticoagulated for several days (warfarin) or days, weeks or months (long-acting anticoagulants) after ingestion of large amounts. There are now sufficient data in young children exposed to anticoagulant rodenticides to
McMahon, Sean R; Brummel-Ziedins, Kathleen; Schneider, David J
Despite advances in interventional and pharmacologic therapy, survivors of myocardial infarction remain at an increased risk of subsequent cardiovascular events. Initial pharmacological management includes both platelet inhibition and parenteral anticoagulation, whereas long-term pharmacological therapy relies on antiplatelet therapy for prevention of thrombotic complications. Biomarkers showing ongoing thrombin generation after acute coronary syndromes suggest that anticoagulants may provide additional benefit in reducing cardiovascular events. We review the pharmacokinetics of novel anticoagulants, clinical trial results, the role of monitoring, and future directions for the use of novel oral anticoagulants in the treatment of coronary artery disease. Clinical trials have shown that long-term use of oral anticoagulants decreases the risk of cardiovascular events, but they do so at a cost of an increased risk of bleeding. Future studies will need to identify optimal treatment combinations for selected patients and conditions that address both the appropriate combination of therapy and the appropriate dosage of each agent when used in combination. PMID:27228186
Stine Funder Jespersen
Full Text Available Background. The knowledge is still sparse about patient related factors, influencing oral anticoagulation therapy (OAC rates, in stroke patients with atrial fibrillation (AF. Aims. To assess the use of OAC in ischemic stroke patients diagnosed with AF and to identify patient related factors influencing the initiation of OAC. Methods. In the nationwide Danish Stroke Registry we identified 55,551 patients admitted with acute ischemic stroke from 2003 to 2011. Frequency analysis was used to assess the use of OAC in patients with AF, and logistic regression was used to determine independent predictors of OAC. Results. 17.1% ( of ischemic stroke patients had AF. OAC prescription rates were increasing, and in 2011 46.6% were prescribed OAC, 42.5% had a contraindication, and 3.7% were not prescribed OAC without a stated contraindication. Younger age, less severe stroke, and male gender were positive predictors of OAC, while excessive alcohol consumption, smoking, and institutionalization were negative predictors of OAC ( values < 0.05. Conclusions. Advanced age, severe stroke, female gender, institutionalization, smoking, and excessive alcohol consumption were associated with lower OAC rates. Contraindications were generally present in patients not in therapy, and the assumed underuse of OAC may be overestimated.
Full Text Available The purpose of this study was to evaluate the influence of the duration of interstitial laser acupuncture therapy effects on neurovegetative and neurobioelectrical parameters like heart rate (HR, heart rate variability (HRV, and electroencephalogram (EEG. We investigated 6 male Sprague-Dawley rats. They underwent 10 min, 20 min, and 30 min interstitial laser acupuncture (in randomized order, with a break of at least 30 min between the different measurement conditions at the acupoint Neiguan. HR changed significantly only during 20 min red laser stimulation, whereas 10 and 30 min stimulation did not induce significant changes. HRV did not change significantly during any of the different durations; however, an increase was found during 20 min irradiation. Neither the LF/HF ratio of HRV nor the integrated EEG showed significant changes. In this study, it could be experimentally proved that some effects of laser acupuncture are time dependent, and therefore the dosage, as well known from theory, also depends on the time factor. We could especially demonstrate that different treatment times lead to different effects on neurovegetative and neurobioelectrical parameters. Further studies are needed to verify or refute these results.
Başaran, Özcan; Dogan, Volkan; Beton, Osman; Tekinalp, Mehmet; Aykan, Ahmet Cağri; Kalaycioğlu, Ezgi; Bolat, Ismail; Taşar, Onur; Şafak, Özgen; Kalcik, Macit; Yaman, Mehmet; İnci, Sinan; Altintaş, Bernas; Kalkan, Sedat; Kirma, Cevat; Biteker, Murat
This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians' adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study).RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression.Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance ≥50 mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50 mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of ≥3.The suboptimal use of NOACs is common because of physicians' poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients. PMID:27583892
Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative
Oh, Doyeun; Kim, Sehyun; Lim, Chang Young; Lee, Jong Seok; Park, Seonyang; Garcia, David [Hrsg.; Crowther, Mark A.; Ageno, Walter
The optimal perioperative anticoagulation management in patients on warfarin therapy is poorly defined due to the lack of randomized trials. Because guidelines are heterogeneous, it was hypothesized that "treatment strategies are not uniform in clinical practice". Between February 2003 and May 2003, a questionnaire with 4 different clinical scenarios was distributed to physicians by e-mail, or direct contact was made by a survey monitor. Two scenarios described the cases of patients with a me...
De Lange, J J; Van Kleef, J W; Van Everdingen, J J E
In a patient with a coagulation disorder, the administration of a local anaesthetic by means of a needle or via the insertion of a catheter into the epidural space or spinal cavity may lead to bleeding and haematoma formation, with a danger of pressure on the spinal cord or nerve roots. Employing the method of the Dutch Institute for Healthcare (CBO) for the development of practice guidelines, a working group of anaesthesiologists, a haematologist and a hospital chemist have drawn up recommendations for neuraxis blockade in combination with anticoagulant therapy. In patients with a clinically acquired tendency toward increased bleeding, the management is highly dependent on the cause of the bleeding tendency. If the patient uses acetylsalicylic acid or clopidogrel, the medication must be withdrawn at least 10 days before neuraxis blockade is started. Therapy with glycoprotein-IIb/IIIa-receptor antagonists is an absolute contra-indication for neuraxis blockade. In patients who are using coumarin derivatives, neuraxis blockade results in an increased risk of a neuraxial haematoma. The coumarin derivative should then be withdrawn and replaced by a different form of anticoagulation. The use of low-molecular-weight heparin at the usual prophylactic dosage is not a contra-indication for neuraxis blockade and the risk of a neuraxial haematoma following neuraxis blockade is also not increased significantly by the subcutaneous administration of unfractionated heparin. PMID:15366721
Wellman, Jessica C; Kraus, Peggy S; Burton, Bradley L; Ensor, Christopher R; Nesbit, Todd W; Ross, Patricia A; Thomas, Michelle L; Streiff, Michael B
PURPOSE. A stepwise approach to development and implementation of a program to standardize and increase pharmacists' involvement in anticoagulation therapy at a large academic medical center is described. SUMMARY. In response to the Joint Commission's national goal of improved patient safety in anticoagulation therapy, a work group of pharmacy administrators, educators, clinical specialists, and decentralized pharmacists at the hospital developed the structure for a comprehensive inpatient anticoagulation program (IAP); the work group also developed a list of required competencies, educational materials, assessment methods, and mechanisms for eliciting feedback from IAP pharmacists and other patient care staff. After completion of training that included structured case-review sessions, a one-on-one shadowing experience, and competency assessment, IAP pharmacists began reviewing clinical and laboratory data on patients receiving warfarin and low-molecular-weight heparins and providing recommendations to physicians, nurse practitioners, and other health care team members. Feedback from other clinicians was generally positive, with a majority of those surveyed indicating that increased pharmacist involvement in anticoagulation monitoring and dosage adjustment resulted in improved patient care; about 80% indicated that they concurred with pharmacists' recommendations at least 75% of the time. Results of a survey of IAP pharmacists indicated increased satisfaction with their daily duties but also a need for improved pharmacist-to-pharmacist communication. CONCLUSION. Case-based advanced training and implementation of an IAP in a tertiary care hospital increased pharmacists' involvement in the management of inpatients receiving anticoagulants. PMID:21546645
Ferreira, Joana Lima; Wipf, Joyce E
Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature. PMID:27235611
@@ VTE of the main treatment for anticoagulant thera-py, anticoagulant therapy drug of choice for low molecu-lar weight heparin (LMWH) for the overwhelming major-ity of clinicians agree that long-term oral anticoagulant therapy is still Vit. K antagonist (mainly warfarin).
Kim, Sehyun; Lim, Chang Young; Lee, Jong Seok; Park, Seonyang; Garcia, David; Crowther, Mark A.; Ageno, Walter
The optimal perioperative anticoagulation management in patients on warfarin therapy is poorly defined due to the lack of randomized trials. Because guidelines are heterogeneous, it was hypothesized that "treatment strategies are not uniform in clinical practice". Between February 2003 and May 2003, a questionnaire with 4 different clinical scenarios was distributed to physicians by e-mail, or direct contact was made by a survey monitor. Two scenarios described the cases of patients with a mechanical heart valve (MHV) in the mitral position, with additional risk factors for a systemic embolism; one undergoing major (scenario 1) and the other minor surgery (scenario 3). Two scenarios described patients with an aortic MHV; one undergoing major (scenario 2) and the other minor (scenario 4) surgery. Different preoperative and postoperative management options were offered. The treatment options for all scenarios were the same. Of the 90 questionnaires distributed, 52 (57.8%) were returned. Hospitalization for full-dose intravenous unfractionated heparin (IV UH) was the most commonly selected strategy in the preoperative phase for scenarios 1 (59%), 2 (42%) and 3 (44%). In scenario 4, 34% chose IV UH. Outpatient, full-dose, subcutaneous UH or low-molecular-weight heparin (LMWH) was the most selected option in the postoperative phase for all scenarios, with the exception of number 4 (52.9% in scenario 1, 34% in scenario 2, 32%, in scenario 3 and 28% in scenario 4). Even among expert clinicians, the management of perioperative anticoagulation is heterogeneous. In particular, the definition of risk categories and the optimal intensity of antithrombotic drugs need to be defined by well-designed prospective studies. PMID:15744807
PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical
Cakir, Volkan, E-mail: email@example.com [Katip Celebi University, Ataturk Training and Research Hospital, Department of Radiology, Division of İnterventional Radiology (Turkey); Gulcu, Aytac, E-mail: firstname.lastname@example.org [Dokuz Eylul University Hospital, Department of Radiology (Turkey); Akay, Emrah, E-mail: email@example.com [Sakarya University Hospital, Department of Radiology (Turkey); Capar, Ahmet E., E-mail: firstname.lastname@example.org [Dokuz Eylul University Hospital, Department of Radiology (Turkey); Gencpinar, Tugra, E-mail: email@example.com [Dokuz Eylul University Hospital, Department of Cardiovascular Surgery (Turkey); Kucuk, Banu, E-mail: firstname.lastname@example.org [Dokuz Eylul University Hospital, Department of Radiology (Turkey); Karabay, Ozalp, E-mail: email@example.com [Dokuz Eylul University Hospital, Department of Cardiovascular Surgery (Turkey); Goktay, A. Yigit, E-mail: firstname.lastname@example.org [Dokuz Eylul University Hospital, Department of Radiology (Turkey)
PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical
Nutescu, Edith A.; Burnett, Allison; Fanikos, John; Spinler, Sarah; Wittkowsky, Ann
Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. Thi...
Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B
Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH. PMID:27137522
Lin, Tao; Bai, Rong; Chen, Ying-wei; Yu, Rong-hui; Tang, Ri-bo; Sang, Cai-hua; Li, Song-nan; Ma, Chang-sheng; Dong, Jian-zeng
Anticoagulation of patients with cardiac tamponade (CT) complicating catheter ablation of atrial fibrillation (AF) is an ongoing problem. The aim of this study was to survey the clinical practice of periprocedural anticoagulation in such patients. This study analyzed the periprocedural anticoagulation of 17 patients with CT complicating AF ablation. Emergent pericardiocentesis was performed once CT was confirmed. The mean drained volume was 410.0 ± 194.1 mL. Protamine sulfate was administered to neutralize heparin (1 mg neutralizes 100 units heparin) in 11 patients with persistent pericardial bleeding and vitamin K1 (10 mg) was given to reverse warfarin in 3 patients with supratherapeutic INR (INR > 2.1). Drainage catheters were removed 12 hours after echocardiography confirmed absence of intrapericardial bleeding and anticoagulation therapy was restored 12 hours after removing the catheter. Fifteen patients took oral warfarin and 10 of them were given subcutaneous injection of LMWH (1 mg/kg, twice daily) as a bridge to resumption of systemic anticoagulation with warfarin. Two patients with a small amount of persistent pericardial effusion were given LMWH on days 5 and 13, and warfarin on days 6 and 24. The dosage of warfarin was adjusted to keep the INR within 2-3 in all patients. After 12 months of follow-up, all patients had no neurological events and no occurrence of delayed CT. The results showed that it was effective and safe to resume anticoagulation therapy 12 hours after removal of the drainage catheter. This may help to prevent thromboembolic events following catheter ablation of AF. PMID:25503659
Lee, C R; Thrasher, K A
The clinical significance of rifampin's induction of warfarin metabolism is well documented, but no published studies or case reports have quantified this interaction with respect to the international normalized ratio (INR). A patient receiving concomitant rifampin and warfarin to treat a mycobacterial infection and intraventricular thrombus, respectively, underwent routine INR testing at a pharmacist-managed anticoagulation clinic to assess his anticoagulation regimen. A 233% increase in warfarin dosage over 4 months proved insufficient to attain a therapeutic INR during long-term rifampin therapy More aggressive titration of the warfarin dosage was needed. In addition, a gradual 70% reduction in warfarin dosage over 4-5 weeks was necessary to maintain a therapeutic INR after rifampin discontinuation, demonstrating the clinically significant offset of this drug interaction. Extensive changes in warfarin dosage are required to attain and maintain a therapeutic INR during the initiation, maintenance, and discontinuation of rifampin. PMID:11601670
Subhash C. Lakhotia
Organisms with heterochromatic sex chromosomes need to compensate for differences in dosages of the sex chromosome-linked genes that have somatic functions. In-depth cytological and subsequent biochemical and molecular studies on dosage compensation started with Mary F. Lyon’s proposal in early 1960s that the Barr body in female mammalian somatic cells represented one of the randomly inactivated and heterochromatinized X chromosomes. In contrast, Drosophila was soon shown to achieve dosage compensation through hypertranscription of single X in male whose chromatin remains more open. Identification of proteins that remodel chromatin either to cause one of the two X chromosomes in somatic cells of very early female mammalian embryos to become condensed and inactive or to remodel the single X in male Drosophila embryos to a more open state for hypertranscription provided important insights into the underlying cellular epigenetic processes. However, the most striking and unexpected discoveries were the identification of long noncoding RNAs (lncRNAs), X- inactive specific transcript (Xist) in mammals and roX1/2 in Drosophila, which were essential for achieving the contrasting chromatin organizations but leading to similar end result in terms of dosage compensation of X-linked genes in females and males. An overview of the processes of X inactivation or hyperactivation in mammals and Drosophila, respectively, and the roles played by Xist, roX1/2 and other lncRNAs in these events is presented.
Nutescu, Edith A; Burnett, Allison; Fanikos, John; Spinler, Sarah; Wittkowsky, Ann
Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE. PMID:26780737
Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.
Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.
DU Xin; MA Chang-sheng; LIU Xiao-hui; DONG Jian-zeng; WANG Jun-nan; CHENG Xiao-jing
@@ Nonvalvular atrial fibrillation (NVAF) is the most common sustained cardiac arrhythmia in clinical practice, which if untreated results in a doubling of cardiovascular morbidity and mortality. AF is an independent predictor of stroke, with an annual risk 5 to 6 times higher than patients in sinus rhythm.1 During recent years, several randomised clinical trials conducted by investigators around the world involving 13 843 participants with NVAF have demonstrated convincingly the value of warfarin therapies for stroke prevention in high risk patients.2-8 However, the dose response of warfarin is complex and its activity is easily altered by concurrent medications, food interactions, alcohol and illnesses. Adherence to medical advice and routine monitoring of the international normalized ratio (INR) is important, because low anticoagulant intensity predisposes the patients to thromboembolic complications and high intensity to haemorrhage. Studies suggested that anticoagulant clinics could improve the quality of anticoagulation control,9 and anticoagulant clinics are common in western countries. However, in China, most AF patients taking warfarin usually attend the outpatient clinic of cardiology, while the quality of anticoagulation control is never investigated. We therefore assessed anticoagulation control in the outpatient clinic of cardiology, and the quality of anticoagulation control since the establishment of anticoagulant clinics.
Full Text Available Objective. This study aimed to examine the effectiveness of the use of oral anticoagulation (OAC medication, recommended by national guidelines for stroke prevention but reportedly underused in AF patients with moderate to high stroke risk. Method. A multicentre and cross-sectional study of undiagnosed AF among out-of-hospital patients over 60 years old was carried out, visiting 3,638 patients at primary health centres or at home for AF diagnosis using the IDC-10 classification. The main outcome measures were CHA2DS2VASC, HAS-BLED scores, cardiovascular comorbidity, pharmacological information, TTR, and SAMe-TT2R2 scores. Results. The main findings were undiagnosed AF in 26.44% of cases; 31.04% registered with AF but not using OAC despite 95.6% having a CHA2DS2VASC≥2 score; a risk of bleeding in important subgroups using OAC without indication (37.50% CHA2DS2VASC 60%.
D'Ascenzo, Fabrizio; Taha, Salma; Moretti, Claudio;
The optimal antiaggregant therapy after coronary stenting in patients receiving oral anticoagulants (OACs) is currently debated. MEDLINE and Cochrane Library were searched for studies reporting outcomes of patients who underwent PCI and who were on triple therapy (TT) or dual-antiplatelet therapy...
Norton, J L; Gibson, D L
The establishment of a pharmacist-managed out-patient anticoagulation clinic in a private community hospital is described. Discussions by pharmacy with office-based physicians at a 187-bed, private, nonprofit community medical center indicated that the traditional system of anticoagulation management was not ideal for the physicians or their patients. Development of a pharmacist-managed anticoagulation clinic began in fall 1993; operations began in spring 1994. Planning included analyzing existing practices, reviewing the relevant literature, obtaining physician input, visiting an established anticoagulation clinic, formulating a business plan, and developing clinical protocols. Collaborative relationships were established with the hospital laboratory, business office, and risk management, information services, and medical records departments. Two pharmacists were trained to work in the clinic and provide coverage 24 hours a day. Services include patient assessment, monitoring of anticoagulation, warfarin dosage adjustment, medication management, patient education, follow-up care, and providing feedback to referring and attending physicians. The clinic has met with physician and patient satisfaction, has reduced the number of admissions to treat warfarin-related bleeding, and has been able to cover its direct costs. A pharmacist-managed anti-coagulation clinic was successfully established in a private community hospital. PMID:8734675
Bouwmeester, Carla; Chim, Christine
Pharmacists are at the forefront when caring for patients requiring anticoagulation resulting from chronic conditions, complex medications therapy, or at risk for drug interactions. As a consequence, there is a greater need for pharmacist-managed anticoagulation clinics in the community setting. This article will review special considerations for oral anticoagulant therapy in the elderly, collaborative therapy management, establishment of policies and procedures, documentation of patient visits, patient counseling, and barriers to successful anticoagulation management. It will also discuss evidence-based guidelines for the use of oral anticoagulants and compare the agents currently approved by the Food and Drug Administration. Finally, barriers to anticoagulation management will be examined, including issues with adherence and communication with patients and health care providers. PMID:23649677
Yelnik, Cecile M; Laskin, Carl A.; Porter, T. Flint; Branch, D Ware; Buyon, Jill P.; Guerra, Marta M; Lockshin, Michael D; Petri, Michelle; Merrill, Joan T; Sammaritano, Lisa R; Kim, Mimi Y; Salmon, Jane E.
Objective We previously reported that lupus anticoagulant (LAC) is the main predictor of poor pregnancy outcome in antiphospholipid antibody (aPL)-positive patients. We sought to confirm this finding in an independent group of patients who were subsequently recruited into the PROMISSE study. Methods The PROMISSE study is a multicentre, prospective, observational study of pregnancy outcomes in women with aPL and/or systemic lupus erythematosus (SLE) that enrolled patients from 2003 to 2015. Al...
Howie, P W
Thromboembolic disorders are still a serious problem in pregnancy and anticoagulants have an important part to play in both treatment and prevention. Warfarin is the most convenient drug to give but can cause maternal and fetal bleeding problems, especially during late pregnancy and delivery. There are also small risks of embryopathy from warfarin in early pregnancy but these may have been overstated. Heparin, which has to be given parenterally, does not cross the placental barrier but can still cause bleeding problems in pregnancy. Full intravenous heparin is only suitable for short-term use, and subcutaneous heparin has been introduced for long-term therapy. This regimen is a useful advance but long-term use still has problems of bruising and maternal bone demineralization. The standard treatment of acute thromboembolic events in pregnancy is continuous intravenous heparin followed by either subcutaneous heparin or warfarin, the latter being changed at 36 weeks gestation. In the prophylaxis of thromboembolism, the trend is towards a more selective approach, anticoagulants being given during pregnancy to those at highest risk and during labour and the puerperium to all with a previous history of thromboembolism. Anticoagulants during pregnancy are necessary in patients with artificial heart valves and, because subcutaneous heparin is not sufficient, warfarin should be used until 36 weeks followed by continuous intravenous heparin until delivery. No method of anticoagulation during pregnancy is entirely free of risk and all management policies must be based on an estimate of risk-benefit ratio in individual patients. PMID:2426029
Koopmans, SA; VanRij, G
A questionnaire was sent to 240 members of the Netherlands Intraocular implant Club (NIOIC) to register their policy followed in 1993 with regard to anticoagulant therapy (ACT) and the use of aspirin in patients having cataract surgery. Ninety-one (32%) forms were suitable for analysis. Most eye sur
Steinberg, Benjamin A; Piccini, Jonathan P
Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin's shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. However, the management of patients taking warfarin or novel agents remains a clinical challenge. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. This review will discuss the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment. PMID:24733535
Samuel P. Hammar
Full Text Available We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto® (rivaroxaban.
Garabedian-Ruffalo, S M; Gray, D R; Sax, M J; Ruffalo, R L
The effectiveness of a pharmacist-managed warfarin anticoagulation clinic in maintaining therapeutic prothrombin times and preventing hospitalizations secondary to inadequate control of anticoagulation was evaluated. Patients who had received warfarin sodium for at least one year before being referred to the anticoagulation clinic were studied using retrospective chart reviews. Clinical pharmacists provided patient education, monitored patients for hemorrhagic and thromboembolic complications, and adjusted warfarin sodium dosage to maintain therapeutic prothrombin times. The patients' primary physicians retained responsibility for overall care and were consulted by pharmacists regarding complications of anticoagulation and patient unreliability. The percentage of patients requiring hospitalization (39% versus 4%) and the percentage of prothrombin times outside the therapeutic range (35.8% versus 14.4%) were significantly higher during the preclinic phase (before referral to the clinic) than during the clinic phase. Eight patients were hospitalized for hemorrhagic complications and four for thromboembolism during the preclinic phase; only one hospitalization for hemorrhage occurred during the clinic phase. The warfarin anticoagulation clinic staffed by specially trained pharmacists provided improved therapy compared with treatment received by patients before their referral to the clinic. PMID:3976675
Dilute Russell's viper venom (DRVV) testing and activated partial thromboplastin time (APTT) have been effectively used in combination for lupus anticoagulant testing. The purpose of our study was to evaluate the role of mixing in activated partial thromboplastin and dilute Russell's viper venom testing for evaluation of lupus anticoagulants. Citrated blood from patients who were not on oral anticoagulant therapy was studied. Mixing study with 1 : 1 normal plasma for elevated APTT and also few samples with elevated screen time was carried out. Elevated APTT was seen in only 48.1% of patients with lupus anticoagulant. Correction of APTT was seen in 27.8% of lupus anticoagulant-positive patients. DRVV test on mixing resulted in 83.8% false-negative values. Integrated DRVV test could be a standalone test for testing lupus anticoagulant. Mixing study may be restricted for patients on oral anticoagulants or patients with strong lupus anticoagulant. PMID:26626041
Ahmad, Yousif; YH Lip, Gregory
Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. This...
Steinberg, Benjamin A; Piccini, Jonathan P.
Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also availabl...
Full Text Available Cecilia Becattini, Alessandra Lignani, Giancarlo AgnelliInternal and Cardiovascular Medicine and Stroke Unit, University of Perugia, ItalyAbstract: Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal anticoagulant should be at least as effective as those currently in use, as well as safe, simple to use, and widely applicable. The majority of new anticoagulants currently under investigation are small molecules with a selective and direct anti-Xa or antithrombin action, allowing oral administration in fixed doses. These new agents are in different phases of clinical development. The anti-Xa agent rivaroxaban and the antithrombin agent dabigatran are already available for the prophylaxis of venous thromboembolism in some countries. Apixaban is in an advanced phase of clinical development and several anti-Xa agents are currently approaching phase III clinical trials. Promising results in terms of efficacy and safety profiles have been obtained with these agents in different clinical conditions. Differences in pharmacokinetics and pharmacodynamics could offer the potential for individualized anticoagulant therapies in the near future.Keywords: anticoagulant therapy, antithrombotic therapy, anticoagulants, direct thrombin inhibitors, factor Xa inhibitors
Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). The treatment needs rapid initial anticoagulaton to minimize the risk of thrombus extension and fata pulmonary embolism, followed by an extended anticoagulation, aimed at preventing recurrent VTE. Till very recently, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging direct oral anticoagulants have the potential to streamline VTE treatment. These agents include oral anticoagulants that target thrombin or factor Xa. This article reviews the characteristics of these agents, describes the results of clinical trials in venous thromboembolic disease and outlines their strengths and weakness. PMID:24167902
Full Text Available Traditional anticoagulants, such as low molecular weight heparin, unfractionated heparin, fondaparinux and vitamin K antagonists, have been the mainstay of treatment of venous thromboembolism (VTE in the clinical hospital setting and after discharge. These anticoagulants are effective, but are associated with some limitations that may lead to their underuse in many settings. Based on the results of large, randomized clinical trials, new oral anticoagulants have been validated for the treatment of acute deep vein thrombosis and pulmonary embolism, and for the prevention of recurrent VTE. These drugs represent a landmark shift in anticoagulation care and may overcome some of the limitations of traditional agents, with the potential of improving adherence to anticoagulation therapy.
Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.
Lewis, S M; Kroner, B A
The literature describing pharmacy involvement with anticoagulation services primarily does not include information about patients' perceptions of this involvement. A 22-question survey was developed and administered to 296 patients enrolled in the anticoagulation clinic at the VA Pittsburgh Health Care System. Excluded patients had fewer than four clinic visits or were followed outside of the anticoagulation clinic. The study period was nine weeks and any missed patients were telephoned. The median response to each question was determined. Similar questions were analyzed for acquiescent trends. Results indicate that, overall, patients are comfortable with pharmacists providing warfarin monitoring and dose adjustments. PMID:10174757
Olesen, Jonas Bjerring; Sørensen, Rikke; Hansen, Morten Lock;
AIMS: Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted. METHODS AND RESULTS: Using Danish nationwide administrative registers, we...... the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and another 20% were started on either rivaroxaban or apixaban. Rivaroxaban and apixaban users generally had a higher predicted risk of stroke and bleeding compared with warfarin and dabigatran users....... Older age, female gender, and prior stroke were some of the factors associated with NOAC use vs. warfarin, whereas chronic kidney disease, myocardial infarction, and heart failure showed the opposite association. CONCLUSION: Among oral anticoagulation-naïve AF patients initiated on oral anticoagulation...
Harper, Paul; Harper, Joe; Hill, Claire
Objective To evaluate the effectiveness of a computerised self-adjusting anticoagulant algorithm to predict appropriate warfarin dosing and to assess its use in clinical practice. Design A 3-year audit of anticoagulant control in patients managed by doctors and pharmacists using computer decision support and an evaluation of the impact of dose adjustments made by the users. Participants 3660 patients on oral anticoagulants; one-third of patients managed by doctors and two-thirds by pharmacists. Setting Anticoagulant supervision in primary care and pharmacies at 60 sites in New Zealand. Main outcome measures The time in the therapeutic range (TTR), the outcome of adherence to the computer dosing algorithm, the percentage of time the clinicians over-ride the algorithm and the impact of their intervention on anticoagulant control. Results A TTR of 72.9% was achieved for all patients. The TTR was significantly better in patients managed by pharmacists than doctors (75.1% versus 67.4%, ppharmacists. Conclusions The clinicians predominantly change the dose when the INR is below the therapeutic range. The changes are not necessary to correct for inaccuracies in the algorithm. The most likely explanation is the clinician's belief that their own dose adjustment would achieve better control; however, in practice, their changes tend to underdose patients. The doctors achieved poorer control than the pharmacists; this is in part due to the action of the doctors over-riding the algorithm. Our results imply that clinicians could achieve better anticoagulant control if they more closely followed the computer algorithm. PMID:25183709
Witt, Daniel M
The Clinical Pharmacy Anticoagulation Service (CPAS) at Kaiser Permanente Colorado grew from a single pharmacist assisting a single physician to a comprehensive service staffed by over 20 employees. CPAS provides care for over 7200 patients with each CPAS pharmacist managing all aspects of anticoagulation therapy for 150 to 500 patients. Unique aspects of CPAS include its centralized organization structure, the use of telepharmacy, collaboration drug therapy management agreement with referring physicians and a robust research agenda. Results of various CPAS research projects have been published in the peer-reviewed medical literature. PMID:18804262
Wooten, James M
For years, the pharmaceutical industry has been trying to find a safe and effective drug to replace warfarin. Although warfarin is an effective anticoagulant, its pharmacology, adverse effects, and risk profiles dictate that patients taking this medication must be monitored judiciously. The US Food and Drug Administration has approved two drugs for commercial use, dabigatran and rivaroxaban, that will compete directly with warfarin for use in specific indications. Because of direct marketing to patients, physicians are being asked to comment on these new medications. This brief review illustrates the data available for the two new drugs when compared to warfarin for the specified indications. For some patients, these drugs may be highly beneficial and offer an excellent alternative to warfarin. For others, warfarin may still be the preferred drug. PMID:23211502
Low leukocyte count secondary to leukocyte aggregation caused by an ethylene diamine tetra acetic acid (EDTA) occur in both benign and malignant disorders. We report a 71-year-old male patient who was admitted to the hospital with acute chest infection. Complete blood count (CBC) collected in ETDA tube and analyzed by sysmex instrument (SE/9500) revealed low hemoglobin level of 9.4g/dl, white blood cell (WBC) count of 8.2x109/L. Peripheral blood smear review shows multiple leukocyte aggregation (one clump in each field). When we asked for another blood sample in citrate anticoagulant, the CBC showed WBC count of 11.8x109/L and neutrophils of 6.26x109/L. This is a case of low leukocyte count secondary to leukocyte aggregation induced by EDTA. (author)
Stanley M. Gartler
In 1914, H. J. Muller postulated the origin of the Y chromosome as having resulted from restricted recombination between homologous sex chromosomes in the male and the accumulation of deleterious mutations. This evolutionary process leads to dosage compensation. This article lays out a brief history of dosage compensation in genetics.
Conte, R R; Kehoe, W A; Nielson, N; Lodhia, H
A pharmacist-managed anticoagulation clinic is described, and information on patient outcome during a nine-year period is presented. Since 1974, a pharmacist has managed an anticoagulation clinic for ambulatory patients and inpatients at San Francisco General Hospital Medical Center. The pharmacist's primary responsibilities include the following: educating patients about their diseases and the importance of drug therapy, monitoring patients' vital signs, performing physical examinations, and adjusting warfarin dosage to maintain prothrombin times within the therapeutic range (1.7-2.5 times normal using control values of 1.0-1.2). These patients are also under the care of their primary physicians. The pharmacist's work is checked by the chief of the cardiac clinic at the end of each clinic session. The effectiveness of the pharmacist in managing clinic patients is reviewed periodically; from January 1975 through June 1984, the pharmacist had treated 140 patients (141 courses of therapy). Of 1792 prothrombin times taken during this time, 1060 (59.2%) were within the therapeutic range of 17-25 seconds, 510 (28.5%) were less than 17 seconds, and 222 (12.4%) were greater than 25 seconds. Only four major hemorrhagic events (0.002 hemorrhages per patient-treatment month) and 89 minor events (0.05 hemorrhages per patient-treatment month) occurred. The recurrence rate of thromboembolic events was 0.007 per patient-treatment month. Pharmacist-managed warfarin therapy in these clinic patients resulted in a level of anticoagulation control and morbidity that was acceptable to physicians. PMID:3788996
Full Text Available Carole Decker,1 Linda Garavalia,2 Brian Garavalia,1 Teresa Simon,3 Matthew Loeb,4 John Spertus6, William Daniel51Mid America Heart Institute at Saint Luke's Hospital in Kansas City Missouri, University of Missouri-Kansas City School of Nursing, 2University of Missouri-Kansas City School of Pharmacy, Kansas City, MO, 3Bristol-Myers Squibb, Princeton, NJ, 4Plaza Primary Care and Geriatrics, 5Saint Luke's Cardiovascular Consultants, Kansas City, MO, 6Mid America Heart Institute at Saint Luke's Hospital in Kansas City Missouri, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USABackground: Warfarin, the most commonly used antithrombotic agent for stroke prophylaxis in atrial fibrillation (AF, requires regular monitoring, frequent dosage adjustments, and dietary restrictions. Clinicians' perceptions of barriers to optimal AF management are an important factor in treatment. Anticoagulation management for AF is overseen by both cardiology and internal medicine (IM practices. Thus, gaining the perspective of specialists and generalists is essential in understanding barriers to treatment. We used qualitative research methods to define key issues in the prescription of warfarin therapy for AF by cardiology specialists and IM physicians.Methods and results: Clinicians were interviewed to identify barriers to warfarin treatment in a large Midwestern city. Interviews were conducted until thematic saturation occurred. Content analysis yielded several themes. The most salient theme that emerged from clinician interviews was use of characteristics other than the patient's CHADS2 score to enact a treatment plan, such as the patient's social situation and past medication-taking behavior. Other themes included patient knowledge, real-world problems, breakdown in communication, and clinician reluctance.Conclusion: Warfarin treatment is associated with many challenges. The barriers identified by clinicians highlight the unmet need associated
Full Text Available Background: The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism (PTE remains controversial. We, therefore, conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE.Methods: We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but without arterial hypotension or shock. The patients were randomly assigned in a single-blind fashion to receive an anticoagulant [Enoxaparin (1 mg/kg twice a day] plus a thrombolytic [Alteplase (100 mg or Streptokinase (1500000 u/2 hours] or an anticoagulant [Enoxaparin (1 mg/kg twice a day] alone. The primary endpoint was in-hospital death or clinical deterioration requiring an escalation of treatment. The secondary endpoints of the study were major bleeding, pulmonary hypertension, right ventricular dilatation at the end of the first week, and exertional dyspnea at the end of the first month.Results: Of 50 patients enrolled, 25 patients were randomly assigned to receive an anticoagulant plus a thrombolytic and the other 25 patients were given an anticoagulant alone. The incidence of the primary endpoints was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group (p value = 0.022. At the time of discharge, pulmonary artery pressure was significantly higher in the anticoagulant-alone group than in the thrombolytic- plus-anticoagulant group (p value = 0.018; however, reduction in the right ventricular size or normalization of the right ventricle showed non-significant differences between the two groups. There was no significant difference regarding the New York Heat Association (NYHA functional class between the two groups at the end of the first month (p value = 0.213. No fatal bleeding or cerebral bleeding
Full Text Available Background/Aim. A single nucleotide polymorphism c.- 1639G>A in the promoter region of vitamin K-epoxide reductase (VKORC1 gene has been found to account for most of the variability in response to oral anticoagulants (OA. The aim of the study was to determine the incidence and the effect of c.-1639G>A polymorphism on the acenocoumarol dosage requirements in the group of patients under stable anticoagulation, and to estimate the variability in response to OA. Methods. Our study included 200 consecutive patients requiring low (n = 43, medium (n = 127 and high (n = 30 acenocoumarol dose. Results. Out of 43 low dose patients, 40 (93 % carried the A allele. The A allele was less frequent in the group of 30 patients requiring high dose: among these patients 13 (43.3% carried the A allele in the heterozygous form and none of them carried AA genotype. The patients with GG genotype required 2.6 times higher dose than the patients carriers of AA genotype (p < 0.0001. In 33 patients (16.5% the overdose occurred during the initiation of anticoagulant therapy and in 11 patients (5.5% it was associated with bleeding. Out of the group of 33 overdosed patients, 27 and 6 patients carried AA and GA genotype, respectively (p < 0.000001. Conclusion. VKORC1 significantly influenced OA dose and predicted individuals predisposed to unstable anticoagulation. The carriers of AA genotype required 2.6 time lower doses of OA than the carriares of GG genotype. Pharmacogenetic testing could predict a high risk of overdose among 28.5 % of our patients - carriers of AA genotype, before anticoagulation therapy initiation.
Pengo, Vittorio; Pegoraro, Cinzia; Cucchini, Umberto; Iliceto, Sabino
A multicenter, observational, retrospective, cross-sectional study of patients, receiving oral anticoagulation therapy (OAT) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF) was conducted in the US, Canada, France, Italy and Spain according to their predominant model of care [routine medical care (RMC) or Anticoagulation Clinic care (ACC)]. The study objectives were to assess anticoagulation control (time in target range), and to describe the features of the local model of care. Consecutive patients were recruited on the basis of a minimum of 60 days of oral anticoagulant treatment over a 12 month period, and clinic and physician details were captured by means of a structured face-to-face or telephone interview. Time in therapeutic range (TTR) was calculated by using linear interpolation between INR values. A total of 1511 patients were recruited, of whom 1445 were included in the analysis of TTR. TTR was higher in ACC (69.5% and 64.9% for Italy and Spain, respectively) with respect to RMC (58.1%, 62.8% and 59.3% for the US, Canada and France, respectively). Mean intervals between INR determinations were between 3 and 4 weeks. Dose changes in case of INR outside therapeutic range were more frequent in Spain and less frequent in France. Striking differences were observed in type of VKA used, specialists involved in patient management, and dosage instructions. Studying of anticoagulation management based on local models of care highlights important discrepancies among countries and suggests further standardization of the management of this important therapy is necessary. PMID:16475046
Full Text Available OBJECTIVES: As the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1, rs7294 (VKORC1, rs1057910 (CYP2C9, rs2108622 (CYP4F2, and rs699664 (GGCX involved in the warfarin action mechanism and the circulatory vitamin K were selected to investigate their polymorphism characteristics and their effects on the pharmacodynamics and pharmacokinetics of warfarin in Chinese population. METHODS: 220 patients with cardiac valve replacement were recruited. International normalized ratio and plasma warfarin concentrations were determined. The five genetic polymorphisms were genotyping by pyro-sequencing. The relationships of maintenance dose, plasma warfarin concentration and INR were assessed among groups categorized by genotypes. RESULTS: rs9923231 and rs7294 in VKORC1 had the analogous genotype frequencies (D': 0.969. 158 of 220 recruited individuals had the target INR (1.5-2.5. Patients with AA of rs9923231 and CC of rs7294 required a significantly lower maintenance dose and plasma concentration than those with AG and TC, respectively. The mean weekly maintenance dose was also significantly lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild homozygote. Eliminating the influence from environment factors (age, body weight and gender, rs9923231 and rs1057910 could explain about 32.0% of the variability in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in plasma concentration. For patients with allele G of rs9923231 and allele T of rs7294, higher plasma concentration was needed to achieve the similar goal INR. CONCLUSIONS: A better understanding of the genetic variants in individuals can be the foundation of warfarin dosing algorithm and facilitate the reasonable and effective use of warfarin in Chinese.
DeLoughery, Thomas G
DeLoughery, Thomas G. Anticoagulation considerations for travel to high altitude. High Alt Med Biol 16:181-185, 2015.-An increasing percentage of the population are on anticoagulation medicine for clinical reasons ranging from stroke prevention in atrial fibrillation to long term prevention of deep venous thrombosis. In recent years, several new direct oral anticoagulants have entered the market. The key questions that should be kept in mind when approaching a potential traveler on anticoagulation are: 1) why is the patient on anticoagulation? 2) do they need to stay on anticoagulation? 3) what are the choices for their anticoagulation? 4) will there be any drug interactions with medications needed for travel? and 5) how will they monitor their anticoagulation while traveling? Knowing the answers to these questions then can allow for proper counseling and planning for the anticoagulated traveler's trip. PMID:26186419
WANG Jing; ZHANG Quanbin; ZHANG Zhongshan; HOU Yun; ZHANG Hong
Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminariajaponica,an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT).The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content,sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.
Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong
Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.
蒋晨阳; 赵莉莉; 王建安; 单江; MOHAMMODBalgaith
Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoag-ulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were random-ly assigned into two groups. Anticoagulation group( Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50 - 70 seconds. Non-anticoagulation group( Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1 (PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded.Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups ( P 0.05) . Three patients in Group A and 2 patients in Group B developed minor limb ischemia( P > 0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B ( P <0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.
JIANG Chen-yang(蒋晨阳); ZHAO Li-li(赵莉莉); WANG Jian-an(王建安); SAN Jiang(单江); MOHAMMOD Balgaith
Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoagulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were randomly assigned into two groups. Anticoagulation group(Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50-70 seconds. Non-anticoagulation group(Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1(PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded. Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups (P0.05). Three patients in Group A and 2 patients in Group B developed minor limb ischemia(P>0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B(P<0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.
Becattini, Cecilia; Lignani, Alessandra; Agnelli, Giancarlo
Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal anticoagulant should be at least as effective as those currently in use, as well as safe, simple to use, and widely applicable. The majority of new anticoagulants currently under investigation are small molecules with a selective and direct anti-Xa or antithrombin action, allowing oral administration in fixed doses. These new agents are in different phases of clinical development. The anti-Xa agent rivaroxaban and the antithrombin agent dabigatran are already available for the prophylaxis of venous thromboembolism in some countries. Apixaban is in an advanced phase of clinical development and several anti-Xa agents are currently approaching phase III clinical trials. Promising results in terms of efficacy and safety profiles have been obtained with these agents in different clinical conditions. Differences in pharmacokinetics and pharmacodynamics could offer the potential for individualized anticoagulant therapies in the near future. PMID:20531960
Kaczorowska, Beata; Pawełczyk, Małgorzata; Przybyła, Monika
Brain stroke is a grave society problem. About 20% ischemic strokes are cardiac related problems. Atrial fibrillation (AF) is the most common cause of ischemic strokes. Decision to deploy anticoagulant treatment with AF patient depends on bleeding and thrombo-embolic risk which summerise scale CHA2DS2VASc and HAS-BLED. Past recent years in AF treatment anticoagulants from the group of vitamin K antagonist were used. At present in brain stroke prevention and systemic emboilment, new oral anticoagulants (NOA) which weren't worst than vitamin K antagonists, and they are recomendet in most cases of AF unrelated with heart valve defets. Useing NOA causes lower risk of bleeding, including intracranial heamorrhage. It is believed that this is related to the selective inhibition of specific coagulation factors, and respect other hemostatic mechanisms. Results from clinical studies NOA are encouraging, but still lacks clear answers regarding, among other things: long-term safety of treatment and economically viable in everyday clinical practice. In addition, to date there is no specific antidote for this group of drugs. PMID:27234866
Carvalho, Claudia M B; Vasanth, Shivakumar; Shinawi, Marwan;
The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects...... with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype...... of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO....
Differences in attitude, education, and knowledge about oral anticoagulation therapy among patients with atrial fibrillation in Europe: result of a self-assessment patient survey conducted by the European Heart Rhythm Association.
Hernández Madrid, Antonio; Potpara, Tatjana S; Dagres, Nikolaos; Chen, Jian; Larsen, Torben B; Estner, Heidi; Todd, Derick; Bongiorni, Maria G; Sciaraffia, Elena; Proclemer, Alessandro; Cheggour, Saida; Amara, Walid; Blomstrom-Lundqvist, Carina
The purpose of this patient survey was to analyse the knowledge about blood thinning medications relative to gender, age, education, and region of residence in patients with atrial fibrillation (AF). A total of 1147 patients with AF [mean age 66 ± 13 years, 529 (45%) women] from eight European countries responded to this survey. Most patients understood that the indication for anticoagulation therapy was to 'thin the blood', but 8.1% responded that the purpose of the medication was to treat the arrhythmia. Patients with college or university grades reported less frequent deviations from their target INR range compared with those without schooling (2.8% vs. 5.1%, P < 0.05). The awareness of anticoagulation-related risk of bleedings was lowest in patients without schooling (38.5%) and highest in those with college and university education (57.0%), P < 0.05. The same pattern was also observed regarding patient's awareness of non-vitamin K antagonist oral anticoagulants (NOACs): 56.5% of the patients with university education and only 20.5% of those without schooling (P < 0.05) knew about NOACs, indicating that information about new anticoagulation therapies remains well below the target. Bleeding events were statistically less frequent in patients on NOACs compared with vitamin K antagonists. The education level and patients' knowledge have a direct influence on the global management of the anticoagulation. PMID:26899998
Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P.; Ismail, Farooq
Objective To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. Methods As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. Results International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%–30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. Conclusion In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients. PMID:27152278
Parks, Anna L; Fang, Margaret C
The number of patients with atrial fibrillation (AF) who are of advanced age or have multiple comorbidities is expected to increase substantially. Older patients with AF generally gain a net benefit from anticoagulation. Guidelines typically recommend anticoagulation. There are multiple challenges in the safe use of anticoagulation in frail patients, including bleeding risk, monitoring and adherence, and polypharmacy. Although there are options for chronic oral anticoagulation, clinicians must understand the unique advantages and disadvantages of these medications when developing a management plan. This article reviews issues surrounding the appropriate use and selection of anticoagulants in complex older patients with AF. PMID:27113150
Truong, Teresa; Armor, Becky L
Warfarin is considered a high-risk drug because of its narrow therapeutic window, variability in dose response, and multitude of drug and food interactions. Although travel advice is available for patients who are taking warfarin, it is geared toward patients who are traveling to developed countries and tends to be lacking in detail. We describe a 53-year-old woman with two mechanical heart valves and chronic atrial fibrillation who was taking warfarin for thromboembolism prophylaxis and had plans to travel to Vietnam for 10 weeks. Three days before her departure, she was prescribed amiodarone for long-term use. As a result of the extended duration of her travel and the complexities of warfarin use, the pharmacists who managed the patient's anticoagulation reviewed several aspects of a comprehensive management approach with the patient for a safe international trip. They assessed the patient's thromboembolic and hemorrhagic risks, and determined which other drugs (e.g., enoxaparin, phytonadione), dosages, and adequate supplies would be required along with warfarin, as well as how to safely transport these drugs during travel. In addition, the logistics of effectively monitoring international normalized ratio (INR) levels were evaluated, and methods of managing multiple potential scenarios were carefully planned out. Contact with the patient was made through pharmacist-directed telephone visits throughout the travel period. A total of 12 telephone visits were conducted with the patient during the 10 weeks of travel. Her INR was supratherapeutic on three occasions and was subtherapeutic once; however, neither enoxaparin nor phytonadione were needed during the travel period, and the patient returned safely to the United States. Effective and safe use of high-risk drugs for patients leaving the United States requires extensive pretravel planning, and pharmacists can play a central role in optimizing therapeutic outcomes for these patients during international travel
Martha L. González-Bárcenas
Full Text Available The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.
Radley, A S; Hall, J; Farrow, M.; Carey, P J
AIMS--To compare the quality of outpatient anticoagulant control before and after the transfer of dosing responsibility to designated trained pharmacists from rotating junior medical staff. METHODS--All International Normalised Ratio (INR) values for an eight month period either side of the staff changeover were assessed for precision of therapeutic control according to described standards. Allowing for patient associated effects, observed and expected frequencies of "successful" control for ...
Chighizola, Cecilia Beatrice; Raschi, Elena; Banzato, Alessandra; Borghi, Maria Orietta; Pengo, Vittorio; Meroni, Pier Luigi
The term "lupus anticoagulant" (LA) refers to a heterogeneous group of immunoglobulins behaving as acquired in vitro inhibitors of coagulation. These antibodies, namely anti-β2GPI and anti-prothrombin antibodies, induce the in vitro elongation of clotting time interfering with phospholipid-dependent coagulation cofactors. Positive LA is associated with thrombosis and pregnancy complications, providing one of the three laboratory criteria for the classification of the anti-phospholipid syndrome. LA is the strongest predictor of clinical events, especially when associated with other anti-phospholipid antibodies. Much more controversial is the risk conveyed by isolated and weak LA. LA detection is technically laborious, envisaging screening, mixing and confirming tests. Hopefully critical issues in LA detection, such as the interference of anticoagulants, will be overcome, in the next future. PMID:26789237
Feher, Gergely; Illes, Zsolt; Komoly, Samuel; Hargroves, David
Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely diverse clinical features, predisposing factors, brain imaging findings, and outcome. Anticoagulation is the cornerstone of CVT management, however, it is not supported by high-quality evicence. Novel oral anticoagulants (NOACs) have been extensively studied in patients with deep vein thrombosis, pulmonary embolism and non-valvular atrial fibrillation. The aim of our work was to review the available evidence for NOACs in the treatment of CVT. Based on our literature search there is insufficient evidence to support the use of NOACs in CVT, although case series with rivaroxaban and dabigatran have showed promising results. PMID:25994451
Full Text Available The short-comings of current anticoagulants have led to the development of newer, albeit more expensive, oral alternatives.Objective: To explore the potential impact the new anticoagulants dabigatran and rivaroxaban in the local hospital setting, in terms of utilisation and subsequent costing.Method: A preliminary costing analysis was performed based on a prospective 2-week clinical audit (29th June - 13th July 2009. Data regarding current anticoagulation management were extracted from the medical files of patients admitted to Ryde Hospital. To model potential costing implications of using the newer agents, the reported incidence of VTE/stroke and bleeding events were obtained from key clinical trials.Results: Data were collected for 67 patients treated with either warfarin (n=46 or enoxaparin (n=21 for prophylaxis of VTE/stroke. At least two-thirds of all patients were deemed suitable candidates for the use of newer oral anticoagulants (by current therapy: warfarin: 65.2% (AF, 34.8% (VTE; enoxaparin: 100%, (VTE. The use of dabigatran in VTE/stroke prevention was found to be more cost-effective than warfarin and enoxaparin due to significantly lower costs of therapeutic monitoring and reduced administration costs. Rivaroxaban was more cost-effective than warfarin and enoxaparin for VTE/stroke prevention when supplier-rebates (33% were factored into costing.Conclusion: This study highlights the potential cost-effectiveness of newer anticoagulants, dabigatran and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer economic advantages, as well as clinical benefits, in the hospital-based management of anticoagulated patients.
Full Text Available Jiyoon C Choi,1 Marco d DiBonaventura,2 Lewis Kopenhafer,2 Winnie W Nelson31LifeScan, Inc, West Chester, PA, 2Health Sciences Practice, Kantar Health, New York, NY, 3Janssen Scientific Affairs LLC, Raritan, NJ, USABackground: Oral dabigatran was recently approved as an alternative to warfarin for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Unlike warfarin, dabigatran has a fixed dosage and few drug interactions, and does not require anticoagulation monitoring or dietary restrictions.Methods: This study aimed to describe and compare characteristics of patients with atrial fibrillation who used dabigatran or only warfarin. Patients with a self-reported diagnosis of atrial fibrillation aged ≥18 years who were receiving (or had received warfarin or dabigatran completed an online survey. Differences in characteristics of dabigatran and warfarin users were tested using chi-squared tests and analysis of variance for categorical and continuous variables, respectively.Results: Overall, 364 patients were surveyed (204 warfarin users, 160 dabigatran users. The mean age was 65.1 years, and 68.7% were male. Dabigatran users were more likely than warfarin users to be female (36.9% versus 27.0% and to have experienced adverse events, including gastrointestinal bleeding, in the 3 months before the survey (21.9% versus 6.9%; P<0.05. Both groups reported high medication adherence (dabigatran users 0.65 versus warfarin users 0.63 missed doses/month. Dabigatran users were more likely than warfarin users to discuss treatment options with their physician before beginning therapy (36.9% versus 24.5%; P<0.05 and less likely to switch anticoagulant medication (10.7% versus 31.9%; P<0.05. Although dabigatran users were more likely to experience adverse events, they reported greater satisfaction with anticoagulation treatment than warfarin users.Conclusion: The efficacy and convenience reported by dabigatran users
Valeska Subiabre, MsCs; Ivan Palomo, PhD; Neftalí Guzmán, PhD; Eduardo Retamales, MsCs; Hugo Henríquez, MsCs; Luis Gonzalez, MsCs
Background: Vitamin K antagonists are drugs that are widely prescribed around the world and their use has helped improve the prognosis of patients with thromboembolic disease. However, a high interindividual variability has been observed in dosage requirements to reach the desired anticoagulation range that could be due to environmental and genetic factors. Studies suggest that ethnicity influences coumarin response, supporting the observed differences in dose requirements across various popu...
Samamaa, M-M; Conard, J; Flaujac, C; Combe, S; Horellou, M-H
Amongst numerous promising anticoagulant molecules, rivaroxaban (Xarelto(®)), dabigatran (Pradaxa(®)) and apixaban (Eliquis(®)) have been registered outside the USA in the prevention of thromboembolic events in patients undergoing total hip or knee prosthetic replacement. Rivaroxaban however has been granted authorisation by the FDA for the thromboprophylaxis after surgery for total hip or knee surgery. Dabigatran has been granted authorisation by the FDA in non-valvular atrial fibrillation (RE-LY trial) while rivaroxaban is expecting approval in this same indication (ROCKET trial). Phase III results in the treatment and in the secondary prevention of established venous thrombosis and pulmonary embolism are encouraging. These small molecules are obtained by chemical synthesis, their molecular weight is lower than 500 daltons. Many coagulation tests may be affected by these molecules. Those modifications should be known in order to avoid misinterpretation of the tests but could also be used to measure plasma concentrations of these products. The choice of a non specific global and readily available test has been documented (Quick time for rivaroxaban and aPTT for dabigatran). Anti-Xa (for rivaroxaban) and anti-IIa (for dabigatran) activities should however be preferred, expressed in ng/ml with calibrated plasmas (containing predetermined concentration of the tested drug). The half-life is around 8 to 12 hours, with a peak activity 2 to 4 hours after ingestion. Dabigatran is mainly eliminated via the kidney, hence requiring dose-adjustment in case of moderate renal insufficiency, and contra-indicated in case of severe renal insufficiency. Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. No data are available in pregnancy or pediatrics, clinical trials are ongoing. There are few interactions with concomitant drugs, which should not be ignored. The short half-life of these new agents compensates for the
Ciurus, Tomasz; Cichocka-Radwan, Anna
Introduction The risk of complications in anticoagulation therapy can be reduced by maximising the percentage of time spent by the patient in the optimal therapeutic range (TTR). However, little is known about the predictors of anticoagulation control. The aim of this paper was to assess the quality of anticoagulant therapy in patients on warfarin and to identify the factors affecting its deterioration. Material and methods We studied 149 patients who required anticoagulant therapy with warfarin due to non-valvular atrial fibrillation and/or venous thromboembolism. Each patient underwent proper training regarding the implemented treatment and remained under constant medical care. Results The mean age of the patients was 68.8 ± 12.6 years, and 59% were male. A total of 2460 international normalised ratio (INR) measurements were collected during the 18-month period. The mean TTR in the studied cohort was 76 ± 21%, and the median was 80%. The level at which high-quality anticoagulation was recorded for this study was based on TTR values above 80%. Seventy-five patients with TTR ≥ 80% were included in the stable anticoagulation group (TTR ≥ 80%); the remaining 74 patients constituted the unstable anticoagulation group (TTR < 80%). According to multivariate stepwise regression analysis, the independent variables increasing the risk of deterioration of anticoagulation quality were: arterial hypertension (OR 2.74 [CI 95%: 1.06-7.10]; p = 0.038), amiodarone therapy (OR 4.22 [CI 95%: 1.30-13.70]; p = 0.017), and obesity (OR 1.11 [CI 95%: 1.02-1.21]; p = 0.013). Conclusions The presence of obesity, hypertension, or amiodarone therapy decreases the quality of anticoagulation with warfarin. High quality of anticoagulation can be achieved through proper monitoring and education of patients. PMID:26855650
... AerobiKa® Cardiology Medications Anticoagulant Medicine Anticoagulants and Drug-Food Interactions COPD Medications Bronchodilators Anti-Inflammatories Antibiotics Managing Your Medications Devices ...
Allione, Alessandra; Di Gaetano, Cornelia; Dani, Nadia; Barberio, Davide; Sieri, Sabina; Krogh, Vittorio; Matullo, Giuseppe
Obesity is an important health problem worldwide. Adipose tissue acts as an endocrine organ that secretes various bioactive substances, called adipokines, including pro-inflammatory biomarkers such as TNF-α, IL-6, leptin and C-reactive protein (CRP) and anti-inflammatory molecules such as adiponectin. The deregulated production of adipokines in obesity is linked to the pathogenesis of various disease processes and monitoring their variation is critical to understand metabolic diseases. The aim of this study was to determine the plasma concentration of adipokines in healthy subjects by multiplexed measurements and the effect of anticoagulants on their levels. Plasma samples from 10 healthy donors were collected in two different anticoagulants (sodium citrate or heparin). All markers, excluding TNF-α, showed significantly higher concentrations in heparinized compared to citrate plasma. However, levels of adipokines in different plasma samples were highly correlated for most of these markers. We reported that different anticoagulants used in the preparation of the plasma samples affected the measurements of some adipokines. The importance of the present results in epidemiology is relevant when comparing different studies in which blood samples were collected with different anticoagulants. PMID:26945995
Becattini, Cecilia; Agnelli, Giancarlo
Venous thromboembolism (VTE) is a common disease associated with high risk for recurrences, death, and late sequelae, accounting for substantial health care costs. Anticoagulant agents are the mainstay of treatment for deep vein thrombosis and pulmonary embolism. The recent availability of oral anticoagulant agents that can be administered in fixed doses, without laboratory monitoring and dose adjustment, is a landmark change in the treatment of VTE. In Phase III trials, rivaroxaban, apixaban, edoxaban (antifactor Xa agents), and dabigatran (an antithrombin agent) were noninferior and probably safer than conventional anticoagulation therapy (low-molecular-weight heparin followed by vitamin K antagonists). These favorable results were confirmed in specific patient subgroups, such as the elderly and fragile. However, some patients, such as those with cancer or with intermediate- to high-risk pulmonary embolism, were underrepresented in the Phase III trials. Further clinical research is required before new oral anticoagulant agents can be considered standard of care for the full spectrum of patients with VTE. PMID:27102510
Elmeros, Morten; Christensen, Thomas Kjær; Lassen, Pia
Anticoagulant rodenticides are widely used to control rodent populations but they also pose a risk of secondary poisoning in non-target predators. Studies on anticoagulant rodenticide exposure of non-target species have mainly reported on frequency of occurrence. They have rarely analyzed variations in residue concentrations. We examine the occurrence and concentrations of five anticoagulant rodenticides in liver tissue from 61 stoats (Mustela erminea) and 69 weasels (Mustela nivalis) from Denmark. Anticoagulant rodenticides were detected in 97% of stoats and 95% of weasels. 79% of the animals had detectable levels of more than one substance. Difenacoum had the highest prevalence (82% in stoats and 88% in weasels) but bromadiolone was detected in the highest concentrations in both stoat (1.290 μg/g ww) and weasel (1.610 μg/g ww). Anticoagulant rodenticide concentrations were highest during autumn and winter and varied with sampling method. Anticoagulant rodenticide concentrations were higher in stoats and weasels with unknown cause of death than in specimens killed by physical trauma. There was a negative correlation between anticoagulant rodenticide concentrations and body condition. Our results suggest that chemical rodent control in Denmark results in an extensive exposure of non-target species and may adversely affect the fitness of some stoats and weasels. PMID:21477845
Graham, S P
The current published literature does not indicate whether the long-term effect of anticoagulant or antiplatelet therapy contributes to mortality reduction in patients with LV dysfunction. Evaluating patients for personal risk for emboli or for ischemic coronary artery events may influence the choice of therapies. As more is learned about the mechanisms of drug effects in different populations, physicians may be better able to direct appropriate therapies. Until that time, one must weigh the risks and benefits of each drug alone and in combination. In NYHA class IV patients, the risk for thrombosis owing to spontaneous clotting increases as does the adverse potential of warfarin and the adverse effects of inhibiting prostaglandin mediated vasodilation by aspirin. In NYHA class I and II patients, the quality of life and convenience of multidrug therapy is weighed against the devastating effect of a major stroke. In less symptomatic patients, the long-term risk for acute coronary events may be higher than previously identified. This would suggest that all patients with depressed LV function should be on some type of antiplatelet or anticoagulant therapy. The current WATCH study will provide much needed information about the outcome differences between these agents. Conclusions based on available data include the following: Heart failure is increasing in incidence and prevalence. Atherosclerotic disease is an important causative factor for the development of heart failure or may be a comorbid condition in these patients. There is a measurable rate of stroke in patients with heart failure, although the cause of death in large studies is more often owing to sudden death or progressive heart failure. Sudden death may be from new ischemic events, asystole, or from ventricular tachyarrhythmias. In patients with heart failure, not all strokes are cardioembolic in origin. The benefits and risks of warfarin may be increased as the EF worsens or heart failure functional class
Yamreudeewong, W; Johnson, J V; Cassidy, T G; Berg, J T
Warfarin is a commonly used oral anticoagulant that is usually initiated after the definitive diagnosis of a certain thromboembolic disorder or disease. Warfarin therapy will usually be prescribed for 6-12 weeks or more, and some patients may continue therapy throughout life, depending on the type of thromboembolic disorder. Major problems associated with warfarin therapy include adverse effects such as bleeding complications and drug-drug or drug-food interactions. In addition, thromboembolic complications may occur due to subtherapeutic dosages of warfarin. The laboratory reference standards for monitoring warfarin therapy are the prothrombin time (PT) and the International Normalized Ratio (INR). While both the PT or INR will reflect the clinical response in the patient, results reported as INR values have been shown to be more accurate than those reported as PT values. Thirty-two patients were enrolled in this study. Our objectives were to compare INR values measured by both the Coumatrak and conventional laboratory method, and to demonstrate the effects of pharmacist intervention on managing patients receiving warfarin therapy. Results from our study reveal that INR monitoring by Coumatrak is similar to the conventional laboratory method. In addition, our study indicates that patients receiving warfarin therapy can be monitored and managed effectively by pharmacists. PMID:8947990
... even if it is not listed below. Aspirin Acetaminophen (e.g., Tylenol, Excedrin) Ibuprofen (e.g., Motrin, ... skin or eyes (jaundice) Rare side effects: Headache Dizziness Shortness of breath Mouth sores or bleeding gums ...
Full Text Available Abstract Background Despite the high frequency with which adverse drug events (ADEs occur in outpatient settings, detailed information regarding these events remains limited. Anticoagulant drugs are associated with increased safety concerns and are commonly involved in outpatient ADEs. We therefore sought to evaluate ambulatory anticoagulation ADEs and the patient population in which they occurred within the Duke University Health System (Durham, NC, USA. Methods A retrospective chart review of ambulatory warfarin-related ADEs was conducted. An automated trigger surveillance system identified eligible events in ambulatory patients admitted with an International Normalized Ratio (INR >3 and administration of vitamin K. Event and patient characteristics were evaluated, and quality/process improvement strategies for ambulatory anticoagulation management are described. Results A total of 169 events in 167 patients were identified from December 1, 2006-June 30, 2008 and included in the study. A median supratherapeutic INR of 6.1 was noted, and roughly half of all events (52.1% were associated with a bleed. Nearly 74% of events resulted in a need for fresh frozen plasma; 64.8% of bleeds were classified as major. A total of 59.2% of events were at least partially responsible for hospital admission. Median patient age was 68 y (range 36-95 y with 24.9% initiating therapy within 3 months prior to the event. Of events with a prior documented patient visit (n = 157, 73.2% were seen at a Duke clinic or hospital within the previous month. Almost 80% of these patients had anticoagulation therapy addressed, but only 60.0% had a follow-up plan documented in the electronic note. Conclusions Ambulatory warfarin-related ADEs have significant patient and healthcare utilization consequences in the form of bleeding events and associated hospital admissions. Recommendations for improvement in anticoagulation management include use of information technology to assist
Rahmat, Nur A; Lip, Gregory Y H
In the last decade, we have witnessed the emergence of the oral non-vitamin K oral anticoagulants (NOACs), which have numerous advantages compared with the vitamin K antagonists, particularly their lack of need for monitoring; as a result their use is increasing. Nonetheless, the NOACs face two...... major challenges: the need for reliable laboratory assays to assess their anticoagulation effect, and the lack of approved antidotes to reverse their action. This article provides an overview of monitoring the anticoagulant effect of NOACs and their potential specific antidotes in development....
Full Text Available Abstract Background The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. Methods MEDLINE and EMBASE databases were searched to identify relevant original articles. Results Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Conclusions Parenteral
Godier, A; Martin, A-C; Rosencher, N; Susen, S
Direct oral anticoagulants (DOAC) are recommended for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism. However, they are associated with hemorrhagic complications. Management of DOAC-induced bleeding remains challenging. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. Therapeutic options also include antidotes: idarucizumab, antidote for dabigatran, has been approved for use whereas andexanet alpha, antidote for anti-Xa agents, and aripazine, antidote for all DOAC, are under development. Other options include hemodialysis for the treatment of dabigatran-associated bleeding and administration of oral charcoal if recent DOAC ingestion. DOAC plasma concentration measurement is necessary to guide DOAC reversal. We propose an update on DOAC-associated bleeding, integrating the availability of dabigatran antidote and the critical place of DOAC concentration measurements. PMID:27297642
Meyer, Barbara J
In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the
Vigano D'Angelo, S; Comp, P C; Esmon, C T; D'Angelo, A.
Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. ...
Taki Galanis, MD
Conclusions: These novel, oral anticoagulant agents are legitimate options for the treatment of VTE. A careful assessment of a patient׳s comorbidities, medication use, and laboratory results should be undertaken before prescribing the new oral anticoagulant agents for patients with VTE.
Acute mesenteric venous thrombosis is potentially lethal because it can result in mesenteric ischemia and, ultimately, bowel infarction requiring surgical intervention. Systemic anticoagulation for the prevention of thrombus propagation is a well-recognized treatment modality and the current mainstay therapy for patients with acute mesenteric venous thrombosis. However, the decision between prompt surgical exploration vs conservative treatment with anticoagulation is somewhat difficult in pat...
Full Text Available BACKGROUND AND AIM OF THE STUDY Optimal duration of oral anticoagulant therapy (OAT in idiopathic venous thromboembolism (VTE is unknown. Indefinite OAT carries an unacceptable risk of major bleeding and prospective studies have demonstrated that OAT is no longer protective after its withdrawal. How to identify the patients at risk for recurrence? D-dimer is a marker of thrombin activity. Early prospective studies showed that elevated D-dimer levels after anticoagulation had a highly predictive value for a recurrent episode. Does D-dimer assay have a role in gauging the appropriate duration of anticoagulant therapy? The PROLONG study tries to answer this question. METHOD D-dimer assay was performed one month after stopping anticoagulation. Patiens with normal D-dimer levels did not resume anticoagulation while patients with elevated D-dimer levels were randomized to discontinue or resume anticoagulation. Study end-points was the composite of recurrent VTE and major bleeding during an average follow-up of 1.4 years. RESULTS The rate of recurrence is significantly higher in patients with elevated D-dimer levels who discontinued anticoagulation. Resuming anticoagulation in this cohort of patients markedly reduces recurrent events without increasing major bleeding. DISCUSSION AND CONCLUSIONS PROLONG study is provocative, because D-dimer assay is simple, thus not requiring dedicated laboratory facilities. D-dimer test has otherwise high sensitivity but low specificity in VTE diagnosis. Aspecifically elevated D-dimer levels are available in the elderly and the majority of patients included in the study were > 65 years old, thus introducing a possible selection bias. Nonetheless the results of the study are useful for the clinician. Prolongation of vitamin K antagonists in patients with elevated D-dimer levels one month after discontinuation of OAT for a first unprovoked episode of VTE results in a favourable risk-benefit relationship. Probably this
Nilsson, Hanna; Grove, E; Larsen, Torben Bjerregaard;
endpoints: all-cause mortality, major thromboembolism and bleeding events, percentage of time within therapeutic International Normalized Ratio (INR) target range (TTR) and variance of the INR value. Patient data was obtained from two databases in the two centers, where all data had been prospectively......Self-management of oral anticoagulant therapy in two centers: 11.000 patient-years of follow-up H Nilsson1,2,3, EL Grove2, TB Larsen3, M Maegaard1, TD Christensen1 1Department of Cardiothoracic and Vascular Surgery & Institute of Clinical Medicine, Aarhus University Hospital, Aarhus; 2Department of...... registered. Results: Results are pending but baseline characteristics (age, gender, indication for anticoagulant therapy) and data on all-cause mortality, major thromboembolism and bleeding events, TTR, INR-variance will be presented at the meeting. Conclusions: We hope to find a good quality of treatment...
Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract from Arthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet Activation.
Jensen, Gitte S; Drapeau, Cassandra; Lenninger, Miki; Benson, Kathleen F
The goal for this study was to evaluate safety regarding anticoagulant activity and platelet activation during daily consumption of an aqueous cyanophyta extract (ACE), containing a high dose of phycocyanin. Using a randomized, double-blind, placebo-controlled study design, 24 men and women were enrolled after informed consent, and consumed either ACE (2.3 g/day) or placebo daily for 2 weeks. The ACE dose was equivalent to ∼1 g phycocyanin per day, chosen based on the highest dose Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. Consuming ACE did not alter markers for platelet activation (P-selectin expression) or serum P-selectin levels. No changes were seen for activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity. Serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen; the difference in AST levels between the two groups was significant at 2 weeks (P < .02). Reduced levels of alanine transaminase (ALT) were also seen in the group consuming ACE (P < .08). Previous studies showed reduction of chronic pain when consuming 1 g ACE per day. The higher dose of 2.3 g/day in this study was associated with significant reduction of chronic pain at rest and when physically active (P < .05). Consumption of ACE showed safety regarding markers pertaining to anticoagulant activity and platelet activation status, in conjunction with rapid and robust relief of chronic pain. Reduction in AST and ALT suggested improvement in liver function and metabolism. PMID:27362442
Walmsley, T. A.; George, P M; Fowler, R. T.
AIMS: To determine if the iron in EDTA anticoagulated plasma samples can be measured by colorimetric assays using Ferrozine. METHODS: Paired samples of serum and EDTA plasma were obtained from 24 patients and analysed by three commercial iron methods. The EDTA plasmas were also analysed using methods modified by the addition of zinc sulphate or with different concentrations of Ferrozine. The iron contamination of EDTA sample tubes was measured by atomic absorption spectroscopy. RESULTS: Two c...
Skelley, Jessica W; Kyle, Jeffrey A; Roberts, Rachel A
To review the use of the novel oral anticoagulant (NOAC) agents for the treatment of heparin-induced thrombocytopenia (HIT) from relevant clinical trial data. A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google-Scholar searches (1966-March 2016) were conducted using the keywords: thrombocytopenia, NOACs, dabigatran, apixaban, rivaroxaban, edoxaban, Xa inhibitor, direct thrombin inhibitor. Articles evaluating the new oral anticoagulants for thrombocytopenia published in English and using human subjects were selected. Eight clinical trials were identified. References cited in identified articles were used for additional citations. Approximately 12 million hospitalized patients each year are exposed to heparin for thromboprophylaxis. HIT, an immune-mediated, prothrombotic adverse reaction is a potential complication of heparin therapy. As a result, heparin products must be immediately withdrawn and replaced by alternative anticoagulants to compensate for the thrombotic risk associated with HIT. Limitations exist with the only currently FDA approved heparin alternative, argatroban. NOACs have been considered as potential alternatives to traditional agents based on their pharmacologic activity. Case reports have indicated positive results in patients, with clinical outcomes and tolerability supporting the use of the NOACs as alternative agents in the treatment of HIT. Positive results have been reported for the use of NOACs in the treatment of HIT. Further robust studies are needed for definitive decision making by clinicians. PMID:27102287
E.A. Akl; S. Gunukula; M. Barba; V.E.D. Yosuico; F.F. van Doormaal; S. Kuipers; S. Middeldorp; H.O. Dickinson; A. Bryant; H. Schuenemann
Background Anticoagulation may improve survival in patients with cancer through an antitumor effect in addition to the perceived antithrombotic effect. Objectives To evaluate the efficacy and safety of parenteral anticoagulants in patients with cancer with no therapeutic or prophylactic indication f
Cohen, I A; Hutchison, T A; Kirking, D M; Shue, M E
Medical records were retrospectively analyzed to evaluate the success of a pharmacist-managed Anticoagulation Surveillance Clinic (ASC). The 78 patients in group I were followed by the ASC. The 17 patients in Group II were followed by other Veterans Administration Medical Center clinics. Demographic characteristics, warfarin indication and potentially complicating conditions were comparable between the groups. Group I patients had shorter intervals between visits to the clinic than Group II patients. Although not statistically different compared to Group II, Group I patients had better prothrombin time control. Group I patients also had fewer complications per treatment year (6.9% vs 9.0%) and received fewer potentially interacting drugs. The ASC was at least as successful as the other clinics in managing patients on warfarin, and results compared very favorably to those reported in the literature for other anticoagulation clinics. PMID:4019790
Jennifer A Martin
Full Text Available Adverse drug reactions, including severe patient bleeding, may occur following the administration of anticoagulant drugs. Bivalirudin is a synthetic anticoagulant drug sometimes employed as a substitute for heparin, a commonly used anticoagulant that can cause a condition called heparin-induced thrombocytopenia (HIT. Although bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this drug. In contrast, medical professionals can quickly reverse the effects of heparin using protamine. This report details the selection of an aptamer to bivalirudin that functions as an antidote in buffer. This was accomplished by immobilizing the drug on a monolithic column to partition binding sequences from nonbinding sequences using a low-pressure chromatography system and salt gradient elution. The elution profile of binding sequences was compared to that of a blank column (no drug, and fractions with a chromatographic difference were analyzed via real-time PCR (polymerase chain reaction and used for further selection. Sequences were identified by 454 sequencing and demonstrated low micromolar dissociation constants through fluorescence anisotropy after only two rounds of selection. One aptamer, JPB5, displayed a dose-dependent reduction of the clotting time in buffer, with a 20 µM aptamer achieving a nearly complete antidote effect. This work is expected to result in a superior safety profile for bivalirudin, resulting in enhanced patient care.
Sudarshan B. Aher; Dattatraya M. Shinkar; Ravindra B. Saudagar
In the drug development enhancement of oral bioavailability of poorly water soluble drugs is one of the most challenging aspects of drug. The pharmaceutical industry face the problem poor dissolution characteristics of water insoluble drug. these problem solve by applying recent techniques “powdered solution technology” or “liquisolid technology”, for prepare water-insoluble drugs into rapid-release solid dosage forms. Design and formulation of this approach is prescribed according to new mat...
Pollack, Charles V
Long-term oral anticoagulant (OAC) therapy is used for the treatment and prevention of thrombosis and thromboembolism. As OAC use is so widespread, emergency physicians are likely to encounter patients on anticoagulant therapy in the emergency department (ED) on a regular basis, either for the same reasons as the population in general or as a result of the increased bleeding risk that OAC use entails.The vitamin K antagonist warfarin has been the standard OAC for several decades, but recently, the newer agents dabigatran etexilate, rivaroxaban and apixaban (collectively, novel OACs, non-vitamin K OACs, or simply 'NOACs') have become available for long-term use. Protocols for assessing and managing warfarin-treated patients in the ED are well established and include international normalised ratio (INR) testing, which helps guide patient management. However, the INR does not give an accurate evaluation of coagulation status with NOACs, and alternative tests are therefore needed for use in emergency settings. This paper discusses what information the INR provides for a patient taking warfarin and which coagulation tests can guide the physician when treating patients on one of the NOACs, as well as other differences in emergency anticoagulation management. PMID:25987596
Fucoidan (FC),an effective anticoagulant constituent extracted from brown algae,was introduced into silk fibroin (SF) for improving its blood compatibility.The SF and SF/FC blend films were characterized by attenuated total reflectance Fourier-transform infrared (ATR-FTIR),X-ray photoelectron spectroscopy (XPS),scanning electron microscopy (SEM) and dynamic contact angle determinator (CA).The in vitro anticoagulant activities of the films were evaluated by activated partial thromboplastin time (APTT),thrombin time (TT) and prothrombin time (PT) measurements.The endothelial cell attachment and proliferation viability on the film were assessed by micropipette aspiration technique and MTT assay,respectively.The testing results indicated that the introduction of FC increased the roughness,hydrophilicity and sulfate component of the film surface without impeding the formation of β-sheet conformation in SF.More important,FC brought excellent anticoagulant activity and better endothelial cell affinity to SF.The SF/FC blend film was hopeful to be used as blood-contacting biomaterials.
Julio Cesar Lazaro
Full Text Available Introduction Electroconvulsive therapy (ECT is considered the most effective treatment for catatonia regardless its underlying condition. The rigid fixed posture and immobility observed in catatonia may lead to several clinical complications, of which, pulmonary embolism (PE is one of the most severe. The rapid improvement of the psychiatric condition in catatonia-related PE is essential, since immobility favors the occurrence of new thromboembolic events and further complications. In that scenario, ECT should be considered, based on a risk-benefit analysis, aiming at the faster resolution of the catatonia. Methods Case report and literature review. Results A 66-years-old woman admitted to the psychiatric ward with catatonia due to a depressive episode presented bilateral PE. Clinically stable, but still severely depressed after a trial of antidepressants, she was treated with ECT in the course of full anticoagulation with enoxaparin. After five ECT sessions, her mood was significantly better and she was walking and eating spontaneously. She did not present complications related either to PE or to anticoagulation. After the eighth ECT session, she evolved with hypomania, which was managed with oral medication adjustments. The patient was completely euthymic at discharge. Conclusion The case we presented provides further evidence to the anecdotal case reports on the safety of ECT in the course of concomitant full anticoagulant therapy after PE, and illustrates how, with the proper precautions, the benefits of ECT in such condition might outweigh its risks.
Full Text Available Sebastian Luger,1 Carina Hohmann,2 Daniela Niemann,1 Peter Kraft,3 Ignaz Gunreben,3 Tobias Neumann-Haefelin,2 Christoph Kleinschnitz,3 Helmuth Steinmetz,1 Christian Foerch,1 Waltraud Pfeilschifter1 1Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, 2Department of Neurology, Klinikum Fulda gAG, Fulda, 3Department of Neurology, University Hospital Würzburg, Würzburg, Germany Background: Oral anticoagulant therapy (OAT potently prevents strokes in patients with atrial fibrillation. Vitamin K antagonists (VKA have been the standard of care for long-term OAT for decades, but non-VKA oral anticoagulants (NOAC have recently been approved for this indication, and raised many questions, among them their influence on medication adherence. We assessed adherence to VKA and NOAC in secondary stroke prevention. Methods: All patients treated from October 2011 to September 2012 for ischemic stroke or transient ischemic attack with a subsequent indication for OAT, at three academic hospitals were entered into a prospective registry, and baseline data and antithrombotic treatment at discharge were recorded. At the 1-year follow-up, we assessed the adherence to different OAT strategies and patients’ adherence to their respective OAT. We noted OAT changes, reasons to change treatment, and factors that influence persistence to the prescribed OAT. Results: In patients discharged on OAT, we achieved a fatality corrected response rate of 73.3% (n=209. A total of 92% of these patients received OAT at the 1-year follow-up. We observed good adherence to both VKA and NOAC (VKA, 80.9%; NOAC, 74.8%; P=0.243 with a statistically nonsignificant tendency toward a weaker adherence to dabigatran. Disability at 1-year follow-up was an independent predictor of lower adherence to any OAT after multivariate analysis, whereas the choice of OAT did not have a relevant influence. Conclusion: One-year adherence to OAT after stroke is strong (>90% and patients
Meegaard, Peter Martin; Holck, Line H V; Pottegård, Anton;
Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation....
Yates, Scott W
No agents are approved to reverse the effects of newer anticoagulants used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. This review focuses on ways to monitor, interrupt, and reverse such anticoagulation.
The prevalence of medical conditions representing a risk for thromboembolic complications and requiring antithrombotic therapy increases gradually with age. Two cases of fatal noncritical organ bleeding complication that occurred during the conversion period from initial fondaparinux to vitamin K antagonist are presented. An 81-year-old obese female patient (body mass index 43 kg/m(2)) with previous postoperative thrombosis underwent uneventful total knee replacement under spinal anesthesia. She presented with popliteal hematoma during conversion to oral anticoagulant. A 92-year-old female patient (body mass index 33 kg/m(2)) with left lower limb thrombosis was referred to our orthopedics department from her senior citizens' home for right lower limb hematoma and ischemia that occurred during conversion to oral anticoagulant. Thromboembolic and bleeding events in the elderly are real public health problems. Specific guidelines dedicated to this particular population are needed, which will improve the management of anticoagulation and decrease risk of complications. PMID:26547115
Full Text Available Abstract Background The beneficial outcomes of oral anticoagulation therapy are dependent upon achieving and maintaining an optimal INR therapeutic range. There is growing evidence that better outcomes are achieved when anticoagulation is managed by a pharmacist with expertise in anticoagulation management rather than usual care by family physicians. This study compared a pharmacist managed anticoagulation program (PC to usual physician care (UC in a family medicine clinic. Methods A retrospective cohort study was carried out in a family medicine clinic which included a clinical pharmacist. In 2006, the pharmacist assumed anticoagulation management. For a 17-month period, the PC group (n = 112 of patients on warfarin were compared to the UC patients (n = 81 for a similar period prior to 2006. The primary outcome was the percentage of time patients' INR was in the therapeutic range (TTR. Secondary outcomes were the percentage of time in therapeutic range within ± 0.3 units of the recommended range (expanded TTR and percentage of time the INR was >5.0 or Results The baseline characteristics were similar between the groups. Fifty-five percent of the PC group was male with a mean age of 67 years; 51% of the UC group was male with a mean age of 71 years. The most common indications for warfarin in both groups were atrial fibrillation, mechanical heart valves and deep vein thrombosis. The TTR was 73% for PC and 65% for UC (p 5 were 0.3% for PC patients and 0.1% for UC (p Conclusion The pharmacist-managed anticoagulation program within a family practice clinic compared to usual care by the physicians achieved significantly better INR control as measured by the percentage of time patients' INR values were kept in both the therapeutic and expanded range. Based on the results of this study, a collaborative family practice clinic using pharmacists and physicians may be an effective model for anticoagulation management with these results verified in future
An adult, intact female Australian shepherd presented for frank vaginal bleeding of unknown duration. The only coagulation profile abnormality upon presentation was mild prolongation of the partial thromboplastin time (PTT). The uterus was removed at surgery and contained a large amount of coagulated blood. Clotting profiles were markedly abnormal48 hours postoperatively. Serum analysis was positive for brodifacoum, an anticoagulant rodenticide. Preoperative coagulation was most likely normalized by vitamin K-1 therapy administered prior to presentation. The only manifestation of anticoagulant rodenticide was hematometra. Rodenticide intoxication should be considered in the differential diagnosis list of hematometra or metrorrhagia
Wei Lai; Shi-Chun Lu; Guan-Yin Li; Chuan-Yun Li; Ju-Shan Wu; Qing-Liang Guo; Meng-Long Wang; Ning Li
AIM:To compare the incidence of early portal or splenic vein thrombosis (PSVT) in patients treated with irregular and regular anticoagulantion alter splenectomy with gastroesophageal devascularization.METHODS:We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010.Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation,respectively.Group A (153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin (LMWH) irregularly.Group B (148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery,followed by oral warfarin and aspirin for one month regularly.The target prothrombin time/international normalized ratio (PT/INR) was 1.25-1.50.Platelet and PT/INR were monitored.Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy.RESULTS:The patients' data were collected and analyzed retrospectively.Among the patients,94 developed early postoperative mural PSVT,including 63patients in group A (63/153,41.17％) and 31 patients in group B (31/148,20.94％).There were 50 (32.67％)patients in group A and 27 (18.24％) in group B with mural PSVT in the main trunk of portal vein.After the administration of thrombolytic,anticoagulant and antiaggregation therapy,complete or partial thrombus dissolution achieved in 50 (79.37％) in group A and 26 (83.87％) in group B.CONCLUSION:Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization,and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy.Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.
Sudarshan B. Aher
Full Text Available In the drug development enhancement of oral bioavailability of poorly water soluble drugs is one of the most challenging aspects of drug. The pharmaceutical industry face the problem poor dissolution characteristics of water insoluble drug. these problem solve by applying recent techniques “powdered solution technology” or “liquisolid technology”, for prepare water-insoluble drugs into rapid-release solid dosage forms. Design and formulation of this approach is prescribed according to new mathematical model given by spires et al. the solubility is Increasing by using a non-volatile solvent which is suitable for drug, their by dissolving the drug in the non volatile solvent it is termed as liquid medicament. This case, the drug is in a solid dosage form, it is held within the powder substrate in solution or, in a solubilized, almost dispersed state, which contributes to the enhanced drug dissolution and release properties. Liquisolid system is characterized by flow behavior, wettability, powder bed hydrophilicity, saturation solubility, drug content, differential scanning calorimetry, Fourier transform infra red spectroscopy, powder x-ray diffraction, scanning electron microscopy, in-vitro release and in-vivo evaluation.
Maiada M Almousilly
Full Text Available Phenytoin sodium was formulated in a solid dosage form using different bases; o/w emulsion base, water soluble base, oleaginous base, and vanishing cream base. Bases were prepared in two different concentrations, 5% and 10% w/w. The diffusion of the drug from each of the above bases was investigated. Results indicated that the effect of the type of ointment base on the release rate of phenytoin sodium is significant. The rate and extent of phenytoin sodium release and diffusion through mouse skin was higher from the water soluble base (10% w/w compared to other ointment bases, the difference was highly significant (P< 0.05.
Maiada M Almousilly; Loay K. Abdulrahman; Sadiq H. Alshmesawy; Fatima A. Tawfiq
Phenytoin sodium was formulated in a solid dosage form using different bases; o/w emulsion base, water soluble base, oleaginous base, and vanishing cream base. Bases were prepared in two different concentrations, 5% and 10% w/w. The diffusion of the drug from each of the above bases was investigated. Results indicated that the effect of the type of ointment base on the release rate of phenytoin sodium is significant. The rate and extent of phenytoin sodium release and diffusion through mouse ...
Menssen, H D; Melber, K; Brandt, N; Thiel, E
Undesirable interactions between anticoagulants and diagnostic test kit procedures so far have prevented the development of a single uniform blood sampling tube. Contrary to K2-EDTA, heparin and other anticoagulants, hirudin only minimally alters blood cells and dissolved blood constituents, thus qualifying as a universal anticoagulant for diagnostic purposes. Automated complete blood counts, automated analyses of clinical chemistry analytes and immunohaematology were performed from hirudinised and routinely processed blood obtained from healthy volunteers (n=35) and hospitalised patients (n=45). Hirudin (400 ATU/ml blood) sufficiently anticoagulated blood for diagnostic purposes. The measurements of automated complete blood counts obtained from K2-EDTA-anticoagulated and hirudinised blood correlated significantly as did the measurements of 24 clinical chemistry analytes from hirudinised plasma and serum. Regression analysis revealed that the results of complete blood counts and clinical chemistry tests were predictable from the respective measurements from hirudinised blood (p=0.001). Immunohaematological tests and cross-matching from hirudinised and native blood of the same donors gave identical results. Single clotting factors, but not global coagulation analytes, could be measured from hirudinised blood. Therefore, a universal hirudin-containing blood sampling tube could be designed for automated analysis of haematological, serological and clinical chemistry analytes. PMID:11798089
Mukhopadhyay, Suman; Frias, Maria A; Chatterjee, Amrita; Yellen, Paige; Foster, David A
The mTOR pathway is a critical regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling has been observed in most cancers and, thus, the mTOR pathway has been extensively studied for therapeutic intervention. Rapamycin is a natural product that inhibits mTOR with high specificity. However, its efficacy varies by dose in several contexts. First, different doses of rapamycin are needed to suppress mTOR in different cell lines; second, different doses of rapamycin are needed to suppress the phosphorylation of different mTOR substrates; and third, there is a differential sensitivity of the two mTOR complexes mTORC1 and mTORC2 to rapamycin. Intriguingly, the enigmatic properties of rapamycin dosage can be explained in large part by the competition between rapamycin and phosphatidic acid (PA) for mTOR. Rapamycin and PA have opposite effects on mTOR whereby rapamycin destabilizes and PA stabilizes both mTOR complexes. In this review, we discuss the properties of rapamycin dosage in the context of anticancer therapeutics. Mol Cancer Ther; 15(3); 347-53. ©2016 AACR. PMID:26916116
Full Text Available In order to search for sulfated polysaccharides in different invertebrate connective tissues and to examine their biological activities, we have isolated three types of polysaccharides from the body wall of the three sea cucumbers Holothuria edulis, Apostichopus japonicas and Holothuria nobilis. The physicochemical properties and anticoagulant activities of these polysaccharides were examined and compared. The chemical composition analysis and nuclear magnetic resonance (NMR analysis indicate that two types of polysaccharides, sulfated fucan and fucosylated chondroitin sulfate (FuCS, were found in all of the three species and in addition a neutral glycan was observed in H. edulis. The neutral α-glucan was firstly obtained from sea cucumber. The same type of polysaccharides from different species of sea cucumbers have similar physicochemical properties and anticoagulant activities, but those of different types of glycans are significantly different, possibly due to their different monosaccharide compositions, electric charges and average molecular weights. The FuCSs have stronger anticoagulant activities than the sulfated fucans, although the molecular sizes of the FuCSs are lower than those of the sulfated fucans, whereas the neutral glucan has no activity, as expected from the absence of sulfate. Thus, anticoagulant activities of the different type of polysaccharides are likely to relate to monosaccharide composition and sulfate content. Preliminary analysis suggests that the sulfation patterns of the FuCSs may result in the difference in anticoagulant activities. Our data could help elucidate the structure-activity relationship of the sea cucumber polysaccharides.
Suzuki, Tatsuhiko; Endo, Jiro
This paper reveals the dosages of decoctions in Shanghanlun in relation of pills and powder formulations, and obtains following results. At the first examination of the system of weight, while Taohongjing shows three kinds of system of weight; [(1)1liang is equivalent to 14 g. (2) 1liang = 7 g (3) 1liang = 1.4 g], he describes the necessity of the corrective system of weight among the decoctions, the pills and the powder formulations. After Song dynasty, Zhusanfa, which is the method of preparing the decoction by placing powder ingredients of prescriptions in water and simmer, have been mainly adopted. In the term of Zhusanfa, although the whole quantities of prescriptions are written with the ancient weight unit, the notation of the dosage is indicated by the current weight unit, Qian. In Shanghanlun, since the dosage form seems to have been changed from the pills or the powders into the decoction, some of decoctions contain impractical dose for decoction. PMID:21796994
Fumagalli, Stefano; Cardini, Francesca; Roberts, Anna T.; Boni, Serena; Gabbai, Debbie; Calvani, Silvia; Casalone Rinaldi, Marta; Manetti, Stefania; Tarantini, Francesca; Marchionni, Niccolò
Background and aims: Atrial fibrillation (AF) is the most common arrhythmia in elderly people, yet oral anticoagulation is underused in the aged. We tried to determine whether new oral anticoagulants (NOA) have greater psychological tolerability than warfarin. Methods: Age-, gender-matched groups of AF patients receiving NOA (N = 15) or warfarin (N = 15) were assessed with the Anti-Clot Treatment Scale (ACTS) and the Perceived Stress Scale (PSS). Results: Patients were old (81 ...
The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products, Nutrition and Allergies to provide a scientific statement on the safety of glucosamine for patients receiving coumarin anticoagulants. More than 40 case reports have been collected by drug-monitoring agencies that...... showed in some patients being prescribed coumarin anticoagulants, especially warfarin, that the International Normalised Ratio (INR) increased after they began taking glucosamine, which indicated an increase in the coagulation time. In most cases the increased INR values were symptomless but in some...... cases haemorrhage occurred in a variety of organs, and in one case this resulted in a persistent vegetative state. The evidence for an interaction between glucosamine and coumarin anticoagulants is strengthened by the observation that in the majority of cases the INR began to fall to normal values when...
Pauline E Jullien
Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.
Jensen, A S; Idorn, L; Nørager, B;
Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events. It is....... Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable...... difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts...
Court, E L
The pathogenesis of the lupus anticoagulant (LA) has been the focus of much research over the past decade, and a plethora of laboratory tests have been developed to detect it. This essay reviews the nature of LA and its pathogenesis, and a number of approaches employed in its diagnosis. These range from well established tests such as the kaolin clotting time (KCT), activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition test (TTI), to the 'newer' tests such as the dilute Russell's viper venom time (DRVVT) and more recent snake venom tests such as the textarin/ecarin ratio and Taipan snake venom time (TSVT). The criteria for diagnosis are discussed, including pre-analytical variables such as sample preparation, and the effects of therapeutic anticoagulants used to treat thrombotic manifestations of the syndrome or an underlying disease process. PMID:9624740
Moreno Villar, A; Nacle López, I; Barbero Hernández, M J; Lizan Tudela, L
In an attempt to minimize the economic impact due to the incorporation of innovative drugs, health authorities have promoted and supported the evaluation and market positioning of drugs, as equivalent therapeutic alternatives. This issue has recently gained importance, possibly due to the current economic crisis. The equivalent therapeutic alternatives are justified by the need to compete on price, and by the authorities recommendation to establish therapeutic equivalence, price and financing of medicinal products at the same time. The establishment of the new oral anticoagulants and the equivalent therapeutic alternatives is a problematic issue if it is based on the absence of direct comparisons between different drugs and the questionable methodology used in the current indirect comparisons. Currently, it is difficult to determine when a new oral anticoagulant is more recommendable than others, but efforts are being made in order to propose alternatives for the decision based on patient characteristics. PMID:26146035
Full Text Available Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 µg/ml was only 4.88-fold higher than that of the low molecular weight heparin Clexane® (4.1 µg/ml, whereas 80 µg/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed.
Gray, David R; Garabedian-Ruffalo, Susan M; Chretien, Steven D
A cost-benefit evaluation of a clinical pharmacist-managed anticoagulation clinic (AC) was performed. Outpatient and hospital records were examined for 26 patients in the treatment group with an AC clinic and 26 patients in the control group. Therapeutic prothrombin times were maintained within the treatment group to a significantly greater extent than within the control group (ppharmacist-managed AC was effective in maintaining therapeutic prothrombin times, and reducing the incidence of hospitalizations resulting from anticoagulation complications, and can be cost-justified based on a cost-benefit analysis. PMID:17341522
Munson, C F; Reid, A J
Novel oral anticoagulants (NOACs) have emerged as a good alternative to warfarin in the prevention of stroke for patients with atrial fibrillation. NOAC use is increasing rapidly; therefore, greater understanding of their use in the perioperative period is important for optimal care. Studies and reviews that reported on the use of NOACs were identified, with particular focus on the perioperative period. PubMed was searched for relevant articles published between January 2000 and August 2015. The inevitable rise in the use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™), edoxaban (Lixiana™) and dabigatran (Pradaxa™) may present a simplified approach to perioperative anticoagulant management due to fewer drug interactions, rapidity of onset of action and relatively short half-lives. Coagulation status, however, cannot reliably be monitored and no antidotes are currently available. When planning for discontinuation of NOACs, special consideration of renal function is required. Advice regarding the management of bleeding complications is provided for consideration in emergency surgery. In extreme circumstances, haemodialysis may be considered for bleeding with the use of dabigatran. NOACs will increasingly affect operative planning in plastic surgery. In order to reduce the incidence of complications associated with anticoagulation, the management of NOACs in the perioperative period requires knowledge of the time of last dose, renal function and the bleeding risk of the planned procedure. Consideration of these factors will allow appropriate interpretation of the current guidelines. PMID:27013144
Full Text Available Objectives: Bee venom (BV is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50, and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Blood samples were obtained from 10 rabbits, and the prothrombin time (PT and the partial thromboplastin time (PTT tests were conducted. The approximate lethal dose (LD values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa, respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2 and melittin, and that can increase the blood clotting times in vitro.
Full Text Available Abstract Background In animals with heteromorphic sex chromosomes, dosage compensation of sex-chromosome genes is thought to be critical for species survival. Diverse molecular mechanisms have evolved to effectively balance the expressed dose of X-linked genes between XX and XY animals, and to balance expression of X and autosomal genes. Dosage compensation is not understood in birds, in which females (ZW and males (ZZ differ in the number of Z chromosomes. Results Using microarray analysis, we compared the male:female ratio of expression of sets of Z-linked and autosomal genes in two bird species, zebra finch and chicken, and in two mammalian species, mouse and human. Male:female ratios of expression were significantly higher for Z genes than for autosomal genes in several finch and chicken tissues. In contrast, in mouse and human the male:female ratio of expression of X-linked genes is quite similar to that of autosomal genes, indicating effective dosage compensation even in humans, in which a significant percentage of genes escape X-inactivation. Conclusion Birds represent an unprecedented case in which genes on one sex chromosome are expressed on average at constitutively higher levels in one sex compared with the other. Sex-chromosome dosage compensation is surprisingly ineffective in birds, suggesting that some genomes can do without effective sex-specific sex-chromosome dosage compensation mechanisms.
Full Text Available Helia Robert-Ebadi, Grégoire Le Gal, Marc RighiniDivision of Angiology and Hemostasis (HRE, MR, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland, and Department of Internal Medicine and Chest Diseases, EA 3878 (GETBO, Brest University Hospital, Brest, France (GLGAbstract: Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH, unfractionated heparin (UFH or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.Keywords: anticoagulation, elderly patients, venous thromboembolism, hemorrhagic risk, atrial fibrillation, thrombin inhibitors, factor Xa
Cecilia Becattini, Alessandra Lignani, Giancarlo AgnelliInternal and Cardiovascular Medicine and Stroke Unit, University of Perugia, ItalyAbstract: Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal...
Robinson, Austin A.; Ikuta, Kevin; Soverow, Jonathan
Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circums...
Hookworms of the genus Ancylostoma secrete an anticoagulant that both inhibits the clotting of human plasma and promotes fibrin clot dissolution. This anticoagulant activity is attributable to a 36,000 dalton proteolytic enzyme. The protease can degrade fibrinogen into five smaller polypeptides that intrinsically have anticoagulating properties, covert plasminogen to a mini-plasminogen-like molecule, and hydrolyze a synthetic peptide substrate with specificity for elastolytic enzymes. It is h...
Rybak, Iwona; Ehle, Michael; Buckley, Leo; Fanikos, John
Dabigatran, rivaroxaban, and apixaban are novel oral anticoagulants that offer major advantages over existing agents. The onset of the anticoagulant effect of these agents is rapid. Each agent has a predictable anticoagulant response that eliminates the need for monitoring. Clinical trials have been completed with all three agents in the prevention and treatment of the three leading causes of cardiovascular death: myocardial infarction, stroke, and venous thromboembolism (VTE). Novel agents h...
Wong, Christopher X; Odutayo, Ayodele; Emdin, Connor A; Kinnear, Ned J; Sun, Michelle T
Atrial fibrillation (AF) is common in patients on dialysis. Although randomized trials of anticoagulation for AF have demonstrated striking reductions in stroke, these trials did not recruit patients on dialysis. We thus undertook this systematic review and meta-analysis of observational studies including patients with AF on dialysis that reported associations of anticoagulation use. Twenty studies involving 529,741 subjects and 31,321 patients with AF on dialysis were identified. Anticoagulation was associated with a 45% (95% CI 13% to 88%) increased risk of any stroke, reflecting a nonsignificant 13% (95% CI -4% to 34%) increased ischemic stroke risk and 38% (95% CI 3% to 85%) increased hemorrhagic stroke risk. There was also a 44% (95% CI 38% to 56%) lower risk of any thromboembolism, and a 31% (95% CI 12% to 53%) increased risk of any bleeding but no clear association with cardiovascular death (relative risk 0.99, 95% CI 0.86 to 1.15) or all-cause mortality (relative risk 0.97, 95% CI 0.90 to 1.04). Incident event rates were similar or worse in patients on anticoagulation. In conclusion, these observational analyses provide little supporting evidence of benefit, and instead suggest harm, from anticoagulation in patients on dialysis with AF. These results raise the possibility that the effects of anticoagulation in patients with AF on dialysis may not be similar to the clear benefit of anticoagulation seen in patients with AF without end-stage renal disease. Randomized trials are required to definitively evaluate the safety and efficacy of anticoagulation for AF in the dialysis setting. PMID:27237624
Full Text Available Abstract Background Treatment with oral anticoagulant may influence the quality of life perception as it promotes changes in the patient's life, not offering an evident symptomatic relief and presenting well defined risks, such as bleeding. In this trial, the influence of chronic use of anticoagulants on the quality of life perception has been analyzed in patients assisted at the anticoagulation outpatient unit. Methods The health related quality of life was evaluated through a cross-section study with a sample composed of 72 patients seen from July 23, 2009 to September 2, 2010 at the Anticoagulation Outpatient Unit of the Federal University of Bahia's University Hospital. The study's population was composed by patients with atrial fibrillation and mechanical heart valve. The patients were submitted to two quality of life evaluation questionnaires: a generic questionnaire - the Medical Outcomes Study SF-36 Health Survey (SF36 - and a specific questionnaire - the Duke Anticoagulation Satisfaction Scale (DASS. Results The quality of life perception of the patients studied, based on both the DASS and the SF36, was positive regarding the treatment with oral anticoagulant. The SF36 presented an average score of 62.2 (± 20.0. Among the SF36 evaluated domains, the physical-emotional aspect was the most compromised one regarding life quality perception. The DASS presented an average score of 67.1 (± 18.2 and the domain presenting a greater compromise was the one related to the treatment inconveniences (annoyances, burdens and obligations. Previous hemorrhagic event, comorbidities, drug interactions with medicines that increase the anticoagulant effect, lower education level in the SF36 and younger age group influence a more negative perception of the quality of life, whereas lower education level in the DASS and the duration of treatment for more than 1 year offer a more positive perception. Conclusion Patients seen at the anticoagulation outpatient
Full Text Available In intrauterine life, hemostasis is maintained by the same components as in extrauterine life (blood platelets, coagulation and fibrinolysis systems, involvement of the vascular wall; in the fetus, however, these components show significant differences of a quantitative/qualitative nature. In the present study, we surveyed the literature on the coagulation system in the fetus. We focused on the velocity of development of the coagulation system, being reflected in the increased concentration of all procoagulants and anticoagulants (a rise from approximately 20% in the middle of pregnancy to about 60% or more in the period of labor; exceptions: factors V, VIII and XIII which in the labor period reach the adult level and screening test results (prothrombin time, aPTT - activated prothrombin time, and thrombin time. Reference values were given for the 19-38 weeks of pregnancy and the labor term. Biochemical features of fetal fibrinogen and PIVKA factors were also discussed. The role of activated protein C (APC in the maintenance of balance between procoagulants and anticoagulants was postulated as well as the role of APC in the formation of thrombin activatable fibrinolysis inhibitor (TAFI.
Park, Joon-Sung; Kim, Gheun-Ho; Kang, Chong Myung; Lee, Chang Hwa
Background/Aims Short hemofilter survival and anticoagulation-related life-threatening complications are major problems in systemic anticoagulation with heparin (SAH) for continuous renal replacement therapy (CRRT). The present study examined if regional anticoagulation with citrate (RAC) using commercially available solutions can overcome the associated problems of SAH to produce economical benefits. Methods Forty-six patients were assigned to receive SAH or RAC. We assessed the coagulation ...
Parikh Vikas C.
Full Text Available A simple, sensitive and accurate UV spectrophotometric method has been developed for the determination of Gemfibrozil in bulk and pharmaceutical tablet dosage formulation. This method obeys Beer’s law in the concentration range of 30-90 µg/ml. with correlation coefficient of 0.9993 and exhibiting maximum absorption at 276 nm with apparent molar absorptivity of 0.1703 × 104 L mole-1 cm-1. The method is accurate and precise and is extended to pharmaceutical tablet dosage forms and there was no interference from any common pharmaceutical additives and excipients. The results of analysis were validated statistically and by recovery studies.
Anticoagulant properties of a crude sulfated polysaccharide from the red marine alga Halymenia floresia (Clemente) C. Agardh = Propriedades anticoagulantes de um polissacarídeo sulfatado bruto da alga marinha vermelha Halymenia floresia (Clemente) C. Agardh
Rodrigo César das Neves Amorim; José Ariévilo Gurgel Rodrigues; Márjory Lima Holanda; Paulo Antônio de Souza Mourão; Norma Maria Barros Benevides
Alternative sources of anticoagulants have arisen as a result of the increasing demand for safer anticoagulant clinical therapy, and the sulfated polysaccharides of seaweeds have gained attention in biomedicine. In this study, crude sulfated polysaccharide fractions (denominated Hf1, Hf2 and Hf3) were obtained from the red marine algaHalymenia floresia and the anticoagulant properties of a soluble crude polysaccharide fraction (Hf2s) were assayed. The three differential extractions yielded 38...
This global map of Mars shows the estimated radiation dosages from cosmic rays reaching the surface, a serious health concern for any future human exploration of the planet.The estimates are based on cosmic-radiation measurements by the Mars radiation environment experiment, an instrument on NASA's Mars 2000 Odyssey spacecraft, plus information about Mars' surface elevations from the laser altimeter instrument on NASA's Mars Global Surveyor. The areas of Mars expected to have the lowest levels of cosmic radiation are where the elevation is lowest, because those areas have more atmosphere above them to block out some of the radiation. Earth's thick atmosphere shields us from most cosmic radiation, but Mars has a much thinner atmosphere than we have on Earth.The colors in the map refer to the estimated annual dose equivalent in rems, a unit of radiation dose. The range is generally from 10 rems(color-coded dark blue) to 20 rems (color coded dark red). Radiation exposure for astronauts on the International Space Station in Earth orbit is typically equivalent to an annualized rate of 20 to 40 rems.NASA's Jet Propulsion Laboratory, Pasadena, Calif. manages the 2001 Mars Odyssey and Mars Global Surveyor missions for NASA's Office of Space Science, Washington D.C. The Mars radiation environment experiment was developed by NASA's Johnson Space Center, Houston. Lockheed Martin Astronautics, Denver, is the prime contractor for Odyssey, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.
Full Text Available Anticoagulation Clinics (ACs are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs, but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs.
临床药师参与抗凝管理服务对经皮球囊二尖瓣成形术后心房颤动患者华法林抗凝效果和安全性影响的随机对照试验%A randomized controlled trial of warfarin anti-coagulation efficacy and safety of clinical pharmacist-participated anticoagulation management for patients with atrial fibrillation after percutaneous balloon mitral valvuloplasty
李峥嵘; 王凌; 石增成; 鲍玉琳
(PBMV). Methods The patients who underwent PBMV were divided into trial group and control group by random number table. The patients in the trial group received the clinical pharmacist-participated AMS. The clinical pharmacist provided adjusted warfarin dosage suggestion to clinician and warfarin anticoagulant education to the patients and their family members. The patients in the control group received warfarin following the visiting doctor's advice. Anticoagulant effect indicators included international normalized ratio( INR)compliance rate,effective anticoagulation rate, anticoagulant deficiency rate and excessive anticoagulation rate. Safety evaluation indicators were embolism and bleeding events during the anticoagulant therapy. Results A total of 131 patients were enrolled in the study. The trial group comprised 68 and the control group 63 patients,respectively. The differences in the patients' age,sex composition,body weight,smoking and drinking habits,degree of mitral stenosis, combined disease,baseline INR,and preliminary warfarin dosage after PBMV were not significant between the 2 groups(all P > 0. 05). The INR compliance rate in the trial group and the control group were 53. 3%(217 / 407)and 41. 8%(155 / 371),respectively(P = 0. 001);effective anticoagulation rates were 55. 9%(38 / 68)and 33. 3%(21 / 63),respectively(P = 0. 016);anticoagulant deficiency rate were 19. 9%(81 /407)and 27. 8%(103 / 371),respectively( P = 0. 003);and the excessive anticoagulation rates were 7. 9%(32 / 407)and 14. 0%(52 / 371),respectively(P = 0. 006). There were 6 and 9 patients developed minor bleeding events and each was one slight embolism in the trial group and the control group, respectively. The incidence rate of adverse reactions in the trial group(10. 3% )was lower than that in the control group(15. 9% ),but the difference was not significant. Conclusion The clinical pharmacist-participated AMS may increase the INR compliance rate and the effective anticoagulation rate
Lluís Cuixart Costa
Full Text Available Introduction. Anticoagulant treatment, despite providing a clear benefit to prevent and treat thrombo-embolic disease, is difficult to manage in routine practice. This is due to individual variability of dosing, narrow therapeutic margin, drug interactions, and side effects. An increasing number of patients admitted to nursing homes are under oral anticoagulant therapy because of deep venous thrombosis and, especially, atrial fibrillation. These are patients with a profile that makes prescription of anticoagulant treatment more difficult - elderly, taking multiple concomitant medications and with multiple ailments. Objetive. We hypothesized that the implementation of a primary care pharmacological follow-up program of oral anticoagulant therapy in patients admitted to nursing homes, with the purpose of coordinating the different professionals and care levels, would lead to greater benefit and reduction of side effects. Methods. A one-year descriptive prospective cohort study was conducted of 27 patients admitted to nursing homes who are under anticoagulation therapy followed by the primary care team. We analyzed different variables obtained from computerized medical records, from which indicators on the program were established (coverage and registration as well as outcome indicators (as defined by the British Committee for Standards in Haematology. Results. The profile of patients under anticoagulation and admitted to nursing homes is elderly (84 years, with a predominance of women (70%, atrial fibrillation as most frequent indication (70.4%, hypertension as major cardiovascular risk factor (92% and most of them on multiple drugs (92%. The analysis of the program results showed excellent coverage and registration indicators (100%. Outcome indicators also showed good results, with percentages of optimal international normalized ratio of 78% (exceeding the defined minimum standard and very low rates of complications (3%. Conclusions. The
Jane Hoover-PlowJoseph J Jacobs Center for Thrombosis and Vascular Biology, Departments of Cardiovascular Medicine and Molecular Cardiology, Lerner Research Institute Cleveland Clinic, Ohio, USAAbstract: The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell ...
Markussen, Mette D.; Heiberg, Ann-Charlotte; Nielsen, Robert;
Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement......Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement...
Salvador, Juan Pablo; Marco, María Pilar
[EN] The present invention relates to the design of haptens that are structurally related to coumarin oral anticoagulant compounds (COAC), to be used for the production of specific antibodies against said type of substances and the subsequent use thereof for the development of diagnosis tools for use in laboratories or in point-of-care (PoC) devices. In particular, the produced antibodies have been used to develop a diagnosis tool that enables the plasma levels of COAC to be quantified in pat...
Drozd, N N; Tolstenkov, A S; Makarov, V A; Miphtakhova, N T; Voyushina, T L; Sergeev, M E
Original synthetic peptide derivatives exhibit anticoagulant activity in vitro and in vivo. They delayed fibrin clot formation from human blood plasma in tests for the intrinsic coagulation pathway (activated partial thromboplastin time) and final stage of plasma coagulation (thrombin time) and inhibited amidolytic activity of thrombin. We determined the minimum effective dose of the most active compound providing a 2-fold lengthening of blood clotting time (activated partial thromboplastin time test and thrombin time test), which persisted for 2-3 h. PMID:19024001
Borst, G H A; Counotte, G H M
Second-generation anticoagulant rodenticides can give rise to unexpected casualties in nontarget species in zoos. The first two offspring of a pair of turkey vultures (Cathartes aura) died of brodifacoum toxicosis. The adult birds fed rodenticide-killed mice to their offspring. There are previous case reports of small carnivorous birds (Dacelo novae-guinae and Tockus deckeni) killed eating poisoned (difenacoum and brodifacoum) mice. Even a granivorous species (Rollulus roulroul) died, probably by contamination of its food by cockroaches that transported the rodenticide. PMID:12216801
Full Text Available Tiffany Lee, Erin Davis, Jason Kielly School of Pharmacy, Memorial University, St John's, NL, Canada Background: Anticoagulant therapies provide management options for potentially life-threatening thromboembolic conditions. They also carry significant safety risks, requiring careful consideration of medication dose, close monitoring, and follow-up. Inpatients are particularly at risk, considering the widespread use of anticoagulants in hospitals. This has prompted the introduction of safety goals for anticoagulants in Canada and the USA, which recommend increased pharmacist involvement to reduce patient harm. The goal of this review is to evaluate the efficacy and safety of pharmacist-led inpatient anticoagulation services compared to usual or physician-managed care. Methods: This narrative review includes articles identified through a literature search of PubMed, Embase, and International Pharmaceutical Abstracts databases, as well as hand searches of the references of relevant articles. Full publications of pharmacist-managed inpatient anticoagulation services were eligible if they were published in English and assessed clinical outcomes. Results: Twenty-six studies were included and further divided into two categories: 1 autonomous pharmacist-managed anticoagulation programs (PMAPs and 2 pharmacist recommendation. Pharmacist management of heparin and warfarin appears to result in improvements in some surrogate outcomes (international normalized ratio [INR] stability and time in INR goal range, while results for others are mixed (time to therapeutic INR, length of stay, and activated partial thromboplastin time [aPTT] measures. There is also some indication that PMAPs may be associated with reduced patient mortality. When direct thrombin inhibitors are managed by pharmacists, there seems to be a shorter time to therapeutic aPTT and a greater percentage of time in the therapeutic range, as well as a decrease in the frequency of medication
Zimmer, Fabian; Harrison, Peter W; Dessimoz, Christophe; Mank, Judith E
In many diploid species, sex determination is linked to a pair of sex chromosomes that evolved from a pair of autosomes. In these organisms, the degeneration of the sex-limited Y or W chromosome causes a reduction in gene dose in the heterogametic sex for X- or Z-linked genes. Variations in gene dose are detrimental for large chromosomal regions when they span dosage-sensitive genes, and many organisms were thought to evolve complete mechanisms of dosage compensation to mitigate this. However, the recent realization that a wide variety of organisms lack complete mechanisms of sex chromosome dosage compensation has presented a perplexing question: How do organisms with incomplete dosage compensation avoid deleterious effects of gene dose differences between the sexes? Here we use expression data from the chicken (Gallus gallus) to show that ohnologs, duplicated genes known to be dosage-sensitive, are preferentially dosage-compensated on the chicken Z chromosome. Our results indicate that even in the absence of a complete and chromosome wide dosage compensation mechanism, dosage-sensitive genes are effectively dosage compensated on the Z chromosome. PMID:27044516
Full Text Available Background: Dried Whitmania pigra is used for the treatment of cardiovascular and cerebrovascular diseases in traditional Chinese medicine and hot water and alcohol extracts also have anticogulant activity. However, a lower molecular weight and more stable anticogulant is needed. Objective: The objective of the following study is to purify and characterize of an anticoagulant oligopeptide from Hirudo (Whitmania pigra Whitman. Materials and Methods: Gel filtration on Sephadex G 50, ion exchange on diethylaminoethyl cellulose, and semi prepared high performance liquid chromatography were used to purify Hirudo. Automated coagulation analyzer was used for evaluating anticoagulant activity. Molecular weight was measured by Matrix assisted laser desorption ionization time of flight mass spectrometry. Amino acid sequence of the oligopeptide was measured by amino acid sequence analyzer. Results: A new anticoagulant, named whitide, isolated from Hirudo was purified, with a molecular weight 1997.1 Da. Amino acid sequence of the oligopeptide was identified as Gly-Pro-ALa-Gly-Hyp-Val-Gly-Ala-Hyp-Gly-Gly-Hyp-Gly-Val-Arg-Gly-Leu-Hyp-Gly-Asp-Arg-Gly. The results revealed that its amino acid sequence had strong homology to various types of collagen. Conclusion: Whitide might be an orally anticoagulant for its hot and trypsin stable.
Atrial fibrillation (AF) increases the risk of stroke.New anticoagulation agents have recently provided alternative and promising approaches.This paper reviews the current state of anticoagulation therapy in AF patients,focusing on various clinical scenarios and on comparisons,where possible,between western and eastern populations.
Rasmussen, Rune Skovgaard; Corell, Pernille; Madsen, Poul;
UNLABELLED: BACKGROUND: Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy. The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within the...
Full Text Available Abstract Background The 'Perception of Anti-Coagulant Treatment Questionnaire' (PACT-Q was developed to assess patients' expectations of, and satisfaction with their anticoagulant treatment. This questionnaire needs to be finalised and psychometrically validated. Methods The PACT-Q was included in the United States, the Netherlands and France into three phase III multinational clinical trials conducted to evaluate efficacy and safety of a new long-acting anticoagulant drug (idraparinux compared to vitamin K antagonist (VKA. PACT-Q was administered to patients with deep venous thrombosis (DVT, atrial fibrillation (AF or pulmonary embolism (PE at Day 1, to assess patients' expectations, and at 3 and 6 months to assess patients' satisfaction and treatment convenience and burden. The final structure of the PACT-Q (Principal Component Analysis – PCA – with Varimax Rotation was first determined and its psychometric properties were then measured with validity of the structure (Multitrait analysis, internal consistency reliability (Cronbach's alpha coefficients and known-group validity. Results PCA and multitrait analyses showed the multidimensionality of the "Treatment Expectations" dimension, comprising 7 items that had to be scored independently. The "Convenience" and "Burden of Disease and Treatment" dimensions of the hypothesised original structure of the questionnaire were combined, thus resulting in 13 items grouped into the single dimension "Convenience". The "Anticoagulant Treatment Satisfaction" dimension remained unchanged and included 7 items. All items of the "Convenience" and "Anticoagulant Treatment Satisfaction" dimensions displayed good convergent and discriminant validity. The internal consistency reliability was good, with a Cronbach's alpha of 0.84 for the "Convenience" dimension, and 0.76 for the "Anticoagulant Treatment Satisfaction" dimension. Known-group validity was good, especially with regard to occurrence of
Weinstock, Matthew J; Uhlmann, Erik J; Zwicker, Jeffrey I
Both venous thromboembolism and intracranial metastases are common complications in the setting of primary brain tumors and metastatic malignancies. Anticoagulation is indicated in the presence of cancer-associated thrombosis in order to limit the risk of pulmonary embolism; however, there is reluctance to initiate anticoagulation in the setting of intracranial metastatic disease due to potential for intracranial hemorrhage. Recent evidence suggests that therapeutic anticoagulation can be safely administered in the setting of metastatic brain tumors. This review examines the current understanding of the pathophysiology of intracranial hemorrhage in malignancy, describes the incidence of intracranial hemorrhage in the setting of brain tumors with therapeutic anticoagulation, and outlines management strategies relevant to the treatment of intracranial hemorrhage in the setting of anticoagulation. PMID:27067980
Caio Julio Cesar dos Santos Fernandes
Full Text Available Worldwide, venous thromboembolism (VTE is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.
Ciurus, Tomasz; Sobczak, Sebastian; Cichocka-Radwan, Anna
Oral direct inhibitors of thrombin and activated factor Xa are approved as new anticoagulant drugs. In contrast to vitamin K antagonists (VKA) and heparins, the new agents have single targets in the coagulation cascade and more predictable pharmacokinetics, but they lack validated and available antidotes. Unlike VKA, they do not require routine monitoring of coagulation. However, the measurement of their pharmacologic effects might be of value in selected patients. They interfere with the routine coagulation tests, which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. The administration of coagulation factors, such as fresh frozen plasma, prothrombin complex concentrates or recombinant activated FVII, can benefit in life-threatening bleeding or emergency surgery. Specific antidotes for non-vitamin K oral anticoagulants are in clinical development. This review aims at answering in a brief and simplified manner some clinical questions. PMID:26336492
Kowalski, Zbigniew; Kowalski, Piotr; Grzegorek, Damian
The optimal and the most effective treatment of pulmonary embolism is still a matter of concern and each day sees a new set of challenges for the world of medicine. The progress, has been made in recent years, improved quality of life and caused much better treatment results. This is difficult issue in patients, receiving anticoagulant therapy, because they require an individual approach and adjustability to the therapeutic possibilities. The benefits of long-term anticoagulant therapy, which decreases relapses of idiopathic venous thromboembolism and diminishes risk of thromboembolic complications, should be taking under consideration. It is still a matter of dispute the time of carrying out of treatment, especially after the first life idiopathic episode of pulmonary embolism. The purpose of this paper is an overview and a summary of the foregoing achievements concerned the standards of idiopathic pulmonary embolism treatment, expecting benefits flowing with using new oral anticoagulants, as an alternative to known for decades Vitamin K antagonist drugs. A lot of information about new oral anticoagulants speaks in favor of their use, but unknown safety of the drugs caused searching the best strategy of pulmonary embolism treatment all the time. PMID:27591448
Fábio Wildson Gurgel Costa
Full Text Available PURPOSE: To conduct a systematized review of the literature about the main local hemostatic measures to control postoperative bleeding in anticoagulated patients. METHODS: A systematized review of literature was performed in the electronic database Medline (PubMed without restriction of the publication date. The eligibility criteria were studies involving maintenance of the anticoagulant therapy, prospective studies, retrospective studies, randomized clinical trials, controlled clinical studies, comparative studies, multicentric studies or case-control studies. Studies discontinuing anticoagulant therapy, case reports, literature reviews, in vitro studies, animal experiments and articles written in language not compatible with the search strategy adopted in this work were excluded. RESULTS: Twenty-four articles that met the adopted eligibility criteria were selected, enrolling 3891 subjects under anticoagulant therapy. A total of 171 cases of hemorrhage was observed. Tranexamic acid was the main local hemostatic measure used to controlling of postoperative bleeding. CONCLUSION: The local hemostatic measures proved to be effective according to previously published studies. Nevertheless, further clinical studies should be conducted to confirm this effectiveness.
Kaliyamoorthy Kalidasan; Velayudham Ravi; Sunil Kumar Sahu; Murugan Lakshmi Maheshwaran; Kathiresan Kandasamy
Objective:To study the spine structure of stingray Himantura imbricata (H. imbricata) and to evaluate the anticoagulant properties of the spine extract obtained through various solvents extracts followed by antibacterial activity against human pathogens. Methods:Spines of H. imbricata were collected from Nagappattinam coast, Tamil Nadu, India and their spines were observed under the light microscope. The grounded spines were subjected to extraction of metabolites using methanol, ethanol, chloroform and acetone. Antibacterial activity was evaluated by disc diffusion technique against 10 human pathogens. Similarly, anticoagulant activity was also assessed by following United States Pharmacopeia method. Results:Light microscopic observation of spine revealed that the venom apparatus of the stingray H. imbricata consisted of two to three spines, glandular tissue and a sheath. The spine extract showed potent antibacterial activity against all tested pathogen. Maximum activity (14 mm) was found against Staphylococcus aureus. Crude extract showed 91.50 USP units/mg of anticoagulant activity. Conclusions: Microscopic observations gave new insight about the spine structure of the stingray. The spine extracts of H. imbricate showed potent activity against human pathogens revealed by the good zone of inhibition. Chloroform extracts conferred the most prominent antibacterial activity. The anticoagulant activity was also comparable with that of standard heparin.
Full Text Available Objective: To study the spine structure of stingray Himantura imbricata (H. imbricata and to evaluate the anticoagulant properties of the spine extract obtained through various solvents extracts followed by antibacterial activity against human pathogens. Methods: Spines of H. imbricata were collected from Nagappattinam coast, Tamil Nadu, India and their spines were observed under the light microscope. The grounded spines were subjected to extraction of metabolites using methanol, ethanol, chloroform and acetone. Antibacterial activity was evaluated by disc diffusion technique against 10 human pathogens. Similarly, anticoagulant activity was also assessed by following United States Pharmacopeia method. Results: Light microscopic observation of spine revealed that the venom apparatus of the stingray H. imbricata consisted of two to three spines, glandular tissue and a sheath. The spine extract showed potent antibacterial activity against all tested pathogen. Maximum activity (14 mm was found against Staphylococcus aureus. Crude extract showed 91.50 USP units/mg of anticoagulant activity. Conclusions: Microscopic observations gave new insight about the spine structure of the stingray. The spine extracts of H. imbricate showed potent activity against human pathogens revealed by the good zone of inhibition. Chloroform extracts conferred the most prominent antibacterial activity. The anticoagulant activity was also comparable with that of standard heparin.
Chan, Noel C; Eikelboom, John W; Weitz, Jeffrey I
The direct oral anticoagulants (DOACs) represent a major advance in oral anticoagulant therapy and have replaced the vitamin K antagonists as the preferred treatment for many indications. By simplifying long-term anticoagulant therapy and improving its safety, the DOACs have the potential to reduce the global burden of thrombosis. Postmarketing studies suggest that the favorable results achieved with DOACs in the randomized controlled trials can be readily translated into practice, but highlight the need for appropriate patient, drug and dose selection, and careful follow-up. Leveraging on their success to date, ongoing studies are assessing the utility of DOACs for the prevention of thrombosis in patients with embolic stroke of unknown source, heart failure, coronary artery disease, peripheral artery disease, antiphospholipid syndrome, and cancer. The purpose of this article is to (1) review the pharmacology of the DOACs, (2) describe the advantages of the DOACs over vitamin K antagonists, (3) summarize the experience with the DOACs in established indications, (4) highlight current challenges and limitations, (5) highlight potential new indications; and (6) identify future directions for anticoagulant therapy. PMID:27126650
E. N. Bochanova
A complex system of hemostasis regulation, insufficient data on drugs pharmacokinetics, multiple factors effecting treatment, including patient’s adherence to therapy, that can lead to the need for the dosage regimen specification are presented.
E. N. Bochanova
Full Text Available A complex system of hemostasis regulation, insufficient data on drugs pharmacokinetics, multiple factors effecting treatment, including patient’s adherence to therapy, that can lead to the need for the dosage regimen specification are presented.
Andrews, Gavin P
Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation. PMID:17855217
McDonald John F
Full Text Available Abstract Background Dosage compensation in Drosophila is the epigenetic process by which the expression of genes located on the single X-chromosome of males is elevated to equal the expression of X-linked genes in females where there are two copies of the X-chromosome. While epigenetic mechanisms are hypothesized to have evolved originally to silence transposable elements, a connection between transposable elements and the evolution of dosage compensation has yet to be demonstrated. Results We show that transcription of the Drosophila melanogaster copia LTR (long terminal repeat retrotransposon is significantly down regulated when in the hemizygous state. DNA digestion and chromatin immunoprecipitation (ChIP analyses demonstrate that this down regulation is associated with changes in chromatin structure mediated by the histone acetyltransferase, MOF. MOF has previously been shown to play a central role in the Drosophila dosage compensation complex by binding to the hemizygous X-chromosome in males. Conclusion Our results are consistent with the hypothesis that MOF originally functioned to silence retrotransposons and, over evolutionary time, was co-opted to play an essential role in dosage compensation in Drosophila.
Han, Youngjin; Cho, Yong-Pil; Ko, Gi-Young; Seo, Dong Wan; Kim, Min-Ju; Kwon, Hyunwook; Kim, Hyangkyoung; Kwon, Tae-Won
The aim of this study was to determine the clinical outcomes of long-term anticoagulation therapy in patients with symptomatic spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) and to evaluate whether conservative treatment with anticoagulation therapy is a safe and effective treatment modality for these patients.In this single center, observational cohort study, data from a prospectively recruiting symptomatic SIDSMA registry, including demographics, risk factors of interest, clinical characteristics and outcomes, and initial and follow-up computed tomography angiography (CTA) findings, were analyzed retrospectively.During an 8-year period, a total of 52 consecutive patients who underwent conservative treatment with the use of long-term anticoagulation were included in this study. Clinical symptoms resolved within 11 days in all except 4 patients (7.7%); 3 received endovascular treatment for persistent symptoms and 1 received surgical repair. The mean duration of anticoagulation therapy was 9 (range: 3-60) months. A follow-up CTA showed complete remodeling in 20 (41.7%) patients, and the mean diameter and the incidence of false lumen thrombosis were also decreased significantly. There was no anticoagulation therapy-related mortality or morbidity except 2 (4.2%) minor bleeding complications, and no symptomatic recurrence or aggravation of the dissection occurred during the mean follow-up period of 47.5 (range: 10-97) months.The present study showed that long-term anticoagulation therapy could result in a high rate of complete remodeling during the natural course of symptomatic SIDSMA. Conservative treatment with long-term anticoagulation therapy could be an optimal treatment strategy for symptomatic SIDSMA. PMID:27100453
Objective: To determine the effectiveness and safety of antiplatelet and anticoagulant agents in the treatment of extracranial internal carotid artery dissection (eICAD). Methods: Antiplatelet and anticoagulant agents were adopted to treat two cases of eICAD in our hospital. The clinical data were retrospectively analyzed and the medical literatures concerning eICAD, which were obtained from Pubmed database, were reviewed. Results: Most researches advocated the empirical use of antiplatelet and anticoagulant agents in eICAD. About 30% of occluded eICAD could be reopened in 8 days and about 60% - 80% in 3 months after the onset of the disease. During the period of treatment, the rate of ischemic stroke recurrence, disability or death was 8.3%-14.3% in anticoagulant group, while it was 7% - 23.7% in antiplatelet group. Conclusion: Antiplatelet agents can be used in patients with eICAD who are contraindicated to anticoagulants. Anticoagulants should be used as early as possible in patients who are not contraindicated to anticoagulants. (authors)
Full Text Available Whether anticoagulation management practices are associated with improved outcomes in elderly patients with acute venous thromboembolism (VTE is uncertain. Thus, we aimed to examine whether practices recommended by the American College of Chest Physicians guidelines are associated with outcomes in elderly patients with VTE. We studied 991 patients aged ≥65 years with acute VTE in a Swiss prospective multicenter cohort study and assessed the adherence to four management practices: parenteral anticoagulation ≥5 days, INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulation, early start with vitamin K antagonists (VKA ≤24 hours of VTE diagnosis, and the use of low-molecular-weight heparin (LMWH or fondaparinux. The outcomes were all-cause mortality, VTE recurrence, and major bleeding at 6 months, and the length of hospital stay (LOS. We used Cox regression and lognormal survival models, adjusting for patient characteristics. Overall, 9% of patients died, 3% had VTE recurrence, and 7% major bleeding. Early start with VKA was associated with a lower risk of major bleeding (adjusted hazard ratio 0.37, 95% CI 0.20-0.71. Early start with VKA (adjusted time ratio [TR] 0.77, 95% CI 0.69-0.86 and use of LMWH/fondaparinux (adjusted TR 0.87, 95% CI 0.78-0.97 were associated with a shorter LOS. An INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulants was associated with a longer LOS (adjusted TR 1.2, 95% CI 1.08-1.33. In elderly patients with VTE, the adherence to recommended anticoagulation management practices showed mixed results. In conclusion, only early start with VKA and use of parenteral LMWH/fondaparinux were associated with better outcomes.
Wiggins, Barbara S; Northup, Amanda; Johnson, Dominic; Senfield, Jeffrey
Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants-rivaroxaban, apixaban, and edoxaban-are substrates for P-glycoprotein (P-gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P-gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45-year-old African-American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patient's medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatran's metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant
Background: Stroke secondary to Atrial Fibrillation is usually due to thrombi formed in the left atrium and left atrial appendage embolizing to cause ischemic stroke. Therefore, in patients with Atrial Fibrillation, antithrombotic therapy is recommended to prevent stroke. Vitamin K antagonist therapy is most widely used antithrombotic therapy for patients with valvular and non valvular AF. Aspirin is recommended only in low risk patients. This study was conducted to determine the stroke prevention practices in local patients with atrial fibrillation who were candidates for anticoagulation therapy. Method: This was descriptive cross sectional study conducted at Cardiovascular Department Lady Reading Hospital Peshawar and Cardiology Department Hayatabad Medical Complex Peshawar. Sampling technique was non probability consecutive. Patients visiting OPD of respective hospitals with EKG evidence of AF and having CHADES VASC score 2 or more or having mitral stenosis and AF were included in the study. Patients with additional indications for anticoagulation were excluded from the study. Results: A total of 205 patients with atrial fibrillation were studied. Mean age was 60.7±14.7 years. Male were 55.6 percentage (n=114) while 44.4 percentage (n=91) were female. Of these 149 (72.7 percentage) were candidates for anticoagulation based on CHA2DS2 VASc score of 2 and more or mitral stenosis with AF. Only 27.5 percentage (n=41) patients were adequately treated with anticoagulant therapy using VKA or novel oral anticoagulant drugs. Majority of them were getting dual antiplatelet therapy (DAPT). Conclusion: Most patients with AF and high risk characteristics for thromboembolism are not receiving proper stroke prevention therapies. (author)
Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials
Boutitie, Florent; Pinede, Laurent; Schulman, Sam; Agnelli, Giancarlo; Raskob, Gary; Julian, Jim; Hirsh, Jack
Objective To determine how length of anticoagulation and clinical presentation of venous thromboembolism influence the risk of recurrence after anticoagulant treatment is stopped and to identify the shortest length of anticoagulation that reduces the risk of recurrence to its lowest level. Design Pooled analysis of individual participants’ data from seven randomised trials. Setting Outpatient anticoagulant clinics in academic centres. Population 2925 men or women with a first venous thromboembolism who did not have cancer and received different durations of anticoagulant treatment. Main outcome measure First recurrent venous thromboembolism after stopping anticoagulant treatment during up to 24 months of follow-up. Results Recurrence was lower after isolated distal deep vein thrombosis than after proximal deep vein thrombosis (hazard ratio 0.49, 95% confidence interval 0.34 to 0.71), similar after pulmonary embolism and proximal deep vein thrombosis (1.19, 0.87 to 1.63), and lower after thrombosis provoked by a temporary risk factor than after unprovoked thrombosis (0.55, 0.41 to 0.74). Recurrence was higher if anticoagulation was stopped at 1.0 or 1.5 months compared with at 3 months or later (hazard ratio 1.52, 1.14 to 2.02) and similar if treatment was stopped at 3 months compared with at 6 months or later (1.19, 0.86 to 1.65). High rates of recurrence associated with shorter durations of anticoagulation were confined to the first 6 months after stopping treatment. Conclusion Three months of treatment achieves a similar risk of recurrent venous thromboembolism after stopping anticoagulation to a longer course of treatment. Unprovoked proximal deep vein thrombosis and pulmonary embolism have a high risk of recurrence whenever treatment is stopped. PMID:21610040
Full Text Available Venous thromboembolism (VTE, encompassing deep vein thrombosis and pulmonary embolism, requires an immediate anticoagulation, that has been carried out so far by administering a parenteral anticoagulant drug (heparin or derivatives overlapped with an oral vitamin K antagonist (VKA, more often warfarin. Several new direct oral anticoagulants (DOACs, with a mechanism of action completely different than VKA, have been developed in recent years. Recent clinical trials have investigated their use in VTE patients showing results at least equal for efficacy and safety, and sometime even better, as the standard anticoagulant treatment. There are differences in the design of the trials. In two cases the involved DOAC was administered immediately after VTE diagnosis as a single drug treatment (rivaroxaban and apixaban, whereas in the other trials (involving dabigatran and edoxaban the DOAC was administered after an initial course of approximately 7 days with heparin or derivatives. Some clinical trials have also investigated the use of DOACs for extended anticoagulant treatment after the acute phase. Aim of this article is to review the results of the currently available clinical trials that have compared the use of DOACs versus the standard of care in patients with VTE.
Full Text Available New oral anticoagulants are an effective and safe alternative to vitamin K antagonists in many fields of clinical practice. The use of the direct inhibitors of activated Factor II (dabigatran and activated Factor X (apixaban and rivaroxaban, both in patients with non-valvular atrial fibrillation (NVAF and those with acute venous thromboembolism (VTE, is of great interest for internal medicine physicians. This paper aims to give practical guidance on management (starting therapy, follow up and bleeding complications of patients treated with dabigatran, rivaroxaban or apixaban for NVAF or acute VTE providing practical tables concerning the phases of therapy, management of complications, drug interaction and dose adjustment if renal impairment occurs.
This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict. PMID:27625521
Muschin, Tegshi; Budragchaa, Davaanyam; Kanamoto, Taisei; Nakashima, Hideki; Ichiyama, Koji; Yamamoto, Naoki; Shuqin, Han; Yoshida, Takashi
Naturally occurring galactomannans were sulfated to give sulfated galactomannans with degrees of substitution of 0.7-1.4 per sugar unit and molecular weights of M¯n=0.6×10(4)-2.4×10(4). Sulfated galactomannans were found to have specific biological activities in vitro such as anticoagulant, anti-HIV and anti-Dengue virus activities. The biological activities were compared with those of standard dextran and curdlan sulfates, which are polysaccharides with potent antiviral activity and low cytotoxicity. It was found that sulfated galactomannans had moderate to high anticoagulant activity, 13.4-36.6unit/mg, compared to that of dextran and curdlan sulfates, 22.7 and 10.0unit/mg, and high anti-HIV and anti-Dengue virus activities, 0.04-0.8μg/mL and 0.2-1.1μg/mL, compared to those curdlan sulfates, 0.1μg/mL, respectively. The cytotoxicity on MT-4 and LCC-MK2 cells was low. Surface plasmon resonance (SPR) of sulfated galactomannans revealed strong interaction with poly-l-lysine as a model compound of virus proteins, and suggested that the specific biological activities might originate in the electrostatic interaction of negatively charged sulfate groups of sulfated galactomannans and positively charged amino groups of surface proteins of viruses. These results suggest that sulfated galactomannans effectively prevented the infection of cells by viruses and the degree of substitution and molecular weights played important roles in the biological activities. PMID:27154517
WANG Jian-qi; SHI Xu-bo; YANG Jin-gang; HU Da-yi
Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxapadn, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.Methods Atotal of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r= 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU,diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin.The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-Ila activities.
Avci, Fikri Y; Karst, Nathalie A; Linhardt, Robert J
Heparin and low molecular weight heparins are major clinical anticoagulants and the drugs of choice for the treatment of deep venous thrombosis. The discovery of an antithrombin binding domain in heparin focused interest on understanding the mechanism of heparin's antithrombotic/ anticoagulant activity. Various heparin-mimetic oligosaccharides have been prepared in an effort to replace polydisperse heparin and low molecular weight heparins with a structurally-defined anticoagulant. The goal of attaining a heparin-mimetic with no unwanted side-effects has also provided motivation for these efforts. This article reviews structure-activity relationship (SAR) of structurally-defined heparin-mimetic oligosaccharides. PMID:14529394
Eduardo B. Saad
Full Text Available Atrial fibrillation is associated with thromboembolic events that may cause important impairment on quality of life. Pulmonary vein isolation is the treatment of choice in cases that are refractory to medical therapy. Once sheaths and catheters are manipulated inside the left atrium, anticoagulation with heparin must be used during the procedure to protect patients from thromboembolic phenomena. Different strategies of anticoagulation are used at different centers. This review summarizes the pathophysiology of thrombus formation in the left atrium, defines which patients are under high risk and describes the main strategies used for anticoagulation.
Full Text Available Vitamin K antagonists (VKA are among the most widely prescribed drugs in the industrialized world. In fact, for decades, VKA have been the only orally available anticoagulant for the primary and secondary prevention of venous and arterial thrombotic events. Their efficacy has been widely demonstrated in a series of studies carried out in the 1990s. Since the incidences of atrial fibrillation and venous thromboembolism increase exponentially with age, the number of anticoagulated patients is destined to increase. This paper examines anticoagulation therapy management with particular attention to the use of VKA.
Yangcheng, Hanyu; Blanco, Michael; Gardner, Candice; Li, Xuehong; Jane, Jay-Lin
The objective of this study was to understand dosage effects of the Waxy gene on the structures of amylose and amylopectin and on the properties of corn starch. Reciprocal crossing of isogenic normal and waxy corn lines was conducted to develop hybrids with different dosages (0, 1, 2, 3) of Waxy gene in the endosperm. The amylose content of starch and proportions of branch chains of DP 17-30 and extra-long branch chains (DP>100) of amylopectin were positively correlated with the Waxy-gene dosage. Proportions of short (DPstarch were negatively correlated with the Waxy-gene dosage, indicating that amylose facilitated dissociation of the surrounding crystalline regions. These results helped us understand the function of granule-bound starch synthase I in the biosynthesis of amylose and amylopectin and impacts of Waxy-gene dosages on the properties of corn starch. PMID:27261752
The gelatin was irradiated for 0-60 kGy dosages by 60Co γ-ray. The relationship of dosage and properties including viscosity, gel strength, mechanical property, molecular weight and protein component was discussed. The results show that there is a negative correlation between the dosage and intrinsic viscosity, relative viscosity, gel strength and molecular weight. With the increase of irradiation dosage, the γ, β, α chain content of gelatin decreases but the small molecules content increases, and relative molecular weight distribution changes wider. The elongation decreases but tensile strength of gelatin film increases. Compared with no irradiation one, the irradiation gelatin has more compact and smooth surface texture. It is assumed that when the limited water and oxygen exist during the irradiation process, cross-linking and degradation of gelatin molecular produce simultaneously and the main reaction is cross-linking. The reaction degree increases with the dosage. (authors)
We have studied the interaction of 125I-antithrombin (125I-AT) with microvascular endothelial cells (RFPEC) to localize the cellular site of anticoagulantly active heparan sulfate proteoglycans (HSPG). The radiolabeled protease inhibitor bound specifically to the above HSPG with a Kd of approximately 50 nM. Confluent monolayer RFPEC cultures exhibited a linear increase in the amount of AT bound per cell for up to 16 d, whereas suspension RFPEC cultures possessed a constant number of protease inhibitor binding sites per cell for up to 5 d. These results suggest that monolayer RFPEC cultures secrete anticoagulantly active HSPG, which then accumulate in the extracellular matrix. This hypothesis was confirmed by quantitative light and EM level autoradiography which demonstrated that the AT binding sites are predominantly located in the extracellular matrix with only small quantities of protease inhibitor complexed to the cell surface. We have also pinpointed the in vivo position of anticoagulantly active HSPG within the blood vessel wall. Rat aortas were perfused, in situ, with 125I-AT, and bound labeled protease inhibitor was localized by light and EM autoradiography. The anticoagulantly active HSPG were concentrated immediately beneath the aortic and vasa vasorum endothelium with only a very small extent of labeling noted on the luminal surface of the endothelial cells. Based upon the above data, we propose a model whereby luminal and abluminal anticoagulantly active HSPG regulate coagulation mechanism activity
Pan, Chang-Jiang, E-mail: email@example.com; Hou, Yan-Hua; Ding, Hong-Yan; Dong, Yun-Xiao
In the present study, poly(ethylene glycol) (PEG) and collagen I were sequentially immobilized on the titanium surface to simultaneously improve the anticoagulation and endothelial cell proliferation. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy analysis confirmed that PEG and collagen I were successfully immobilized on the titanium surface. Water contact angle results suggested the excellent hydrophilic surface after the immobilization. The anticoagulation experiments demonstrated that the immobilized PEG and collagen I on the titanium surface could not only obviously prevent platelet adhesion and aggregation but also prolong activated partial thromboplastin time (APTT), leading to the improved blood compatibility. Furthermore, immobilization of collagen to the end of PEG chain did not abate the anticoagulation. As compared to those on the pristine and PEG-modified titanium surfaces, endothelial cells exhibited improved proliferative profiles on the surface modified by the sequential immobilization of PEG and collagen in terms of CCK-8 assay, implying that the modified titanium may promote endothelialization without abating the blood compatibility. Our method may be used to modify the surface of blood-contacting biomaterials such as titanium to promote endothelialization and improve the anticoagulation, it may be helpful for development of the biomedical devices such as coronary stents, where endothelializaton and excellent anticoagulation are required.
Bungard, Tammy J; Gardner, Leslie; Archer, Stephen L.; Hamilton, Peter; Ritchie, Bruce; Tymchak, Wayne; Tsuyuki, Ross T.
Background Anticoagulation management services (AMSs) are widely used for anticoagulation management in many countries. Our AMS is a pharmacist-run ambulatory clinic with a physician advisory committee that manages patients referred with complicated anticoagulation histories. This paper assesses the adequacy of anticoagulation, rates of anticoagulant-related events and associated health care resource utilization for patients before and after referral to our AMS. Methods Consecutive patients r...
Lassen, Michael R
For many years, vitamin K antagonists, unfractionated heparins, low-molecular-weight heparins and a pentasaccharide were the only anticoagulant drugs available for the prevention of venous thromboembolism after surgery. However, their benefits were associated with disadvantages, such as their...
Dimova, Cena; Evrosimovska, Biljana; Pandilova, Maja; Kovacevska, Ivona; Zabokova-Bilbilova, Efka
Aim of this study is to review the evidence of different therapy approach, to highlight the areas of major concern and to suggest specific oral surgery treatment for patients on oral anticoagulants. The aim of operative treatment is to minimize the risk of hemorrhage while continuing to protect the patient against thromboembolism formation. The ordinary treatment includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. However, this practice may...
Dimova, Cena; Papakoca, Kiro; Kovacevska, Ivona; Kamceva, Gordana
INTRODUCTIONS: The oral surgeons are frequently asked to manage patients who are receiving oral anticoagulants. The goal of treatment is to minimize the risk of hemorrhage while continuing to protect the patient against thromboembolism formation. The ordinary treatment includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. AIM:However, this practice may logically increase the risk of a potentially life-threatening thromboembolism. Thus, thi...
The oral and maxillofacial surgeons are frequently asked to manage patients who are receiving oral anticoagulants. The goal of treatment is to minimize the risk of hemorrhage while continuing to protect the patient against thromboembolism formation. The ordinary treatment includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. However, this practice may logically increase the risk of a potentially life-threatening thromboembolism. Thus, this is...
The oral and maxillofacial surgeons are frequently asked to manage patients who are receiving oral anticoagulants. The goal of treatment is to minimize the risk of hemorrhage while continuing to protect the patient against thromboembolism formation. The ordinary treatment includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. However, this practice may logically increase the risk of a potentially life-threatening thromboembolism. Thus, this is...
Marcelo Kropf; Cleidson Alves Bergami; Felipe Dias Leal; Claudia Oliveira Dias Passos; Zilda de Santana Gonsalves; Isabela Laudares Marques; Isabela Azevedo Mota; Marcele Lima Monte Gonçalves
Anticoagulant therapy is essential for the prevention of risks associated with the formation of thrombus in patients after surgery, especially in orthopedics. Recently, new oral anticoagulants were introduced in the therapeutic arsenal. This fact is important, because the current drug of choice in clinical practice is enoxaparin, a low molecular weight heparin. As all injecting drugs, enoxaparin may reduce patients' adherence to treatment by dissatisfaction with and resistance to the administ...
Dimova, Cena; Evrosimovska, Biljana; Papakoca, Kiro; Georgiev, Zlatko; Angelovska, Bistra; Ristoska, Sonja
Introduction:The ordinary treatment of anticoagulated patients includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. However, this practice may logically increase the risk of a potentially life-threatening thromboembolism, so this issue is still controversial. The aim of the study was to evaluate the antifibrinolitic mouthwash solution (tranexamic acid) as a local haemostatic modality after oral surgery interventions. Methods:To realize the a...
Barrios, Annette C.; Ventura, Hector O.; Milani, Richard V.
Clinical privileging of pharmacists and the effective use of support staff and information technology have helped create an efficient pharmacist-operated anticoagulation clinic at Ochsner Clinic Foundation that will support future growth efforts for improved patient care. Developed by Ochsner's Department of Cardiology, the pharmacist-operated anticoagulation clinic cares for 2000 patients with a clinical pharmacist, staff pharmacist, registered nurse, and medical assistants. Patients are man...
VALCHEV, Ivan; Binev, Rumen; YORDANOVA, Veska; Nikolov, Yordan
The newest measures for the control of harmful rodent populations are from the anticoagulant rodenticide group, which are divided into 2 subgroups: first and second generations, and indandione derivatives. Non-target organisms are potentially at risk of direct consumption of baits (primary hazard) and of eating poisoned rodents (secondary hazard). Anticoagulant rodenticides inhibit the enzyme vitamin K-dependent carboxylase and thus impair the reactivation of vitamin K1, indirectly affecting ...
Prashanth Panduranga; Mohammed El-Deeb; Chitra Jha
Choosing the best anticoagulant therapy for a pregnant patient with a mechanical prosthetic valve is controversial and the published international guidelines contain no clear-cut consensus on the best approach. This is due to the fact that there is presently no anticoagulant which can reliably decrease thromboembolic events while avoiding damage to the fetus. Current treatments include either continuing oral warfarin or substituting warfarin for subcutaneous unfractionated heparin or low-mole...
Fadi Shamoun; Hiba Obeid; Harish Ramakrishna
Atrial fibrillation continues to be a significant source of morbidity and mortality worldwide. Effective anticoagulation remains the cornerstone of outpatient and inpatient treatment. The use of the new generation of anticoagulants (NOACs) continues to grow. Recently published data indicate their cost-effectiveness and overall safety in stroke prevention; compared to vitamin K antagonists, they can be prescribed in fixed doses for long-term therapy without the need for coagulation monitoring....
Chang, Grace; Yeh, James J
Phlegmasia cerulea dolens (PCD) is an aggressive and life-threatening form of venous thrombosis complicated by ischemic necrosis. Massive thrombosis extends to collateral veins resulting in venous congestion with fluid sequestration in the interstitium causing collapse of arterioles, which progresses to ischemia and, if severe, circulatory collapse and shock. The mortality rate for PCD is as high as 40%, especially when gangrene develops. PCD has been associated with acquired thrombophilias, including malignancy and antiphospholipid syndrome (APS). We present a unique case of a patient with PCD refractory to anticoagulant and thrombolytic therapy, whose fulminant course was attributed to concurrent cholangiocarcinoma and antiphospholipid antibodies identified by a positive lupus anticoagulant assay. This case highlights the importance of uncovering precipitating causes of thromboembolism, which may offer prognostic information and may necessitate therapy beyond anticoagulation and thrombolysis to reduce the morbidity of PCD. The current literature on PCD and APS, along with their associations with malignancy, is reviewed. PMID:24553060
Armentano, Antonio; Iammarino, Marco; Lo Magro, Sonia; Muscarella, Marilena
Poisoning of domestic animals is frequently caused by anticoagulant rodenticides. Validation and applications of a rapid and reliable method for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin) in baits and animal livers using high-performance liquid chromatography with fluorescence detection are reported herein. The methodology was validated by an in-house validation model at 2.5 mg/kg, which is the level commonly found in the tissues of poisoned domestic animals. The 8 anticoagulants can be determined at the concentration range of 1.25-100 mg/kg with determination coefficients higher than 0.992. A recovery value from 70% to 109% was observed for all the studied molecules. The results of the validation process demonstrate suitability for application in official analysis and for monitoring purposes of animal poisoning by anticoagulant rodenticides. PMID:22379046
Full Text Available L Bellamy1, N Rosencher1, BI Eriksson21Anaesthesiology Department, Hôpital Cochin (AP-HP, René Descartes University, Paris 75014 France; 2Orthopaedic Department, University Hospital Sahlgrenska/Ostra, Gothenburg, SwedenAbstract: The recent development of new oral anticoagulants, of which dabigatran etexilate is currently at the most advanced stage of development, is the greatest advance in the provision of convenient anticoagulation therapy for many years. A new oral anticoagulation treatment, dabigatran etexilate, is already on the market in Europe. The main interest probably will be to improve the prescription and the adherence to an effective thromboprophylaxis in medical conditions such as atrial fibrillation without bleeding side effects, without the need for monitoring coagulation, and without drug and food interactions such as vitamin K anticoagulant (VKA treatment. Dabigatran is particularly interesting for extended thromboprophylaxis after major orthopedic surgery in order to avoid daily injection for a month. However, oral long-term treatments such as VKA are not systematically associated with a higher compliance level than injected treatments such as low-molecular-weight heparins. Indeed, adherence to an oral treatment, instead of the usual daily injection in major orthopedic surgery, is complex, and based not only on the frequency of dosing but also on patient motivation, understanding, and socio-economic status. New oral anticoagulants may be useful in this way but education and detection of risk factors of nonadherence to treatment are still essential.Keywords: oral anticoagulant, adherence, compliance, education, dabigatran
Kuznetsov, M R; Leontyev, S G; Neskhodimov, L A; Tolstikhin, V Yu; Khotinskiy, A A
Adequate anticoagulant therapy is a general approach to treatment of deep vein thrombosis. However, the duration of anticoagulant therapy is not strictly specified in everyday clinical practice. The present article deals with various approaches to selecting the duration of therapy with anticoagulants based on the findings of studies, national and foreign clinical guidelines. The minimal duration of therapy for deep vein thrombosis and pulmonary thromboembolism amounts to 3 months in accordance with the national and American recommendations. For some cohorts of patients, continuation of therapy above 3 months is considered: patients with idiopathic thrombosis (the recommended duration of therapy of not less than 6 months), patients having persisting risk factor for relapse of thrombosis on termination of the main therapeutic course, oncological patients (6 month therapy followed by assessing the risk and benefit of continuing therapy with anticoagulants). Prolonged therapy of venous thromboembolism using unfractionated heparin or low-molecular-weight heparin followed by changing over to vitamin K antagonists is associated with decreased risk for thrombosis relapse approximately by 90%, however increasing the risk of haemorrhage. Currently, as an alternative, it is possible to consider administration of novel oral anticoagulants (rivaroxaban, dabigatran, apixaban) which beside high efficacy are associated with less risk of bleeding. The route of administration, no necessity to control the INR, and the minimal number of drug and food interactions make administration of new oral anticoagulants an attractive alternative to therapy with heparins and vitamin K antagonists. PMID:27100556
and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin or once-weekly dosing (ie, idraparinux and idrabiotaparinux, as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban. In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies.Keywords: anticoagulants, venous thromboembolism, cancer, dabigatran, apixaban, rivaroxaban
Elung-Jensen, Thomas; Heisterberg, Jens; Sonne, Jesper;
concentration of enalaprilat afforded the same degree of renoprotection, blood pressure control and minimisation of proteinuria as a high concentration, during 12 months of follow-up. The high-dosage treatment was associated with a more pronounced tendency to hyperkalaemia. Thus, there seems to be no indication...
Hamada, Yukihiro; Kawasumi, Noriyo; Hirai, Jun; Yamagishi, Yuka; Mikamo, Hiroshige
Voriconazole (VRCZ), a broad-spectrum triazole, is served in two dosage forms-injection and oral. VRCZ is difference dosage of oral and intravenous administration writing a medical package insert in Japan. 6 mg/kg intravenous injection (IV) twice daily for first day as initial loading dose, followed by 3-4 mg/kg IV twice daily between meals is recommended. 300 mg orally twice daily for first day as initial loading dose, followed by 150-200 mg orally twice daily between meals is recommended. Patients weighing over 40 kg, 200 mg orally twice daily between meals is recommended. Patients weighing under 40 kg, 100 mg orally twice daily between meals is recommended, increase to 150 mg twice daily if inadequate response. This study evaluated VRCZ trough concentration and oral dosage in the 23 cases which administered VRCZ to analysis for TDM in Aichi University Hospital. Spearman rank correlation coefficient was calculated to examine relationships among variables. The level of statistical significance was set at p=0.05. All data were analyzed and processed on JMP 8 (SAS Institute Japan). There was a significant positive correlation between VRCZ trough concentration and dose/weight (r=0.47 poral dosage is appropriate to administer dose/weight (mg/kg) twice a day as same as IV. PMID:25566590
Maryam Taherkhani; Adineh Taherkhani; SeyedReza Hashemi; Taraneh Faghihi-Langroodi; Roxana Sadeghi; Mohammadreza Beyranvand
Background: The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism (PTE) remains controversial. We, therefore, conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE.Methods: We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but w...
Enriquez, Andres; Lip, Gregory Y H; Baranchuk, Adrian
In recent years, non-vitamin K oral anticoagulants (NOACs) have emerged as an alternative to warfarin for the prevention and treatment of thrombo-embolic disease. Large randomized trials have demonstrated that these agents, which act by directly targeting thrombin (dabigatran) and factor Xa....... New specific antidotes (e.g. idarucizumab, andexanet alfa, and ciraparantag) show promising data, and may soon become available for clinical use. In this article, we review the pharmacology of these agents, the incidence and outcomes of haemorrhagic complications, the available strategies for...
Full Text Available When nurses perform their tasks, they manage situations where maths knowledge is required. Such a situation is the calculation of medication dosage. Aim: The literature review of papers relevant with the mathematical knowledge and drug calculation skills of nurses and nursing students. Material-Method: A search of published research and review articles from January 1989 until March 2012, has been conducted in Pubmed database. The search terms used were: nurses, mathematics skills, numeracy skills and medication dosology calculation skills. Results: Literature review showed that many studies focus in the mathematical knowledge and drug dosage calculation competency of nursing students. Results from these studies revealed that nursing students had poor mathematical knowledge and drug dosage calculation skills. In contrast with students, professional nurses are more likely to have sufficient skills in drug calculations. Apart from the papers analyzing calculation skills' assessment, several studies examined educational interventions in the context of calculation skills enhancement. Accuracy and proficiency in the dosage calculation of medications is a preventive factor of errors made at medication preparation and administration. Conclusion: Mathematical knowledge and drug dosage calculation abilities are interrelated concepts and essential clinical skills for the nurse. The fact that nursing students do not have adequate skills for calculating medications' dosage, might be an issue that schools of nursing education should focus in. Further research of the drug dosage calculation skills is considered essential.
D. S. Zapryanova
Full Text Available Dynamics of the content in the goats’ blood (at the instant the sample was taken, and then after 3, 6 and 24 hours under influence of 4 anticoagulants (sodium fluoride, sodium citrate, heparin and complexon III were studied. Long term storage of the blood samples resulted in the glucose level decrease. It was mostly pronounced under the sodium citrate treatment.
Drozd, N N; Tolstenkov, A S; Makarov, V A; Kuznetsova, T A; Besednova, N N; Shevchenko, N M; Zvyagintseva, T N
Fucoidans isolated from Fucus evanescens and Laminaria cichorioides kelp can inhibit thrombin and factor Xa of the blood coagulation system. In rats, intravenous injection of fucoidans dose-dependently increased anticoagulant activity of the plasma. Fucoidans can form complexes with protamine sulfate. The observed quantitative differences in the action of fucoidans can result from different sulfation degree and the presence of various types of glycoside bonds in polysaccharide molecules. PMID:17415470
Isabelle M Henry
Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and
Yang, Jie; Wang, Yuanhong; Jiang, Tingfu; Lv, Lv; Zhang, Boyuan; Lv, Zhihua
A controlled Cu(2+) catalytic free-radical depolymerization process of fucosylated chondroitin sulfate from sea cucumber Apostichopus japonicus was established. The results showed a good linear relationship between 1/Mw and time during the depolymerization. A series of fractions with different molecular weight were obtained, and the physicochemical properties of them were investigated and compared utilizing the chemical method, IR spectra and NMR spectra. The results showed no significant variations of the backbone and branches structures during the depolymerization. Furthermore, the anticoagulant activities of the depolymerized fractions were evaluated by the activated partial thromboplastin time (APTT). The APTT decreases in proportion to the molecular weight following a linear relationship and the prolongation of APTT activity requires at least oligosaccharide of 4 trisaccharide units (about 4000 Da). Their anticoagulant activity of low molecular weight fraction (Mw = 24,755 Da) is similar to LMWH with significantly less bleeding risk. The results suggest that the low molecular weight fraction could be used as a novel anticoagulant with less undesired side effects. PMID:25260572
Guo, Weihua; Zhu, Jian; Cheng, Zhenping; Zhang, Zhengbiao; Zhu, Xiulin
Polished 316 L stainless steel (SS) was first treated with air plasma to enhance surface hydrophilicity and was subsequently allowed to react with 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane to introduce an atom transfer radical polymerization (ATRP) initiator. Accordingly, the surface-initiated atom transfer radical polymerization of polyethylene glycol methacrylate (PEGMA) was carried out on the surface of the modified SS. The grafting progress was monitored by water contact angle measurements, X-ray photoelectron spectroscopy and atomic force microscopy. The polymer thickness as a function different polymerization times was characterized using a step profiler. The anticoagulative properties of the PEGMA modified SS surface were investigated. The results showed enhanced anticoagulative to acid-citrate-dextrose (ACD) blood after grafting PEGMA on the SS surface. PMID:21528878
Adepoju, GKA; Adeyemi, T
Aim: Citrus aurantifolia (Family Rutaceae) is commonly known as a familiar food and medicine, and s therapeutic effectiveness in a variety of diseases has been suggested in traditional medicine. Various complementary and alternative medicines (CAM) have been shown to interact with orthodox medicines. Hence, the aim of this study is to investigate such a phenomenon particularly the interaction of lime fruit juice with warfarin. Materials and Method: Wistar strain albino rats of both sexes weighing between 190 and 230g were administered with oral doses of the respective drugs used depending on the groups of animals. Effects on the anticoagulant activity of warfarin were determined by standard laboratory methods. Result: Lime fruit juice caused a reduction in the anticoagulant activity of warfarin. Conclusion: This finding has shown that CAM can interact with orthodox medicines hence, warfarin prescribers need to be aware of the usage of CAM and monitor the international normalized ratio (INR) of their patients more frequently. PMID:21042484
Rens, Willem; Wallduck, Margaret S.; Lovell, Frances L.; Ferguson-Smith, Malcolm A; Ferguson-Smith, Anne C.
X chromosome dosage compensation in female eutherian mammals is regulated by the noncoding Xist RNA and is associated with the differential acquisition of active and repressive histone modifications, resulting in repression of most genes on one of the two X chromosome homologs. Marsupial mammals exhibit dosage compensation; however, they lack Xist, and the mechanisms conferring epigenetic control of X chromosome dosage compensation remain elusive. Oviparous mammals, the monotremes, have multi...
The nutrition content, microelement and sense index of the irradiated ginkgo biloba were studied. The results showed that there were no difference in the content of crud fat and microelement between treatment with high dosage irradiation and contrast. The total soluble sugar and carbohydrate in the ginkgo biloba after high dosage irradiation increased 84% and 6.6%-25.3% respectively, but the vitamin C decreased 27.7%-50.3%. The index of color, hardness and odour decreased as the irradiation dosage increased
Omer F. Karatas
Full Text Available PURPOSE: A considerable percentage of patients with benign prostatic hyperplasia (BPH also have additional cardiac pathologies, which often require anticoagulant therapy. The aim of this study was to evaluate the efficacy and safety of photoselective vaporization of the prostate (PVP for BPH in cardiac patients receiving anticoagulant therapy. MATERIALS AND METHODS: A total of 67 patients suffering from BPH and high risk cardiac pathologies were operated on using laser prostatectomy. All patients had cardiac pathologies with bleeding disorders requiring anticoagulant use, and underwent standard urologic evaluation for BPH. Patients were treated with laser prostatectomy for relief of the obstruction using the KTP/532 laser energy at 80 W. RESULTS: The mean patient age was 71.4 years (range 55-80. Mean prostate volume on transrectal ultrasonography was 73.2 mL (range 44-120. Operation time ranged from 40 to 90 min, with an average value of 55 min. The average hospital stay was 48 hours (range 12-72 and the Foley catheters were removed within 48 hours, with a mean catheterization time of 34.2 ± 5.9 hours (0-48. No patient required an additional procedure due to severe bleeding necessitating intervention during the early postoperative phase. Mean International symptoms scoring system (IPSS values and post voiding residual volume decreased and peak urinary flow rate increased (p < 0.001. Our results showed that the mean prostate volume had decreased by 53% at 6 months. CONCLUSIONS: High-power photo selective laser vaporization prostatectomy is a feasible, safe, and effective alternative for the minimal invasive management of BPH, particularly in cardiac patients receiving anticoagulant therapy.
Brendan L Limone
Full Text Available OBJECTIVE: To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF. PATIENTS AND METHODS: We searched Medline, Embase, NHSEED and HTA databases and the Tuft's Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation models of newer agents for SPAF. RESULTS: Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%, European (39% and Canadian (17% perspectives. Models typically assumed patients between 65-73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER for a newer anticoagulant (dabigatran 110 mg (n = 4/150 mg (n = 2; rivaroxaban (n = 1 vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547-$86,000 for dabigatran 150 mg, $20,713-$150,000 for dabigatran 110 mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400-$25,059 vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results. CONCLUSIONS: Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent.
Full Text Available OBJECTIVE: To compare the effects of antiplatelets and anticoagulants on stroke and death in patients with acute cervical artery dissection. DESIGN: Systematic review with Bayesian meta-analysis. DATA SOURCES: The reviewers searched MEDLINE and EMBASE from inception to November 2012, checked reference lists, and contacted authors. STUDY SELECTION: Studies were eligible if they were randomised, quasi-randomised or observational comparisons of antiplatelets and anticoagulants in patients with cervical artery dissection. DATA EXTRACTION: Data were extracted by one reviewer and checked by another. Bayesian techniques were used to appropriately account for studies with scarce event data and imbalances in the size of comparison groups. DATA SYNTHESIS: Thirty-seven studies (1991 patients were included. We found no randomised trial. The primary analysis revealed a large treatment effect in favour of antiplatelets for preventing the primary composite outcome of ischaemic stroke, intracranial haemorrhage or death within the first 3 months after treatment initiation (relative risk 0.32, 95% credibility interval 0.12 to 0.63, while the degree of between-study heterogeneity was moderate (τ(2 = 0.18. In an analysis restricted to studies of higher methodological quality, the possible advantage of antiplatelets over anticoagulants was less obvious than in the main analysis (relative risk 0.73, 95% credibility interval 0.17 to 2.30. CONCLUSION: In view of these results and the safety advantages, easier usage and lower cost of antiplatelets, we conclude that antiplatelets should be given precedence over anticoagulants as a first line treatment in patients with cervical artery dissection unless results of an adequately powered randomised trial suggest the opposite.
Weippl, G; Michos, N; Bolla, K; Stocker, H
The antipyretic effect of single doses of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) syrup, administered at dose levels of 1, 2, 3, 4, 5, 7.5, and 10 mg/kg b.w., was tested in a randomized double-blind and a subsequent open study. The test populations consisted of 100 children in the double-blind study and 40 patients in the open test (20 subjects/group). The patients' age ranged from 2 to 12 years; the lowest initial rectal temperature was 39.0 degrees C. The treatment groups were homogeneous as to demographic data. The temperature was reduced in all treatment groups. In the double-blind study the mean value dropped under the subfebrile threshold of 38.0 degrees C only in the group on 5 mg/kg and remained then constant for up to 6 h following administration. No sufficient antipyretic effect was obtained with lower doses. The results of the additional open study with doses of 7.5 and 10 mg/kg indicated good antipyretic effect. This effect was not, however, superior to that obtained with 5 mg/kg. Pulse and respiratory rates returned to normal within 1.5 h following administration, except in patients on 1 mg/kg. A total of 10 patients, homogeneously distributed in the treatment groups, experienced vomiting as an adverse reaction. Short-term hypotonia was seen in one subject on 7.5 mg/kg. The results obtained show that single doses of suprofen upward of 5 mg/kg b.w. exert satisfactory, long-lasting, antipyretic effect on children. PMID:3911961
Rasmussen, Rasmus V; Snygg-Martin, Ulrika; Olaison, Lars;
-hospital mortality was 23% (95% CI: 17-29%), and there was no significant difference between those with or without anticoagulation. CONCLUSIONS: We found no increased risk of cerebral haemorrhage in S. aureus IE patients receiving anticoagulation. Anticoagulation was associated with a reduced risk of cerebral events...... before initiation of antibiotics. Data support the continuance of anticoagulation in S. aureus IE patients when indicated.......OBJECTIVES: To study the impact of anticoagulation on major cerebral events in patients with left-sided Staphylococcus aureus infective endocarditis (IE). METHODS: A prospective cohort study; the use of anticoagulation and the relation to major cerebral events was evaluated separately at onset...
Colding, H; Møller, S; Andersen, G E
Ampicillin and gentamicin were given continuously i.v. to 36 newborn infants using a dosage schedule and the results were compared with those obtained in an earlier study including 88 infants who received individually calculated dosages. With the dosage schedule the variation in the serum...... concentrations of antibiotics was smaller in the same child throughout the treatment course, but greater between the infants. The 95% limits for the serum concentrations of antibiotics were, however, nearly the same in the two treatment groups, and the use of a dosage schedule is therefore recommended. Serum...
Tarik; Khouya; Mhamed; Ramchoun; Abdelbassat; Hmidani; Souliman; Amrani; Hicham; Harnafi; Mohamed; Benlyas; Younes; Filali; Zegzouti; Chakib; Alem
Objective: To evaluate the anti-inflammatory, anticoagulant and antioxidant effects of aqueous extracts of thyme varieties from Moroccan.Methods: The aqueous extracts of tree medicinal plants [Thymus atlanticus(T. atlanticus), Thymus satureioides and Thymus zygis(T. zygis)] were screened for their antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl radical-scavenging, ferric reducing antioxidant power assay, radical scavenging activity method, the inhibition of 2,2’-azobis(2-amidinopropane) dihydrochloride that induces oxidative erythrocyte hemolysis and thiobarbituric acid reactive substances assay. The anti-inflammatory activity of aqueous extracts was evaluated in vivo using croton oil-induced ear edema and carrageenan-induced paw edema in mice and rats, respectively. This extracts were evaluated in vitro for their anticoagulant activity at the different concentrations by partial thromboplastin time and prothrombin time activated. Results: All thyme varieties were found to possess considerable antioxidant activity and potent anti-inflammatory activity in the croton oil-induced edema. Administration of aqueous extracts of two varieties(50 mg/kg)(T. zygis and T. atlanticus) reduced significantly the carrageenaninduced paw edema similar to non-steroidal anti-inflammatory drug(indomethacin, 10 mg/kg). In partial thromboplastin time and prothrombin time tests, T. atlanticus and T. zygis extracts showed the strongest anticoagulant activity. In contrast, Thymus satureioides did not show the anticoagulant activity in these tests. Conclusions: All aqueous extracts possess considerable antioxidant activity and are rich in total polyphenol and flavonoid but they act differently in the process of inflammatory and coagulation studied. This study shows great variability of biological activities in thyme varieties.
Tantawy, Mahmoud A.; El-Ragehy, Nariman A.; Hassan, Nagiba Y.; Abdelkawy, Mohamed
Apixaban (a novel anticoagulant agent) was subjected to a stress stability study including acid, alkali, oxidative, photolytic, and thermal degradation. The drug was found to be only liable to acidic and alkaline hydrolysis. The degradation product was then isolated and identified by IR and GC-mass spectrometry. Four spectrophotometric methods, namely; first derivative (D1), derivative ratio (DR), ratio difference (RD) and mean centering of ratio spectra (MCR), have been suggested for the determination of apixaban in presence of its hydrolytic degradation product. The proposed methods do not require any preliminary separation step. The accuracy, precision and linearity ranges of the proposed methods were determined, and the methods were validated as per ICH guidelines and the specificity was assessed by analyzing synthetic mixtures containing different percentages of the degradation product with the drug. The developed methods were successfully applied for the determination of apixaban in bulk powder and its tablet dosage form.
Jones, Sophie; McLoughlin, Siobhan; Piovesan, Dana; Savoia, Helen; Monagle, Paul; Newall, Fiona
The complexity of managing children with chronic disease has led to an increase in the use of long-term warfarin therapy. Time in therapeutic range (TTR) is the preferred method for determining efficacy and stability of warfarin management. This study aimed to determine the TTR achievement and incidence of adverse events among pediatric warfarin patients managed by an anticoagulation clinic over 12 months and to compare TTR achievement between patients self-testing (PST) at home and those monitored using routine methods. International normalized ratio (INR) results reported for 2012 for children currently having their warfarin therapy managed by a dedicated pediatric anticoagulation clinic were analyzed. Warfarin-related adverse events were recorded. A total of 164 patients were included. In total, 93 children performed PST and 71 children tested their INR at a hospital or pathology service. TTR achievement for the cohort was 67.1% (95% confidence interval, 64.4-69.7). A total of 69.2% of INR tests conducted at home were within the TTR compared with 64.3% of INR tests conducted at a hospital or pathology service (P=0.07). One major bleeding event occurred and there was 1 thrombotic episode. PST demonstrated noninferior warfarin stability compared with routine methods. Routine outcome evaluation of pediatric anticoagulation management within single institutions is necessary to confirm the success of such programs. PMID:26808370
Full Text Available Jinlei Li, Thomas Halaszynski Department of Anesthesiology, Yale University, Yale New Haven Hospital, New Haven, CT, USA Abstract: Incidence of hemorrhagic complications from neuraxial blockade is unknown, but classically cited as 1 in 150,000 epidurals and 1 in 220,000 spinals. However, recent literature and epidemiologic data suggest that for certain patient populations the frequency is higher (1 in 3,000. Due to safety concerns of bleeding risk, guidelines and recommendations have been designed to reduce patient morbidity/mortality during regional anesthesia. Data from evidence-based reviews, clinical series and case reports, collaborative experience of experts, and pharmacology used in developing consensus statements are unable to address all patient comorbidities and are not able to guarantee specific outcomes. No laboratory model identifies patients at risk, and rarity of neuraxial hematoma defies prospective randomized study so “patient-specific” factors and “surgery-related” issues should be considered to improve patient-oriented outcomes. Details of advanced age, older females, trauma patients, spinal cord and vertebral column abnormalities, organ function compromise, presence of underlying coagulopathy, traumatic or difficult needle placement, as well as indwelling catheter(s during anticoagulation pose risks for significant bleeding. Therefore, balancing between thromboembolism, bleeding risk, and introduction of more potent antithrombotic medications in combination with regional anesthesia has resulted in a need for more than “consensus statements” to safely manage regional interventions during anticoagulant/thromboprophylactic therapy. Keywords: antithrombotics, novel oral anticoagulant, regional, neurologic dysfunction, hematoma, peripheral nerve blockade
Aaron B. Holley
Full Text Available Introduction. Controversy remains over the optimal length of anticoagulation following idiopathic venous thromboembolism. We sought to determine if a longer, finite course of anticoagulation offered additional benefit over a short course in the initial treatment of the first episode of idiopathic venous thromboembolism. Data Extraction. Rates of deep venous thrombosis, pulmonary embolism, combined venous thromboembolism, major bleeding, and mortality were extracted from prospective trials enrolling patients with first time, idiopathic venous thromboembolism. Data was pooled using random effects meta-regression. Results. Ten trials, with a total of 3225 patients, met inclusion criteria. For each additional month of initial anticoagulation, once therapy was stopped, recurrent venous thromboembolism (0.03 (95% CI: −0.28 to 0.35; =.24, mortality (−0.10 (95% CI: −0.24 to 0.04; =.15, and major bleeding (−0.01 (95% CI: −0.05 to 0.02; =.44 rates measured in percent per patient years, did not significantly change. Conclusions: Patients with an initial idiopathic venous thromboembolism should be treated with 3 to 6 months of secondary prophylaxis with vitamin K antagonists. At that time, a decision between continuing with indefinite therapy can be made, but there is no benefit to a longer (but finite course of therapy.
Full Text Available Ji Wang, Chengchu Zhu Department of Cardiothoracic Surgery, Taizhou Hospital, Wenzhou Medical University, Linhai, Zhejiang, People’s Republic of China Abstract: Hypercoagulable state and disorganized angiogenesis are two conspicuous characteristics during tumor progression. There are a considerable number of clinical trials focusing on the effects of anticoagulant and antiangiogenic drugs on the survival of cancer patients. Favorable outcomes have been observed. Excessive blood coagulation not only causes cancer-associated thrombosis, which is a common complication and is the second leading cause of death in patients, but also decreases intratumoral perfusion rates and drug delivery by reducing the effective cross-sectional area of blood vessels. Meanwhile, structural and functional abnormalities of the tumor microvasculature also compromise convective drug transport and create a hypoxic and acidic microenvironment. Vascular normalization strategy can temporarily recover the abnormal state of tumor vasculature by improving blood density, dilation, and leakiness, resulting in enhanced penetration of chemotherapies and oxygen within a short time window. In this article, we first review the evidence to support the opinion that anticoagulant and antiangiogenic therapy can improve cancer survival through several underlying mechanisms. Next, we speculate on the feasibility and value of the combined strategy and discuss whether such a combination has a synergistic antineoplastic effect in cancer patients by way of increasing blood vessel perfusion and drug distribution. Keywords: tumor microenvironment, anticoagulation, antiangiogenesis, vascular normalization, tumor perfusion
Nagai, Mirei; Iwasaki, Kiyotaka; Umezu, Mitsuo; Ozaki, Makoto
Thrombogenic reactions under multiple interactions of pharmacological agents, doses, and materials have not been well understood yet. The aim of this study was to investigate the ability to simultaneously compare thrombogenic reactions to different combinations of anticoagulants, doses, and blood-contacting materials, in a single human blood using an in vitro test method. Four venous blood samples were drawn from each of six healthy volunteers into syringes that contained two different amounts of heparin and argatroban to set the activated clotting time (ACT) to approximately 200 or 500 s, respectively. The four blood samples from each volunteer were immediately poured into two clinical-grade extracorporeal circulation tubes: a polyvinyl chloride (PVC) tube and a poly(2-methoxyethyl acrylate)-coated (PMEA) PVC tube. These tubes with an inner diameter of 12.7 mm were rotated at 183 rpm in a 37°C chamber for 10 min. The results indicated that the in vitro thrombogenicity test method was capable of assessing differences in platelet factor 4 and β-thromboglobulin increases among different combinations of the two materials, two anticoagulants, and two ACTs. Higher amounts of total plasma proteins were absorbed on PVC tubes than on PMEA-coated tubes when using the same anticoagulant and dose. These data elucidate that the in vitro thrombogenicity test method is useful for the simultaneous quantitative evaluation of the influences of various combinations of materials, pharmacological agents, and doses on thrombogenicity in a single human blood. PMID:24652689
Robben, J H; Kuijpers, E A; Mout, H C
The plasma concentration, plasma half-life (t1/2), and mean residence time (MRT) of rodenticide anticoagulants were determined in 21 dogs in which a preliminary diagnosis of anticoagulant rodenticide poisoning had been made. Brodifacoum, difethialone, and difenacoum were detected by high-performance liquid chromatography (HPLC) in the plasma of 13, 3, and 2 dogs, respectively. At presentation the plasma concentration ranged from below the detection limit (10 ng/L) to 851 ng/L. Toxin could not be detected in 3 dogs, despite these animals showing characteristic coagulation disturbances and a positive response to therapy with vitamin K1. In 7 dogs the estimated t1/2 of brodifacoum ranged from 0.9 to 4.7 (median 2.4) days with a MRT of 1.9 to 3.7 (median 2.8) days. In 2 dogs the individual t1/2 of difethialone was 2.2 and 3.2 days and the MRT was 2.3 and 2.8 days, respectively. Two dogs died during emergency treatment. Treatment in the remaining 19 dogs consisted of the administration of vitamin K1 and supportive therapy. The dose of vitamin K1 was reduced in a stepwise manner as long as the prothrombin time remained within physiological limits. The variation in initial plasma concentrations of the anticoagulants combined with the results of treatment support the idea that an individual therapeutic approach is warranted. PMID:9477532
Rowe, F P; Plant, C J; Bradfield, A
Laboratory and field trials were conducted to determine the efficacy of the anticoagulant rodenticide bromadiolone against the house mouse (Mus musculus). In laboratory feeding tests, family groups of warfarin-resistant mice maintained in pens and conditioned to feeding on plain foods were offered pinhead oatmeal bait containing bromadiolone at 0.005%. Overall mortality in replicated 21-day poison treatments was 55/58 or 94.8%. Six field trials were carried out, using the same poison bait, against mice infesting farm buildings. Treatment success, estimated from the results of census baitings conducted before and after treatment, ranged between 60.4% and 100%, mean 92.4%. In equivalent field trials using difenacoum, another newly developed anticoagulant rodenticide, the control achieved ranged between 70.2% and 100%, mean 96.0%. Five field trials, three involving bromadiolone and two difenacoum, were not completely successful and the surviving mice were removed for laboratory examination. In 21-day toxicity tests, each animal was fed the poison bait offered to it earlier in the field. Bromadiolone and difenacoum gave kills of 12/21 (57.1%) and 9/11 (81.8%) respectively. The possible emergence of mouse populations resistant to these anticoagulants is considered. PMID:7288171
Brooks, J E; Htun, P T; Naing, H
The baseline susceptibility of the lesser bandicoot rat, Bandicota bengalensis, from Rangoon, Burma, to five anticoagulant rodenticides was established with no-choice feeding in the laboratory. The susceptibility of lesser bandicoots to the several poisons (brodifacoum, difenacoum, diphacinone, coumatetralyl, and warfarin) was such that they were offered at a 0.001% concentration. B. bengalensis was most susceptible to brodifacoum, and in descending order, difenacoum, coumatetralyl, diphacinone and warfarin. In comparison with Rattus norvegicus on warfarin at 0.005%, B. bengalensis proved more susceptible. Feeding tests at 0.005% concentration indicated that a 1-day feeding on brodifacoum and difenacoum would result in complete mortality, whereas coumatetralyl and warfarin would require 4 days feeding to a 100% kill. Brodifacoum and difenacoum are recommended at 0.002-0.005% bait concentrations and coumatetralyl at 0.005--0.01% concentrations for the control of B. bengalensis in the field in Rangoon. The use of any anticoagulant material in rat control should be alternated with acute toxicants to retard the possible development of anticoagulant resistance. PMID:6444311
Boros, Melanie L; Rybarczyk, Amy M; Gallegos, Patrick J; Zimmerman, Jacob P
This retrospective cohort study was completed to describe the impact of short-term therapy interruptions on anticoagulation control in patients receiving warfarin. Patients seen in a pharmacist-managed anticoagulation clinic were included if they were on a stable warfarin dose and then underwent a planned interruption in therapy. Patients were excluded if phytonadione was administered before the interruption or if medications known to interact with warfarin were altered during the interruption. Data were analyzed for 2 groups: (1) patients with a single interruption in therapy (group 1) and (2) patients with a single interruption in therapy plus patients with an extended interruption in therapy (group 2). The primary endpoint was the change in weekly maintenance warfarin dose from preinterruption to postinterruption. Evaluation of 199 patients resulted in 31 interruptions in group 1 and 34 interruptions in group 2. A change in dose was required in 58% of patients in group 1 and 56% of patients in group 2. The mean absolute change in dose was 2.03 ± 2.79 mg (P anticoagulation control and the direction of this dose change cannot be predicted. PMID:23011173
Muscarella, Marilena; Armentano, Antonio; Iammarino, Marco; Palermo, Carmen; Amorena, Michele
This study evaluates the presence of anticoagulant rodenticides in animals with a diagnosis of suspected poisoning and in bait samples. The survey was carried out from 2010 to 2012, in 2 regions of South Italy (Puglia and Basilicata) on 300 organs of animals and 90 suspected bait samples. The qualitative and quantitative analyses were conducted using an analytical method based on high‑performance liquid chromatography (HPLC) with fluorimetric detection (FLD) for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin). The presence of anticoagulant rodenticides was detected in 33 organs of animals (11% of the total) and 6 bait samples (7% of the total). The most commonly detected compound was coumachlor (47% of 39 positive samples) followed by bromadiolone (24%), and brodifacoum (11%). The species mostly involved in anticoagulant rodenticide poisoning were dogs and cats. This study emphasizes the relevance of the determinations of anticoagulant rodenticides in cases of suspected poisoning in veterinary practice. PMID:27393877
Full Text Available Due to their mechanism of action, the new oral anticoagulants are named direct oral anticoagulants (DOACs. Dabigatran is a selective, competitive, direct inhibitor of thrombin (Factor IIa while rivaroxaban, apixaban and edoxaban act by directly inhibiting the activated Factor X (FXa in a selective and competitive manner. DOACs have a relatively short half-life and almost immediate anticoagulant activity, and rapidly reach the plasma peak concentration. Therefore, they do not need a phase of overlapping with parenteral anticoagulants. After their withdrawal, their removal is sufficiently rapid, although influenced by renal function. Dabigatran is the only DOACs to be administered as a pro-drug and becomes active after drug metabolization. The route of elimination of dabigatran is primarily renal, whereas FXa inhibitors are mainly eliminated by the biliary-fecal route. The drug interactions of DOACs are mainly limited to drugs that act on P-glycoprotein for dabigatran and on P-glycoprotein and/or cytochrome P3A4 for anti-Xa. DOACs have no interactions with food. Given their linear pharmacodynamics, with a predictable dose/response relationship and anticoagulant effect, DOACs are administered at a fixed dose and do not require routine laboratory monitoring.
Klein, Jeffrey A.; Jeske, Daniel R.
BACKGROUND: Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses wer...
Burrell, C D
The realities of the marketplace dictate that pharmaceutical companies seek to develop higher unit dosage forms. Technical problems not infrequently hinder such development. In low doses once-a-day medication with psychotropics is possible and practical. The potential for adverse reactions frequently renders it desirable to divide higher daily doses into two separate doses, one given in the morning and the other in the evening. PMID:1233527
Full Text Available The new oral direct anticoagulants (DOACs could represent a new frontier for management of thromboembolic diseases. However, the new drugs have limitations that need to be considered. Despite the fact that their efficacy and safety profile are at least not inferior to comparators, bleeding risk represents the most feared complication, as for all the antithrombotic drugs. Bleeding risk increases with conditions that interfere with pharmacokinetics, in addition to the risk strictly linked to patients or their co-morbidities. Since all DOACs are excreted from kidneys (even though at different percentages according to the different molecules, renal impairment represents one of the leading causes of DOACs accumulation and bleeding risk. Moderate renal failure is the main condition in which dose adjustment of DOACs could be required, while severe renal impairment represents an absolute contraindication for their use. Renal function must, therefore, be carefully monitored before prescription and during assumption. The older population is at higher bleeding risk, and dose adjustment of DOACs could be required. Although to a lesser degree than oral anticoagulant vitamin K antagonists, DOACs can have drug interactions, especially with P-glycoprotein and cytochrome P3A4 inducers or inhibitors, and these interactions must be taken into account in real practice to avoid accumulation or under dosage. The concomitant use of other drugs, especially antithrombotics, may expose the patients to bleeding risk by reducing the hemostatic properties.
Full Text Available Piperlonguminine (PL, an important component of Piperlongum fruits, is known to exhibit anti-hyperlipidemic, antiplateletand anti-melanogenic activities. Here, the anticoagulantactivities of PL were examined by monitoring activatedpartial-thromboplastin-time (aPTT, prothrombin-time (PT, andthe activities of thrombin and activated factor X (FXa. Theeffects of PL on the expressions of plasminogen activatorinhibitor type 1 (PAI-1 and tissue-type plasminogen activator(t-PA were also tested in tumor necrosis factor-α (TNF-αactivated HUVECs. The results showed that PL prolonged aPTTand PT significantly and inhibited the activities of thrombin andFXa. PL inhibited the generation of thrombin and FXa inHUVECs. In accordance with these anticoagulant activities, PLprolonged in vivo bleeding time and inhibited TNF-α inducedPAI-1 production. Furthermore, PAI-1/t-PA ratio was significantlydecreased by PL. Collectively, our results suggest that PLpossesses antithrombotic activities and that the current studycould provide bases for the development of new anticoagulantagents. [BMB Reports 2013; 46(10: 484-489
Haustein, K O
Anticoagulants of the cumarin-type (warfarin, phenprocoumon, and acenocoumarol) are drugs for the long-term treatment and prevention of thromboembolic disorders. Because of their narrow therapeutic range, many patients have bleedings of variable severity or have recurrent thrombotic events. For this reason, the study of the pharmacokinetic parameters of phenprocoumon (PPC), considering its influence on blood clotting factors, is of high interest. The elimination kinetics of PPC, its interaction with phytomenadion (vitamin K), and the pharmacokinetic behavior of the anticoagulant under steady-state conditions have been investigated in studies with healthy volunteers and patients taking anticoagulants. The maintenance dose and the plasma levels of PPC were correlated with prothrombin time (PT) in 89 patients treated with PPC. Varying parameters in each patient (e.g., elimination kinetics of PPC, activity of the cumarin-dependent blood-clotting factors, endogenous phytomenadion stores), render it impossible to use a different means of monitoring than that of PT determination. PMID:10327214
Nutescu, Edith A; Shapiro, Nancy L; Chevalier, Aimee; Amin, Alpesh N
For over 50 years, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to traditional agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. These traditional agents are fraught with limitations that complicate their clinical use. A variety of novel anticoagulants with improved pharmacologic and clinical profiles have recently been introduced or are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of low-molecular-weight heparins, factor Xa inhibitors, and direct thrombin inhibitors. Because of their convenience and ease of use, some of these novel compounds are competing with the traditional anticoagulants and are needed additions to the antithrombotic arsenal. PMID:15853173
Poposka, Lidija; Boskov, Vladimir; Risteski, Dejan; Taleski, Jane; Georgievska-Ismail, Ljubica
INTRODUCTION: In patients with an implanted pacemaker, asymptomatic atrial fibrillation (AF) is associated with an increased risk of thrombo-embolic complications. There is still no consensus which duration of episodes of atrial fibrillation should be taken as an indicator for inclusion of oral anticoagulation therapy (OAC). MATERIAL AND METHODS: A total of 104 patients who had no AF episodes in the past and have an indication for permanent pacing were included in the study. RESULTS: During an average follow-up of 18 months, 33 of the patients developed episodes of AF. Inclusion of OAC was performed in 17 patients, in whom AF was recorded, although in all patients CHA2DS2-VASc score was ≥ 1. The inclusion of OAC showed a statistically significant correlation with increasing duration of episodes of AF (r = 0.502, p = 0.003). During the follow-up period none of the patients developed thrombo-embolic complication. CONCLUSION: Considering that our group of patients had no thrombo-embolic events, we could conclude that dividing the AF episodes in less than 1% in 24 hours and longer than 1% within 24 hours could be an indicator for decision-making to include OAK if the CHA2DS2-VASc score is ≥ 1. PMID:27335594
To evaluate the complications and outcome of anticoagulation therapy in pregnant females with valvular heart diseases. All pregnant females with prosthetic heart valves admitted in Armed Forces Institute of Cardiology from Jan 2004 to Dec 2004 were included in this study Basic demographic data including age, duration of pregnancy and complications observed were recorded. Warfarin was replaced with un-fractionated heparin (UFH) in first trimester and after that warfarin was continued with a targeted INR between 2.0-3.0. At 36 weeks warfarin was stopped and UFH was added; however, if patient went into spontaneous labour before this then immediate caesarian section was performed and UFH was restarted 4-6 hours after delivery along with oral warfarin. Out of 21 patients, sixteen (76.1%) had mitral valve diseases and five (23.9%) had both mitral and atrial. Majority (42.3%)of patients were in age group 26-30 years. Eleven (52.2%) reported in 9th month of gestation. Complications observed were hypertension (1), transient ischaemic attacks (1), pulmonary embolism (1), haemoptysis (1) and abortion (1). All patients, except one had successful completion of pregnancy. No case of foetal abnormality was seen. In 76% patients, daily dose of warfarin was <5 mg. Thrombo-prophylaxis in pregnancy with warfarin and UFH with an INR of 2.0-3.0 is effective in preventing thrombotic complications in females with mechanical valves without resulting in increase hemorrhagic complications. (author)
Full Text Available Amber L Beitelshees,1,* Deepak Voora,2,* Joshua P Lewis,1,* 1Program for Personalized and Genomic Medicine and Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA; 2Center for Applied Genomics & Precision Medicine, Department of Medicine, Duke School of Medicine, Durham, NC, USA*All authors contributed equally to this work Abstract: In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin and anticoagulation (ie, warfarin medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor and anticoagulant (dabigatran agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and
Dillon Carla; Twells Laurie; Bishop Lisa; Young Stephanie; Hawboldt John; O'Shea Patrick
Abstract Background The beneficial outcomes of oral anticoagulation therapy are dependent upon achieving and maintaining an optimal INR therapeutic range. There is growing evidence that better outcomes are achieved when anticoagulation is managed by a pharmacist with expertise in anticoagulation management rather than usual care by family physicians. This study compared a pharmacist managed anticoagulation program (PC) to usual physician care (UC) in a family medicine clinic. Methods A retros...
Feher, G; Illes, Z; Komoly, S; Hargroves, D
(NOACs) have been extensively studied in patients with deep vein thrombosis (DVT), pulmonary embolism (PE) and non-valvular atrial fibrillation (NVAF). The aim of our work to review the available evidence for NOACs in the treatment of CVT. Based on our literature search there is insufficient evidence to......Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely diverse clinical features, predisposing factors, brain imaging findings, and outcome. Anticoagulation is the cornerstone of CVT management, however, it is not supported by high-quality evicence. Novel oral anticoagulants...
Hankey, Graeme J; Norrving, Bo; Hacke, Werner; Steiner, Thorsten
Each year, 1·0–2·0% of individuals with atrial fibrillation and 0·1–0·2% of those with venous thromboembolism who are receiving one of the novel oral anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to experience an acute ischemic stroke. Additionally, 0·2–0·5% of individuals with atrial fibrillation who are receiving one of the novel oral anticoagulants can be expected to experience an intracranial hemorrhage. This opinion piece addresses the current literature and offer...
Soltysiak, Jolanta; Warzywoda, Alfred; Kociński, Bartłomiej; Ostalska-Nowicka, Danuta; Benedyk, Anna; Silska-Dittmar, Magdalena; Zachwieja, Jacek
Background Regional citrate anticoagulation (RCA) is one of the methods used to prevent clotting in continuous renal replacement therapy (CRRT). The aim of this study was to describe the outcomes and complications of RCA-CRRT in comparison to heparin anticoagulation (HA)-CRRT in critically ill children. Methods This study was a retrospective review of 30 critically ill children (16 on RCA- and 14 on HA-CRRT) who underwent at least 24 h of CRRT. The mean body weight of the children was 8.69 ± ...
Pitrák, V; Hadacová, I; Hochová, I; Hoch, J
Chronic anticoagulant treatment is administered mostly for cardiological reasons. Cumarin derivatires are used in the majority of cases (Warfarin, Pelentan). It is necessary to monitor this treatment regularly and to control the dose according to the INR value. Different complications can occur; the haemorrhage represents a serious one. The authors discuss several aspects of anticoagulant therapy and possible prevention of the complications. The importance of the problems is demonstrated on the authors' clinical experience--two cases of haemorrhage after Warfarin administration simulating an acute surgical event. PMID:11482149
Full Text Available BACKGROUND: Dabigatran etexilate (DE is a new oral direct thrombin inhibitor. Clinical trials point towards a favourable risk-to-benefit profile of DE compared to warfarin. In this study, we evaluated whether hemorrhagic transformation (HT occurs after experimental stroke under DE treatment as we have shown for warfarin. METHODS: 44 male C57BL/6 mice were pretreated orally with 37.5 mg/kg DE, 75 mg/kg DE or saline and diluted thrombin time (dTT and DE plasma concentrations were monitored. Ischemic stroke was induced by transient middle cerebral artery occlusion (tMCAO for 1 h or 3 h. We assessed functional outcome and HT blood volume 24 h and 72 h after tMCAO. RESULTS: After 1 h tMCAO, HT blood volume did not differ significantly between mice pretreated with DE 37.5 mg/kg and controls (1.5±0.5 µl vs. 1.8±0.5 µl, p>0.05. After 3 h tMCAO, DE-anticoagulated mice did also not show an increase in HT, neither at the dose of 37.5 mg/kg equivalent to anticoagulant treatment in the therapeutic range (1.3±0.9 µl vs. control 2.3±0.5 µl, p>0.05 nor at 75 mg/kg, clearly representing supratherapeutic anticoagulation (1.8±0.8 µl, p>0.05. Furthermore, no significant increase in HT under continued anticoagulation with DE 75 mg/kg could be found at 72 h after tMCAO for 1 h (1.7±0.9 µl vs. control 1.6±0.4 µl, p>0.05. CONCLUSION: Our experimental data suggest that DE does not significantly increase hemorrhagic transformation after transient focal cerebral ischemia in mice. From a translational viewpoint, this indicates that a continuation of DE anticoagulation in case of an ischemic stroke might be safe, but clearly, clinical data on this question are warranted.
Full Text Available Background: Anticoagulation therapy is a routine treatment in patients with hemorrhagic cerebral venous thrombosis (CVT. However, fear of hemorrhagic complications and deterioration course following anticoagulation often disturbs the responsible physician.Methods: This was a Prospective observational study on consecutive CVT patients with hemorrhagic venous infarction or subarachnoid hemorrhage (SAH admitted in Ghaem Hospital, Mashhad, Iran, during 2006-2012. The diagnosis of CVT in suspected cases was confirmed by magnetic resonance imaging/magnetic resonance venography (MRI/MRV, and computerized tomography (CT angiography following established diagnostic criteria. Demographic data, clinical manifestations from onset to end of the observation period, location of thrombus, location and size of infarction and hemorrhage, and clinical course during treatment were recorded. Choice of the treatment was left to the opinion of the treating physician. Clinical course during 1 week of treatment was assessed based on the baseline modified National Institute of Health Stroke Scale (NIHSS score. Three or more points decrease or increase of modified NIHSS after 1 week of treatment was considered as improvement or deterioration courses, respectively. Other clinical courses were categorized as stabilization course.Results: 102 hemorrhagic CVT patients (80 females,22 males with mean age of 38.6 ± 8 years were prospectively investigated. Of the 102 hemorrhagic CVT patients in the acute phase, 52 patients (50.9% were anticoagulated with adjusted dose intravenous heparin infusion and 50 cases (49.1% received subcutaneous enoxaparin 1mg/Kg twice daily. Decreased consciousness had a significant effect on the clinical course of the patients (X2 = 9.493, df = 2, P = 0.009. Presence of SAH had no significant effect on the clinical course of our anticoagulated hemorrhagic CVT cases (X2 = 0.304, df = 2,P = 0.914. Extension of Infarction in more than two thirds of a
Verso, Melina; Agnelli, Giancarlo; Prandoni, Paolo
Patients with cancer account for 20 % of cases of venous thromboembolism (VTE). Cancer patients are at increased risk for VTE during the entire course of their disease, also in absence of traditional VTE risk factors. Furthermore, patients with VTE and cancer have an estimated risk of bleeding of 15-20 % per year while on anticoagulant treatment. For these reasons, treatment of acute VTE in patients with cancer remains a clinical challenge. In clinical studies, which included about 27,000 patients, new oral anticoagulants (NOACs) have been shown to be as effective and safe as conventional anticoagulation (heparin given with and followed by vitamin K antagonists) for the treatment of VTE. In these studies, 1227 patients with active cancer were enrolled. Preliminary results of subgroup analyses and meta-analyses of randomized clinical trials suggest that NOACs could represent an alternative to conventional anticoagulation in patients with active cancer. Further "ad hoc" studies evaluating the clinical benefit of treatment with NOACs in patients with VTE and cancer are needed. PMID:25840679