A Bloody Mess: An Unusual Case of Diffuse Alveolar Hemorrhage Because of Warfarin Overdose.

PubMed

Heffler, Enrico; Campisi, Raffaele; Ferri, Sebastian; Crimi, Nunzio

2016-01-01

We herein present the case of a patient with frank hemoptysis and hematuria, dyspnea, and cough. The patient was known to be affected by Chronic Obstructive Pulmonary Disease (COPD) and dilated cardiomyopathy with atrial fibrillation. For this latter condition, he was supposed to take 1.25 mg warfarin daily. Laboratory findings revealed very high levels of International Normalized Ratio (INR) (16), and the patient referred that he self-increased warfarin dose to 5 mg daily since 8 days before the onset of symptoms. Computed tomography scan revealed diffuse bilateral signs of alveolar hemorrhage with hydroaerial levels within emphysematous cysts. Wafarin was immediately stopped and changed with 220 mg dabigatran daily, and he was properly treated to restore a normal coagulation status. We concluded for a case of diffuse alveolar hemorrhage because of warfarin overdose.

Intracranial hemorrhage in infective endocarditis: A case report

PubMed Central

Aziz, Fahad; Perwaiz, Saira; Penupolu, Sudheer; Doddi, Sujatha; Gongireddy, Srinivas

2011-01-01

Cerebral hemorrhage occurs rarely in infective endocarditis. Here, we present an interesting case of infective endocarditis complicated by sever cerebral hemorrhage. Later, his blood culture grew S bovis. To the best of our knowledge, this is the first ever reported case of S Bovis infective endocarditis complicated by extensive intracranial hemorrhage. PMID:22263076

Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials.

PubMed

Ntaios, George; Papavasileiou, Vasileios; Diener, Hans-Chris; Makaritsis, Konstantinos; Michel, Patrik

2017-08-01

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: "atrial fibrillation" and "anticoagulation" and "warfarin" and "previous stroke or transient ischemic attack." Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed

Rivaroxaban Versus Dabigatran or Warfarin in Real-World Studies of Stroke Prevention in Atrial Fibrillation: Systematic Review and Meta-Analysis.

PubMed

Bai, Ying; Deng, Hai; Shantsila, Alena; Lip, Gregory Y H

2017-04-01

This study was designed to evaluate the effectiveness and safety of rivaroxaban in real-world practice compared with effectiveness and safety of dabigatran or warfarin for stroke prevention in atrial fibrillation through meta-analyzing observational studies. Seventeen studies were included after searching in PubMed for studies reporting the comparative effectiveness and safety of rivaroxaban versus dabigatran (n=3), rivaroxaban versus Warfarin (n=11), or both (n=3) for stroke prevention in atrial fibrillation. Overall, the risks of stroke/systematic thromboembolism with rivaroxaban were similar when compared with those with dabigatran (stroke/thromboembolism: hazard ratio, 1.02; 95% confidence interval, 0.91-1.13; I 2 =70.2%, N=5), but were significantly reduced when compared with those with warfarin (hazard ratio, 0.75; 95% confidence interval, 0.64-0.85; I 2 =45.1%, N=9). Major bleeding risk was significantly higher with rivaroxaban than with dabigatran (hazard ratio, 1.38; 95% confidence interval, 1.27-1.49; I 2 =26.1%, N=5), but similar to that with warfarin (hazard ratio, 0.99; 95% confidence interval, 0.91-1.07; I 2 =0.0%, N=6). Rivaroxaban was associated with increased all-cause mortality and gastrointestinal bleeding, but similar risk of acute myocardial infarction and intracranial hemorrhage when compared with dabigatran. When compared with warfarin, rivaroxaban was associated with similar risk of any bleeding, mortality, and acute myocardial infarction, but a higher risk of gastrointestinal bleeding and lower risk of intracranial hemorrhage. In this systematic review and meta-analysis, rivaroxaban was as effective as dabigatran, but was more effective than warfarin for the prevention of stroke/thromboembolism in atrial fibrillation patients. Major bleeding risk was significantly higher with rivaroxaban than with dabigatran, as was all-cause mortality and gastrointestinal bleeding. Rivaroxaban was comparable to warfarin for major bleeding, with an

A convolutional neural network for intracranial hemorrhage detection in non-contrast CT

NASA Astrophysics Data System (ADS)

Patel, Ajay; Manniesing, Rashindra

2018-02-01

The assessment of the presence of intracranial hemorrhage is a crucial step in the work-up of patients requiring emergency care. Fast and accurate detection of intracranial hemorrhage can aid treating physicians by not only expediting and guiding diagnosis, but also supporting choices for secondary imaging, treatment and intervention. However, the automatic detection of intracranial hemorrhage is complicated by the variation in appearance on non-contrast CT images as a result of differences in etiology and location. We propose a method using a convolutional neural network (CNN) for the automatic detection of intracranial hemorrhage. The method is trained on a dataset comprised of cerebral CT studies for which the presence of hemorrhage has been labeled for each axial slice. A separate test dataset of 20 images is used for quantitative evaluation and shows a sensitivity of 0.87, specificity of 0.97 and accuracy of 0.95. The average processing time for a single three-dimensional (3D) CT volume was 2.7 seconds. The proposed method is capable of fast and automated detection of intracranial hemorrhages in non-contrast CT without being limited to a specific subtype of pathology.

Recurrent, Delayed Hemorrhage Associated with Edoxaban after Deep Brain Stimulation Lead Placement

PubMed Central

Garber, Sarah T.; Schrock, Lauren E.; House, Paul A.

2013-01-01

Factor-Xa inhibitors like edoxaban have been shown to have comparable or superior rates of stroke and systemic embolization prevention to warfarin while exhibiting lower clinically significant bleeding rates. The authors report a case of a man who presented with delayed, recurrent intracranial hemorrhage months after successful deep brain stimulator placement for Parkinson disease while on edoxaban for atrial fibrillation. Further reports on the use of novel anticoagulants after intracranial surgery are acutely needed to help assess the true relative risk they pose. PMID:23365773

CT-detected intracranial hemorrhage among patients with head injury in Lagos, Nigeria.

PubMed

Eze, Cletus Uche; Abonyi, Livinus Chibuzo; Olowoyeye, Omodele; Njoku, Jerome; Ohagwu, Christopher; Babalola, Sherifat

2013-01-01

To evaluate the computed tomography (CT) findings of intracranial hemorrhage among patients with head trauma in Lagos, Nigeria. In this retrospective, cross-sectional study, a convenience sample of 500 patients with head trauma who had diagnostic cranial CT scans was selected. All the radiological reports and CT scans of patients with head trauma were retrieved in the hospitals selected as study sites. The reports were sorted into 2 groups - normal findings and intracranial bleeding. The reports of intracranial bleeding were sorted again into different classes of intracranial bleeding as identified by the radiologist who reported it. All data were analyzed using the Epi Info public domain software package. The chi-square test was used to measure the statistical significance of study results at P < .05. Most of the study subjects (68%) were men. Traffic accidents accounted for 44% of all the head traumas found in the study, and 58% of the head traumas resulted in intracranial bleeding. Among the hemorrhages found, 37% were intracerebral, 25% were subdural, 16% were intraventricular, 15% were subarachnoid, and 7% were epidural. Intracranial hemorrhage was a common consequence of acute head trauma sustained from traffic accidents in the population studied, with intracerebral hemorrhage being the most prevalent type. Traffic accidents are the main cause of acute head trauma in Lagos, Nigeria. The use of CT for early diagnosis of intracranial hemorrhage appears justifiable.

12/15-Lipoxygenase Inhibition or Knockout Reduces Warfarin-Associated Hemorrhagic Transformation After Experimental Stroke.

PubMed

Liu, Yu; Zheng, Yi; Karatas, Hulya; Wang, Xiaoying; Foerch, Christian; Lo, Eng H; van Leyen, Klaus

2017-02-01

For stroke prevention, patients with atrial fibrillation typically receive oral anticoagulation. The commonly used anticoagulant warfarin increases the risk of hemorrhagic transformation (HT) when a stroke occurs; tissue-type plasminogen activator treatment is therefore restricted in these patients. This study was designed to test the hypothesis that 12/15-lipoxygenase (12/15-LOX) inhibition would reduce HT in warfarin-treated mice subjected to experimental stroke. Warfarin was dosed orally in drinking water, and international normalized ratio values were determined using a Coaguchek device. C57BL6J mice or 12/15-LOX knockout mice were subjected to transient middle cerebral artery occlusion with 3 hours severe ischemia (model A) or 2 hours ischemia and tissue-type plasminogen activator infusion (model B), with or without the 12/15-LOX inhibitor ML351. Hemoglobin was determined in brain homogenates, and hemorrhage areas on the brain surface and in brain sections were measured. 12/15-LOX expression was detected by immunohistochemistry. Warfarin treatment resulted in reproducible increased international normalized ratio values and significant HT in both models. 12/15-LOX knockout mice suffered less HT after severe ischemia, and ML351 reduced HT in wild-type mice. When normalized to infarct size, ML351 still independently reduced hemorrhage. HT after tissue-type plasminogen activator was similarly reduced by ML351. In addition to its benefits in infarct size reduction, 12/15-LOX inhibition also may independently reduce HT in warfarin-treated mice. ML351 should be further evaluated as stroke treatment in anticoagulated patients suffering a stroke, either alone or in conjunction with tissue-type plasminogen activator. © 2017 American Heart Association, Inc.

18F-positron-emitting/fluorescent labeled erythrocytes allow imaging of internal hemorrhage in a murine intracranial hemorrhage model

PubMed Central

Wang, Ye; An, Fei-Fei; Chan, Mark; Friedman, Beth; Rodriguez, Erik A; Tsien, Roger Y; Aras, Omer

2017-01-01

An agent for visualizing cells by positron emission tomography is described and used to label red blood cells. The labeled red blood cells are injected systemically so that intracranial hemorrhage can be visualized by positron emission tomography (PET). Red blood cells are labeled with 0.3 µg of a positron-emitting, fluorescent multimodal imaging probe, and used to non-invasively image cryolesion induced intracranial hemorrhage in a murine model (BALB/c, 2.36 × 108 cells, 100 µCi, <4 mm hemorrhage). Intracranial hemorrhage is confirmed by histology, fluorescence, bright-field, and PET ex vivo imaging. The low required activity, minimal mass, and high resolution of this technique make this strategy an attractive alternative for imaging intracranial hemorrhage. PET is one solution to a spectrum of issues that complicate single photon emission computed tomography (SPECT). For this reason, this application serves as a PET alternative to [99mTc]-agents, and SPECT technology that is used in 2 million annual medical procedures. PET contrast is also superior to gadolinium and iodide contrast angiography for its lack of clinical contraindications. PMID:28054494

Evaluation of Bleeding Events Requiring Hospitalization in Patients With Atrial Fibrillation Receiving Dabigatran, Warfarin, or Antiplatelet Therapy.

PubMed

Riley, Tanya R; Gauthier-Lewis, Mary L; Sanchez, Chelsea K; Riley, Treavor T

2017-04-01

To determine the incidence and severity of bleeding events requiring hospitalization among patients with atrial fibrillation (AF) receiving anticoagulants (dabigatran or warfarin) or antiplatelet agents (eg, aspirin and clopidogrel). This was a single-center, retrospective cohort study involving 1494 patients with AF hospitalized from November 1, 2010, to November 1, 2011, with prior warfarin, dabigatran, or antiplatelet therapy. Overall bleeding events in the dabigatran group compared to the warfarin group were 24% and 12%, respectively ( P = .004). Of these events, individually, there were no significant differences in major (56% vs 58%, P = .88), life-threatening (25% vs 36%, P = .38), or minor bleeding (44% vs 42%, P = .06). Gastrointestinal (GI) bleeding occurred more in the dabigatran group compared to the warfarin group ( P = .02). Intracranial bleeding occurred in 15% of patients in the warfarin group and did not occur at all in the dabigatran group. Warfarin patients had significantly more overall bleeding events compared to antiplatelet therapy ( P < .001), with an increasing trend seen in major bleeding ( P = .06). GI bleeding, however, favored the warfarin group over the antiplatelet group (48% vs 73%, P = .04). Anticoagulation with dabigatran was associated with an overall increased occurrence of bleeding requiring hospital admission compared to warfarin. GI bleeding was more prevalent with dabigatran and antiplatelets than with warfarin. There were more intracranial hemorrhages seen in the warfarin group.

Hypophosphatemia after nontraumatic intracranial hemorrhage.

PubMed

Junttila, E; Koskenkari, J; Ala-Kokko, T

2017-07-01

The aim of this study was to assess the incidence and contributing factors of hypophosphatemia and the association with poor long-term outcome after nontraumatic intracranial hemorrhage. This was a prospective, observational study of patients with nontraumatic intracranial hemorrhage (i.e., aneurysmal or perimesencephalic subarachnoid hemorrhage, or spontaneous intracerebral or intraventricular hemorrhage) treated in the intensive care unit (ICU) at our university hospital. Plasma phosphate concentrations were measured serially in 2-day sections during the 6 day study period. The ICU mortality was recorded, 3-month and 1-year outcomes were assessed using the Glasgow Outcome Scale. One hundred patients were enrolled. The frequency of hypophosphatemia (Pi ≤ 0.65 mmol/l) was 70%. Chronic hypertension, acute hydrocephalus, and diffuse brain edema were more common in patients with hypophosphatemia compared with normophosphatemics (44% vs. 21%, P = 0.021; 59% vs. 33%, P = 0.021; and 43% vs. 13%, P = 0.004, respectively). Hypophosphatemic patients had higher maximum SOFA scores [10 (7-11) vs. 7.5 (5.75-10), P = 0.024]. Initial phosphate concentration correlated inversely with APACHE II score on admission (ρ = -0.304, P = 0.002) and SOFA score on the first ICU day (ρ = -0.269, P = 0.008). There was no difference in outcome between hypophosphatemic and normophosphatemic patients. In all five patients with severe hypophosphatemia (Pi < 0.32 mmol/l) the functional outcome was good. Hypophosphatemia was common in this patient population. The outcome was similar between hypophosphatemic and normophosphatemic patients. Chronic hypertension, acute hydrocephalus, diffuse brain edema and higher SOFA scores were more common in patients with hypophosphatemia. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

PubMed

Marques-Matos, Cláudia; Alves, José Nuno; Marto, João Pedro; Ribeiro, Joana Afonso; Monteiro, Ana; Araújo, José; Silva, Fernando; Grenho, Fátima; Viana-Baptista, Miguel; Sargento-Freitas, João; Pinho, João; Azevedo, Elsa

2017-08-01

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA 2 DS 2 VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39-1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55-2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants

Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

PubMed

Patel, Manesh R; Mahaffey, Kenneth W; Garg, Jyotsna; Pan, Guohua; Singer, Daniel E; Hacke, Werner; Breithardt, Günter; Halperin, Jonathan L; Hankey, Graeme J; Piccini, Jonathan P; Becker, Richard C; Nessel, Christopher C; Paolini, John F; Berkowitz, Scott D; Fox, Keith A A; Califf, Robert M

2011-09-08

The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).

Quality of anticoagulation control and hemorrhage risk among African American and European American warfarin users.

PubMed

Limdi, Nita A; Brown, Todd M; Shendre, Aditi; Liu, Nianjun; Hill, Charles E; Beasley, Timothy M

2017-10-01

We evaluated whether percent time in target range (PTTR), risk of over-anticoagulation [international normalized ratio (INR)>4], and risk of hemorrhage differ by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on the risk of hemorrhage by race. Among 1326 warfarin users, PTTR was calculated as the percentage of interpolated INR values within the target range of 2.0-3.0. PTTR was also categorized as poor (PTTR<60%), good (60≤PTTR<70%), or excellent (PTTR≥70%) anticoagulation control. Over-anticoagulation was defined as INR more than 4 and major hemorrhages included serious, life-threatening, and fatal bleeding episodes. Logistic regression and survival analyses were carried out to evaluate the association of race with PTTR (≥60 vs. <60) and major hemorrhages, respectively. Compared with African Americans, European Americans had higher PTTR (57.6 vs. 49.1%; P<0.0001) and were more likely to attain 60≤PTTR<70% (22.9 vs. 13.1%; P<0.001) or PTTR of at least 70% (26.9 vs. 18.2%; P=0.001). Older (>65 years) patients without venous thromboembolism indication and chronic kidney disease were more likely to attain PTTR of at least 60%. After accounting for clinical and genetic factors, and PTTR, African Americans had a higher risk of hemorrhage [hazard ratio (HR)=1.58; 95% confidence interval (CI): 1.04-2.41; P=0.034]. Patients with 60≤PTTR<70% (HR=0.62; 95% CI: 0.38-1.02; P=0.058) and PTTR of at least 70% (HR=0.27; 95% CI: 0.15-0.49; P<0.001) had a lower risk of hemorrhage compared with those with PTTR less than 60%. Despite the provision of warfarin management through anticoagulation clinics, African Americans achieve a lower overall PTTR and have a significantly higher risk of hemorrhage. Personalized medicine interventions tailored to African American warfarin users need to be developed.

Management and Outcomes of Bleeding Events in Patients in the Emergency Department Taking Warfarin or a Non-Vitamin K Antagonist Oral Anticoagulant.

PubMed

Singer, Adam J; Quinn, Adam; Dasgupta, Neil; Thode, Henry C

2017-01-01

Most comparisons of bleeding patients who are taking warfarin or a non-vitamin K oral anticoagulant (NOAC) have been limited to admitted patients and major bleeding events in well-controlled, clinical trial settings. We describe the clinical characteristics, interventions, and outcomes in patients who are taking warfarin or a NOAC who presented to the emergency department (ED) with any bleeding event. We conducted a structured, retrospective, observational study of nonvalvular atrial fibrillation, pulmonary embolism, or deep vein thrombosis warfarin- or NOAC-treated patients presenting with any bleeding event to a large, academic ED between January 2012 and March 2015. We used descriptive statistics to summarize baseline characteristics, treatments, and outcomes and performed subgroup analyses based on the type of anticoagulant and site of bleeding. The electronic search yielded 95 cases of patients taking a NOAC (i.e., dabigatran [33], rivaroxaban [32], or abixaban [30]) and 342 patients taking warfarin. Reversal agents were rarely used in all anticoagulant groups. Case fatality rates were similar among warfarin- and NOAC-treated patients for gastrointestinal bleeding (7% vs. 7%) and intracranial hemorrhage (18% vs. 4%), respectively. After adjustment for other factors, only intracranial hemorrhage (odds ratio 4.4; 95% confidence interval 1.4-13.3) was associated with mortality. Despite the rare use of reversal strategies, mortality was low and outcomes were comparable among patients with bleeding events presenting to the ED while taking a NOAC compared with warfarin. Copyright © 2016 Elsevier Inc. All rights reserved.

Activated Prothrombin Complex Concentrate versus Plasma for Reversal of Warfarin-Associated Hemorrhage.

PubMed

Rowe, Anthony Shaun; Mahbubani, Pinky S; Bucklin, Mason H; Clark, Christopher T; Hamilton, Leslie A

2016-11-01

To evaluate the efficacy and safety of an activated four-factor prothrombin complex concentrate (aPCC) versus plasma for the reversal of warfarin-associated hemorrhage. Single-center, retrospective cohort analysis of adult patients with warfarin-associated hemorrhage treated with either aPCC or plasma. Patients received either aPCC or plasma as treatment for warfarin-associated hemorrhage between January 1, 2011, and July 1, 2013. Patients with missing data points were excluded from the final analysis. Of the 276 patients included in the final analysis, 128 received aPCC and 148 received plasma. None. Those patients who received aPCC achieved a lower posttreatment INR (1.1 [0.1] vs 1.6 [0.5]; p<0.05). In addition, patients who received aPCC had a 4.3 times higher odds of achieving an INR of less than 1.4 (97 [75.8%] vs 65 [43.9%]; p<0.05; odds ratio [OR] = 4.3 [95% confidence interval (CI) 2.6-7.3]). When controlling for vitamin K administration, history of diabetes mellitus, receipt of the recommended reversal agent dose, and pretreatment INR, aPCC administration remained an independent predictor for achieving an international normalized ratio (INR) of less than 1.4 in the first 24 hours after treatment (OR = 3.75 [95% CI 2.11-6.65]; p<0.001). In addition, there was no statistical difference between the groups with regard to occurrences of infusion reaction, pulmonary embolism, deep vein thrombosis, stroke, or myocardial infarction. Compared with patients who received plasma, patients who received aPCC achieved a lower posttreatment INR, had a larger INR change, and were more likely to achieve an INR less than the prespecified goal. Those patients who received aPCC did not have a higher incidence of thromboembolic events. © 2016 Pharmacotherapy Publications, Inc.

Cost-Effectiveness of Apixaban Compared with Warfarin for Stroke Prevention in Atrial Fibrillation

PubMed Central

Lee, Soyon; Mullin, Rachel; Blazawski, Jon; Coleman, Craig I.

2012-01-01

Background Apixaban was shown to be superior to adjusted-dose warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation (AF) and at least one additional risk factor for stroke, and associated with reduced rates of hemorrhage. We sought to determine the cost-effectiveness of using apixaban for stroke prevention. Methods Based on the results from the Apixaban Versus Warfarin in Patients with Atrial Fibrillation (ARISTOTLE) trial and other published studies, we constructed a Markov model to evaluate the cost-effectiveness of apixaban versus warfarin from the Medicare perspective. The base-case analysis assumed a cohort of 65-year-old patients with a CHADS2 score of 2.1 and no contraindication to oral anticoagulation. We utilized a 2-week cycle length and a lifetime time horizon. Outcome measures included costs in 2012 US$, quality-adjusted life-years (QALYs), life years saved and incremental cost-effectiveness ratios. Results Under base case conditions, quality adjusted life expectancy was 10.69 and 11.16 years for warfarin and apixaban, respectively. Total costs were $94,941 for warfarin and $86,007 for apixaban, demonstrating apixaban to be a dominant economic strategy. Upon one-way sensitivity analysis, these results were sensitive to variability in the drug cost of apixaban and various intracranial hemorrhage related variables. In Monte Carlo simulation, apixaban was a dominant strategy in 57% of 10,000 simulations and cost-effective in 98% at a willingness-to-pay threshold of $50,000 per QALY. Conclusions In patients with AF and at least one additional risk factor for stroke and a baseline risk of ICH risk of about 0.8%, treatment with apixaban may be a cost-effective alternative to warfarin. PMID:23056642

Secondary intracranial subarachnoid hemorrhage due to spinal missile injury.

PubMed

Smialek, J E; Chason, J L; Kshirsagar, V; Spitz, W U

1981-04-01

Fresh intracranial subarachnoid hemorrhage may occur secondary to blast-type injury of the spinal cord. This phenomenon is demonstrated in four cases of gunshot and shotgun wounds involving the spinal column. The significance of such a finding is that the subarachnoid hemorrhage should not be construed to represent an independent injury. Such an erroneous conclusion could jeopardize a theory of self-defense in a homicidal shooting.

Intracranial drug delivery for subarachnoid hemorrhage.

PubMed

Macdonald, Robert Loch; Leung, Ming; Tice, Tom

2012-01-01

Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.

Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice: A Retrospective Cohort Study.

PubMed

Go, Alan S; Singer, Daniel E; Toh, Sengwee; Cheetham, T Craig; Reichman, Marsha E; Graham, David J; Southworth, Mary Ross; Zhang, Rongmei; Izem, Rima; Goulding, Margie R; Houstoun, Monika; Mott, Katrina; Sung, Sue Hee; Gagne, Joshua J

2017-12-19

Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited. To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving dabigatran versus warfarin in practice. Retrospective cohort. National U.S. Food and Drug Administration Sentinel network. Adults with atrial fibrillation initiating dabigatran or warfarin therapy between November 2010 and May 2014. Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identified from hospital claims among propensity score-matched patients starting treatment with dabigatran or warfarin. Among 25 289 patients starting dabigatran therapy and 25 289 propensity score-matched patients starting warfarin therapy, those receiving dabigatran did not have significantly different rates of ischemic stroke (0.80 vs. 0.94 events per 100 person-years; hazard ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR, 0.89 [CI, 0.72 to 1.09]) but were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR, 0.51 [CI, 0.33 to 0.79]) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR, 1.88 [CI, 1.22 to 2.90]). However, the strength and significance of the association between dabigatran use and myocardial infarction varied in sensitivity analyses and by exposure definition (HR range, 1.13 [CI, 0.78 to 1.64] to 1.43 [CI, 0.99 to 2.08]). Older patients and those with kidney disease had higher gastrointestinal bleeding rates with dabigatran. Inability to examine outcomes by dabigatran dose (unacceptable covariate balance between matched patients) or quality of warfarin anticoagulation (few patients receiving warfarin had available international normalized ratio values). In matched adults with atrial fibrillation treated in

Dual-energy bone removal computed tomography (BRCT): preliminary report of efficacy of acute intracranial hemorrhage detection.

PubMed

Naruto, Norihito; Tannai, Hidenori; Nishikawa, Kazuma; Yamagishi, Kentaro; Hashimoto, Masahiko; Kawabe, Hideto; Kamisaki, Yuichi; Sumiya, Hisashi; Kuroda, Satoshi; Noguchi, Kyo

2018-02-01

One of the major applications of dual-energy computed tomography (DECT) is automated bone removal (BR). We hypothesized that the visualization of acute intracranial hemorrhage could be improved on BRCT by removing bone as it has the highest density tissue in the head. This preliminary study evaluated the efficacy of a DE BR algorithm for the head CT of trauma patients. Sixteen patients with acute intracranial hemorrhage within 1 day after head trauma were enrolled in this study. All CT examinations were performed on a dual-source dual-energy CT scanner. BRCT images were generated using the Bone Removal Application. Simulated standard CT and BRCT images were visually reviewed in terms of detectability (presence or absence) of acute hemorrhagic lesions. DECT depicted 28 epidural/subdural hemorrhages, 17 contusional hemorrhages, and 7 subarachnoid hemorrhages. In detecting epidural/subdural hemorrhage, BRCT [28/28 (100%)] was significantly superior to simulated standard CT [17/28 (61%)] (p = .001). In detecting contusional hemorrhage, BRCT [17/17 (100%)] was also significantly superior to simulated standard CT [11/17 (65%)] (p = .0092). BRCT was superior to simulated standard CT in detecting acute intracranial hemorrhage. BRCT could improve the detection of small intracranial hemorrhages, particularly those adjacent to bone, by removing bone that can interfere with the visualization of small acute hemorrhage. In an emergency such as head trauma, BRCT can be used as support imaging in combination with simulated standard CT and bone scale CT, although BRCT cannot replace a simulated standard CT.

Noninvasive assessment of the intracranial pressure in non-traumatic intracranial hemorrhage.

PubMed

Vaiman, Michael; Sigal, Tal; Kimiagar, Itzhak; Bekerman, Inessa

2016-12-01

The article describes the modified technique of measuring the diameters of the optic nerve sheath (ONSD) for assessment of the intracranial pressure (ICP) in patients with intracerebral or subarachnoid hemorrhage (SAH). The CT scans of 443 patients were analyzed retrospectively. The ONSDs were measured at 3mm behind the globe and at the point where the ophthalmic artery crosses the optic nerve. The ONSD/eyeball transverse diameter (ETD) ratio was calculated. The correlation analysis was performed with the Glasgow Coma Scale score, Hemispheric Stroke Scale score, Glasgow Outcome Score, and invasive ICP readings. ONSD was enlarged in 95% of patients with intracerebral hemorrhage or SAH. Pathological ONSDs were 6.6±0.8mm (cut-off value >5.5mm; p<0.05). ONSD/ETD ratio was 0.29±0.05 against normative 0.19±0.02 (p<0.01) with no correlation with initial Glasgow Coma Scale score or Hemispheric Stroke Scale score. There was an inverse correlation between ONSD/ETD ratio and Glasgow Outcome Score (r=-0.7) and direct correlation with invasive ICP readings. This study provides further evidence that in patients with intracranial hemorrhage and SAH, the presence of ONSD greater than a threshold of 5.5mm is significantly predictive of invasively measured elevated ICP. The prediction of raised ICP can be further refined by measuring ONSD at the point where the optic nerve and the ophthalmic artery cross, and by determining the ratio between the ONSD and ETD. Copyright © 2016 Elsevier Ltd. All rights reserved.

The acute management of intracerebral hemorrhage: a clinical review.

PubMed

Elliott, Justine; Smith, Martin

2010-05-01

Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. The major risk factors for ICH include chronic arterial hypertension and oral anticoagulation. After the initial hemorrhage, hematoma expansion and perihematoma edema result in secondary brain damage and worsened outcome. A rapid onset of focal neurological deficit with clinical signs of increased intracranial pressure is strongly suggestive of a diagnosis of ICH, although cranial imaging is required to differentiate it from ischemic stroke. ICH is a medical emergency and initial management should focus on urgent stabilization of cardiorespiratory variables and treatment of intracranial complications. More than 90% of patients present with acute hypertension, and there is some evidence that acute arterial blood pressure reduction is safe and associated with slowed hematoma growth and reduced risk of early neurological deterioration. However, early optimism that outcome might be improved by the early administration of recombinant factor VIIa (rFVIIa) has not been substantiated by a large phase III study. ICH is the most feared complication of warfarin anticoagulation, and the need to arrest intracranial bleeding outweighs all other considerations. Treatment options for warfarin reversal include vitamin K, fresh frozen plasma, prothrombin complex concentrates, and rFVIIa. There is no evidence to guide the specific management of antiplatelet therapy-related ICH. With the exceptions of placement of a ventricular drain in patients with hydrocephalus and evacuation of a large posterior fossa hematoma, the timing and nature of other neurosurgical interventions is also controversial. There is substantial evidence that management of patients with ICH in a specialist neurointensive care unit, where treatment is directed toward monitoring and managing cardiorespiratory variables and intracranial pressure, is associated with improved outcomes. Attention must be given to fluid

Intracranial hemorrhage in congenital bleeding disorders.

PubMed

Tabibian, Shadi; Motlagh, Hoda; Naderi, Majid; Dorgalaleh, Akbar

2018-01-01

: Intracranial hemorrhage (ICH), as a life-threatening bleeding among all kinds of congenital bleeding disorders (CBDs), is a rare manifestation except in factor XIII (FXIII) deficiency, which is accompanied by ICH, early in life, in about one-third of patients. Most inherited platelet function disorders (IPFDs) are mild to moderate bleeding disorders that can never experience a severe bleeding as in ICH; however, Glanzmann's thrombasthenia, a common and severe inherited platelet function disorder, can lead to ICH and occasional death. This bleeding feature can also be observed in grey platelet syndrome, though less frequently than in Glanzmann's thrombasthenia. In hemophilia, intracerebral hemorrhage is affected by various risk factors one of which is the severity of the disease. The precise prevalence of ICH in these patients is not clear but an estimated incidence of 3.5-4% among newborns with hemophilia is largely ascertained. Although ICH is a rare phenomenon in CBDs, it can be experienced by every patient with severe hemophilia A and B, FXIII deficiency (FXIIID), FVIID, FXD, FVD, FIID, and afibrinogenemia. Upon observing the general signs and symptoms of ICH such as vomiting, seizure, unconsciousness, and headache, appropriate replacement therapies and cranial ultrasound scans must be done to decrease ICH-related morbidity and mortality.

Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

PubMed

Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

2017-07-01

Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding. Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Colloid cyst mimicking intracranial hemorrhage after head trauma.

PubMed

Buyukkaya, Ayla; Buyukkaya, Ramazan; Özel, Mehmet Ali; Sarıtas, Ayhan

2015-02-01

Trauma patients consist vast majority of the patients who admit to emergency department, and most of them have a head trauma. A 58-year-old patient was taken to emergency department with head trauma, and a hyperdense lesion neighboring to third ventricle was detected. A diagnosis of colloid cyst was made in the patient who was being followed up for hemorrhage. In patients with head trauma, colloid cyst may easly be confused with intracranial hemorrhage due to hyperdensity. The aim of this report is to emphasize the importance of clinical thinking in the differential diagnosis of hyperdense lesion on computed tomography imaging of a patient with head injury.

Effect of inter-tissue inductive coupling on multi-frequency imaging of intracranial hemorrhage by magnetic induction tomography

NASA Astrophysics Data System (ADS)

Xiao, Zhili; Tan, Chao; Dong, Feng

2017-08-01

Magnetic induction tomography (MIT) is a promising technique for continuous monitoring of intracranial hemorrhage due to its contactless nature, low cost and capacity to penetrate the high-resistivity skull. The inter-tissue inductive coupling increases with frequency, which may lead to errors in multi-frequency imaging at high frequency. The effect of inter-tissue inductive coupling was investigated to improve the multi-frequency imaging of hemorrhage. An analytical model of inter-tissue inductive coupling based on the equivalent circuit was established. A set of new multi-frequency decomposition equations separating the phase shift of hemorrhage from other brain tissues was derived by employing the coupling information to improve the multi-frequency imaging of intracranial hemorrhage. The decomposition error and imaging error are both decreased after considering the inter-tissue inductive coupling information. The study reveals that the introduction of inter-tissue inductive coupling can reduce the errors of multi-frequency imaging, promoting the development of intracranial hemorrhage monitoring by multi-frequency MIT.

Fatal Intracranial Hemorrhage in a Patient with Severe Dengue Fever

PubMed Central

Sam, Jo Ee; Gee, Teak Sheng; Wahab, Nasser Abdul

2018-01-01

Dengue fever has been a major cause of morbidity and mortality in subtropical and tropical countries. We report a rare case of severe dengue with spontaneous intracranial hemorrhage. A search of literature through PubMed revealed that the largest series analyzed so far only included five cases. A 47-year-old man presented with 7 days history of fever, headache, myalgia, and vomiting with hematemesis. On the day of presentation, he had reduced consciousness and an episode of generalized tonic-clonic seizure. His Glasgow Coma Scale was E1V1M3 with anisocoria. Postresuscitation computed tomography of the brain revealed a right subdural and left thalamic hemorrhage. His blood investigations revealed thrombocytopenia, dengue virus type 1 nonstructural protein antigen test was positive, dengue IgM negative, and dengue IgG positive. A right decompressive craniectomy was done. Unfortunately, the patient died soon after. Spontaneous intracranial hemorrhage in patients with dengue fever is an uncommon entity but usually carry a grave prognosis. To date, there has been no clear management guideline for such cases, as both operative and nonoperative approaches have their own inherent risks. PMID:29492121

Derivation and Validation of a Serum Biomarker Panel to Identify Infants With Acute Intracranial Hemorrhage.

PubMed

Berger, Rachel Pardes; Pak, Brian J; Kolesnikova, Mariya D; Fromkin, Janet; Saladino, Richard; Herman, Bruce E; Pierce, Mary Clyde; Englert, David; Smith, Paul T; Kochanek, Patrick M

2017-06-05

Abusive head trauma is the leading cause of death from physical abuse. Missing the diagnosis of abusive head trauma, particularly in its mild form, is common and contributes to increased morbidity and mortality. Serum biomarkers may have potential as quantitative point-of-care screening tools to alert physicians to the possibility of intracranial hemorrhage. To identify and validate a set of biomarkers that could be the basis of a multivariable model to identify intracranial hemorrhage in well-appearing infants using the Ziplex System. Binary logistic regression was used to develop a multivariable model incorporating 3 serum biomarkers (matrix metallopeptidase-9, neuron-specific enolase, and vascular cellular adhesion molecule-1) and 1 clinical variable (total hemoglobin). The model was then prospectively validated. Multiplex biomarker measurements were performed using Flow-Thru microarray technology on the Ziplex System, which has potential as a point-of-care system. The model was tested at 3 pediatric emergency departments in level I pediatric trauma centers (Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Primary Children's Hospital, Salt Lake City, Utah; and Lurie Children's Hospital, Chicago, Illinois) among well-appearing infants who presented for care owing to symptoms that placed them at increased risk of abusive head trauma. The study took place from November 2006 to April 2014 at Children's Hospital of Pittsburgh, June 2010 to August 2013 at Primary Children's Hospital, and January 2011 to August 2013 at Lurie Children's Hospital. A mathematical model that can predict acute intracranial hemorrhage in infants at increased risk of abusive head trauma. The multivariable model, Biomarkers for Infant Brain Injury Score, was applied prospectively to 599 patients. The mean (SD) age was 4.7 (3.1) months. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89

Dabigatran versus warfarin in patients with atrial fibrillation.

PubMed

Connolly, Stuart J; Ezekowitz, Michael D; Yusuf, Salim; Eikelboom, John; Oldgren, Jonas; Parekh, Amit; Pogue, Janice; Reilly, Paul A; Themeles, Ellison; Varrone, Jeanne; Wang, Susan; Alings, Marco; Xavier, Denis; Zhu, Jun; Diaz, Rafael; Lewis, Basil S; Darius, Harald; Diener, Hans-Christoph; Joyner, Campbell D; Wallentin, Lars

2009-09-17

Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051). In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number

Anesthetic management of pial synangiosis and intracranial hemorrhage with a Fontan circulation.

PubMed

Subramaniam, Balachundhar; Soriano, Sulpicio G; Michael Scott, R; Kussman, Barry D

2006-01-01

We report the case of a 11-year-old girl with Moyamoya syndrome, who had undergone staged-repair of tricuspid atresia to a Fontan circulation, scheduled to undergo bilateral pial synangiosis. Surgery for the first hemisphere was complicated by intracranial hemorrhage requiring an emergency craniotomy. The case highlights the importance of understanding Fontan physiology and its interrelationship with the cerebral circulation in the setting of cerebrovascular insufficiency and raised intracranial pressure.

Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes.

PubMed

Hylek, Elaine M; Held, Claes; Alexander, John H; Lopes, Renato D; De Caterina, Raffaele; Wojdyla, Daniel M; Huber, Kurt; Jansky, Petr; Steg, Philippe Gabriel; Hanna, Michael; Thomas, Laine; Wallentin, Lars; Granger, Christopher B

2014-05-27

This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding. Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. All patients who received at least 1 dose of a study drug were included. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. Factors associated with major hemorrhage were identified using a multivariable Cox model. The on-treatment safety population included 18,140 patients. The rate of major hemorrhage among patients in the apixaban group was 2.13% per year compared with 3.09% per year in the warfarin group (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.60 to 0.80; p < 0.001). Compared with warfarin, major extracranial hemorrhage associated with apixaban led to reduced hospitalization, medical or surgical intervention, transfusion, or change in antithrombotic therapy. Major hemorrhage followed by mortality within 30 days occurred half as often in apixaban-treated patients than in those receiving warfarin (HR 0.50, 95% CI: 0.33 to 0.74; p < 0.001). Older age, prior hemorrhage, prior stroke or transient ischemic attack, diabetes, lower creatinine clearance, decreased hematocrit, aspirin therapy, and nonsteroidal anti-inflammatory drugs were independently associated with an increased risk. Apixaban, compared with warfarin, was associated with fewer intracranial hemorrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal consequences at 30 days in cases of major hemorrhage. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Increased Risk of Post-Thrombolysis Intracranial Hemorrhage in Acute Ischemic Stroke Patients with Leukoaraiosis: A Meta-Analysis

PubMed Central

Lin, Qianqian; Li, Zhong; Wei, Rui; Lei, Qingfeng; Liu, Yunyun; Cai, Xiaodong

2016-01-01

Background Leukoaraiosis is common in patients with acute ischemic stroke. The results from many studies investigating the association between leukoaraiosis and intracranial hemorrhage after thrombolysis remain conflicting. Methods A meta-analysis was performed to compare the risk of post-thrombolytic intracranial hemorrhage in patients with and without leukoaraiosis. Relevant reports were identified by searching PubMed, EmBase, Cochrane Library, and ISI Web of Science through December 2015 using a combination of subjective and random terms. Eligible studies that were original articles with a clear definition of leukoaraiosis and intracranial hemorrhage were selected and analyzed. Funnel plots, Egger’s test, and Begg’s test were conducted to assess the publication bias. Sensitivity analysis was also performed to evaluate the influence of each individual study. Results Eleven trials that enrolled 6912 participants were included. There was a significantly increased risk for acute ischemic stroke patients with leukoaraiosis (odds ratio: 1.89, 95% confidence interval 1.51–2.37, P<0.001). Low heterogeneity and less publication bias was detected among these studies. The results of both computed tomography and magnetic resonance imaging performed on the subgroups of leukoaraiosis were significant. Furthermore, an association between leukoaraiosis and symptomatic intracranial hemorrhage was also confirmed. The odds ratios remained stable with no obvious variations on the sensitivity analysis. The limitations consisted of types of including trials and not matching some baseline variables. Conclusions The results of this meta-analysis show that leukoaraiosis approximately doubles the incidence of intracranial hemorrhage after thrombolytic therapy. However, it does not critically affect decision making regarding thrombolysis for patients with acute ischemic stroke. Additional investigations are required. PMID:27096292

Predictors of warfarin use in atrial fibrillation in the United States: a systematic review and meta-analysis

PubMed Central

2012-01-01

Background Despite warfarin's marked efficacy, not all eligible patients receive it for stroke prevention in AF. The aim of this meta-analysis was to evaluate the association between prescriber and/or patient characteristics and subsequent prescription of warfarin for stroke prevention in patients with atrial fibrillation (AF). Methods Observational studies conducted in the US using multivariate analysis to determine the relationship between characteristics and the odds of receiving warfarin for stroke prevention were identified in MEDLINE, EMBASE and a manual review of references. Effect estimates of prescriber and/or patient characteristics from individual studies were pooled to calculate odds ratios (ORs) with 95% confidence intervals. Results Twenty-eight studies reporting results of 33 unique multivariate analyses were identified. Warfarin use across studies ranged from 9.1%-79.8% (median = 49.1%). There was a moderately-strong correlation between warfarin use and year of study (r = 0.60, p = 0.002). Upon meta-analysis, characteristics associated with a statistically significant increase in the odds of warfarin use included history of cerebrovascular accident (OR = 1.59), heart failure (OR = 1.36), and male gender (OR = 1.12). Those associated with a significant reduction in the odds of warfarin use included alcohol/drug abuse (OR = 0.62), perceived barriers to compliance (OR = 0.87), contraindication(s) to warfarin (OR = 0.81), dementia (OR = 0.32), falls (OR = 0.60), gastrointestinal hemorrhage (OR = 0.47), intracranial hemorrhage (OR = 0.39), hepatic (OR = 0.59), and renal impairment (OR = 0.69). While age per 10-year increase (OR = 0.78) and advancing age as a dichotomized variable (cut-off varied by study) (OR = 0.57) were associated with significant reductions in warfarin use; qualitative review of results of studies evaluating age as a categorical variable did not confirm this relationship. Conclusions Warfarin use has increased somewhat over time. The

Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

PubMed

Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

2012-01-01

The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

Safety and effectiveness of rivaroxaban and warfarin in moderate-to-advanced CKD: real world data.

PubMed

Di Lullo, Luca; Tripepi, Giovanni; Ronco, Claudio; De Pascalis, Antonio; Barbera, Vincenzo; Granata, Antonio; Russo, Domenico; Di Iorio, Biagio Raffaele; Paoletti, Ernesto; Ravera, Maura; Fusaro, Maria; Bellasi, Antonio

2018-06-07

In recent years, novel anticoagulant drugs have been introduced in the clinical armamentarium and have progressively gained momentum. Although their use is increasing among CKD patients, some skepticism about their risk-benefit ratio still persists. We sought to investigate the safety and effectiveness of rivaroxaban in a cohort of moderate-to-advanced CKD patients. This observational, retrospective, longitudinal study involved 347 consecutive CKD stage 3b-4 (according to NKF-KDOQI guidelines) patients enrolled from 8 cardiac outpatient clinics between March 2015 and October 2017. All patients received anticoagulation (100 warfarin vs. 247 rivaroxaban) as part of their non-valvular atrial fibrillation management at the attending physician's discretion. Clinical effectiveness (defined as the occurrence of ischemic stroke, venous thromboembolism, or transient ischemic attack) and safety (intracranial hemorrhage, gastrointestinal or other bleeding) were assessed separately. Over a mean follow-up period of 16 ± 0.3 months, 25 stroke episodes (15 hemorrhagic, and 10 ischemic) occurred in 24 warfarin treated patients vs. none in the rivaroxaban arm. There were 5 vs. 0 episodes of deep venous thrombosis and 8 vs. 2 major episodes of bleeding in the warfarin and rivaroxaban groups, respectively. In contrast, the proportion of minor episodes of bleeding was similar between groups. Rivaroxaban seems a safe and effective therapeutic option in CKD stage 3b-4 patients. However, future randomized controlled trials are needed to definitively establish the role of rivaroxaban in CKD patients.

The Effects of Vasospasm and Re-Bleeding on the Outcome of Patients with Subarachnoid Hemorrhage from Ruptured Intracranial Aneurysm.

PubMed

Filipce, Venko; Caparoski, Aleksandar

2015-01-01

Vasospasm and re-bleeding after subarachnoid hemorrhage from ruptured intracranial aneurysm are devastating complication that can severely affect the outcome of the patients. We are presenting a series of total number of 224 patients treated and operated at our Department due to subarachnoid hemorrhage, out of which certain number developed vasospasm and re-bleeding. We are evaluating the effect of these complications on the outcome of the patients according to the Glasgow Outcome Scale at the day of discharge. In our experience both vasospasm and ReSAH can significantly influence the outcome of patients with subarachnoid hemorrhage from ruptured intracranial aneurysm.

[POSITIVE END-EXPIRATORY PRESSURE (PEEP) INFLUENCES ON INTRACRANIAL PRESSURE, SYSTEMIC HEMODYNAMICS AND PULMONARY GAS EXCHANGE IN PATIENTS WITH INTRACRANIAl HEMORRHAGE IN CRITICAL STATE].

PubMed

Solodov, A A; Petrikov, S S; Krylov, V V

2016-01-01

Positive end-expiratory pressure is one of the main parameters of respiratory support influencing the gas exchange. However, despite the number ofpositive effects, PEEP can compromise venous outflow from the cranial cavity, increased intracranial pressure, decreased venous return and cardiac output and, consequently, reduced blood pressure and cerebral perfusion. The article presents the results of a survey of 39 patients with intracranial hemorrhage in critical state, undergoing respiratory support with different levels of positive end-expiratory pressure. Increasing of PEEP to 15 cm H2O had no adverse effect on mean arterial pressure, heart rate and cerebral perfusion pressure and led only to an clinical insignificant increase (maximum on 2.4 +/- 5.1 mmHg) in intracranial pressure. The greatest hemodynamic changes were observed with increasing PEEP up to 20 cm H2O in patients with preserved compliance ofthe respiratory system. The instability of cerebral perfusion and intracranial pressure associated with a decrease in cardiac output and preload and the exhaustion of compensatory mechanism of peripheral vascular resistance. High levels of PEEP despite the trend towards Cstat reduction will not lead to an increase in the content of extravascular lung water Thus a gradual increase of PEEP to 15 cm H2O can be safe and effective method of improving pulmonary gas exchange in patients with intracranial hemorrhage in critical state.

Warfarin interaction with Matricaria chamomilla

PubMed Central

Segal, Robert; Pilote, Louise

2006-01-01

No cases have been reported of Matricaria chamomilla potentiating the effects of warfarin. Nevertheless there is a theoretical risk for potentiation, since the herb is thought to be a coumarin constituent. We describe the case of a 70-year-old woman who, while being treated with warfarin, was admitted to hospital with multiple internal hemorrhages after having used chamomile products (tea and body lotion) to soothe upper respiratory tract symptoms. Patient education on the potential risk of taking chamomile products while being treated with warfarin is necessary to avoid such occurrences. PMID:16636327

Warfarin interaction with erythromycin.

PubMed

Sato, R I; Gray, D R; Brown, S E

1984-12-01

The drug interaction between warfarin and erythromycin is not well known. We report a case in which erythromycin was observed to markedly potentiate warfarin anticoagulation, resulting in hemorrhage in a patient treated for Legionella pneumonia. The morbidity of this drug interaction is enhanced in elderly patients who have infection accompanied by anorexia and/or fever and who are receiving intravenous erythromycin. The well-documented, temporal relationship established erythromycin as the interacting drug.

Evaluation of the role of 8-iso-PGF levels at multiple sites during intracranial hemorrhage in pediatric patients.

PubMed

Qi, B-X; Yao, H; Shang, L; Sheng, L-P; Wang, X-C; Zhu, L; Zhang, X-X; Wang, J-P; Fang, D-H

2017-09-01

The present study was planned to explore the role of 8-isomeric-prostaglandinF2α (8-iso-PGF2α) levels at the multiple sites of cerebrospinal fluid in children with intracranial hemorrhage. 90 children with intracranial hemorrhage were admitted to Surgery Intensive Care Unit (SICU) of our hospital from January to December 2013 and were selected as study subjects. They were divided into group A (n=30), group B (n=30) and group C (n=30). The group A was given conventional treatment, the group B was treated with minimally invasive puncture and the group C was treated with cerebrospinal fluid decompression. After 1 d, 2 d, 3 d, and 7 d of hospitalization, enzyme-linked immunosorbent assay (ELISA) was used to detect the 8-iso-PGF2α levels in peripheral blood of children in all groups. On the day of admission and 10 d after treatment, 3 groups of children were implemented with brain nuclear magnetic resonance spectroscopy for metabolite analyses. On the day of admission there were no significant differences in the 8-iso-PGF2α levels among group A, B and C. Further, after 1 d, 3 d, 7 d of hospital stay, the 8-iso-PGF2α levels in peripheral blood showed a gradual downward trend, and decline range of the group C was greater than that of group A and B (p < 0.05). After 10 days of treatment, there were significant differences in the bilateral temporal lobe and hippocampal NAA/Creatinine (Cr), Cho/Cr, mI/Cr and NAA/mI among group A, B, and C. The survival rate of group C was higher than that of group A and B (p < 0.05). On the other hand, the prevalence of sequelae was significantly lower than that of group A and B (p < 0.05). The amount of blood loss in children with intracranial hemorrhage was positively correlated with the levels of 8-iso-PGF2α in peripheral blood (r = 0.546, p < 0.05) as observed by Spearman correlation analysis. 8-iso-PGF2α plays an important role in the pathogenesis of intracranial hemorrhage, and could be utilized as a biomarker of oxidative

Anti-epileptic Drug (AED) Use in Subarachnoid Hemorrhage (SAH) and Intracranial Hemorrhage (ICH).

PubMed

Feng, Rui; Mascitelli, Justin; Chartrain, Alexander G; Margetis, Konstantinos; Mocco, J

2017-01-01

Aneurysmal subarachnoid hemorrhage (aSAH) and spontaneous intracranial hemorrhage (ICH) are frequently associated with epileptic complications. The use of anti-epileptic drugs (AEDs) for seizure prophylaxis, however, is controversial. In patients with aSAH, nonconvulsive status epilepticus has been associated with poor outcome. Effect of other forms of less severe epileptiform activity on clinical outcome remains unclear. Evidence on efficacy of AEDs in reducing seizure incidence is also mixed. However, increasing number of studies suggest that AEDs may have significant adverse effects on outcome, especially with phenytoin. Similarly, in patients with ICH, the impact of seizures that do not progress to status epilepticus on clinical outcome is controversial, and whether prophylactic AED use has independent effects on outcome remains ambiguous. Currently, there are no large scale randomized control trials investigating the efficacy and safety of AED prophylaxis in patients with hemorrhagic stroke. There are also no trials comparing the efficacy and safety of the different AEDs. Survey based studies have found a wide range of prescribing patterns across treatment centers and clinicians for seizure prophylaxis in patients with hemorrhagic stroke. The lack of clear guidelines and recommendations also highlights the paucity of good quality evidence in this area. In conclusion, a well-designed randomized, double blinded, and appropriately powered trial is needed to evaluate the incidence as well as clinical outcomes in patients with aSAH and ICH who received AED prophylaxis versus controls. The results will be extremely valuable in providing evidence to establish management guidelines for patients with hemorrhagic stroke. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Net clinical benefit of rivaroxaban compared with warfarin in atrial fibrillation: Results from ROCKET AF.

PubMed

Barnett, Adam S; Cyr, Derek D; Goodman, Shaun G; Levitan, Bennett S; Yuan, Zhong; Hankey, Graeme J; Singer, Daniel E; Becker, Richard C; Breithardt, Günter; Berkowitz, Scott D; Halperin, Jonathan L; Hacke, Werner; Mahaffey, Kenneth W; Nessel, Christopher C; Fox, Keith A A; Patel, Manesh R; Piccini, Jonathan P

2018-04-15

The aim of this study was to determine the net clinical benefit (NCB) of rivaroxaban compared with warfarin in patients with atrial fibrillation. This was a retrospective analysis of 14,236 patients included in ROCKET AF who received at least one dose of study drug. We analyzed NCB using four different methods: (1) composite of death, stroke, systemic embolism, myocardial infarction, and major bleeding; (2) method 1 with fatal or critical organ bleeding substituted for major bleeding; (3) difference between the rate of ischemic stroke or systemic embolism minus 1.5 times the difference between the rate of intracranial hemorrhage; and (4) weighted sum of differences between rates of death, ischemic stroke or systemic embolism, intracranial hemorrhage, and major bleeding. Rivaroxaban was associated with a lower risk of the composite outcome of death, myocardial infarction, stroke, or systemic embolism (rate difference per 10,000 patient-years [RD]=-86.8 [95% CI -143.6 to -30.0]) and fatal or critical organ bleeding (-41.3 [-68 to -14.7]). However, rivaroxaban was associated with a higher risk of major bleeding other than fatal or critical organ bleeding (55.9 [14.7 to 97.2]). Method 1 showed no difference between treatments (-35.5 [-108.4 to 37.3]). Methods 2-4 favored treatment with rivaroxaban (2: -96.8 [-157.0 to -36.8]; 3: -65.2 [-112.3 to -17.8]; 4: -54.8 [-96.0 to -10.2]). Rivaroxaban was associated with favorable NCB compared with warfarin. The NCB was attributable to lower rates of ischemic events and fatal or critical organ bleeding. Copyright © 2017 Elsevier B.V. All rights reserved.

A Retrospective Propensity Score-Matched Early Thromboembolic Event Analysis of Prothrombin Complex Concentrate vs Fresh Frozen Plasma for Warfarin Reversal Prior to Emergency Neurosurgical Procedures.

PubMed

Agarwal, Prateek; Abdullah, Kalil G; Ramayya, Ashwin G; Nayak, Nikhil R; Lucas, Timothy H

2017-06-29

Reversal of therapeutic anticoagulation prior to emergency neurosurgical procedures is required in the setting of intracranial hemorrhage. Multifactor prothrombin complex concentrate (PCC) promises rapid efficacy but may increase the probability of thrombotic complications compared to fresh frozen plasma (FFP). To compare the rate of thrombotic complications in patients treated with PCC or FFP to reverse therapeutic anticoagulation prior to emergency neurosurgical procedures in the setting of intracranial hemorrhage at a level I trauma center. Sixty-three consecutive patients on warfarin therapy presenting with intracranial hemorrhage who received anticoagulation reversal prior to emergency neurosurgical procedures were retrospectively identified between 2007 and 2016. They were divided into 2 cohorts based on reversal agent, either PCC (n = 28) or FFP (n = 35). The thrombotic complications rates within 72 h of reversal were compared using the χ 2 test. A multivariate propensity score matching analysis was used to limit the threat to interval validity from selection bias arising from differences in demographics, laboratory values, history, and clinical status. Thrombotic complications were uncommon in this neurosurgical population, occurring in 1.59% (1/63) of treated patients. There was no significant difference in the thrombotic complication rate between groups, 3.57% (1/28; PCC group) vs 0% (0/35; FFP group). Propensity score matching analysis validated this finding after controlling for any selection bias. In this limited sample, thrombotic complication rates were similar between use of PCC and FFP for anticoagulation reversal in the management of intracranial hemorrhage prior to emergency neurosurgical procedures. Copyright © 2017 by the Congress of Neurological Surgeons

[Severe rhabdomyolysis and intracranial hemorrhage associated with synthetic cannabinoid: a case report].

PubMed

Tanei, Takafumi; Morita, Yoshiki; Yashima, Akihito; Wakita, Hiroyuki; Takebayashi, Shigenori; Nakahara, Norimoto; Wakabayashi, Toshihiko

2014-09-01

A 28-year-old male presented with language and behavior disorders a few days prior to examination. Magnetic resonance images and cerebral angiography revealed an arteriovenous malformation (AVM) in the right frontal lobe. The size of the nidus was 2.0 cm, and it was fed by the middle cerebral arteries and drained by the superior sagittal and transverse sinuses. The AVM was completely surgically resected without any complications. Ten months after the surgery, the patient presented with behavior disorders again and general convulsion. Computed tomography showed a small intracranial hemorrhage at the right frontal lobe, where the AVM was located. Blood examination revealed severe rhabdomyolysis (CK:536,620U/L)and acute kidney injury (Cr:5.20mg/dL). After admission, it became clear that the patient had used synthetic cannabinoid (SC). SC refers to a variety of herbal/chemical mixtures, which mimic the effects of marijuana. Little data is available on the psychopathological and physical effects of SC. This is the first report of severe rhabdomyolysis and intracranial hemorrhage associated with SC use in Japan.

Effects of Recombinant Activated Factor VII in Traumatic Nonsurgical Intracranial Hemorrhage

DTIC Science & Technology

2006-09-01

with inhibitors to factors VIII and IX, and it is ap- proved in Europe for the treatment of patients with acquired hemophilia, congenital FVII deficiency...GARY P. WRATTEN SURGICAL SYMPOSIUM Effects of Recombinant Activated Factor VII in Traumatic Nonsurgical Intracranial Hemorrhage Christopher E. White...OBJECTIVE: To determine whether treatment with recombi- nant activated factor VII (rFVIIa) will prevent progression of bleeding in nonsurgical

New Oral Anticoagulants May Be Particularly Useful for Asian Stroke Patients

PubMed Central

Bang, Oh Young; Hong, Keun-Sik; Heo, Ji Hoe; Koo, Jaseong; Kwon, Sun U.; Yu, Kyung-Ho; Bae, Hee-Joon; Lee, Byung-Chul; Yoon, Byung-Woo

2014-01-01

Atrial fibrillation (AF) is an emerging epidemic in both high-income and low-income countries, mainly because of global population aging. Stroke is a major complication of AF, and AF-related ischemic stroke is more disabling and more fatal than other types of ischemic stroke. However, because of concerns about bleeding complications, particularly intracranial hemorrhage, and the limitations of a narrow therapeutic window, warfarin is underused. Four large phase III randomized controlled trials in patients with non-valvular AF (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) demonstrated that new oral anticoagulants (NOACs) are superior or non-inferior to warfarin as regards their efficacy in preventing ischemic stroke and systemic embolism, and superior to warfarin in terms of intracranial hemorrhage. Among AF patients receiving warfarin, Asians compared to non-Asians are at higher risk of stroke or systemic embolism and are also more prone to develop major bleeding complications, including intracranial hemorrhage. The extra benefit offered by NOACs over warfarin appears to be greater in Asians than in non-Asians. In addition, Asians are less compliant, partly because of the frequent use of herbal remedies. Therefore, NOACs compared to warfarin may be safer and more useful in Asians than in non-Asians, especially in stroke patients. Although the use of NOACs in AF patients is rapidly increasing, guidelines for the insurance reimbursement of NOACs have not been resolved, partly because of insufficient understanding of the benefit of NOACs and partly because of cost concerns. The cost-effectiveness of NOACs has been well demonstrated in the healthcare settings of developed countries, and its magnitude would vary depending on population characteristics as well as treatment cost. Therefore, academic societies and regulatory authorities should work together to formulate a scientific healthcare policy that will effectively reduce the burden of AF-related stroke in

Gastrointestinal bleeding risk of non-vitamin K oral anticoagulants is similar to warfarin - a Japanese retrospective cohort study
.

PubMed

Shirai, Tsuguru; Yamamoto, Takatsugu; Kawasugi, Kazuo; Kuyama, Yasushi; Kita, Hiroto

2016-11-01

Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding. Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011. Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding. Risk of gastrointestinal hemorrhage in patients taking non-vitamin K oral anticoagulants was similar to that in patients taking warfarin. The dominant bleeding site was the lower gastrointestinal tract.
.

A Population-Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin

PubMed Central

Pincus, D; Gomes, T; Hellings, C; Zheng, H; Paterson, JM; Mamdani, MM; Juurlink, DN

2013-01-01

Most drug interaction resources suggest that levothyroxine can dramatically potentiate the effect of warfarin. However, the mechanistic basis of the interaction is speculative, and little evidence supports a meaningful drug interaction. We conducted a population-based nested case–control study to examine the risk of hospitalization for hemorrhage following the initiation of levothyroxine in a cohort of 260,076 older patients receiving warfarin. In this group, we identified 10,532 case subjects hospitalized for hemorrhage and 40,595 controls. In the primary analysis, we found no association between hospitalization for hemorrhage during warfarin therapy and initiation of levothyroxine in the preceding 30 days (adjusted odds ratio 1.11, 95% confidence interval 0.67–1.86). Secondary analyses using more remote initiation of levothyroxine also found no association. These findings suggest that concerns about a clinically meaningful levothyroxine–warfarin drug interaction are not justified. Drug interaction resources that presently characterize this interaction as important should reevaluate this classification. PMID:23093318

Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study.

PubMed

Yoon, Chang-Yun; Noh, Juhwan; Jhee, Jong Hyun; Chang, Tae Ik; Kang, Ea Wha; Kee, Youn Kyung; Kim, Hyoungnae; Park, Seohyun; Yun, Hae-Ryong; Jung, Su-Young; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Kang, Shin-Wook; Kim, Changsoo; Yoo, Tae-Hyun

2017-09-01

The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models. Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P =0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P =0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P =0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P =0.470). Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications. © 2017 American Heart Association, Inc.

Risk of bleeding with dabigatran in atrial fibrillation.

PubMed

Hernandez, Inmaculada; Baik, Seo Hyon; Piñera, Antonio; Zhang, Yuting

2015-01-01

It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice. To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data. In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011. Dabigatran users (n = 1302) and warfarin users (n = 8102). We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities. Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of

Efficacy and safety of rivaroxaban versus warfarin in patients from mainland China with nonvalvular atrial fibrillation: A subgroup analysis from the ROCKET AF trial.

PubMed

Sun, Yihong; Hu, Dayi; Stevens, Susanna; Lokhnygina, Yuliya; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Piccini, Jonathan P; Singer, Daniel E; Fox, Keith A A; Patel, Manesh R

2017-08-01

The ROCKET AF study evaluated once-daily rivaroxaban versus dose-adjusted warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). In this analysis, we compared rivaroxaban with warfarin in patients with AF from China, East Asia, and the rest of the world (ROW). We assessed baseline demographics and interaction of treatment effects of rivaroxaban versus warfarin among patients from mainland China, other East Asian countries, and ROW. Of the 14,236 patients enrolled in the per-protocol population, 495 were from mainland China, 433 from other East-Asian regions, and 13,308 from the rest of the world (ROW). At baseline, patients from China had significantly higher rates of previous stroke/transient ischemic attack (TIA) compared with patients from other East Asian regions and ROW (79.6%, 44.6%, 51.6% respectively; p<0.0001) and lower rates of VKA use (33.7%, 66.7%, 63.4%, respectively; p<0.0001). The rates of stroke or systemic embolism among those on warfarin while on treatment was 5.23% in patients from China, 1.82% in those from other East Asian regions, and 2.07% from ROW; on rivaroxaban, the rates were 2.29% in patients from China, 1.86% in those from other east Asian regions, and 1.67% from ROW. There were no significant treatment-by-region interactions for any efficacy or safety outcome (all p>0.12). Numerically higher rates of intracranial bleeding were seen in patients from China receiving warfarin versus rivaroxaban. In patients from China, rates of intracranial hemorrhage were numerically lower among those receiving rivaroxaban and consistent with the overall trial. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767. Copyright © 2017 Elsevier Ltd. All rights reserved.

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y H

2015-08-11

Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality

Predictors for Symptomatic Intracranial Hemorrhage After Endovascular Treatment of Acute Ischemic Stroke.

PubMed

Hao, Yonggang; Yang, Dong; Wang, Huaiming; Zi, Wenjie; Zhang, Meng; Geng, Yu; Zhou, Zhiming; Wang, Wei; Xu, Haowen; Tian, Xiguang; Lv, Penghua; Liu, Yuxiu; Xiong, Yunyun; Liu, Xinfeng; Xu, Gelin

2017-05-01

Symptomatic intracranial hemorrhage (SICH) pose a major safety concern for endovascular treatment of acute ischemic stroke. This study aimed to evaluate the risk and related factors of SICH after endovascular treatment in a real-world practice. Patients with stroke treated with stent-like retrievers for recanalizing a blocked artery in anterior circulation were enrolled from 21 stroke centers in China. Intracranial hemorrhage was classified as symptomatic and asymptomatic ones according to Heidelberg Bleeding Classification. Logistic regression was used to identify predictors for SICH. Of the 632 enrolled patients, 101 (16.0%) were diagnosed with SICH within 72 hours after endovascular treatment. Ninety-day mortality was higher in patients with SICH than in patients without SICH (65.3% versus 18.8%; P <0.001). On multivariate analysis, baseline neutrophil ratio >0.83 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.24-3.46), pretreatment Alberta Stroke Program Early Computed Tomography Score of <6 (OR, 2.27; 95% CI, 1.24-4.14), stroke of cardioembolism type (OR, 1.91; 95% CI, 1.13-3.25), poor collateral circulation (OR, 1.97; 95% CI, 1.16-3.36), delay from symptoms onset to groin puncture >270 minutes (OR, 1.70; 95% CI, 1.03-2.80), >3 passes with retriever (OR, 2.55; 95% CI, 1.40-4.65) were associated with SICH after endovascular treatment. Incidence of SICH after thrombectomy is higher in Asian patients with acute ischemic stroke. Cardioembolic stroke, poor collateral circulation, delayed endovascular treatment, multiple passes with stent retriever device, lower pretreatment Alberta Stroke Program Early Computed Tomography Score, higher baseline neutrophil ratio may increase the risk of SICH. © 2017 American Heart Association, Inc.

[Neurologic complications of subarachnoid hemorrhage due to intracranial aneurysm rupture].

PubMed

Rama-Maceiras, P; Fàbregas Julià, N; Ingelmo Ingelmo, I; Hernández-Palazón, J

2010-12-01

The high rates of morbidity and mortality after subarachnoid hemorrhage due to spontaneous rupture of an intracranial aneurysm are mainly the result of neurologic complications. Sixty years after cerebral vasospasm was first described, this problem remains unsolved in spite of its highly adverse effect on prognosis after aneurysmatic rupture. Treatment is somewhat empirical, given that uncertainties remain in our understanding of the pathophysiology of this vascular complication, which involves structural and biochemical changes in the endothelium and smooth muscle of vessels. Vasospasm that is refractory to treatment leads to cerebral infarction. Prophylaxis, early diagnosis, and adequate treatment of neurologic complications are key elements in the management of vasospasm if neurologic damage, lengthy hospital stays, and increased use of health care resources are to be avoided. New approaches to early treatment of cerebral lesions and cortical ischemia in cases of subarachnoid hemorrhage due to aneurysm rupture should lead to more effective, specific management.

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage.

PubMed

Chang, Ronald; Folkerson, Lindley E; Sloan, Duncan; Tomasek, Jeffrey S; Kitagawa, Ryan S; Choi, H Alex; Wade, Charles E; Holcomb, John B

2017-02-01

Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. "Early plasma" was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71-1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20-9.35). Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial

Life-threatening intracranial bleeding in a newborn with congenital cytomegalovirus infection: late-onset neonatal hemorrhagic disease.

PubMed

Dallar, Yildiz; Tiras, Ulku; Catakli, Tulin; Gulal, Gonul; Sayar, Yavuz; Selvar, Beray; Alioglu, Bulent

2011-02-01

The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.

The impact of combined use of fall-risk medications and antithrombotics on injury severity and intracranial hemorrhage among older trauma patients.

PubMed

Hohmann, Natalie; Hohmann, Lindsey; Kruse, Michael

2014-01-01

Use of fall-risk medications (medications that increase risk of falling in the elderly as defined by Beers criteria, STOPP/START criteria, and other literature) or antithrombotics is common in the elderly, and the impact of their concomitant use should be assessed in regards to fall injuries. The primary objective of this study is to assess the simultaneous outpatient use of fall-risk medications and antithrombotics in elderly fall-patients, and secondarily to analyze the injury severity score and occurrence of intracranial hemorrhage. Consecutive chart review at a level 2 trauma center in California, USA from August 01, 2009 to October 31, 2010. Records included 112 patients at least 65 years of age admitted with an outpatient fall. Fisher's exact and Student's t-tests were used (alpha 0.05, two-tailed) to examine prescribing patterns, intracranial hemorrhage occurrence, and injury severity score. Regression adjusted for antithrombotic and fall-risk medication type and number, opiate use, co-morbidities, age, and gender. Thirty-nine percent (44/112) of outpatients were prescribed antithrombotics plus fall-risk medications. The mean injury severity score (ISS) was 13.3 (range 1-26, standard deviation 7.2) for patients taking both medication classes versus 9.7 (range 1-25, standard deviation 7.5) for patients taking antithrombotics alone (p = 0.027). Additionally, in patients over 80 years of age, intracranial hemorrhage occurred more frequently with the use of antithrombotics plus fall-risk medications versus antithrombotics alone (18/29 = 62.1% versus 7/24 = 29.2%, p = 0.027, odds ratio = 3.974, 95% confidence interval = 1.094-15.010). Multivariate analyses showed an independent relationship between intracranial hemorrhage occurrence and type of therapy, as well as injury severity score and simultaneous therapy with fall-risk medications and antithrombotics. Simultaneous prescribing of antithrombotics and fall-risk medications is common. For

Comparative effectiveness of dabigatran and rivaroxaban versus warfarin for the treatment of non-valvular atrial fibrillation

PubMed Central

Bengtson, Lindsay GS; Lutsey, Pamela L.; Chen, Lin Y.; MacLehose, Richard F.; Alonso, Alvaro

2016-01-01

Background Effectiveness data on novel oral anticoagulants (NOACs) versus warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) by prior warfarin use are limited. Methods We used data from the US MarketScan databases from 2009–2012. NVAF patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users. Propensity score-adjusted Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) for relevant endpoints in NOACs versus warfarin users. Separate analyses were conducted to compare anticoagulant-naïve users of NOACs and those switching from warfarin. Results Among 32,918 dabigatran, 3,301 rivaroxaban, and 109,447 warfarin users with NVAF, 225 intracranial bleeds, 1035 ischemic strokes, 958 myocardial infarctions, and 1842 gastrointestinal bleeds were identified. Compared to warfarin users, patients initiating NOACs had similar ischemic stroke rates and lower intracranial bleeding rates, while the gastrointestinal bleeding rate was higher in dabigatran users than warfarin users. Associations of dabigatran with ischemic stroke risk differed between anticoagulant-naïve initiators and patients switching from warfarin; dabigatran was associated with lower ischemic stroke rates in naïve users (HR 0.65, 95%CI 0.52–0.82) but not in switchers (HR 1.20, 95%CI 0.95–1.51), compared to warfarin. Risk of stroke and bleeding was not different between rivaroxaban and warfarin users. Conclusions Real-world effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in published clinical trials. However, harms and benefits of switching from warfarin to dabigatran need to be evaluated. PMID:27889397

Racial differences in vascular risk factors and outcomes of patients with intracranial atherosclerotic arterial stenosis.

PubMed

Waddy, Salina P; Cotsonis, George; Lynn, Michael J; Frankel, Michael R; Chaturvedi, Seemant; Williams, Janice E; Chimowitz, Marc

2009-03-01

Atherosclerotic intracranial stenosis is an important cause of stroke in blacks, yet there are limited data on vascular risk factors and outcome. We analyzed the vascular risk factors and outcomes of blacks and whites in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. Baseline characteristics and outcomes (ischemic stroke, brain hemorrhage, or vascular death combined and ischemic stroke alone) were compared between blacks (n=174) and whites (n=331) using univariate and multivariate analyses. Blacks were significantly (P<0.05) more likely than whites to be/have: female, hypertension history, diabetes history, higher LDL, higher total cholesterol, lower triglycerides, unmarried, unemployed, nonprivate insurance, no insurance, stroke as qualifying event, <70% stenosis, symptomatic anterior circulation vessel, no antithrombotic medication before qualifying event, and no family history of myocardial infarction. Blacks more frequently reached an end point of ischemic stroke, brain hemorrhage or vascular death (28% versus 20%; hazard ratio of 1.49, 95% CI 1.03 to 2.17, P=0.03), had a higher 2-year event rate (0.28 versus 0.19), and reached the end point of ischemic stroke alone (25% versus 16% at 2 years; hazard ratio of 1.62, P=0.017). In multivariate analysis, race was associated with ischemic stroke (P=0.0488) but not with the end point ischemic stroke, brain hemorrhage or vascular death (P=0.188). Blacks with intracranial stenosis are at higher risk of stroke recurrence than whites. This risk warrants additional study of factors contributing to stroke in blacks and highlights the need for aggressive risk factor management in blacks to prevent recurrence.

Outcome in adult patients with hemorrhagic moyamoya disease after combined extracranial-intracranial bypass.

PubMed

Jiang, Hanqiang; Ni, Wei; Xu, Bin; Lei, Yu; Tian, Yanlong; Xu, Feng; Gu, Yuxiang; Mao, Ying

2014-11-01

The outcome of patients with hemorrhagic moyamoya disease (MMD) after cerebral revascularization is uncertain. The purpose of this study was to delineate the efficacy of this surgical method in the treatment of hemorrhagic MMD. Between January 2007 and August 2011, a consecutive cohort of 113 patients with hemorrhagic MMD was enrolled into this prospective single-center cohort study. The surgical method was combined direct and indirect bypass. The cumulative probability of the primary end point (all stroke and deaths from surgery through 30 days after surgery and ipsilateral recurrent hemorrhage afterward) was analyzed. The angiographic outcome was measured by the following parameters: bypass patency, reduction of basal MMD vessels, improved degree of dilation, and branch extension of the anterior choroidal and posterior communicating arteries (AChA-PCoA). Of the 113 enrolled cases, CT scans revealed pure intraventricular hemorrhage (IVH) in 63 cases (55.7%), pure intracranial hemorrhage (ICH) in 14 cases (12.4%), and ICH with IVH in 36 cases (31.9%). In 74 of 113 hemorrhagic hemispheres (65.5%), the AChA-PCoA was extremely dilated with extensive branches beyond the choroidal fissure. A total of 114 surgeries were performed. No patient suffered ischemic or hemorrhagic stroke through 30 days after surgery. Ipsilateral rebleeding occurred in 5 patients, 4 of whom died of the rebleeding event. The cumulative probability of the primary end point was 0% at 1 year and 1.9% at 2 years. The annual rebleeding rate was 1.87%/person/year. The improvement in AChA-PCoA extension was observed in 75 of 107 operated hemispheres (70.1%), which was higher than that in 7 of 105 unoperated hemispheres (35.2%). Revascularization may provide a benefit over conservative therapy for hemorrhagic MMD patients. The improvement of dilation and branch extension of AChA-PCoA might be correlated with the low rebleeding rate.

Bleeding rates in Veterans Affairs patients with atrial fibrillation who switch from warfarin to dabigatran.

PubMed

Vaughan Sarrazin, Mary S; Jones, Michael; Mazur, Alexander; Chrischilles, Elizabeth; Cram, Peter

2014-12-01

Clinical trial data suggest that dabigatran and warfarin have similar rates of major bleeding but higher rates of gastrointestinal bleeding. These findings have not been evaluated outside of a clinical trial. We evaluated the relative risks of any, gastrointestinal, intracranial, and other bleeding for Veterans Affairs patients who switched to dabigatran after at least 6 months on warfarin, compared with patients who continued on warfarin. We used national Veterans Affairs administrative encounter and pharmacy data from fiscal years 2010-2012 to identify 85,344 patients with atrial fibrillation who had been taking warfarin for at least 180 days before June 2011, of whom 1394 (1.7%) received dabigatran (150 mg) during the next 15 months. Dates of the first occurrence of each type of bleed and dates of death from June 2011 to September 2012 were determined. Baseline and time-dependent patient characteristics were identified, including comorbid conditions, stroke and bleeding risk scores, and time in therapeutic range for international normalized ratios. Marginal structural models were used to address selection bias in the longitudinal observational data. Weighted logistic regression models were fit using generalized estimating equations and reflected baseline and time-dependent covariates and weekly indicators of anticoagulant type (warfarin or dabigatran). Compared with patients who never used dabigatran, patients who used dabigatran at least once were younger, were more likely to be white, had lower international normalized ratio time in therapeutic range on warfarin, had lower stroke risk scores, and had similar bleeding risk scores. Overall, 10,734 patients experienced bleeding events, including 131 events after dabigatran use. The risk-adjusted rate of any bleeding was higher with dabigatran compared with warfarin, which was largely driven by a 54% higher risk of gastrointestinal bleeding with dabigatran. Rates of intracranial, other bleeding, and death were

Reversible coma and Duret hemorrhage after intracranial hypotension from remote lumbar spine surgery: case report.

PubMed

Bonow, Robert H; Bales, James W; Morton, Ryan P; Levitt, Michael R; Zhang, Fangyi

2016-03-01

Intracranial hypotension is a rare condition caused by spontaneous or iatrogenic CSF leaks that alter normal CSF dynamics. Symptoms range from mild headaches to transtentorial herniation, coma, and death. Duret hemorrhages have been reported to occur in some patients with this condition and are traditionally believed to be associated with a poor neurological outcome. A 73-year-old man with a remote history of spinal fusion presented with syncope and was found to have small subdural hematomas on head CT studies. He was managed nonoperatively and discharged with a Glasgow Coma Scale score of 15, only to return 3 days later with obtundation, fixed downward gaze, anisocoria, and absent cranial nerve reflexes. A CT scan showed Duret hemorrhages and subtle enlargement of the subdural hematomas, though the hematomas remained too small to account for his poor clinical condition. Magnetic resonance imaging of the spine revealed a large lumbar pseudomeningocele in the area of prior fusion. His condition dramatically improved when he was placed in the Trendelenburg position and underwent repair of the pseudomeningocele. He was kept flat for 7 days and was ultimately discharged in good condition. On long-term follow-up, his only identifiable deficit was diplopia due to an internuclear ophthalmoplegia. Intracranial hypotension is a rare condition that can cause profound morbidity, including tonsillar herniation and brainstem hemorrhage. With proper identification and treatment of the CSF leak, patients can make functional recoveries.

Laboratory assessment of warfarin reversal with global coagulation tests versus international normalized ratio in patients with intracranial bleeding.

PubMed

Voils, Stacy A; Martin, Erika J; Mohammed, Bassem M; Bayrlee, Ahmad; Brophy, Donald F

2015-06-01

We assess the in-vivo relationship between international normalized ratio (INR) and global coagulation tests in patients with life-threatening bleeding who received prothrombin complex concentrate (PCC) for warfarin reversal. This was a prospective pilot study in adult patients with intracranial bleeding related to anticoagulation with warfarin. Thromboelastography (TEG), thrombin generation parameters and INR were assessed at baseline, 30  min, 2 and 24  h after PCC. Changes in laboratory parameters and relationship between INR and global coagulation tests were assessed over time. Eight patients mean [standard deviation (SD)] age 72 (16) were included and received mean (SD) dose of PCC 24 (5) units/kg. Four patients died during the study, all with INR values more than 1.5 thirty minutes after PCC. Mean (SD) INR was 3.0 (1.3) and decreased significantly to 1.8 (0.48) thirty minutes after PCC (P < 0.01). Baseline endogenous thrombin potential and thrombin peak were 890  nmol/min and 123  nmol and increased significantly to 1943  nmol/min (P < 0.01) and 301  nmol (P < 0.01) 30  min after PCC administration. Reaction (R)-time decreased significantly (P = 0.02), and maximum amplitude and overall coagulation index (CI) significantly increased during treatment (P < 0.01, respectively). Thrombin generation and TEG values corrected after PCC administration; however, INR did not fully correct. Patients that died tended to be older with prolonged INR values across the study period. INR and TEG values correlated well with thrombin generation before administration of PCC, but this relationship was lost afterward.

Continuous monitoring of intracranial pressure for prediction of postoperative complications of hypertensive intracerebral hemorrhage.

PubMed

Yu, S-X; Zhang, Q-S; Yin, Y; Liu, Z; Wu, J-M; Yang, M-X

2016-11-01

This study evaluates the value of continuous dynamic monitoring of intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage to predict early postoperative complications. Data from 80 patients treated in our hospital from February 2014 to February 2015 were analyzed. The patients all underwent decompressive craniectomies, and their ICP changes were monitored invasively and continuously for 1 to 7 days after surgery. The average blood loss during surgery for the group of patients was 65.3 ± 12.4 ml and the mean GCS score 8.7 ± 2.4. Cases were divided into three groups according to ICP values to compare early postoperative complications of the groups: a normal and mildly increased group (51 cases), a moderately increased group (19 cases) and a severely increased group (10 cases). To validate the analysis we first showed that comparisons among groups based on gender, age, systolic pressure, diastolic pressure, bleeding time, blood loss, operation time, craniectomy localization, and preoperative mannitol dosage yielded no statistically significant differences. In contrast, the following comparisons produced statistically significant differences: the comparison of postoperative Glasgow Coma Scale (GCS) scores showing that the lower intracranial pressure, the higher the GCS score; the postoperative rehemorrhage, cerebral edema and death ratios showing the higher the intracranial pressure, the higher the rehemorrhage ratio; the average ICP and the time to occurrence of rehemorrhage, cerebral edema or cerebral infarction, showing the relationship between the average ICP and the time to a complication. Patients with higher ICP averages suffered a complication of rehemorrhage within the first 9.6 ± 2.5 hours on average. Nevertheless, the comparison of GCS scores in those patients and the others showed no significant differences. Based on the findings, the dynamic monitoring of intracranial pressure can early and sensitively predict postoperative

Serum creatinine may indicate risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator (IV tPA).

PubMed

Marsh, Elisabeth B; Gottesman, Rebecca F; Hillis, Argye E; Urrutia, Victor C; Llinas, Rafael H

2013-11-01

Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient's neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a "symptomatic" hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR <60 mL/min per 1.73 m²). Student paired t tests, Fisher exact tests, and multivariable logistic regression (adjusted for demographics and vascular risk factors) were used to evaluate the relationship between renal impairment and ICH. Fifty-seven (25%) of the 224 patients had

Serum Creatinine May Indicate Risk of Symptomatic Intracranial Hemorrhage After Intravenous Tissue Plasminogen Activator (IV tPA)

PubMed Central

Marsh, Elisabeth B.; Gottesman, Rebecca F.; Hillis, Argye E.; Urrutia, Victor C.

2013-01-01

Abstract Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient’s neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a “symptomatic” hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR <60 mL/min per 1.73 m2). Student paired t tests, Fisher exact tests, and multivariable logistic regression (adjusted for demographics and vascular risk factors) were used to evaluate the relationship between renal impairment and ICH. Fifty-seven (25%) of the 224

Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2.

PubMed

Morihara, Ryuta; Yamashita, Toru; Kono, Syoichiro; Shang, Jingwei; Nakano, Yumiko; Sato, Kota; Hishikawa, Nozomi; Ohta, Yasuyuki; Heitmeier, Stefan; Perzborn, Elisabeth; Abe, Koji

2017-09-01

This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue-type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin-pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease-activated receptor-1, -2, -3, and -4 (PAR-1, -2, -3, and -4). After pretreatment with warfarin (0.2 mg/kg/day), low-dose rivaroxaban (60 mg/kg/day), high-dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty-four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin-pretreated group compared with the rivaroxaban-treated group. PAR-1, -2, -3, and -4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri-ischemic lesion. Warfarin pretreatment enhanced the expression of PAR-1 and PAR-2 in the peri-ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban-pretreated compared with warfarin-pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR-1 and PAR-2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial).

PubMed

Washam, Jeffrey B; Hellkamp, Anne S; Lokhnygina, Yuliya; Piccini, Jonathan P; Berkowitz, Scott D; Nessel, Christopher C; Becker, Richard C; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Singer, Daniel E; Patel, Manesh R

2017-08-15

Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS 2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF. Copyright © 2017

Optical imaging of intracranial hemorrhages in newborns: modern strategies in diagnostics and direction for future research

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Semyachkina-Glushkovskaya, O. V.; Lychagov, V. V.; Bibikova, O. A.; Sindeev, S. S.; Pavlova, O. N.; Shuvalova, E. P.; Tuchin, V. V.

2014-05-01

Using Doppler optical coherence tomography (DOCT) we study stress-related intracranial hemorrhages (ICHs) in newborn rats. We investigate a masked stage of ICH development that corresponds to the first 4 h after the stress. We show that this period is characterized by significant changes in the diameter of the sagittal vein and the velocity of the cerebral venous blood flow (CVBF). We discuss diagnostic abilities of wavelet-based methods and consider an adaptive technique allowing us to reveal clearest distinctions in the dynamics of CVBF between normal and stressed newborn rats. Finally, we conclude that the venous insufficiency in newborns and a reduced response of the sagittal vein to adrenaline are related to important prognostic markers of the risk of ICH development.

Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban

PubMed Central

Pfeilschifter, Waltraud; Steinstraesser, Thurid; Paulus, Patrick; Zeiner, Pia Susan; Bohmann, Ferdinand; Theisen, Alf; Lindhoff-Last, Edelgard; Penski, Cornelia; Wagner, Marlies; Mittelbronn, Michel

2016-01-01

New oral anticoagulants for the prevention of stroke and systemic embolism in patients with atrial fibrillation have recently been introduced. In this translational study, we explored the risk of long-term anticoagulation on intracerebral hemorrhage under sustained severe arterial hypertension. We initiated anticoagulation with warfarin or apixaban in spontaneously hypertensive rats prone to develop severe hypertension and subsequent intracerebral bleeding complications. A non-anticoagulated group served as control. During an 11-week-study period, blood pressure, anticoagulation parameters, and clinical status were determined regularly. The incidence of histopathologically proven intracerebral hemorrhage was defined as the primary endpoint. Both warfarin and apixaban anticoagulation was fairly stable during the study period, and all rats developed severe hypertension. Intracerebral hemorrhage was determined in 29% (4/14) of warfarin rats and in 10% (1/10) of apixaban rats. Controls did not show cerebral bleeding complications (chi-square not significant). Mortality rate at study termination was 33% (2/6) in controls, 43% (6/14) in the warfarin group, and 60% (6/10) in the apixaban group. Animals died from extracerebral complications in most cases. Our study describes an experimental intracerebral hemorrhage model in the context of sustained hypertension and long-term anticoagulation. Extracerebral bleeding complications occurred more often in warfarin-treated animals compared with apixaban and control rats. PMID:27189904

Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial.

PubMed

Mant, Jonathan; Hobbs, F D Richard; Fletcher, Kate; Roalfe, Andrea; Fitzmaurice, David; Lip, Gregory Y H; Murray, Ellen

2007-08-11

Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation, but whether this benefit outweighs the increased risk of bleeding in elderly patients is unknown. We assessed whether warfarin reduced risk of major stroke, arterial embolism, or other intracranial haemorrhage compared with aspirin in elderly patients. 973 patients aged 75 years or over (mean age 81.5 years, SD 4.2) with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (target international normalised ratio 2-3) or aspirin (75 mg per day). Follow-up was for a mean of 2.7 years (SD 1.2). The primary endpoint was fatal or disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, or clinically significant arterial embolism. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN89345269. There were 24 primary events (21 strokes, two other intracranial haemorrhages, and one systemic embolus) in people assigned to warfarin and 48 primary events (44 strokes, one other intracranial haemorrhage, and three systemic emboli) in people assigned to aspirin (yearly risk 1.8%vs 3.8%, relative risk 0.48, 95% CI 0.28-0.80, p=0.003; absolute yearly risk reduction 2%, 95% CI 0.7-3.2). Yearly risk of extracranial haemorrhage was 1.4% (warfarin) versus 1.6% (aspirin) (relative risk 0.87, 0.43-1.73; absolute risk reduction 0.2%, -0.7 to 1.2). These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation, unless there are contraindications or the patient decides that the benefits are not worth the inconvenience.

Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?

PubMed

Go, Alan S; Hylek, Elaine M; Chang, Yuchiao; Phillips, Kathleen A; Henault, Lori E; Capra, Angela M; Jensvold, Nancy G; Selby, Joe V; Singer, Daniel E

2003-11-26

Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear. To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting. Cohort study assembled between July 1, 1996, and December 31, 1997, and followed up through August 31, 1999. Large integrated health care system in Northern California. Of 13,559 adults with nonvalvular atrial fibrillation, 11,526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline. Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files. Among 11,526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25,341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of

Vitamin K2 for the reversal of warfarin-related coagulopathy.

PubMed

Hifumi, Toru; Takada, Hiroaki; Ogawa, Daisuke; Suzuki, Kenta; Hamaya, Hideyuki; Shinohara, Natsuyo; Abe, Yuko; Takano, Koshiro; Kawakita, Kenya; Hagiike, Masanobu; Koido, Yuichi; Kuroda, Yasuhiro

2015-08-01

The American Heart Association/American College of Cardiology Foundation recommends vitamin K1 for warfarin-related coagulopathy. In Japan, vitamin K2 is used more commonly for such purpose. The difference between vitamins K1 and K2 in reversing warfarin-related coagulopathy has not been discussed. Herein, we report a case that was reversed with vitamin K2; alterations in vitamins K1 and K2 levels and coagulation markers are also presented.

Management of minor head injury in patients receiving oral anticoagulant therapy: a prospective study of a 24-hour observation protocol.

PubMed

Menditto, Vincenzo G; Lucci, Moira; Polonara, Stefano; Pomponio, Giovanni; Gabrielli, Armando

2012-06-01

Patients receiving warfarin who experience minor head injury are at risk of intracranial hemorrhage, and optimal management after a single head computed tomography (CT) scan is unclear. We evaluate a protocol of 24-hour observation followed by a second head CT scan. In this prospective case series, we enrolled consecutive patients receiving warfarin and showing no intracranial lesions on a first CT scan after minor head injury treated at a Level II trauma center. We implemented a structured clinical pathway, including 24-hour observation and a CT scan performed before discharge. We then evaluated the frequency of death, admission, neurosurgery, and delayed intracranial hemorrhage. We enrolled and observed 97 consecutive patients. Ten refused the second CT scan and were well during 30-day follow-up. Repeated CT scanning in the remaining 87 patients revealed a new hemorrhage lesion in 5 (6%), with 3 subsequently hospitalized and 1 receiving craniotomy. Two patients discharged after completing the study protocol with 2 negative CT scan results were admitted 2 and 8 days later with symptomatic subdural hematomas; neither received surgery. Two of the 5 patients with delayed bleeding at 24 hours had an initial international normalized ratio greater than 3.0, as did both patients with delayed bleeding beyond 24 hours. The relative risk of delayed hemorrhage with an initial international normalized ratio greater than 3.0 was 14 (95% confidence interval 4 to 49). For patients receiving warfarin who experience minor head injury and have a negative initial head CT scan result, a protocol of 24-hour observation followed by a second CT scan will identify most occurrences of delayed bleeding. An initial international normalized ratio greater than 3 suggests higher risk. Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Bleeding risk with dabigatran, rivaroxaban, warfarin, and antiplatelet agent in Asians with non-valvular atrial fibrillation

PubMed Central

Tu, Hui-Tzu; Kuo, Chi-Tai; Chang, Shang-Hung; Wu, Lung-Sheng; Lee, Hsin-Fu; See, Lai-Chu

2017-01-01

It is not understood if dabigatran or rivaroxaban are superior to antiplatelet agents (AA) for safety outcomes in Asians with non-valvular atrial fibrillation (NVAF). In this study we evaluated the bleeding risk of dabigatran, rivaroxaban, warfarin and AA in Asians with NVAF. This national retrospective cohort study analyzed 6,600, 3,167, 5,338 and 8,238 consecutive NVAF patients taking dabigatran, rivaroxaban, warfarin or AAs (including aspirin, clopidogrel or ticlopidine), respectively, from June 1, 2012 to December 31, 2013. Propensity-score weighting was used to balance covariates across study groups. Patients were followed until the first occurrence of any bleeding outcome or the end of the study. The CHA2DS2-VASc scores were 4.1±1.6, 4.1±1.6, 3.3±1.8 and 2.4±1.6 for the dabigatran, rivaroxaban, warfarin, and AA groups, respectively. There were 5,822 (88.2%) and 164 (5.2%) patients taking low dose dabigatran and rivaroxaban, respectively. Hazard ratios (95% confidence intervals) for dabigatran, rivaroxaban, or warfarin versus AA were: intracranial hemorrhage, 0.36 (0.23-0.57;PP=0.0037) and 1.34 (0.89-2.02;P=0.1664); gastrointestinal bleeding, 0.44 (0.32-0.59;PP=0.0189); and all hospitalized major bleeding, 0.41 (0.32-0.53;PP=0.0644) and 0.90 (0.70-1.16;P=0.4130) after adjustment. The risk reduction of all major bleeding for dabigatran versus AA persisted on subgroup analysis. In conclusion, we observed that dabiagtran was associated with a lower risk of all major bleeding in Asians with NVAF, whereas rivaroxaban had a similar risk of all major bleeding compared with antiplatelet agents after adjustment of comorbidities. PMID:29228736

Hypertonic/Hyperoncotic Resuscitation from Shock: Reduced Volume Requirement and Lower Intracranial Pressure

DTIC Science & Technology

1989-10-01

in Dogs with Hemorrhagic Shock and an Intracranial Mass. Seventh International Symposium on Intracranial Pressure and Brain Injury , Ann Arbor, Michigan...with Hemorrhagic Shock and an Intracranial Mass. Seventh International Symposium on Intracranial Pressure and Brain Injury . Intracranial Pressure VII...and MCI US groups. Discussion: Following this severe insult a iETTiFMT3-a clinical head injury combined wit6i hemorrha Ic shock, a cobntnc/h rcctc

Benefit of Anticoagulation Therapy in Hyperthyroidism-Related Atrial Fibrillation.

PubMed

Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Lip, Gregory Y H; Lam, Karen Siu-Ling; Tse, Hung-Fat; Siu, Chung-Wah

2015-08-01

Existing data on the risk of ischemic stroke in hyperthyroidism-related atrial fibrillation (AF) and the impact of long-term anticoagulation in these patients, particularly those with self-limiting AF, remain inconclusive. Risk of stroke in hyperthyroidism-related AF is the same as nonhyperthyroid counterparts. This was a single-center observational study of 9727 Chinese patients with nonvalvular AF from July 1997 to December 2011. Patients with AF diagnosed concomitantly with hyperthyroidism were identified. Primary and secondary endpoints were defined as hospitalization with ischemic stroke and intracranial hemorrhage in the first 2 years. Patient characteristics, duration of AF, and choice of antithrombotic therapy were recorded. Self-limiting AF was defined as <7 days' duration. Out of 9727 patients, 642 (6.6%) had concomitant hyperthyroidism and AF at diagnosis. For stroke prevention, 136 and 243 patients (21.1% and 37.9%) were prescribed warfarin and aspirin, respectively, whereas the remaining patients (41.0%) received no therapy. Ischemic stroke occurred in 50 patients (7.8%), and no patient developed hemorrhagic stroke. Patients with CHA2 DS2 -VASc of 0 did not develop stroke. Warfarin effectively reduced the incidence of stroke compared with aspirin or no therapy in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF, but not in those with self-limiting AF or CHA2 DS2 -VASc of 0. Presence of hyperthyroidism did not confer additional risk of ischemic stroke compared with nonhyperthyroid AF. Patients with hyperthyroidism-related AF are at high risk of stroke (3.9% per year). Warfarin confers stroke prevention in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF. Overall stroke risk was lower in hyperthyroid non-self-limiting AF patients compared with nonhyperthyroid counterparts. © 2015 Wiley Periodicals, Inc.

Aspirin plus dipyridamole has the highest surface under the cumulative ranking curves (SUCRA) values in terms of mortality, intracranial hemorrhage, and adverse event rate among 7 drug therapies in the treatment of cerebral infarction.

PubMed

Zhang, Jian-Jun; Liu, Xin

2018-03-01

The standardization for the clinical use of drug therapy for cerebral infarction (CI) has not yet determined in some aspects. In this paper, we discussed the efficacies of different drug therapies (aspirin, aspirin plus dipyridamole, aspirin plus clopidogrel, aspirin plus warfarin, cilostazol, warfarin, and ticlopidine) for CI. We searched databases of PubMed and Cochrane Library from the inception to April, 2017, randomized controlled trials (RCTs) met the inclusion and exclusion criteria were enrolled in this study. The network meta-analysis integrated evidences of direct and indirect comparisons to assess odd ratios (OR) and surface under the cumulative ranking curves (SUCRA) value. Thirteen eligible RCTs including 7 drug therapies were included into this network meta-analysis. The network meta-analysis results showed that CI patients who received aspirin plus dipyridamole presented lower mortality when compared with those received aspirin plus clopidogrel (OR = 0.46, 95% CI = 0.18-0.99), indicating aspirin plus dipyridamole therapy had better efficacy for CI. As for intracranial hemorrhage (ICH), stroke recurrence, and adverse event (AE) rate, there were no significant differences of efficacy among 7 drug therapies. Besides, SUCRA values demonstrated that in the 7 drug therapies, aspirin plus dipyridamole therapy was more effective than others (mortality: 80.67%; ICH: 76.6%; AE rate: 90.2%). Our findings revealed that aspirin plus dipyridamole therapy might be the optimum one for patients with CI, which could help to improve the survival of CI patients.

Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation

PubMed Central

Hernandez, Inmaculada; Zhang, Yuting; Brooks, Maria M.; Chin, Paul K.L.; Saba, Samir

2016-01-01

Background and Purpose Little is known about the clinical outcomes associated with post-hemorrhage anticoagulation resumption for atrial fibrillation. This study had two objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran; and second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran. Methods Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the combined risk of ischemic stroke and all-cause mortality, and the risk of recurrent bleeding between treatment groups. Results Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR0.66; 95% CI, 0.32-1.33). Conclusions Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed. PMID:27909200

Perimesencephalic nonaneurysmal subarachnoid hemorrhage caused by transverse sinus thrombosis: A case report and review of literature.

PubMed

Fu, Fang-Wang; Rao, Jie; Zheng, Yuan-Yuan; Song, Liang; Chen, Wei; Zhou, Qi-Hui; Yang, Jian-Guang; Ke, Jiang-Qiong; Zheng, Guo-Qing

2017-08-01

Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH) is characterized by a pattern of extravasated blood restricted to the perimesencephalic cisterns, normal angiographic findings, and an excellent prognosis with an uneventful course and low risks of complication. The precise etiology of bleeding in patients with PNSAH has not yet been established. The most common hypothesis is that PNSAH is venous in origin. Intracranial venous hypertension has been considered as the pivotal factor in the pathogenesis of PNSAH. The underlying venous pathology such as straight sinus stenosis, jugular vein occlusion may contribute to PNSAH. We describe a patient in whom transverse sinus thrombosis preceded intracranial venous hypertension and PNSAH. These findings supported that the source of the subarachnoid hemorrhage is venous in origin. A 45-year-old right-handed man was admitted to the hospital with a sudden onset of severe headache associated with nausea, vomiting, and mild photophobia for 6 hours. The patient was fully conscious and totally alert. An emergency brain computed tomography (CT) revealed an acute subarachnoid hemorrhage restricted to the perimesencephalic cisterns. CT angiography revealed no evidence of an intracranial aneurysm or underlying vascular malformation. Digital subtraction angiography of arterial and capillary phases confirmed the CT angiographic findings. Assessment of the venous phase demonstrated right transverse sinus thrombosis. Magnetic resonance imaging confirmed the diagnosis of cerebral venous sinus thrombosis (CVST). Lumbar puncture revealed an opening pressure of 360 mmH2O, suggestive of intracranial venous hypertension. Grave disease was diagnosed by endocrinological investigation. Low-molecular-weight heparin, followed by oral warfarin, was initiated immediately as the treatment for cerebral venous sinus thrombosis and PNSAH. The patient discharged without any neurologic defect after 3 weeks of hospital stay. MR venography

Management of gastrointestinal bleeding in patients anticoagulated with dabigatran compared with warfarin: a retrospective, comparative case review.

PubMed

Manatsathit, Wuttiporn; Al-Hamid, Hussein; Leelasinjaroen, Pornchai; Hashmi, Usman; McCullough, Peter A

2014-06-01

Dabigatran etexilate, was found to be effective for stroke prevention in patients with non-valvular atrial fibrillation. Given its predictable pharmacodynamics, laboratory monitoring is not required. Moreover, the risks of overall bleeding, intracranial bleeding, and life-threatening hemorrhage from dabigatran were found to be lower than warfarin. However, a higher risk of gastrointestinal (GI) bleeding caused by dabigatran from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial has raised the concern regarding clinical outcomes of patients with GI bleeding caused by dabigatran compared with warfarin. We retrospectively studied patients who were hospitalized for GI bleeding from dabigatran compared with warfarin with therapeutic anticoagulation monitoring during 2009 to 2012. Initial laboratory findings at presentation, number of transfused packed red blood cells (PRBCs), acute kidney injury, clinical outcomes (e.g., hypotension, tachycardia), length of stay, and death were compared. Thirteen patients taking dabigatran and 26 patients who were on warfarin with therapeutic international normalized ratio (INR) were hospitalized during the study period. Demographic data and baseline parameters between the two groups were not significantly different except for concurrent aspirin use (84.6% vs. 50%, P=0.036). Fifty-four percent of patients taking dabigatran did not have activated partial thromboplastin time (aPTT) level performed at presentation (7/13). The patients with GI bleeding from warfarin received significantly more PRBC transfusions compared with the dabigatran group (1.92±2.2 vs. 0.69±1.1 units, P=0.024). After controlling for initial hemoglobin and history of chronic kidney disease by using multivariate analysis, the patients in the warfarin group were likely to receive more PRBC. Hypotension at presentation was more common in GI bleeding caused by warfarin than dabigatran but the P value was insignificant (30.8% vs. 7.7%, P=0

Portable Wideband Microwave Imaging System for Intracranial Hemorrhage Detection Using Improved Back-projection Algorithm with Model of Effective Head Permittivity

PubMed Central

Mobashsher, Ahmed Toaha; Mahmoud, A.; Abbosh, A. M.

2016-01-01

Intracranial hemorrhage is a medical emergency that requires rapid detection and medication to restrict any brain damage to minimal. Here, an effective wideband microwave head imaging system for on-the-spot detection of intracranial hemorrhage is presented. The operation of the system relies on the dielectric contrast between healthy brain tissues and a hemorrhage that causes a strong microwave scattering. The system uses a compact sensing antenna, which has an ultra-wideband operation with directional radiation, and a portable, compact microwave transceiver for signal transmission and data acquisition. The collected data is processed to create a clear image of the brain using an improved back projection algorithm, which is based on a novel effective head permittivity model. The system is verified in realistic simulation and experimental environments using anatomically and electrically realistic human head phantoms. Quantitative and qualitative comparisons between the images from the proposed and existing algorithms demonstrate significant improvements in detection and localization accuracy. The radiation and thermal safety of the system are examined and verified. Initial human tests are conducted on healthy subjects with different head sizes. The reconstructed images are statistically analyzed and absence of false positive results indicate the efficacy of the proposed system in future preclinical trials. PMID:26842761

Portable Wideband Microwave Imaging System for Intracranial Hemorrhage Detection Using Improved Back-projection Algorithm with Model of Effective Head Permittivity

NASA Astrophysics Data System (ADS)

Mobashsher, Ahmed Toaha; Mahmoud, A.; Abbosh, A. M.

2016-02-01

Intracranial hemorrhage is a medical emergency that requires rapid detection and medication to restrict any brain damage to minimal. Here, an effective wideband microwave head imaging system for on-the-spot detection of intracranial hemorrhage is presented. The operation of the system relies on the dielectric contrast between healthy brain tissues and a hemorrhage that causes a strong microwave scattering. The system uses a compact sensing antenna, which has an ultra-wideband operation with directional radiation, and a portable, compact microwave transceiver for signal transmission and data acquisition. The collected data is processed to create a clear image of the brain using an improved back projection algorithm, which is based on a novel effective head permittivity model. The system is verified in realistic simulation and experimental environments using anatomically and electrically realistic human head phantoms. Quantitative and qualitative comparisons between the images from the proposed and existing algorithms demonstrate significant improvements in detection and localization accuracy. The radiation and thermal safety of the system are examined and verified. Initial human tests are conducted on healthy subjects with different head sizes. The reconstructed images are statistically analyzed and absence of false positive results indicate the efficacy of the proposed system in future preclinical trials.

Oral warfarin intake affects skin inflammatory cytokine responses in rats.

PubMed

Aleksandrov, Aleksandra Popov; Mirkov, Ivana; Zolotarevski, Lidija; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

2017-09-01

Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation.

PubMed

Hankey, Graeme J; Stevens, Susanna R; Piccini, Jonathan P; Lokhnygina, Yuliya; Mahaffey, Kenneth W; Halperin, Jonathan L; Patel, Manesh R; Breithardt, Günter; Singer, Daniel E; Becker, Richard C; Berkowitz, Scott D; Paolini, John F; Nessel, Christopher C; Hacke, Werner; Fox, Keith A A; Califf, Robert M

2014-05-01

Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73). Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

Pretreatment Blood Brain Barrier Damage and Post Treatment Intracranial Hemorrhage in Patients Receiving IV tPA

PubMed Central

Leigh, Richard; Jen, Shyian S.; Hillis, Argye E.; Krakauer, John W.; Barker, Peter B.

2014-01-01

Background and Purpose Early blood brain barrier (BBB) damage after acute ischemic stroke (AIS) has previously been qualitatively linked to subsequent intracranial hemorrhage (ICH). In this quantitative study, it was investigated whether the amount of BBB damage evident on pre-tPA MRI scans was related to the degree of post-tPA ICH in patients with AIS. Methods Analysis was performed on a database of patients with AIS provided by the STIR and VISTA Imaging Investigators. Patients with perfusion-weighted imaging (PWI) lesions >10mL and negative gradient-recalled echo (GRE) imaging prior to IV tPA were included. Post processing of the PWI source images was performed to estimate changes in BBB permeability within the perfusion deficit relative to the unaffected hemisphere. Follow-up GRE images were reviewed for evidence of ICH and divided into three groups according to ECASS criteria: no hemorrhage (NH), hemorrhagic infarction (HI), and parenchymal hematoma (PH). Results 75 patients from the database met the inclusion criteria, 28 of whom experienced ICH, of which 19 were classified as HI, and nine were classified as PH. The mean permeability (±standard deviations), expressed as an index of contrast leakage, was 17.0%±8.8 in the NH group, 19.4%±4.0 in the HI group, and 24.6%±4.5 in the PH group. Permeability was significantly correlated with ICH grade in univariate (p=0.007) and multivariate (p=0.008) linear regression modeling. Conclusions A PWI-derived index of BBB damage measured prior to IV tPA is associated with the severity of ICH after treatment in patients with AIS. PMID:24876245

Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials.

PubMed

Akins, Paul T; Feldman, Harvey A; Zoble, Robert G; Newman, David; Spitzer, Stefan G; Diener, Hans-Christoph; Albers, Gregory W

2007-03-01

Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA. We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin < or =100 mg/d. Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events. Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

Intracerebral Hemorrhages in Adults with Community Associated Bacterial Meningitis in Adults: Should We Reconsider Anticoagulant Therapy?

PubMed Central

Mook-Kanamori, Barry B.; Fritz, Daan; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

2012-01-01

Objective To study the incidence, clinical presentation and outcome of intracranial hemorrhagic complications in adult patients with community associated bacterial meningitis. Methods Nationwide prospective cohort study from all hospitals in the Netherlands, from 1 March 2006, through 31 December 2010. Results Of the 860 episodes of bacterial meningitis that were included, 24 were diagnosed with intracranial hemorrhagic complications: 8 upon presentation and 16 during clinical course. Clinical presentation between patients with or without intracranial hemorrhage was similar. Causative bacteria were Streptococcus pneumoniae in 16 patients (67%), Staphylococcus aureus in 5 (21%), Pseudomonas aeruginosa and Listeria monocytogenes both in 1 patient (4%). Occurrence of intracranial hemorrhage was associated with death (63% vs. 15%, P<0.001) and unfavorable outcome (94% vs. 34%, P<0.001). The use of anticoagulants on admission was associated with a higher incidence of intracranial hemorrhages (odds ratio 5.84, 95% confidence interval 2.17–15.76). Conclusion Intracranial hemorrhage is a rare but devastating complication in patients with community-associated bacterial meningitis. Since anticoagulant therapy use is associated with increased risk for intracranial hemorrhage, physicians may consider reversing or temporarily discontinuing anticoagulation in patients with bacterial meningitis. PMID:23028898

Monitoring intracranial pressure based on F-P

NASA Astrophysics Data System (ADS)

Cai, Ting; Tong, Xinglin; Chen, Guangxi

2013-09-01

Intracranial pressure is an important monitoring indicator of neurosurgery. In this paper we adopt all-fiber FP fiber optic sensor, using a minimally invasive operation to realize real-time dynamic monitoring intracranial pressure of the hemorrhage rats, and observe their intracranial pressure regularity of dynamic changes. Preliminary results verify the effectiveness of applications and feasibility, providing some basis for human brain minimally invasive intracranial pressure measurement.

Association between Champagne Bottle Neck Sign of Internal Carotid Artery and Ipsilateral Hemorrhagic Stroke in Patients with Moyamoya Disease.

PubMed

Wang, Jian; Chen, Gong; Yang, Yongbo; Zhang, Bing; Jia, Zhongzhi; Gu, Peiyuan; Wei, Dong; Ji, Jing; Hu, Weixing; Zhao, Xihai

2018-06-15

To assess the association between champagne bottle neck sign (CBNS) in carotid artery and intracranial hemorrhage in patients with moyamoya disease (MMD). From January 2016 to December 2017, a total of 76 consecutive patients with MMD without definite risk factors associated intracranial hemorrhage who underwent preoperative angiography were included in this retrospective study. CBNS was defined as luminal diameter of internal carotid artery (ICA)/common carotid artery (CCA) ≤ 0.5 on angiographic imaging. The right and left cerebral hemisphere in each patient was separately identified as hemorrhagic and none-hemorrhagic. The association between CBNS and intracranial hemorrhage was analyzed. Of 76 MMD patients, intracranial hemorrhage was found in 44 (28.9%) hemispheres of 152 and 6.8% (3/44) had multiple events. Compared carotid arteries without intracranial hemorrhage in the ipsilateral hemispheres, those with intracranial hemorrhage in the ipsilateral hemispheres had significantly smaller luminal diameter ratio of ICA/CCA (0.49 ± 0.11 vs. 0.55 ± 0.12, p < 0.01) and higher prevalence of CBNS (63.7% vs. 41.7%, p = 0.01). For hemispheres with intracranial hemorrhage, those with ipsilateral carotid artery CBNS had significantly higher prevalence of hemorrhage at posterior territories than those without (57.1% vs. 23.1%, p=0.05). Logistic regression revealed that CBNS was significantly associated with ipsilateral intracranial hemorrhage before (OR, 2.45; 95% CI, 1.19-5.05; p=0.02) and after (OR, 3.43; 95% CI, 1.50-7.87; p<0.01) adjusted for female, lenticulostriate anastomosis, and choroidal anastomosis. CBNS is significantly associated with intracranial hemorrhage at ipsilateral hemisphere in MMD patients, particularly for intracranial hemorrhage at posterior territories. Copyright © 2018. Published by Elsevier Inc.

The "focus on aneurysm" principle: Classification and surgical principles of management of concurrent arterial aneurysm with arteriovenous malformation causing intracranial hemorrhage.

PubMed

Jha, Vikas; Behari, Sanjay; Jaiswal, Awadhesh K; Bhaisora, Kamlesh Singh; Shende, Yogesh P; Phadke, Rajendra V

2016-01-01

Concurrent arterial aneurysms (AAs) occurring in 2.7-16.7% patients harboring an arteriovenous malformation (AVM) aggravate the risk of intracranial hemorrhage. We evaluate the variations of aneurysms simultaneously coexisting with AVMs. A classification-based management strategy and an abbreviated nomenclature that describes their radiological features is also proposed. Tertiary care academic institute. Test of significance applied to determine the factors causing rebleeding in the groups of patients with concurrent AVM and aneurysm and those with only AVMs. Sixteen patients (5 with subarachnoid hemorrhage and 11 with intracerebral/intraventricular hemorrhage; 10 with low flow [LF] and 6 with high flow [HF] AVMs) underwent radiological assessment of Spetzler Martin (SM) grading and flow status of AA + AVM. Their modified Rankin's score (mRS) at admission was compared with their follow-up (F/U) score. Pre-operative mRS was 0 in 5, 2 in 6, 3 in 1, 4 in 3 and 5 in 1; and, SM grade I in 5, II in 3, III in 3, IV in 4 and V in 1 patients, respectively. AA associated AVMs were classified as: (I) Flow-related proximal (n = 2); (II) flow-related distal (n = 3); (III) intranidal (n = 5); (IV) extra-intranidal (n = 2); (V) remote major ipsilateral (n = 1); (VI) remote major contralateral (n = 1); (VII) deep perforator related (n = 1); (VIII) superficial (n = 1); and (IX) distal (n = 0). Their treatment strategy included: Flow related AA, SM I-III LF AVM: aneurysm clipping with AVM excision; nidal-extranidal AA, SM I-III LF AVM: Excision or embolization of both AA + AVM; nidal-extranidal and perforator-related AA, SM IV-V HF AVM: Only endovascular embolization or radiosurgery. Surgical decision-making for remote AA took into account their ipsilateral/contralateral filling status and vessel dominance; and, for AA associated with SM III HF AVM, it varied in each patient based on diffuseness of AVM nidus, flow across arteriovenous fistula and eloquence of cortex. Follow up (F

Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature.

PubMed

Winkelhorst, Dian; Kamphuis, Marije M; de Kloet, Liselotte C; Zwaginga, Jaap Jan; Oepkes, Dick; Lopriore, Enrico

2016-05-01

The most feared bleeding complication in fetal and neonatal alloimmune thrombocytopenia (FNAIT) is an intracranial hemorrhage (ICH). However, FNAIT may also lead to other severe bleeding problems. The aim was to analyze this spectrum and evaluate the occurrence of severe hemorrhages other than ICH in fetuses or neonates with FNAIT. A retrospective chart analysis of cases of FNAIT presenting with severe bleeding complications other than ICH at our institution from 1990 to 2015 was conducted. Additionally, a review of the literature was performed to identify case reports and case series on FNAIT presenting with extracranial hemorrhage. Of 25 fetuses or neonates with severe bleeding due to FNAIT, three had isolated severe internal organ hemorrhage other than ICH, two pulmonary hemorrhages and one gastrointestinal hemorrhage. Two of these three neonates died due to this bleeding. Eighteen cases of extracranial bleeding complications as a first presentation of FNAIT were found in the literature, including ocular, gastrointestinal, spinal cord, pulmonary, renal, subgaleal, and genitourinary hemorrhages. Bleeding complications other than ICH may be more extensive, and the presentation of FNAIT may have a greater spectrum than previously described. A high index of suspicion on the possible diagnosis of FNAIT with any bleeding complication in a fetus or neonate may enable adequate diagnostics, adequate treatment, and appropriate follow-up in future pregnancies, as is especially relevant for FNAIT. © 2016 AABB.

Dabigatran Versus Warfarin After Bioprosthesis Valve Replacement for the Management of Atrial Fibrillation Postoperatively: DAWA Pilot Study.

PubMed

Durães, André Rodrigues; de Souza Roriz, Pollianna; de Almeida Nunes, Bianca; Albuquerque, Felipe Pinho E; de Bulhões, Fábio Vieira; de Souza Fernandes, Andre Mauricio; Aras, Roque

2016-06-01

Dabigatran is a direct thrombin inhibitor shown to be an effective alternative to warfarin in patients with non-valvular atrial fibrillation (AF). We evaluated the use of dabigatran in patients with bioprosthetic mitral and/or aortic valve replacement and AF. We selected 34 and randomized 27 patients in a 1:1 ratio to receive dabigatran or warfarin. The primary endpoint was the presence of a new intracardiac thrombus at 90 days, by transesophageal echocardiogram (TEE). Secondary endpoints included the development of dense spontaneous echo contrast (SEC) and incidence of stroke (ischemic or hemorrhagic), myocardium infarction, valve thrombosis and peripheral embolic events. The trial was terminated prematurely because of low enrollment. There were 27 patients in total: 15 patients placed in the dabigatran group and 12 in the warfarin group. After 90 days, one patient (8.3 %) in the warfarin group and none in the dabigatran group had developed a new intracardiac thrombus. In the dabigatran group, two patients (13.3 %) developed dense SEC versus one patient (8.3 %) in the warfarin group. In the warfarin group, one patient (8.3 %) presented ischemic stroke, and none did in the dabigatran group. We observed no cases of hemorrhagic stroke, valve thrombosis, embolic events or myocardial infarction in either group throughout the study. However, one patient (6.7 %) in the dabigatran group had a fully recovered transient ischemic attack and one patient in the warfarin group died of heart failure. The use of dabigatran appears to be similar to warfarin in preventing the formation of intracardiac thrombus. Clinicaltrials.gov NCT01868243.

Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design.

PubMed

Pullicino, Patrick; Thompson, John L P; Barton, Bruce; Levin, Bruce; Graham, Susan; Freudenberger, Ronald S

2006-02-01

Warfarin is widely prescribed for patients with heart failure without level 1 evidence, and an adequately powered randomized study is needed. The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction study is a National Institutes of Health-funded, randomized, double-blind clinical trial with a target enrollment of 2860 patients. It is designed to test with 90% power the 2-sided primary null hypothesis of no difference between warfarin (International Normalized Ratio 2.5-3) and aspirin (325 mg) in 3- to 5-year event-free survival for the composite endpoint of death, or stroke (ischemic or hemorrhagic) among patients with cardiac ejection fraction < or =35% who do not have atrial fibrillation or mechanical prosthetic heart valves. Secondary analyses will compare warfarin and aspirin for reduction of all-cause mortality, ischemic stroke, and myocardial infarction (MI), balanced against the risk of intracerebral hemorrhage, among women and African Americans; and compare warfarin and aspirin for prevention of stroke alone. Randomization is stratified by site, New York Heart Association (NYHA) heart class (I vs II-IV), and stroke or transient ischemic attack (TIA) within 1 year before randomization versus no stroke or TIA in that period. NYHA class I patients will not exceed 20%, and the study has a target of 20% (or more) patients with stroke or TIA within 12 months. Randomized patients receive active warfarin plus placebo or active aspirin plus placebo, double-blind. The results should help guide the selection of optimum antithrombotic therapy for patients with left ventricular dysfunction.

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

PubMed

Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

2015-04-01

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study

PubMed Central

Hogg, Kerstin; Bahl, Bharat; Latrous, Meriem; Scaffidi Argentina, Sarina; Thompson, Jesse; Chatha, Aasil Ayyaz; Castellucci, Lana; Stiell, Ian G.

2015-01-01

Background: Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants. Methods: We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period. Results: A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12

Apixaban versus warfarin in patients with atrial fibrillation.

PubMed

Granger, Christopher B; Alexander, John H; McMurray, John J V; Lopes, Renato D; Hylek, Elaine M; Hanna, Michael; Al-Khalidi, Hussein R; Ansell, Jack; Atar, Dan; Avezum, Alvaro; Bahit, M Cecilia; Diaz, Rafael; Easton, J Donald; Ezekowitz, Justin A; Flaker, Greg; Garcia, David; Geraldes, Margarida; Gersh, Bernard J; Golitsyn, Sergey; Goto, Shinya; Hermosillo, Antonio G; Hohnloser, Stefan H; Horowitz, John; Mohan, Puneet; Jansky, Petr; Lewis, Basil S; Lopez-Sendon, Jose Luis; Pais, Prem; Parkhomenko, Alexander; Verheugt, Freek W A; Zhu, Jun; Wallentin, Lars

2011-09-15

Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb

Warfarin use and the risk of mortality, stroke, and bleeding in hemodialysis patients with atrial fibrillation.

PubMed

Kai, Brandon; Bogorad, Yuliya; Nguyen, Leigh-Anh N; Yang, Su-Jau; Chen, Wansu; Spencer, Hillard T; Shen, Albert Y-J; Lee, Ming-Sum

2017-05-01

The optimal management of stroke prophylaxis in hemodialysis patients with atrial fibrillation is controversial. The purpose of this study was to determine the risk of mortality, stroke, and bleeding associated with the use of warfarin in hemodialysis patients with atrial fibrillation. This was a retrospective, population-based study of hemodialysis patients with atrial fibrillation between January 1, 2006, and September 30, 2015. Association of warfarin use with mortality, stroke, and bleeding was determined by propensity score-matched, Cox proportional hazard models. Among the 4286 patients with atrial fibrillation on hemodialysis, 989 (23%) were prescribed warfarin. Propensity score matching was used to identify 888 matched pairs with similar baseline characteristics. Warfarin use was associated with lower risk of all-cause death (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.69-0.84) and lower risk of ischemic stroke (HR 0.68, 95% CI 0.52-0.91). Warfarin use was not associated with a higher risk of hemorrhagic stroke (HR 1.2, 95% CI 0.6-2.2) or gastrointestinal bleeding (HR 0.97, 95% CI 0.77-1.2). The treatment effect was largest in the group with the best international normalized ratio control as measured by time in therapeutic range. Subgroup analyses showed warfarin use was associated with survival benefit in most subgroups. The 2 subgroups that did not benefit were patients with a history of hemorrhagic stroke and patients with concurrent aspirin use. Warfarin use is associated with lower all-cause mortality and ischemic stroke, without significantly increasing the risk of bleeding in hemodialysis patients with atrial fibrillation. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Recurrent hemorrhage from corpus luteum during anticoagulant therapy.

PubMed Central

Wong, K. P.; Gillett, P. G.

1977-01-01

A 43-year old woman had recurrent massive intraperitoneal hemorrhage from rupture of a hemorrhagic corpus luteum in two successive menstrual cycles while receiving anticoagulant therapy. Left oophorectomy was performed on the first occasion and right salpingo-oophorectomy with left salpingectomy on the second. While the precise incidence cannot be determined, rupture from a hemorrhagic corpus luteum appears to be a rare but potentially catastrophic complication of anticoagulant therapy. Hence possible ovarian hemorrhage should be considered in women of reproductive age receiving heparin or sodium warfarin therapy. PMID:844024

Integrating Genomic Based Information into Clinical Warfarin (Coumadin®) Management: An Illustrative Case Report

PubMed Central

LaSala, Anthony; Bower, Bruce; Windemuth, Andreas; White, C. Michael; Kocherla, Mohan; Seip, Richard; Duconge, Jorge; Ruaño, Gualberto

2013-01-01

Warfarin is a well established oral anticoagulant for the treatment of thromboembolic disorders. Warfarin therapy is complicated by a narrow therapeutic index and marked inter-individual dose variability with therapeutic doses ranging from 1 mg to 10 mg/day.1 Recently genetic variation and resultant drug metabolizing polymorphisms have been found to contribute to warfarin dose variability with resultant hemorrhagic or thromboembolic complications. Cytochrome P450 2C9 alters the rate of warfarin metabolism and clearance. A second enzyme, vitamin K epoxide reductase comple (VKOR) binds and reduces vitamin K which is necessary for activation of clotting Factors II, VII, IX and X. The VKORC1 gene encodes for vitamin K epoxide reductase complex subunit 1, a key component of VKOR. The combination of physiologic factors (30%), CYP2C9 variations (20%) and VKORC1 variants (25%) accounts for approximately 75% of warfarin dose variability. This illustrative case report demonstrates the clinical importance of this new information. Clinicians need to incorporate these new genomic findings into appropriate management of warfarin dose anticoagulation. PMID:18763667

Ischemic stroke and intracranial hemorrhage in patients with recurrent glioblastoma multiforme, treated with bevacizumab.

PubMed

Auer, Timo A; Renovanz, Mirjam; Marini, Federico; Brockmann, Marc A; Tanyildizi, Yasemin

2017-07-01

Bevacizumab (BVZ), a monoclonal antibody directed against vascular endothelial growth factor (VEGF), has been suspected to increase the incidence of ischemic stroke (IS) and intracranial hemorrhage (ICH) in GBM patients. Intracranial vascular events, such as IS and ICH, were retrospectively analyzed in 364 MRI scans of 82 patients with recurrent GBM (1st/2nd/3rd relapse). Out of these 82 patients, 40 were treated with BVZ (178 scans) in addition to basic treatment, whereas 42 patients matching for age and gender received basic treatment (186 scans). Distribution of typical vascular risk factors between both groups was analyzed retrospectively. In seven out of 82 patients (8%) vascular events were detected in MRI. Four vascular events were recorded in the BVZ-group (3 IS and 1 ICH), and 3 vascular events were found in the Control-group (1 IS and 2 ICH; p > 0.05 between both groups). Likewise, vascular risk factors (arterial hypertension, diabetes mellitus, obesity, former vascular event, hyperlipidemia, tobacco consumption and/or hypercholesterolemia) did not differ significantly between both groups. BVZ treatment does not seem to be associated with an increased risk for vascular events in patients with GBM in recurrence.

Stent-Grafts in the Management of Hemorrhagic Complications Related to Hemostatic Closure Devices: Report of Two Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giansante Abud, Daniel; Mounayer, Charbel; Saint-Maurice, Jean Pierre

We report 2 cases of hemorrhagic complications related to use of the Angio-Seal hemostatic closure device that were successfully managed with stent-grafts. Two patients with subarachnoid hemorrhage were referred to our departments for endovascular treatment of ruptured intracranial aneurysms. The treatment was performed through a femoral access; the sheaths were removed immediately after the procedures, and the punctures sites closed by Angio-Seals. Both patients presented clinical signs of hypovolemic shock after treatment. The diagnosis of active bleeding through the puncture site was made by emergency digital subtraction angiography. The lesions were managed with stent-grafts. The use of stent-grafts proved tomore » be efficient in the management of these life-threatening hemorrhagic complications following the use of the Angio-Seal hemostatic closure device.« less

Fecal hemoglobin excretion in elderly patients with atrial fibrillation: combined aspirin and low-dose warfarin vs conventional warfarin therapy.

PubMed

Blackshear, J L; Baker, V S; Holland, A; Litin, S C; Ahlquist, D A; Hart, R G; Ellefson, R; Koehler, J

1996-03-25

Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalization ratio,<1.5] plus 325 mg/d of enteric-coated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. Among the 63 at high risk of stroke, abnormal values (>2mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean ( +/- SD) values were more for those randomly assigned to receive combined therapy (1.7 +/- 3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0 +/- 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (+/- SD) HemoQuant value of 0.8 +/- 0.7mg of hemoglobin per gram of stool 1 month after entry in the study. Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.

[Congenital anomalies of cerebral artery and intracranial aneurysm].

PubMed

Nakajima, K; Ito, Z; Hen, R; Uemura, K; Matsuoka, S

1976-02-01

It is well known that congenital anomalies such as polycystic kidney, aortic coarctation, Marfan syndrome, Ehler-Danlos syndrome are apt to be complicated by intracranial aneurysms. In this report we attempt to reveal the relation and incidence between cerebrovascular anomalies and intracranial aneurysms. The etiology of aneurysms has been discussed, too. 12 cases of persistent trigeminl artery, 2 cases of persistent hypoglossal artery and 11 cases of fenestration were obtained from 3841 patients who were angiographically examined in our clinic for 5 years. The incidence is 0.31%, 0.05% and 0.29%, respectively. Persistent trigeminal arteries were complicated by 2 cases of intracranial aneurysms and one case of arterivenous malformations (AVM), persistent hypoglossal arteries were complicated by one case of aneurysm, and fenestrations were complicated by 2 cases of aneurysms and one case of AVM. One case of congenital agenesis of right internal carotid artery was obtained which was complicated by aneurysm of anterior communicating artery. Totally, 8 cases of aneurysms and AVM were obtained from 26 cases of cerebrovascular anomalies (incidence 30.8%). On the other hand, thalamic or caudate hemorrhage revealed the highest incidence of complication of intracranial aneurysms among intracerebral hematomas (10.7%). Compared with the incidence of aneurysms between cerebro vascular anomalies (30.8%) and thalamic or caudate hemorrhage (10.7%), the difference is statistically signigicant (P less than 0.05). The cause of intracranial aneurysm has not yet been clarified. But it is well accepted that the defect of tunica media vasorum is most responsible factor as to the occurrence of intracranial aneurysms. We concluded that the genetic error of cerebral vessels including defect of media caused intracranial aneurysms, and this result was supported from the evidence that cerebrovascular anomalies showed statistically high incidence of complication of intracranial aneurysms.

An Unusual Consolidation: Lobar Pulmonary Hemorrhage Due to Antithrombotic Therapy.

PubMed

D'Amore, Katrina; Traficante, David; McGovern, Terrance; Propersi, Marco; Barnes, Stacey

2017-11-01

Alveolar hemorrhage is a rare yet devastating clinical entity if not identified and treated aggressively. Exceedingly rare are the cases of anticoagulant-induced alveolar hemorrhage with very few cases described in the current literature. The nonspecific presentation of an alveolar hemorrhage makes its diagnosis and appropriate treatment difficult in the emergency department. We report a case of a patient on warfarin for atrial fibrillation who was initially misdiagnosed as having community-acquired pneumonia, but subsequently was identified to have a fatal alveolar hemorrhage.

Epidemiology of Mild Traumatic Brain Injury with Intracranial Hemorrhage: Focusing Predictive Models for Neurosurgical Intervention.

PubMed

Orlando, Alessandro; Levy, A Stewart; Carrick, Matthew M; Tanner, Allen; Mains, Charles W; Bar-Or, David

2017-11-01

To outline differences in neurosurgical intervention (NI) rates between intracranial hemorrhage (ICH) types in mild traumatic brain injuries and help identify which ICH types are most likely to benefit from creation of predictive models for NI. A multicenter retrospective study of adult patients spanning 3 years at 4 U.S. trauma centers was performed. Patients were included if they presented with mild traumatic brain injury (Glasgow Coma Scale score 13-15) with head CT scan positive for ICH. Patients were excluded for skull fractures, "unspecified hemorrhage," or coagulopathy. Primary outcome was NI. Stepwise multivariable logistic regression models were built to analyze the independent association between ICH variables and outcome measures. The study comprised 1876 patients. NI rate was 6.7%. There was a significant difference in rate of NI by ICH type. Subdural hematomas had the highest rate of NI (15.5%) and accounted for 78% of all NIs. Isolated subarachnoid hemorrhages had the lowest, nonzero, NI rate (0.19%). Logistic regression models identified ICH type as the most influential independent variable when examining NI. A model predicting NI for isolated subarachnoid hemorrhages would require 26,928 patients, but a model predicting NI for isolated subdural hematomas would require only 328 patients. This study highlighted disparate NI rates among ICH types in patients with mild traumatic brain injury and identified mild, isolated subdural hematomas as most appropriate for construction of predictive NI models. Increased health care efficiency will be driven by accurate understanding of risk, which can come only from accurate predictive models. Copyright © 2017 Elsevier Inc. All rights reserved.

Intracranial hemorrhage and other symptoms in infants associated with human parechovirus in Vienna, Austria.

PubMed

Kurz, Herbert; Prammer, Ruth; Bock, Wolfgang; Ollerieth, Robert; Bernert, Günther; Zwiauer, Karl; Aberle, Judith H; Aberle, Stephan W; Fazekas, Tamas; Holter, Wolfgang

2015-12-01

The human parechovirus (HPeV), mainly genotype 3, may cause severe illness in young infants and neonates, including sepsis-like illness and central nervous system (CNS) infection. We lack data concerning the impact and symptoms of HPeV infection in infants in Austria. The aim of the study is to evaluate the spectrum of symptoms and findings in infants with the parechovirus in Vienna and its environs. Patients younger than 3 months of age, with clinically suspected sepsis-like illness or CNS infection and a positive polymerase chain reaction (PCR) for HPeV, were included in the study. Medical records were analyzed retrospectively. Twenty patients were included in the study from 2009 to 2013. The most frequent manifestations were fever and neurological symptoms (89 and 80 %, respectively). Fifty percent of the infants had white blood cell counts out of range. The most notable aspect was cerebral hemorrhage in three neonates, which has not been reported earlier in association with HPeV infection. In Austria, HPeV is a relevant pathogen in sepsis-like disease in infants. The clinical presentation is similar to that described in other studies; cerebral hemorrhage is a new aspect. • Parechovirus infection can cause severe illness in infants. • Symptoms have been described to involve all organs; sepsis-like signs, fever, and irritability are most frequent. • Also in Austria, HPeV plays an important role in severe illnesses in infants. • Severe intracranial hemorrhage is described as a new finding.

Warfarin compared with aspirin for older Chinese patients with stable coronary heart diseases and atrial fibrillation complications.

PubMed

Liu, Xinbing; Huang, Hongman; Yu, Jianhua; Cao, Guoliang; Feng, Liuliu; Xu, Qitan; Zhang, Shufu; Zhou, Mingcheng; Li, Yigang

2014-06-01

To compare the therapeutic warfarin and aspirin efficacies for treatments of atrial fibrillation (AF) complicated with stable coronary heart disease particularly in older Chinese patients. In our prospective study 101 patients with AF and stable coronary heart disease older than 80 years were randomized into two groups. One group (n = 51) basically received 1.25 mg/day warfarin per os, followed by addition of 0.5 - 1.0 mg/day from day 3 - 5 if the international normalized ratio (INR) was initially < 1.5 and in order to achieve a maintained INR between 1.6 and 2.5 (warfarin group). The second group (n = 50) received 100 mg aspirin per day (control group). All patients were medicated and monitored for a period of 2 years. The primary endpoint was the occurrence of ischemic stroke or systemic embolism, and the composite secondary endpoint was non-fatal myocardial infarction and all causes of death. For safety evaluation, the hemorrhage rates were recorded. The warfarin medication was superior regarding the overall occurrence of ischemic stroke or systemic embolism as well as non-fatal myocardial infarction and all causes of death outcomes compared to aspirin administration during the 2 years of medication (17.6% vs. 36.0%, p = 0.03), while there was no significant difference of mild (5 vs. 4), severe (2 vs. 1), and fatal (1 vs. 1) hemorrhage incidences between the warfarin and aspirin groups (p > 0.05). Warfarin was found to be more efficacious than aspirin for an anticoagulation therapy of older Chinese patients with AF and stable coronary heart disease.

Bleeding events among new starters and switchers to dabigatran compared with warfarin in atrial fibrillation.

PubMed

Larsen, Torben Bjerregaard; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Skjøth, Flemming; Rosenzweig, Mary; Lip, Gregory Y H

2014-07-01

The bleeding risk among patients with atrial fibrillation is higher early after initiating therapy with vitamin K antagonists (VKAs). Evidence is limited on how prior VKA experience affects bleeding risk when initiating novel oral anticoagulant therapy. We investigated this among patients with atrial fibrillation initiating dabigatran therapy. By using nationwide Danish prescription and patient registries, we identified 11,315 first-time dabigatran users with atrial fibrillation. Warfarin controls were matched in a 2:1 ratio according to VKA experience status. The average follow-up time was 13 months. Across the 6 combinations of treatment (dabigatran 110 mg, dabigatran 150 mg, and warfarin) and VKA experience status (naive or experienced), VKA-naïve warfarin initiators had the highest rate of any bleeding event. Cox regressions adjusted for baseline characteristics showed reductions relative to this group ranging from 19% for VKA-experienced dabigatran 110 mg users (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66-1.00) to 41% for VKA-experienced dabigatran 150 mg users (HR, 0.59; 95% CI, 0.46-0.75). Among switchers to dabigatran from warfarin, when comparing with warfarin-persisting users, the rate of any bleeding was nonsignificantly decreased for switchers to dabigatran 150 mg (HR, 0.80; 95% CI, 0.62-1.03) but not for switchers to dabigatran 110 mg (HR, 1.12; 95% CI, 0.90-1.41). Results for major bleeding were similar. Crude rates of fatal, intracranial, and gastrointestinal bleeding were low. VKA-naïve warfarin initiators had the highest overall bleeding rate. We found no evidence of marked excess of overall bleeding events when comparing dabigatran with warfarin users, irrespective of prior VKA experience. Copyright © 2014 Elsevier Inc. All rights reserved.

Differentiation of low-attenuation intracranial hemorrhage and calcification using dual-energy computed tomography in a phantom system

PubMed Central

Nute, Jessica L.; Roux, Lucia Le; Chandler, Adam G.; Baladandayuthapani, Veera; Schellingerhout, Dawid; Cody, Dianna D.

2015-01-01

Objectives Calcific and hemorrhagic intracranial lesions with attenuation levels of <100 Hounsfield Units (HU) cannot currently be reliably differentiated by single-energy computed tomography (SECT). The proper differentiation of these lesion types would have a multitude of clinical applications. A phantom model was used to test the ability of dual-energy CT (DECT) to differentiate such lesions. Materials and Methods Agar gel-bound ferric oxide and hydroxyapatite were used to model hemorrhage and calcification, respectively. Gel models were scanned using SECT and DECT and organized into SECT attenuation-matched pairs at 16 attenuation levels between 0 and 100 HU. DECT data were analyzed using 3D Gaussian mixture models (GMMs), as well as a simplified threshold plane metric derived from the 3D GMM, to assign voxels to hemorrhagic or calcific categories. Accuracy was calculated by comparing predicted voxel assignments with actual voxel identities. Results We measured 6,032 voxels from each gel model, for a total of 193,024 data points (16 matched model pairs). Both the 3D GMM and its more clinically implementable threshold plane derivative yielded similar results, with >90% accuracy at matched SECT attenuation levels ≥50 HU. Conclusions Hemorrhagic and calcific lesions with attenuation levels between 50 and 100 HU were differentiable using DECT in a clinically relevant phantom system with >90% accuracy. This method warrants further testing for potential clinical applications. PMID:25162534

Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis.

PubMed

Xu, Wei-Wei; Hu, Shen-Jiang; Wu, Tao

2017-07-01

Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs. We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods. Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg). Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.

Intracerebral hemorrhage after external ventricular drain placement: an evaluation of risk factors for post-procedural hemorrhagic complications.

PubMed

Rowe, A Shaun; Rinehart, Derrick R; Lezatte, Stephanie; Langdon, J Russell

2018-03-07

The objective of this study was to evaluate and identify the risk factors for developing a new or enlarged intracranial hemorrhage (ICH) after the placement of an external ventricular drain. A single center, nested case-control study of individuals who received an external ventricular drain from June 1, 2011 to June 30, 2014 was conducted at a large academic medical center. A bivariate analysis was conducted to compare those individuals who experienced a post-procedural intracranial hemorrhage to those who did not experience a new bleed. The variables identified as having a p-value less than 0.15 in the bivariate analysis were then evaluated using a multivariate logistic regression model. Twenty-seven of the eighty-one study participants experienced a new or enlarged intracranial hemorrhage after the placement of an external ventricular drain. Of these twenty-seven patients, 6 individuals received an antiplatelet within ninety-six hours of external ventricular drain placement (p = 0.024). The multivariate logistic regression model identified antiplatelet use within 96 h of external ventricular drain insertion as an independent risk factor for post-EVD ICH (OR 13.1; 95% CI 1.95-88.6; p = 0.008). Compared to those study participants who did not receive an antiplatelet within 96 h of external ventricular drain placement, those participants who did receive an antiplatelet were 13.1 times more likely to exhibit a new or enlarged intracranial hemorrhage.

Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation.

PubMed

Namba, Sayaka; Yamaoka-Tojo, Minako; Kakizaki, Ryota; Nemoto, Teruyoshi; Fujiyoshi, Kazuhiro; Hashikata, Takehiro; Kitasato, Lisa; Hashimoto, Takuya; Kameda, Ryo; Meguro, Kentaro; Shimohama, Takao; Tojo, Taiki; Ako, Junya

2017-08-01

In recent years, direct oral anticoagulants (DOACs) of dabigatran, rivaroxaban, apixaban, edoxaban, which are all alternatives to warfarin, have been released. The use of DOACs is becoming more widespread in the clinical management of thrombotic stroke risk in patients with atrial fibrillation (AF). In large-scale clinical trials of each drug, DOACs were reported to inhibit intracranial hemorrhage, stroke, and death compared to warfarin. Warfarin is an endogenous vitamin K antagonist; therefore, patients who are taking warfarin must be prohibited from taking vitamin K. Vitamin K is an essential cofactor required for the ɤ-carboxylation of vitamin K-dependent proteins including coagulation factors, osteocalcin (OC), matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6). OC is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification in the vessel wall. GAS6 prevents the apoptosis of vascular smooth muscle cells. Therefore, decrease of blood vitamin K levels may cause osteoporosis, vascular calcification, and the inhibition of vessels angiogenesis. This study aimed to evaluate the effects of changing from warfarin to rivaroxaban on bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction. We studied 21 consecutive patients with persistent or chronic AF, who were treated with warfarin at least for 12 months. Warfarin administration was changed to rivaroxaban (10 or 15 mg/day) in all patients. Osteopontin (OPN), bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were measured. Pulse wave velocity (PWV) and augmentation index (AI) were also measured as atherosclerosis assessments. All measurements were done before and six months after the rivaroxaban treatment. There was a significant increase in serum level of BAP compared to baseline (12.5 ± 4.6 to 13.4 ± 4.1 U/L, P < 0.01). In contrast, there was a significant decrease in the serum level of ucOC (9

Hemorrhagic Transformation of Scrub Typhus Encephalitis: A Rare Entity.

PubMed

Kim, H-C; Yoon, K-W; Yoo, D-S; Cho, C-S

2015-12-01

Central nervous system (CNS) involvement of scrub typhus infection is well known. Most CNS involvement of scrub typhus infection present as meningitis or encephalitis. We report on a patient suffering from hemorrhagic transformation of intracranial lesions caused by Orientia tsutsugamushi. A 53-year-old female farmer who was infected by scrub typhus was treated with doxycycline and recovered from the systemic illness. However, headache persisted. Brain radiologic studies revealed acute intracranial hemorrhage and enhancing lesion, which implied a CNS involvement. Hemorrhagic transformation of encephalitis by scrub typhus is very rare complication and to our best knowledge, this is the first report of hemorrhagic transformation of scrub typhus encephalitis. Clinician should consider the possibility of hemorrhagic transformation of encephalitis in cases of scrub typhus infection.

Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.

PubMed

Lanitis, T; Cotté, F E; Gaudin, A F; Kachaner, I; Kongnakorn, T; Durand-Zaleski, I

2014-08-01

To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective. A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections. Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110 mg, dabigatran in sequential dosages, dabigatran 150 mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY. Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As

Rationale, design, and preliminary results of the Quebec Warfarin Cohort Study.

PubMed

Perreault, Sylvie; Shahabi, Payman; Côté, Robert; Dumas, Stéphanie; Rouleau-Mailloux, Étienne; Feroz Zada, Yassamin; Provost, Sylvie; Mongrain, Ian; Dorais, Marc; Huynh, Thao; Kouz, Simon; Diaz, Ariel; Blostein, Mark; de Denus, Simon; Turgeon, Jacques; Ginsberg, Jeffrey; Lelorier, Jacques; Lalonde, Lyne; Busque, Lambert; Kassis, Jeannine; Talajic, Mario; Tardif, Jean-Claude; Dubé, Marie-Pierre

2018-05-01

Over- and undercoagulation with warfarin are associated with hemorrhagic and thromboembolic events, respectively. Genetic and clinical factors affect warfarin response, and the causes of this variability remain unclear. We present descriptive statistics and test for predictors of poor anticoagulation control. The Quebec Warfarin Cohort (QWC) comprises 1059 new warfarin users, with prospective follow-up using telephone questionnaires every 3 months for 1 year, and using healthcare administrative databases (RAMQ and Med-Echo) for 5 years prior to cohort entry and up to 10 years following active patient participation. Genetic material was collected, and genotyping of CYP2C9 and VKORC1 genes was conducted. Measured outcomes included the percentage of time patients spent within therapeutic range, anticoagulation control, warfarin dose, bleeding, and thromboembolic events. We report baseline characteristics and outcomes after 1 year of follow-up. Poor anticoagulation control was defined as time in therapeutic range <60% in the 3- to 12-month interval. Participants had a mean age of 71 years, and 62% were men. The most common indication for warfarin was atrial fibrillation (87%). Mean time in therapeutic range was 56% (±25%) in the 3 months following warfarin initiation, and 70% (±21%) in the 3- to 12-month interval. During follow-up, the rate of stroke or systemic embolism was 1.8 events per 100 person-years; for major bleeding events, 3.3 events per 100 person-years. Independent predictors of poor anticoagulation control were chronic kidney disease, heart failure, dyslipidemia, and age. The QWC represents a good research cohort to investigate clinical and genetic factors in a warfarin-anticoagulated population. © 2018 Wiley Periodicals, Inc.

To Bleed or Not to Bleed: That is the Question. The Side Effects of Apixaban.

PubMed

Ciccone, Marco Matteo; Zito, Annapaola; Devito, Fiorella; Maiello, Maria; Palmiero, Pasquale

2018-01-01

Apixaban is a new oral anticoagulant (NOACs: Novel Oral Anticoagulant), like dabigatran, rivaroxaban, and edoxaban. All of them are prescribed to patients with non valvular atrial fibrillation or venous thromboembolism, to replace warfarin, because of the lower probability of bleeding, however they can cause bleeding by themselves. Bleeding is an adverse event in patients taking anticoagulants. It is associated with a significant increase of morbidity and risk of death. However, these drugs should be used only for the time when anticoagulation is strictly required, especially when used for preventing deep vein thrombosis. Prolonged use increases the risk of bleeding. In the ARISTOTLE Trial Apixaban, compared with warfarin, was associated with a lower rate of intracranial hemorrhages and less adverse consequences following extracranial hemorrhage. Many physicians still have limited experience with new oral anticoagulants and about bleeding risk managment. We reviewed the available literature on extracranial and intracranial bleeding concerning apixaban. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation

PubMed Central

Culebras, Antonio; Messé, Steven R.; Chaturvedi, Seemant; Kase, Carlos S.; Gronseth, Gary

2014-01-01

Objective: To update the 1998 American Academy of Neurology practice parameter on stroke prevention in nonvalvular atrial fibrillation (NVAF). How often do various technologies identify previously undetected NVAF? Which therapies reduce ischemic stroke risk with the least risk of hemorrhage, including intracranial hemorrhage? The complete guideline on which this summary is based is available as an online data supplement to this article. Methods: Systematic literature review; modified Delphi process recommendation formulation. Major conclusions: In patients with recent cryptogenic stroke, cardiac rhythm monitoring probably detects occult NVAF. In patients with NVAF, dabigatran, rivaroxaban, and apixaban are probably at least as effective as warfarin in preventing stroke and have a lower risk of intracranial hemorrhage. Triflusal plus acenocoumarol is likely more effective than acenocoumarol alone in reducing stroke risk. Clopidogrel plus aspirin is probably less effective than warfarin in preventing stroke and has a lower risk of intracranial bleeding. Clopidogrel plus aspirin as compared with aspirin alone probably reduces stroke risk but increases the risk of major hemorrhage. Apixaban is likely more effective than aspirin for decreasing stroke risk and has a bleeding risk similar to that of aspirin. Major recommendations: Clinicians might obtain outpatient cardiac rhythm studies in patients with cryptogenic stroke to identify patients with occult NVAF (Level C) and should routinely offer anticoagulation to patients with NVAF and a history of TIA/stroke (Level B). Specific patient considerations will inform anticoagulant selection in patients with NVAF judged to need anticoagulation. PMID:24566225

Characteristics of Hemorrhagic Stroke following Spine and Joint Surgeries.

PubMed

Yang, Fei; Zhao, Jianning; Xu, Haidong

2017-01-01

Hemorrhagic stroke can occur after spine and joint surgeries such as laminectomy, lumbar spinal fusion, tumor resection, and total joint arthroplasty. Although this kind of stroke rarely happens, it may cause severe consequences and high mortality rates. Typical clinical symptoms of hemorrhagic stroke after spine and joint surgeries include headache, vomiting, consciousness disturbance, and mental disorders. It can happen several hours after surgeries. Most bleeding sites are located in cerebellar hemisphere and temporal lobe. A cerebrospinal fluid (CSF) leakage caused by surgeries may be the key to intracranial hemorrhages happening. Early diagnosis and treatments are very important for patients to prevent the further progression of intracranial hemorrhages. Several patients need a hematoma evacuation and their prognosis is not optimistic.

The “focus on aneurysm” principle: Classification and surgical principles of management of concurrent arterial aneurysm with arteriovenous malformation causing intracranial hemorrhage

PubMed Central

Jha, Vikas; Behari, Sanjay; Jaiswal, Awadhesh K.; Bhaisora, Kamlesh Singh; Shende, Yogesh P.; Phadke, Rajendra V.

2016-01-01

Context: Concurrent arterial aneurysms (AAs) occurring in 2.7-16.7% patients harboring an arteriovenous malformation (AVM) aggravate the risk of intracranial hemorrhage. Aim: We evaluate the variations of aneurysms simultaneously coexisting with AVMs. A classification-based management strategy and an abbreviated nomenclature that describes their radiological features is also proposed. Setting: Tertiary care academic institute. Statistics: Test of significance applied to determine the factors causing rebleeding in the groups of patients with concurrent AVM and aneurysm and those with only AVMs. Subjects and Methods: Sixteen patients (5 with subarachnoid hemorrhage and 11 with intracerebral/intraventricular hemorrhage; 10 with low flow [LF] and 6 with high flow [HF] AVMs) underwent radiological assessment of Spetzler Martin (SM) grading and flow status of AA + AVM. Their modified Rankin's score (mRS) at admission was compared with their follow-up (F/U) score. Results: Pre-operative mRS was 0 in 5, 2 in 6, 3 in 1, 4 in 3 and 5 in 1; and, SM grade I in 5, II in 3, III in 3, IV in 4 and V in 1 patients, respectively. AA associated AVMs were classified as: (I) Flow-related proximal (n = 2); (II) flow-related distal (n = 3); (III) intranidal (n = 5); (IV) extra-intranidal (n = 2); (V) remote major ipsilateral (n = 1); (VI) remote major contralateral (n = 1); (VII) deep perforator related (n = 1); (VIII) superficial (n = 1); and (IX) distal (n = 0). Their treatment strategy included: Flow related AA, SM I-III LF AVM: aneurysm clipping with AVM excision; nidal-extranidal AA, SM I-III LF AVM: Excision or embolization of both AA + AVM; nidal-extranidal and perforator-related AA, SM IV-V HF AVM: Only endovascular embolization or radiosurgery. Surgical decision-making for remote AA took into account their ipsilateral/contralateral filling status and vessel dominance; and, for AA associated with SM III HF AVM, it varied in each patient based on diffuseness of AVM nidus, flow

Survival Outcomes After Intracranial Hemorrhage in Liver Disease.

PubMed

Lagman, Carlito; Nagasawa, Daniel T; Azzam, Daniel; Sheppard, John P; Chen, Cheng Hao Jacky; Ong, Vera; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Kaldas, Fady M; Pouratian, Nader; Busuttil, Ronald W; Yang, Isaac

2018-05-15

Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.

Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

PubMed

Uchiyama, Shinichiro; Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

2014-01-01

The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Association of Proton Pump Inhibitors with Reduced Risk of Warfarin-related Serious Upper Gastrointestinal Bleeding

PubMed Central

Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Smalley, Walter E.; Daugherty, James R.; Dupont, William D.; Stein, C. Michael

2016-01-01

Background & Aims Proton-pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective non-steroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. Methods This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow up. The study endpoints were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Results Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% CI, 0.63–0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94–1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84–1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39–0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. Conclusions In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper

Single Phase Dual-energy CT Angiography: One-stop-shop Tool for Evaluating Aneurysmal Subarachnoid Hemorrhage.

PubMed

Ni, Qian Qian; Tang, Chun Xiang; Zhao, Yan E; Zhou, Chang Sheng; Chen, Guo Zhong; Lu, Guang Ming; Zhang, Long Jiang

2016-05-25

Aneurysmal subarachnoid hemorrhages have extremely high case fatality in clinic. Early and rapid identifications of ruptured intracranial aneurysms seem to be especially important. Here we evaluate clinical value of single phase contrast-enhanced dual-energy CT angiograph (DE-CTA) as a one-stop-shop tool in detecting aneurysmal subarachnoid hemorrhage. One hundred and five patients who underwent true non-enhanced CT (TNCT), contrast-enhanced DE-CTA and digital subtraction angiography (DSA) were included. Image quality and detectability of intracranial hemorrhage were evaluated and compared between virtual non-enhanced CT (VNCT) images reconstructed from DE-CTA and TNCT. There was no statistical difference in image quality (P > 0.05) between VNCT and TNCT. The agreement of VNCT and TNCT in detecting intracranial hemorrhage reached 98.1% on a per-patient basis. With DSA as reference standard, sensitivity and specificity on a per-patient were 98.3% and 97.9% for DE-CTA in intracranial aneurysm detection. Effective dose of DE-CTA was reduced by 75.0% compared to conventional digital subtraction CTA. Thus, single phase contrast-enhanced DE-CTA is optimal reliable one-stop-shop tool for detecting intracranial hemorrhage with VNCT and intracranial aneurysms with DE-CTA with substantial radiation dose reduction compared with conventional digital subtraction CTA.

Single Phase Dual-energy CT Angiography: One-stop-shop Tool for Evaluating Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Ni, Qian Qian; Tang, Chun Xiang; Zhao, Yan E; Zhou, Chang Sheng; Chen, Guo Zhong; Lu, Guang Ming; Zhang, Long Jiang

2016-01-01

Aneurysmal subarachnoid hemorrhages have extremely high case fatality in clinic. Early and rapid identifications of ruptured intracranial aneurysms seem to be especially important. Here we evaluate clinical value of single phase contrast-enhanced dual-energy CT angiograph (DE-CTA) as a one-stop-shop tool in detecting aneurysmal subarachnoid hemorrhage. One hundred and five patients who underwent true non-enhanced CT (TNCT), contrast-enhanced DE-CTA and digital subtraction angiography (DSA) were included. Image quality and detectability of intracranial hemorrhage were evaluated and compared between virtual non-enhanced CT (VNCT) images reconstructed from DE-CTA and TNCT. There was no statistical difference in image quality (P > 0.05) between VNCT and TNCT. The agreement of VNCT and TNCT in detecting intracranial hemorrhage reached 98.1% on a per-patient basis. With DSA as reference standard, sensitivity and specificity on a per-patient were 98.3% and 97.9% for DE-CTA in intracranial aneurysm detection. Effective dose of DE-CTA was reduced by 75.0% compared to conventional digital subtraction CTA. Thus, single phase contrast-enhanced DE-CTA is optimal reliable one-stop-shop tool for detecting intracranial hemorrhage with VNCT and intracranial aneurysms with DE-CTA with substantial radiation dose reduction compared with conventional digital subtraction CTA. PMID:27222163

Warfarin Pharmacogenomics in Diverse Populations.

PubMed

Kaye, Justin B; Schultz, Lauren E; Steiner, Heidi E; Kittles, Rick A; Cavallari, Larisa H; Karnes, Jason H

2017-09-01

Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin-related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race-specific or admixture-based algorithms may facilitate improved genotype-guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype-guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene-drug pairs and development of clinical recommendations for pharmacogenetic testing. © 2017 Pharmacotherapy Publications, Inc.

Intracranial bleeding: epidemiology and relationships with antithrombotic treatment in 241 cerebral hemorrhages in Reggio Emilia.

PubMed

Nicolini, Alberto; Ghirarduzzi, Angelo; Iorio, Alfonso; Silingardi, Mauro; Malferrari, Giovanni; Baldi, Giovanni

2002-09-01

Anticoagulant (AC) and antiplatelet (AP) drugs are effectively used in the prevention of thromboembolic events, with the trade-off of bleeding side effects, particularly intracranial. The aim of this study was to determine the incidence of intracranial bleeding in the population of Reggio Emilia and to investigate the potential effect of AC and AP drugs. We reviewed all the patients admitted for cerebral hemorrhages to our hospital between April 1998 and September 2000. Data were collected with a standardized form. All the patients were followed-up to estimate long-term mortality. Chi(2) and t-tests were used as appropriate. Logistic regression analysis was performed to test predictors of mortality. Pharmaceutical department data were employed to estimate the total number of patients receiving AC and AP drugs. We found 241 cases (107/134 female/male, mean age 61 years, 133/107 spontaneous/traumatic events, 0.32/1,000/year overall). Twenty-nine and 47 of these patients were being given AC or AP drugs, respectively (4.9/1,000/year and 3.7/1,000/year). The relative risk of intracranial bleeding was 11.5 in AP and 15.3 in AC treated patients. Two patients (one underwent neurosurgery and one thrombolytic treatment) were excluded from mortality and risk factors analysis. Six patients were lost from follow-up and excluded from mortality analysis. Overall mortality was 100/233 (42.9%); mortality in traumatic events was 25/103 (24.2%) versus 75/130 (57.7%) in spontaneous events. Mortality was 19/29 (65.5%), 26/47 (55.3%) and 55/157 (35%) in AC recipients, AP recipients, and untreated patients, respectively. This increased risk was mainly confined to traumatic events (p = 0.06), without difference between AC and AP recipients. At the time of the event, the mean duration of oral AC treatment was 26.3 months (range 1-120). Mean INR was = 3.1 (range 1.6-8.8). Mortality was significantly predicted by the Glasgow Coma Scale Score (GCS) at admission (p < 0.0001), by the type of

[Comparison of the intracranial pressure value in patients with hypertensive intracerebral hemorrhage treated with traditional craniotomy and puncture drainage].

PubMed

Song, Shao-jun; Fei, Zhou; Zhang, Xiang

2003-09-01

To compare the difference of intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage (HICH) treated with two surgical procedures, traditional craniotomy and puncture drainage. One hundred and twelve cases with HICH were randomly divided into two groups. In one group, 60 patients were operated by traditional craniotomy and in another group, 52 cases by puncture drainage and urokinase treatment. In the meantime, ICP was monitored by placing catheter in lateral ventricle on the contralateral side of the hemorrhage. ICP values were recorded after operation at once, at 24 hours, 72 hours and 1 week. Although all the patients showed increased ICP, the increasing degree in patients treated with traditional craniotomy had lower ICP values (P<0.05 or P<0.01). Traditional craniotomy has advantages over puncture drainage for patients with HICH at least with respect to decreasing ICP.

Occult large epidural hemorrhage in a newborn infant after in-hospital fall.

PubMed

Sato, R

2018-05-23

Management of newborn infants fell in-hospital is especially challenging given the limited signs and symptoms of intracranial hemorrhage in this age group. We present a case of a four day old well appearing newborn infant found to have a severe epidural hemorrhage requiring emergent surgical drainage. Development of imaging protocols for newborn infants suffering in-hospital falls need to consider the potential consequences of missing actionable intracranial hemorrhage when relying on clinical observation as a management strategy.

Noninvasive Intracranial Pressure Determination in Patients with Subarachnoid Hemorrhage.

PubMed

Noraky, James; Verghese, George C; Searls, David E; Lioutas, Vasileios A; Sonni, Shruti; Thomas, Ajith; Heldt, Thomas

2016-01-01

Intracranial pressure (ICP) should ideally be measured in many conditions affecting the brain. The invasiveness and associated risks of the measurement modalities in current clinical practice restrict ICP monitoring to a small subset of patients whose diagnosis and treatment could benefit from ICP measurement. To expand validation of a previously proposed model-based approach to continuous, noninvasive, calibration-free, and patient-specific estimation of ICP to patients with subarachnoid hemorrhage (SAH), we made waveform recordings of cerebral blood flow velocity in several major cerebral arteries during routine, clinically indicated transcranial Doppler examinations for vasospasm, along with time-locked waveform recordings of radial artery blood pressure (APB), and ICP was measured via an intraventricular drain catheter. We also recorded the locations to which ICP and ABP were calibrated, to account for a possible hydrostatic pressure difference between measured ABP and the ABP value at a major cerebral vessel. We analyzed 21 data records from five patients and were able to identify 28 data windows from the middle cerebral artery that were of sufficient data quality for the ICP estimation approach. Across these windows, we obtained a mean estimation error of -0.7 mmHg and a standard deviation of the error of 4.0 mmHg. Our estimates show a low bias and reduced variability compared with those we have reported before.

Prevalence of serious bleeding events and intracranial hemorrhage in patients receiving activated protein C: a systematic review and meta-analysis.

PubMed

Khan, Ajmal; Agarwal, Ritesh; Aggarwal, Ashutosh N; Gupta, Dheeraj

2010-07-01

Activated protein C reduces 28-day mortality in patients with severe sepsis, but its anticoagulant properties entail a risk of bleeding. The aim of this systematic review was to evaluate the prevalence of serious bleeding events in patients receiving activated protein C. We searched the MEDLINE and EMBASE databases for studies that described the prevalence of serious bleeding events and intracranial hemorrhage in patients receiving activated protein C. We calculated the bleeding rates by calculating proportions and 95% CIs for each study, and then pooled the data to derive a pooled proportion and 95% CI. Our search yielded 17 studies, which included 10,679 patients. The occurrence of serious bleeding events in patients receiving activated protein C ranged from 0.5% to 9.6%, and the pooled prevalence was 3.3% (95% CI 2.4-4.4%) by the random effects model. The occurrence of intracranial hemorrhage ranged from 0% to 1.4%, and the pooled prevalence was 0.44% (95% CI 0.31-0.6%). Sensitivity analysis showed a higher prevalence of bleeding in the observational studies than in the randomized controlled trials. There was substantial clinical and statistical heterogeneity, but no evidence of publication bias. Activated protein C is associated with significant risk of bleeding, so strict inclusion and exclusion criteria should be set prior to administering activated protein C.

The Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial

ClinicalTrials.gov

2018-04-24

Cerebral Hemorrhage; Stroke; Hypertension; Diabetes; Anticoagulant-induced Bleeding; Cerebral Vascular Disorder; Brain Disorder; Hemorrhage; Intracranial Hemorrhages; Cardiovascular Diseases; Central Nervous System Diseases

Neonatal venous cerebral hemorrhage. Report of two cases.

PubMed

Misra, Sanjay N; Misra, Ashish K

2003-10-15

Intracranial pathological changes can occur as a result of impaired craniocervical venous return. Thrombosis of central venous access catheters was demonstrated in two neonates born at 38 and 27 weeks' gestation. Neither infant developed hemorrhage of prematurity as confirmed on cranial ultrasonography. Clinical evidence of vena cava thrombosis and associated spontaneous intraventricular hemorrhage developed on Day 24 and 36, respectively, and these findings were confirmed on imaging studies. In one infant the hemorrhage was accompanied by communicating hydrocephalus. The cause of the intracranial disease was attributable to the retrograde cerebral venous congestion. This, together with the primitive venous bed developing in the periventricular region, was associated with the spontaneous hemorrhage in the region of the foramen of Monro. To the authors' knowledge, this is the first report in the English-language literature of spontaneous neonatal intracerebral hemorrhage, due to thrombosis of the superior or inferior vena cava. The natural history of this condition is resolution without sequelae after appropriate therapeutic intervention for the vena cava thrombosis.

Patients' perspectives on taking warfarin: qualitative study in family practice

PubMed Central

Dantas, Guilherme Coelho; Thompson, Barbara V; Manson, Judith A; Tracy, C Shawn; Upshur, Ross EG

2004-01-01

Background Despite the well-documented benefits of using warfarin to prevent stroke, physicians remain reluctant to initiate therapy, and especially so with the elderly owing to the higher risk of hemorrhage. Prior research suggests that patients are more accepting of the risk of bleeding than are physicians, although there have been few qualitative studies. The aim of this study was to employ qualitative methods to investigate the experience and perspective of individuals taking warfarin. Methods We conducted face-to-face interviews with 21 older patients (12 male, 9 female) who had been taking warfarin for a minimum of six months. Participants were patients at a family practice clinic situated in a large, tertiary care teaching hospital. We used a semistructured interview guide with four main thematic areas: decision-making, knowledge/education, impact, and satisfaction. Data were analysed according to the principles of content analysis. Results and Discussion Participants tended to have minimal input into the decision to initiate warfarin therapy, instead relying in great part on physicians' expertise. There appeared to be low retention of information received regarding the therapy; half the patients in our sample possessed only a superficial level of understanding of the risks and benefits. This notwithstanding, participants reported a high level of satisfaction with the care provided and a low level of impact on their day-to-day lives. Conclusions Minimal patient involvement in the initial decision and modest knowledge did not appear to diminish satisfaction with warfarin management. At the same time, care providers exert a tremendous influence on the initiation of warfarin therapy and should strive to incorporate patient preferences and expectations into the decision-making process. PMID:15268764

Aggressive blood pressure treatment of hypertensive intracerebral hemorrhage may lead to global cerebral hypoperfusion: Case report and imaging perspective.

PubMed

Gavito-Higuera, Jose; Khatri, Rakesh; Qureshi, Ihtesham A; Maud, Alberto; Rodriguez, Gustavo J

2017-12-28

Hypoperfusion injury related to blood pressure decrease in acute hypertensive intracerebral hemorrhage continues to be a controversial topic. Aggressive treatment is provided with the intent to stop the ongoing bleeding. However, there may be additional factors, including autoregulation and increased intracranial pressure, that may limit this approach. We present here a case of acute hypertensive intracerebral hemorrhage, in which aggressive blood pressure management to levels within the normal range led to global cerebral ischemia within multiple border zones. Global cerebral ischemia may be of concern in the management of hypertensive hemorrhage in the presence of premorbid poorly controlled blood pressure and increased intracranial pressure.

Association of Proton Pump Inhibitors With Reduced Risk of Warfarin-Related Serious Upper Gastrointestinal Bleeding.

PubMed

Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Smalley, Walter E; Daugherty, James R; Dupont, William D; Stein, C Michael

2016-12-01

Proton pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow-up. The study end points were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63-0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94-1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84-1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39-0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper gastrointestinal bleeding; the

Influence of Sampling on the Determination of Warfarin and Warfarin Alcohols in Oral Fluid

PubMed Central

Lomonaco, Tommaso; Ghimenti, Silvia; Piga, Isabella; Biagini, Denise; Onor, Massimo; Fuoco, Roger; Di Francesco, Fabio

2014-01-01

Background and Objective The determination of warfarin, RS/SR- and RR/SS-warfarin alcohols in oral fluid may offer additional information to the INR assay. This study aimed to establish an optimized sampling technique providing the best correlation between the oral fluid and the unbound plasma concentrations of these compounds. Materials and Methods Samples of non-stimulated and stimulated oral fluid, and blood were collected from 14 patients undergoing warfarin therapy. After acidification, analytes were extracted with a dichloromethane/hexane mixture and determined by HPLC with fluorescence detection. Plasma samples were also ultrafiltered for the determination of the unbound fraction. The chromatographic separation was carried out in isocratic conditions with a phosphate buffer/methanol mobile phase on a C-18 reversed-phase column. The absence of interfering compounds was verified by HPLC-ESI-Q-TOF. Results Stimulation generally increased the oral fluid pH to values close to blood pH in about 6 minutes. The concentration of warfarin and RS/SR-warfarin alcohols in oral fluid followed the same trend, whereas the concentration of RR/SS-warfarin alcohols was not affected. Six minute stimulation with chewing gum followed by collection with a polyester swab was the best sampling procedure, with a good repeatability (RSD <10%) and relatively low inter-subject variability (RSD  = 30%) of the oral fluid to plasma ratio. This procedure provided strong correlations between the measured oral fluid and unbound plasma concentration of warfarin (r  =  0.92, p <0.001) and RS/SR-warfarin alcohols (r  =  0.84, p <0.001), as well as between stimulated oral fluid and total plasma concentration of warfarin (r  =  0.78, p <0.001) and RS/SR-warfarin alcohols (r  =  0.81, p <0.001). Conclusion The very good correlation between oral fluid and unbound plasma concentration of warfarin and RS/SR-warfarin alcohols suggests that oral fluid analysis could provide

Identifying major hemorrhage with automated data: results of the Veterans Affairs study to improve anticoagulation (VARIA).

PubMed

Jasuja, Guneet K; Reisman, Joel I; Miller, Donald R; Berlowitz, Dan R; Hylek, Elaine M; Ash, Arlene S; Ozonoff, Al; Zhao, Shibei; Rose, Adam J

2013-01-01

Identifying major bleeding is fundamental to assessing the outcomes of anticoagulation therapy. This drives the need for a credible implementation in automated data for the International Society of Thrombosis and Haemostasis (ISTH) definition of major bleeding. We studied 102,395 patients who received 158,511 person-years of warfarin treatment from the Veterans Health Administration (VA) between 10/1/06-9/30/08. We constructed a list of ICD-9-CM codes of "candidate" bleeding events. Each candidate event was identified as a major hemorrhage if it fulfilled one of four criteria: 1) associated with death within 30days; 2) bleeding in a critical anatomic site; 3) associated with a transfusion; or 4) was coded as the event that precipitated or was responsible for the majority of an inpatient hospitalization. This definition classified 11,240 (15.8%) of 71, 338 candidate events as major hemorrhage. Typically, events more likely to be severe were retained at higher rates than those less likely to be severe. For example, Diverticula of Colon with Hemorrhage (562.12) and Hematuria (599.7) were retained 46% and 4% of the time, respectively. Major, intracranial, and fatal hemorrhage were identified at rates comparable to those found in randomized clinical trials however, higher than those reported in observational studies: 4.73, 1.29, and 0.41 per 100 patient years, respectively. We describe here a workable definition for identifying major hemorrhagic events from large automated datasets. This method of identifying major bleeding may have applications for quality measurement, quality improvement, and comparative effectiveness research. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ruptured intracranial aneurysm in patients with osteogenesis imperfecta: 2 familial cases and a systematic review of the literature.

PubMed

Gaberel, T; Rochey, A; di Palma, C; Lucas, F; Touze, E; Emery, E

2016-12-01

Osteogenesis imperfecta is an inherited connective tissue disorder that causes bone fragility. Vascular complications have been described, but only few cases of ruptured intracranial aneurysm have been reported. We first described 2 familial cases of ruptured intracranial aneurysm and then conducted a systematic review of the literature. A mother and her daughter with a typical history of osteogenesis imperfecta presented with subarachnoid hemorrhage, which was related to a posterior communicating artery aneurysm in both cases. The mother had early rebleeding and died. The aneurysm was excluded by coiling in the daughter. Despite occurrence of hydrocephalus and delayed cerebral ischemia, she had an excellent functional outcome. A systematic review of the literature identified seven additional cases. None of the cases were in fact familial. All patients had a previous medical history of multiple fractures. Seven aneurysms were resolved, three by surgical clipping and four by endovascular procedure. No periprocedural complication was reported. One patient died prematurely and 6 experienced good functional outcome. We report the first familial cases of aneurysmal subarachnoid hemorrhage in osteogenesis imperfecta patients. Intracranial aneurysms are probably linked to a collagen pathology, which is at the origin of osteogenesis imperfecta. In cases of aneurysmal subarachnoid hemorrhage in an osteogenesis imperfecta family, intracranial aneurysm screenings in the relatives showing osteogenesis imperfecta should be considered. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Anosmia after perimesencephalic nonaneurysmal hemorrhage.

PubMed

Greebe, Paut; Rinkel, Gabriël J E; Algra, Ale

2009-08-01

Anosmia frequently occurs after aneurysmal subarachnoid hemorrhage not only after clipping, but also after endovascular coiling. Thus, at least in part, anosmia is caused by the hemorrhage itself and not only by surgical treatment. However, it is unknown whether anosmia is related to rupture of the aneurysm with sudden increase in intracranial pressure or to the presence of blood in the basal cisterns. Therefore, we studied the prevalence of anosmia in patients with nonaneurysmal perimesencephalic hemorrhage. We included all patients admitted to our hospital with perimesencephalic hemorrhage between 1983 and 2005. Patients were interviewed with a structured questionnaire. We calculated the proportion of patients with anosmia with corresponding 95% CIs. Nine of 148 patients (6.1%; 95% CI, 2.8% to 11%) had noticed anosmia shortly after the perimesencephalic hemorrhage. In 2, the anosmia had disappeared after 8 to12 weeks; in the other 7, it still persisted after a mean period of follow-up of 9 years. Anosmia occurs in one of every 16 patients with perimesencephalic hemorrhage, which is lower than previously reported rates after coiling in patients with subarachnoid hemorrhage but higher than rates after coiling for unruptured aneurysms. These data suggest that blood in the vicinity of the olfactory nerves plays a role in the development of anosmia.

A Blown Pupil and Intracranial Hemorrhage in a 4-Week-Old: A Case of Delayed Onset Vitamin K Deficiency Bleeding, a Rare "Can't Miss" Diagnosis.

PubMed

Enz, Ryley; Anderson, Robert S

2016-08-01

Infants are at risk for vitamin K deficiency bleeding (VKDB) because of limited stores of vitamin K (VK) at birth and a low concentration of VK in human breast milk. Therefore, the administration of intramuscular (IM) VK at birth has been recommended since 1961 in the United States. Infants who do not receive IM VK and who are exclusively breast-fed are at increased risk for VKDB. While VKDB is rare, a common presentation of late onset VKDB is intracranial hemorrhage. We report the case of a 4-week-old infant who presented to the emergency department with lethargy and a grossly dilated right pupil. The parents denied trauma. A computed tomography scan revealed a right-sided subdural hematoma with midline shift. The infant's international normalized ratio was >10.9 and his prothrombin time PT was >120 seconds. VK was administered and the child was transferred to a tertiary care center for emergent neurosurgery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The difficult part of making this critical diagnosis is considering it. Any bleeding in a newborn without trauma should prompt inquiry regarding neonatal VK administration and a serum prothrombin time level. Fortunately, once the diagnosis is made, therapy in the emergency department can be lifesaving and is familiar to emergency physicians. Treatment parallels usual care for the adult with excess anticoagulation caused by warfarin. Prompt intravenous VK is universally accepted. Studies to support fresh frozen plasma or prothrombin complex concentrate are lacking but make good clinical sense for life-threatening bleeding. Copyright © 2016 Elsevier Inc. All rights reserved.

Continued Use of Warfarin in Veterans with Atrial Fibrillation After Dementia Diagnosis.

PubMed

Orkaby, Ariela R; Ozonoff, Al; Reisman, Joel I; Miller, Donald R; Zhao, Shibei; Rose, Adam J

2017-02-01

To determine the effectiveness of warfarin in older adults with dementia. Retrospective cohort study. Department of Veterans Affairs national healthcare system. Veterans aged 65 and older (73% aged ≥75, 99% male, 91% white) who had been receiving warfarin for nonvalvular atrial fibrillation for at least 6 months, were newly diagnosed with dementia in fiscal year 2007 or 2008, and were not enrolled in Medicare Advantage (n = 2,572). The onset of dementia was defined according to International Classification of Diseases, Ninth Revision, code. Participants were followed for up to 4 years for persistence of warfarin therapy, anticoagulation control, major hemorrhage, ischemic stroke, and all-cause mortality. The average CHADS2 score was 3.3 ± 1.3. After a diagnosis of dementia, 405 individuals (16%) persisted on warfarin therapy. Unadjusted Cox proportional hazards analysis demonstrated a protective effect of warfarin in prevention of ischemic stroke (hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.46-0.89, P = .008), major bleeding (HR = 0.72, 95% CI = 0.55-0.94, P = .02), and all-cause mortality (HR = 0.66, 95% CI = 0.55-0.79, P < .001). Using propensity score matching, the protective effect of continuing warfarin persisted in prevention of stroke (HR = 0.74, 95% CI = 0.54-0.996, P = .047) and mortality (HR = 0.72, 95% CI = 0.60-0.87, P < .001), with no statistically significant decrease in risk of major bleeding (HR = 0.78, 95% CI = 0.61-1.01, P = .06). Discontinuing warfarin after a diagnosis of dementia is associated with a significant increase in stroke and mortality. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Endovascular Treatments in Combination with Extracranial-Intracranial Bypass for Complex Intracranial Aneurysms.

PubMed

Sato, Kenichi; Endo, Hidenori; Fujimura, Miki; Endo, Toshiki; Matsumoto, Yasushi; Shimizu, Hiroaki; Tominaga, Teiji

2018-05-01

Although most intracranial aneurysms can be treated with microsurgery or endovascular procedure alone, a subset of aneurysms may require a combined approach. The purpose of this study was to assess the efficacy of endovascular interventions combined with bypass surgery for the treatment of complex intracranial aneurysms. We retrospectively reviewed medical records from a prospectively maintained patient database to identify patients who underwent endovascular treatment of an intracranial aneurysm at our institutes between 2007 and 2017. We recruited patients who received a preplanned combination of endovascular treatment and extracranial-intracranial bypass surgery. Forty-four patients (44 aneurysms) were treated with a combined approach. Twenty-four patients presented with subarachnoid hemorrhage. Treatment strategies included endovascular parent artery occlusion with the bypass surgery to restore cerebral blood flow (n = 12), endovascular trapping with bypass surgery to isolate incorporated branches (n = 12), and intra-aneurysmal coil embolization with bypass surgery to isolate incorporated branches (n = 20). During a mean period of 35.6 months, follow-up catheter angiography was performed in 35 of 44 patients (79.5%) and demonstrated complete aneurysm obliteration in 29 patients (82.9%) and bypass patency in 33 (94.3%). The postoperative aneurysm-related mortality and morbidity rates were 6.8% and 13.6%, respectively. Combined endovascular and surgical bypass procedures are useful for the treatment of complex intracranial aneurysms when conventional surgical or endovascular techniques are not feasible and show acceptable rates of morbidity and mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

Case of Subarachnoid Hemorrhage Caused by Tuberculous Aneurysm.

PubMed

Liu, Wei; Li, Chuanfeng; Liu, Xianming; Xu, Zhiming; Kong, Lu

2018-02-01

Subarachnoid hemorrhage caused by rupture of tuberculosis associated aneurysm is a rare complication. In this paper, we report a case of intracranial tuberculum with adjacent intracerebral inflammatory aneurysm which caused subarachnoid hemorrhage and brain abscess formation. A 28-year-old man presented with sudden onset of severe headache. He was diagnosed with pulmonary tuberculosis 8 years ago, and had been treated with antituberculosis medications for 6 months. Head computed tomography showed a small hematoma in the left sylvian fissure with subarachnoid hemorrhage. Cerebral digital subtraction angiography was performed and no aneurysm was found. He was discharged after nonsurgical treatment. Three weeks later, he came back to our department with complaint of aphasia. Magnetic resonance images showed a cystic lesion with mass effect. During operation, we encounter the brain abscess and were surprised to find a middle cerebral artery aneurysm while dissecting. The abscess was totally removed, and the aneurysm was secured by clipping. The aneurysm was suspected of being inflammatory in nature and associated with the patient's tuberculosis. Tuberculosis in the central nervous system may present as tuberculoma and tuberculous meningitis. Vasculitis secondary to tuberculous meningitis can cause infarcts, and, rarely, aneurysm formation. This case report illustrated a rare case of intracranial infectious aneurysm related to tuberculosis and complicated by hemorrhage and brain abscess. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors associated with failure to correct the international normalised ratio following fresh frozen plasma administration among patients treated for warfarin-related major bleeding. An analysis of electronic health records.

PubMed

Menzin, J; White, L A; Friedman, M; Nichols, C; Menzin, J; Hoesche, J; Bergman, G E; Jones, C

2012-04-01

This study assessed the frequency and factors associated with failure to correct international normalised ratio (INR) in patients administered fresh frozen plasma (FFP) for warfarin-related major bleeding. This retrospective database analysis used electronic health records from an integrated health system. Patients who received FFP between 01/01/2004 and 01/31/2010, and who met the following criteria were selected: major haemorrhage diagnosis the day before to the day after initial FFP administration; INR ≥2 on the day before or the day of FFP and another INR result available; warfarin prescription within 90 days. INR correction (defined as INR ≤1.3) was evaluated at the last available test up to one day following FFP. A total of 414 patients met selection criteria (mean age 75 years, 53% male, mean Charlson score 2.5). Patients presented with gastrointestinal bleeding (58%), intracranial haemorrhage (38%) and other bleed types (4%). The INR of 67% of patients remained uncorrected at the last available test up to one day following receipt of FFP. In logistic regression analysis, the INR of patients who were older, those with a Charlson score of 4 or greater, and those with non-ICH bleeds (odds ratio vs. intracranial bleeding 0.48; 95% confidence interval 0.31-0.76) were more likely to remain uncorrected within one day following FFP administration. In an alternative definition of correction, (INR ≤1.5), 39% of patients' INRs remained uncorrected. For a substantial proportion of patients, the INRs remain inadequately or uncorrected following FFP administration, with estimates varying depending on the INR threshold used.

Comparison of the Effectiveness and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Newly Diagnosed Atrial Fibrillation.

PubMed

Hernandez, Inmaculada; Zhang, Yuting; Saba, Samir

2017-11-15

No studies have performed direct pairwise comparisons of the effectiveness and safety of warfarin and the new oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban. Using 2013 to 2014 claims from a 5% random sample of Medicare beneficiaries, we identified patients newly diagnosed with atrial fibrillation who initiated apixaban, dabigatran, rivaroxaban, warfarin, or no oral anticoagulation therapy in 2013 to 2014. Outcomes included the composite of ischemic stroke, systemic embolism (SE) and death, any bleeding event, gastrointestinal bleeding, intracranial bleeding, and treatment persistence. We constructed Cox proportional hazard models to compare outcomes between each pair of treatment groups. The composite risk of ischemic stroke, SE, and death was lower for NOACs than for warfarin: hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76 to 0.98 for apixaban; 0.73, 95% CI 0.63 to 0.86 for dabigatran; and 0.82, 95% CI 0.75 to 0.89 for rivaroxaban, all compared with warfarin. There were no differences in effectiveness across NOACs. The risk of any bleeding was lower with apixaban than with warfarin, but higher with rivaroxaban than with warfarin. Apixaban (HR 0.69, 95% CI 0.60 to 0.79) and dabigatran (HR 0.79, 95% CI 0.69 to 0.92) were associated with lower bleeding risk than rivaroxaban. Treatment persistence was highest for apixaban (82%), and lowest for dabigatran and warfarin (64%) (p value <0.001). Compared with warfarin, NOACs are more effective in preventing stroke but their risk of bleeding varies, with rivaroxaban having higher risk than warfarin. Altogether, apixaban had the most favorable effectiveness, safety, and persistence profile. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatic uptake and storage of warfarin. The relation with the target enzyme vitamin K 2,3-epoxide reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thijssen, H.H.; Baars, L.G.

The mechanisms of the reported dose-dependent warfarin pharmacokinetics were investigated using (/sup 14/C)warfarin. When administered in microdoses (9 micrograms i.v.) to rats (male Wistars, 270-300 g), a steep distribution phase (T1/2 = 0.25 hr) was followed by a relatively slow beta-phase (T1/2 = 40 hr). The observed volume of distribution was 390 ml. This pharmacokinetic behavior contrasted highly with the one seen for higher (greater than 0.2 mg/kg) doses (unlabeled) warfarin; volume of distribution = 45 ml, T1/2 = 12.5 hr. If a macrodose (0.2 mg/kg) preceded (16 hr) the microdose, normal pharmacokinetics were observed for the latter, suggesting amore » saturable deep compartment. The administration of 4-hydroxycoumarins (i.e., acenocoumarol, phenprocoumon and warfarin) after the microdose of (/sup 14/C)warfarin was in its beta-phase caused a rapid rise of plasma (/sup 14/C)warfarin indicating (/sup 14/C)warfarin to be displaced from the deep compartment. The rate of appearance of (/sup 14/C)warfarin was 0.3 hr-1 irrespective the 4-hydroxycoumarin used. The hepatic distribution of (/sup 14/C)warfarin was investigated and the effect of a displacer thereupon. Fifty-three hours after the (/sup 14/C)warfarin administration, the liver contained about 40% of the dose; 45% of it was bound to microsomes. The administration of acenocoumarol (0.2 mg/kg) at 48 hr, halved the liver content. (/sup 14/C)warfarin was redistributed from microsomes (-65%) and from the 10,000 X g pellet (-65%) into the cytosol (+260%) and the plasma (+320%). Microsomal bound (/sup 14/C)warfarin in vitro could not be washed out or be displaced unless dithiothreitol (50 mM) was included in the washing buffers.« less

Management of intracranial aneurysms associated with arteriovenous malformations.

PubMed

Flores, Bruno C; Klinger, Daniel R; Rickert, Kim L; Barnett, Samuel L; Welch, Babu G; White, Jonathan A; Batjer, H Hunt; Samson, Duke S

2014-09-01

Intracranial or brain arteriovenous malformations (BAVMs) are some of the most interesting and challenging lesions treated by the cerebrovascular neurosurgeon. It is generally believed that the combination of BAVMs and intracranial aneurysms (IAs) is associated with higher hemorrhage rates at presentation and higher rehemorrhage rates and thus with a more aggressive course and natural history. There is wide variation in the literature on the prevalence of BAVM-associated aneurysms (range 2.7%-58%), with 10%-20% being most often cited in the largest case series. The risk of intracranial hemorrhage in patients with unruptured BAVMs and coexisting IAs has been reported to be 7% annually, compared with 2%-4% annually for those with BAVM alone. Several different classification systems have been applied in an attempt to better understand the natural history of this combination of lesions and implications for treatment. Independent of the classification used, it is clear that a few subtypes of aneurysms have a direct hemodynamic correlation with the BAVM itself. This is exemplified by the fact that the presence of a distal flow-related or an intranidal aneurysm appears to be associated with an increased hemorrhage risk, when compared with an aneurysm located on a vessel with no direct supply to the BAVM nidus. Debate still exists regarding the etiology of the association between those two vascular lesions, the subsequent implications for patients' risk of hemorrhagic stroke, and finally the determination of which patients warrant treatment and when. The ultimate goals of the treatment of a BAVM associated with an IA are to prevent hemorrhage, avoid stepwise neurological deterioration, and eliminate the mortality risk associated with recurrent hemorrhagic events. The treatment is only justifiable if the risks associated with an intervention are lower than or equivalent to the long-term risks of disability or mortality caused by the lesion itself. When faced with this

Effectiveness and outcome of management strategies for dabigatran- or warfarin-related major bleeding events.

PubMed

Majeed, Ammar; Hwang, Hun-Gyu; Eikelboom, John W; Connolly, Stuart; Wallentin, Lars; Feuring, Martin; Brueckmann, Martina; Noack, Herbert; Yusuf, Salim; Schulman, Sam

2016-04-01

Strategies used for the management of dabigatran-related major bleeding events (MBEs), and their effectiveness have not been systematically evaluated. Reports on 1034 individuals experiencing 1121 MBEs (696 on dabigatran, and 425 on warfarin) in 5 phase III randomized controlled trials were assessed independently by two investigators. MBEs were managed either by drug discontinuation only (37%), or drug discontinuation with either transfusion of only red cell concentrates (38%), or plasma (23%). Few MBEs (2%) were treated with coagulation factor concentrates. The effectiveness of the management was assessed as good in significantly larger proportion of MBEs on dabigatran (91%) than on warfarin (84%, odds ratio [OR] 1.68; 95% confidence interval [CI], 1.14-2.49), which was consistent with the lower 30-day mortality (OR (OR 0.66; 95% CI, 0.44-1.00)). The effectiveness of bleeding management in non-traumatic bleeding was better in patients with dabigatran than with warfarin (OR 1.82; 95% CI, 1.18-2.79) but was similar in traumatic bleeding (OR 0.75; 95% CI, 0.25-2.30). The relative effectiveness of management of bleeding and 30-day mortality rates across other key subgroups of patients or sites of bleeding, the use of platelet inhibitors, age-, sex- and renal function subgroups, were comparable in MBEs on dabigatran or warfarin. Despite the unavailability of a specific antidote at the time of these studies, bleeding in patients receiving dabigatran was managed in the overwhelming majority of patients without coagulation factor concentrates, with comparable or superior effectiveness and lower 30-day mortality rates versus those who bleed while receiving warfarin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of warfarin with congestive heart failure and peripheral artery occlusive disease in hemodialysis patients with atrial fibrillation.

PubMed

Lee, Kuo-Hua; Li, Szu-Yuan; Liu, Jin-Sin; Huang, Chi-Ting; Chen, Ying-Ying; Lin, Yao-Ping; Hsu, Chih-Cheng; Tarng, Der-Cherng

2017-05-01

The effect of warfarin on the risk of cardiovascular (CV) disease is unknown among chronic hemodialysis patients with atrial fibrillation (HD-AF). Population-based propensity score and prescription time-distribution matched cohort study including 6719 HD-AF patients with CHA 2 DS 2 -VASc score ≥ 2 were divided into warfarin users and nonusers and followed-up for CV events and death. Warfarin treatment in HD-AF patients with AF preceding HD was associated with higher risks of developing congestive heart failure [hazard ratio (HR)=1.82, 95% confidence interval (CI)=1.29-2.58, p<0.01], peripheral artery occlusive disease (HR=3.42, 95% CI=1.86-6.31, p<0.01), and aortic valve stenosis (HR=3.20, 95% CI=1.02-9.98, p<0.05). Warfarin users were not associated with risks of ischemic or hemorrhagic stroke and all-cause mortality as compared to nonusers. Warfarin may be associated with vascular calcification, increasing the risks of congestive heart failure and peripheral artery occlusive disease among HD-AF patients. Copyright © 2017. Published by Elsevier Taiwan LLC.

[in-hospital mortality in patient with acute ischemic and hemorrhagic stroke].

PubMed

Sadamasa, Nobutake; Yoshida, Kazumichi; Narumi, Osamu; Chin, Masaki; Yamagata, Sen

2011-09-01

There is a lack of evidence to compare in-hospital mortality with different types of stroke. The purpose of this study was to elucidate the in-hospital mortality after acute ischemic/hemorrhagic stroke and compare the factors associated with the mortality among stroke subtypes. All patients admitted to Kurashiki Central Hospital in Japan between January 2009 and December 2009, and diagnosed with acute ischemic/hemorrhagic stroke were included in this study. Demographics and clinical data pertaining to the patients were obtained from their medical records. Out of 738 patients who had an acute stroke, 53 (7.2%) died in the hospital. The in-hospital mortality was significantly lower in the cerebral infarction group than in the intracerebral hemorrhage and subarachnoid hemorrhage group (3.5%, 15.1%, and 17.9%, respectively; P<0.0001). Age was significantly lower in the subarachnoid hemorrhage group than in the other 2 groups. With regard to past history, diabetes mellitus was significantly found to be a complication in mortality cases of intracranial hemorrhage. Further investigation is needed to clarify the effect of diabetes on mortality after intracranial hemorrhage.

Delayed chronic intracranial subdural hematoma complicating resection of a tanycytic thoracic ependymoma.

PubMed

Maugeri, Rosario; Giugno, Antonella; Graziano, Francesca; Visocchi, Massimiliano; Giller, Cole; Iacopino, Domenico Gerardo

2016-01-01

To demonstrate that the diagnosis of an intracranial subdural hematoma should be considered for patients presenting with acute or delayed symptoms of intracranial pathology following resection of a spinal tumor. We present a case of a 57-year-old woman found to have a chronic subdural hematoma 1 month following resection of a thoracic extramedullary ependymoma. Evacuation of the hematoma through a burr hole relieved the presenting symptoms and signs. Resolution of the hematoma was confirmed with a computed tomography (CT) scan. Headache and other symptoms not referable to spinal pathology should be regarded as a warning sign of an intracranial subdural hematoma, and a CT scan of the head should be obtained. The mechanism of the development of the hematoma may be related to the leakage of cerebrospinal fluid with subsequent intracranial hypotension leading to an expanding subdural space and hemorrhage.

An assessment of the iPad 2 as a CT teleradiology tool using brain CT with subtle intracranial hemorrhage under conventional illumination.

PubMed

Park, Joon Bum; Choi, Hyuk Joong; Lee, Jeong Hun; Kang, Bo Seung

2013-08-01

We examined the potential of the iPad 2 as a teleradiologic tool for evaluating brain computed tomography (CT) with subtle hemorrhage in the conventional lighting conditions which are common situations in the remote CT reading. The comparison of the clinician's performance was undertaken through detecting hemorrhage by the iPad 2 and the clinical liquid crystal display (LCD) monitor. We selected 100 brain CT exams performed for head trauma or headache. Fifty had subtle radiological signs of intracranial hemorrhage (ICH), while the other 50 showed no significant abnormality. Five emergency medicine physicians reviewed these brain CT scans using the iPad 2 and the LCD monitor, scoring the probability of ICH on each exam on a five-point scale. Result showed high sensitivities and specificities in both devices. We generated receiver operating characteristic curves and calculated the average area under the curve of the iPad 2 and the LCD (0.935 and 0.900). Using the iPad 2 and reliable internet connectivity, clinicians can provide remote evaluation of brain CT with subtle hemorrhage under suboptimal viewing condition. Considering the distinct advantages of the iPad 2, the popular out-of-hospital use of mobile CT teleradiology would be anticipated soon.

Prediction models for intracranial hemorrhage or major bleeding in patients on antiplatelet therapy: a systematic review and external validation study.

PubMed

Hilkens, N A; Algra, A; Greving, J P

2016-01-01

ESSENTIALS: Prediction models may help to identify patients at high risk of bleeding on antiplatelet therapy. We identified existing prediction models for bleeding and validated them in patients with cerebral ischemia. Five prediction models were identified, all of which had some methodological shortcomings. Performance in patients with cerebral ischemia was poor. Background Antiplatelet therapy is widely used in secondary prevention after a transient ischemic attack (TIA) or ischemic stroke. Bleeding is the main adverse effect of antiplatelet therapy and is potentially life threatening. Identification of patients at increased risk of bleeding may help target antiplatelet therapy. This study sought to identify existing prediction models for intracranial hemorrhage or major bleeding in patients on antiplatelet therapy and evaluate their performance in patients with cerebral ischemia. We systematically searched PubMed and Embase for existing prediction models up to December 2014. The methodological quality of the included studies was assessed with the CHARMS checklist. Prediction models were externally validated in the European Stroke Prevention Study 2, comprising 6602 patients with a TIA or ischemic stroke. We assessed discrimination and calibration of included prediction models. Five prediction models were identified, of which two were developed in patients with previous cerebral ischemia. Three studies assessed major bleeding, one studied intracerebral hemorrhage and one gastrointestinal bleeding. None of the studies met all criteria of good quality. External validation showed poor discriminative performance, with c-statistics ranging from 0.53 to 0.64 and poor calibration. A limited number of prediction models is available that predict intracranial hemorrhage or major bleeding in patients on antiplatelet therapy. The methodological quality of the models varied, but was generally low. Predictive performance in patients with cerebral ischemia was poor. In order to

Warfarin Pharmacogenetics

PubMed Central

Johnson, Julie A.; Cavallari, Larisa H.

2014-01-01

The cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase complex 1 (VKORC1) genotypes have been strongly and consistently associated with warfarin dose requirements, and dosing algorithms incorporating genetic and clinical information have been shown to be predictive of stable warfarin dose. However, clinical trials evaluating genotype-guided warfarin dosing produced mixed results, calling into question the utility of this approach. Recent trials used surrogate markers as endpoints rather than clinical endpoints, further complicating translation of the data to clinical practice. The present data do not support genetic testing to guide warfarin dosing, but in the setting where genotype data are available, use of such data in those of European ancestry is reasonable. Outcomes data are expected from an on-going trial, observational studies continue, and more work is needed to define dosing algorithms that incorporate appropriate variants in minority populations; all these will further shape guidelines and recommendations on the clinical utility of genotype-guided warfarin dosing. PMID:25282448

[The randomized study of efficiency and safety of antithrombotic therapy in nonvalvular atrial fibrillation: warfarin compared with aspirin].

PubMed

Hu, Da-yi; Zhang, He-ping; Sun, Yi-hong; Jiang, Li-qing

2006-04-01

To investigate whether warfarin is more effective and superior to aspirin for the prevention of thromboembolism in nonvalvular atrial fibrillation in Chinese. In a multicenter randomized trial, the patients diagnosed as nonvalvular atrial fibrillation were randomized to receive aspirin 150 mg - 160 mg once daily or adjusted-dose warfarin (international normalized ratio, 2.0 - 3.0). We compared the effect of the two therapy on the primary end point of ischemic stroke or death from any cause and on the combined end-point (stroke, death, peripheral arteries embolism, TIA, acute myocardial infarction, serious bleeding) during a median follow-up period of 19 months. Of the 704 patients, 420 (59.7%) were male. The average patient age was (63.3 +/- 9.9) years. The median follow-up period is 19 months. The mean dose of warfarin was (3.2 +/- 0.7) mg. Compared with aspirin, the primary end point of death or ischemic stroke was reduced by warfarin (2.7% vs 6.0%, P = 0.03, OR 0.44, 95% CI 0.198 - 0.960) and the relative risk decreased by 56%. The thromboembolism event in the aspirin group was significantly higher than that in warfarin group (10.6% vs 5.4%, P = 0.01, OR 0.48, 95% CI 0.269 - 0.858). There was no significant differences of the mortality rate between the two groups (1.2% vs 2.2%, P > 0.05). The secondary end point was nonsignificantly reduced in warfarin group than that in aspirin group, while the combined end point is statistically decreased by adjusted-dose warfarin (8.4% vs 13.0%, P = 0.047). Warfarin treatment was associated with increased bleeding rate compared to aspirin (6.9% vs 2.4%, P < 0.05), although the major bleeding rate is rather low (1.5%). All the major bleeding events occurred with INR above 3.0. Randomized control study demonstrated that anticoagulation with adjusted-dosed warfarin (INR 2.0 - 3.0) can significantly reduced the risk of thromboembolism event with slightly increased hemorrhage, compared to aspirin in Chinese population. Under

Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Hoffman, Elaine B; Deenadayalu, Naveen; Ezekowitz, Michael D; Camm, A John; Weitz, Jeffrey I; Lewis, Basil S; Parkhomenko, Alexander; Yamashita, Takeshi; Antman, Elliott M

2014-03-15

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the

Warfarin-acetaminophen drug interaction revisited.

PubMed

Shek, K L; Chan, L N; Nutescu, E

1999-10-01

Physicians and pharmacists routinely advise patients receiving warfarin to take acetaminophen for pain or fever because of its relative safety; however, a recent study questioned the safety of such practice. A comprehensive search of MEDLINE and IPA for human studies and case reports from 1966-1999 revealed evidence that acetaminophen may potentiate the effect of warfarin by a mechanism that has yet to be elucidated. Due to lack of a safer alternative, acetaminophen still should be the analgesic and antipyretic of choice in patients taking warfarin, as long as excessive amounts and prolonged administration (> 1.3 g acetaminophen/day for > 2 wks) are avoided. With the high degree of interpatient variability and the unpredictability of various drug-drug interactions with warfarin, close and frequent monitoring of international normalized ratios is the key for safe oral anticoagulation therapy.

Terson syndrome in aneurysmal subarachnoid hemorrhage-its relation to intracranial pressure, admission factors, and clinical outcome.

PubMed

Joswig, Holger; Epprecht, Lorenz; Valmaggia, Christophe; Leschka, Sebastian; Hildebrandt, Gerhard; Fournier, Jean-Yves; Stienen, Martin Nikolaus

2016-06-01

A large number of reports have not been able to clarify the pathophysiology of Terson syndrome (TS) in aneurysmal subarachnoid hemorrhage (aSAH). Prospective single-center study on aSAH patients. Fundoscopic and radiological signs of TS were assessed. The opening intracranial pressure (ICP) in patients who required a ventriculostomy was recorded with a manometer. Six out of 36 included patients had TS (16.7 %), which was associated with unfavorable admission scores. Twenty-nine patients (80.5 %) required ventriculostomy; TS was associated with higher ICP (median, 40 vs. 15 cm cmH2O, p = .003); all patients with TS had pathological ICP values of >20 cmH2O. Patients with a ruptured aneurysm of the anterior cerebral artery complex were ten times as likely to suffer from TS (OR 10.0, 95 % CI 1.03-97.50). Detection of TS on CT had a sensitivity of 50 %, a specificity of 98.4 %, a positive predictive value of 83.3 %, and a negative predictive value of 92.4 %. Mortality was 45 times as high in patients with TS (OR 45.0, 95 % CI 3.86-524.7) and neurologic morbidity up until 3 months post-aSAH was significantly higher in patients with TS (mRS 4-6; 100 vs. 17 %; p = .001). Our findings demonstrate an association between raised ICP and the incidence of TS. TS should be ruled out in aSAH patients presenting comatose or with raised ICP to ensure upfront ophthalmological follow-up. In alert patients without visual complaints and a TS-negative CT scan, the likelihood for the presence of TS is very low.

Retrobulbar Hematoma from Warfarin Toxicity and the Limitations of Bedside Ocular Sonography

DTIC Science & Technology

2010-05-01

Nontraumatic RBH occurs rarely and has been associated with arteriovenous malformations,1 following thrombolysis,2 Type IV Ehlers - Danlos Syndrome ,3...infarction. N Engl J Med. 2007; 357:1448-9. 3. Shaikh S, Braun M, Eliason J. Spontaneous retrobulbar hemorrhage in type IV Ehlers - Danlos syndrome . Am J...compartment syndrome . DISCUSSION We believe this is the first case report of a nontraumatic RBH associated with warfarin toxicity. Our patient also had

Relative Expression of PBMC MicroRNA-133a Analysis in Patients Receiving Warfarin After Mechanical Heart Valve Replacement

PubMed Central

Kabiri Rad, Hamid; Mazaheri, Mahta; Dehghani Firozabadi, Ali

Background: MicroRNAs (miRNAs) are implicated in various biological processes including anticoagulation. However, the modulation of miRNA by pharmacological intervention such as warfarin treatment in patients receiving warfarin has not been disclosed yet. The aim of this study work was to assess the effect of warfarin drug on expression level of mir-133a-3p in patients with mechanical heart valve replacement. Methods: In this research, the expression level of miRNA-133a-3p was analyzed in Peripheral Blood Mononuclear Cells (PBMCs) from mechanical valve replacement patients who had received warfarin for at least 3 months continuously. Quantitative RT-PCR method was used for this assay. Results: Our findings indicated a significant diffrence between the rate of miR-133a-3p expression in individuals receiving warfarin and the control group (p<0.01). There was also a statistically significant difference in miR-133a-3p expression in patients with different ages (p<0.05) suggesting that the rate of miR-133a-3p expression in persons receiving warfarin is related to age. However, other variables like warfarin dose, International Normalized Ratio (INR), gender, and Body Mass Index (BMI) were not significantly effective on the miR-133a-3p experssion rate in individuals receving warfarin. Conclusion: Based on our results, it can be concluded that miR-133a-3p is involved in the coagulation pathway. The recent result indicates that warfarin affects the expression of miR-133a. This expression may be potentially important for treatment by anticoagulants. Awareness of the time course of miRNA expression profile can improve efficiency of response to warfarin. PMID:29296264

Risk of Intracranial Hemorrhage From Statin Use in Asians: A Nationwide Cohort Study.

PubMed

Chang, Chia-Hsuin; Lin, Chin-Hsien; Caffrey, James L; Lee, Yen-Chieh; Liu, Ying-Chun; Lin, Jou-Wei; Lai, Mei-Shu

2015-06-09

Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a previous history of stroke. Patients initiating statin therapy between 2005 and 2009 without a previous history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (International Classification of Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1 096 547 statin initiators with an average follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval spanning 1.00 (0.94-1.19). Similar nonsignificant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted hazard ratio 1.36 [1.11-1.67]). In general, no association was observed between cumulative statin use and the risk of ICH among subjects without a previous history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution. © 2015 American Heart Association, Inc.

Imaging of Hemorrhagic Stroke.

PubMed

Hakimi, Ryan; Garg, Ankur

2016-10-01

Hemorrhagic stroke comprises approximately 15% to 20% of all strokes. This article provides readers with an understanding of the indications and significance of various neuroimaging techniques available for patients presenting with hemorrhagic strokes of distinct causes. The most common initial neuroimaging study is a noncontrast head CT, which allows for the identification of hemorrhage. Once an intracranial hemorrhage has been identified, the pattern of blood and the patient's medical history, neurologic examination, and laboratory studies lead the practitioner to pursue further neuroimaging studies to guide the medical, surgical, and interventional management. Given that hemorrhagic stroke constitutes a heterogeneous collection of diagnoses, the subsequent neuroimaging pathway necessary to better evaluate and care for these patients is variable based on the etiology.With an increasing incidence and prevalence of atrial fibrillation associated with the aging population and the introduction of three new direct factor Xa inhibitors and one direct thrombin inhibitor to complement vitamin K antagonists, oral anticoagulant use continues to increase. Patients on oral anticoagulants have a sevenfold to tenfold increased risk for intracerebral hemorrhage (ICH). Furthermore, patients who have an ICH associated with oral anticoagulant use have a higher mortality rate than those with primary ICH. Despite the reduced incidence of hypertension-related ICH over the past decade, it is expected that the incidence of ICH will continue to increase. Neuroimaging studies are integral to the identification of hemorrhagic stroke, determination of the underlying etiology, prevention of hematoma expansion, treatment of acute complications, and treatment of the underlying etiology, if indicated. Neuroimaging is essential for prognostication and thus directly impacts patient care.

Warfarin-related recurrent knee haemarthrosis treated with arterial embolisation and intra-articular injection of tranexamic acid

PubMed Central

Kunugiza, Yasuo; Nakamura, Yoshiharu; Mikami, Koji; Suzuki, Shozo

2015-01-01

Haemarthrosis is an uncommon complication of anticoagulation therapy. Tranexamic acid (TXA) has a high clinical value for the treatment of bleeding due to fibrinolysis. We describe a case of a 61-year-old woman with a mechanical heart valve who presented with warfarin-related recurrent haemarthrosis of her right knee, which recurred after transarterial embolisation. Intra-articular injection of TXA led to a cessation of haemarthrosis without any adverse event for 1 year. Intra-articular injection of TXA may be an effective treatment for warfarin-related haemarthrosis. PMID:26142391

[Enantioselective determinination of R-warfarin/S-warfarin in human plasma using liquid chromatography-tandem mass spectrometry and its application in a drug-drug interaction study].

PubMed

Jin, Shu; Zhang, Yi-Fan; Chen, Xiao-Yan; Liu, Ke; Zhong, Da-Fang

2012-01-01

To study the drug-drug interaction of morinidazole and warfarin and its application, a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of R-warfarin/S-warfarin in human plasma. In a random, two-period crossover study, 12 healthy volunteers received a single oral dose of 5 mg racemic warfarin in the absence and presence of morinidazole. Blood samples were collected according to a pre-designed time schedule. R-warfarin, S-warfarin and methyclothiazide were extracted with ethylether : methylenechloride (3 : 2), then separated on a Astec Chirobiotic V (150 mm x 4.6 mm ID, 5 microm) column using 5 mmol x L(-1) ammonium acetate (pH 4.0) - acetonitrile as mobile phase at a flow-rate of 1.5 mL x min(-1). The mobile phase was splitted and 0.5 mL x min(-1) was introduced into MS. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM). The resolution of warfarin enantiomers is 1.56. The linear calibration curves for R-warfarin and S-warfarin both were obtained in the concentration range of 5 - 1 000 ng x mL(-1). Intra- and inter-day relative standard deviation (RSD) for R-warfarin and S-warfarin over the entire concentration range across three validation runs was both less than 10%, and relative error (RE) ranged from -4.9% to 0.7%, separately. The method herein described is effective and convenient, and suitable for the study of metabolic interaction between morinidazole and warfarin. The results showed that coadministration of warfarin with morinidazole did not affect the pharmacokinetics of either R-warfarin or S-warfarin.

Long-term outcome in elderly patients after operation for traumatic intracranial hemorrhage.

PubMed

Cipolle, Mark D; Geffe, Kevin; Getchell, John; Reed, James F; Fulda, Gerard; Sugarman, Michael; Tinkoff, Glen H

2014-08-01

This study examined outcomes in elderly TBI patients who underwent a cranial operation. We identified TBI patients > or = 65 who underwent a cranial operation from January 1, 2004 to December 31, 2008. Data collected included: age, admission GCS, mechanism of injury, ISS, Head AIS, type of operation, hemorrhage acuity, time to operation, pre-hospital warfarin or clopidogrel, and in-hospital death. Survivors were contacted by phone to determine an Extended Glasgow Outcome Score (GOSE). A favorable outcome was defined as having a GOSE of > or = 5 at follow-up, an unfavorable outcome was defined as: in-hospital death, death within one year of injury, and a GOSE < 5 at follow-up. Chi-square and student's t-test were used. One hundred sixty-four elderly TBI patients underwent cranial surgery. Mean age was 79.2 +/- 7.6 years. Most patients: had a ground level fall (86.0%), suffered a subdural hematoma (95.1%), and underwent craniotomy (89.0%). Twenty-eight percent died in the hospital and another 20.1% died within one year. Fifty-six patients were eligible for a GOSE interview of these: 17 were lost to follow-up, seven refused the GOSE interview, 22 had a GOSE > or = 5, and ten had a GOSE < 5. Mean follow-up was 42.6 +/- 14.9 months. Of all the factors analyzed, only older age was associated with an unfavorable outcome. While age was associated with outcome, we were unable to demonstrate any other early factors that were associated with long-term functional outcome in elderly patients that underwent a cranial operation for TBI.

Use of warfarin in long-term care: a systematic review

PubMed Central

2012-01-01

Background The use of warfarin in older patients requires special consideration because of concerns with comorbidities, interacting medications, and the risk of bleeding. Several studies have suggested that warfarin may be underused or inconsistently prescribed in long-term care (LTC); no published systematic review has evaluated warfarin use for stroke prevention in this setting. This review was conducted to summarize the body of published original research regarding the use of warfarin in the LTC population. Methods A systematic literature search of the PubMed, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library was conducted from January 1985 to August 2010 to identify studies that reported warfarin use in LTC. Studies were grouped by (1) rates of warfarin use and prescribing patterns, (2) association of resident and institutional characteristics with warfarin prescribing, (3) prescriber attitudes and concerns about warfarin use, (4) warfarin management and monitoring, and (5) warfarin-related adverse events. Summaries of study findings and quality assessments of each study were developed. Results Twenty-two studies met the inclusion criteria for this review. Atrial fibrillation (AF) was the most common indication for warfarin use in LTC and use of warfarin for stroke survivors was common. Rates of warfarin use in AF were low in 5 studies, ranging from 17% to 57%. These usage rates were low even among residents with high stroke risk and low bleeding risk. Scored bleeding risk had no apparent association with warfarin use in AF. In physician surveys, factors associated with not prescribing warfarin included risk of falls, dementia, short life expectancy, and history of bleeding. International normalized ratio was in the target range approximately half of the time. The combined overall rate of warfarin-related adverse events and potential events was 25.5 per 100 resident months on warfarin therapy. Conclusions Among residents with AF

Acute fatal hemorrhage from previously undiagnosed cerebral arteriovenous malformations in children: a single-center experience.

PubMed

Riordan, Coleman P; Orbach, Darren B; Smith, Edward R; Scott, R Michael

2018-06-01

OBJECTIVE The most significant adverse outcome of intracranial hemorrhage from an arteriovenous malformation (AVM) is death. This study reviews a single-center experience with pediatric AVMs to quantify the incidence and characterize clinical and radiographic factors associated with sudden death from the hemorrhage of previously undiagnosed AVMs in children. METHODS A single-center database review of the period from 2006 to 2017 identified all patients with a first-time intracranial hemorrhage from a previously undiagnosed AVM. Clinical and radiographic data were collected and compared between patients who survived to hospital discharge and those who died at presentation. RESULTS A total of 57 patients (average age 10.8 years, range 0.1-19 years) presented with first-time intracranial hemorrhage from a previously undiagnosed AVM during the study period. Of this group, 7/57 (12%) patients (average age 11.5 years, range 6-16 years) suffered hemorrhages that led directly to their deaths. Compared to the cohort of patients who survived their hemorrhage, patients who died were 4 times more likely to have an AVM in the posterior fossa. No clear pattern of antecedent triggering activity (sports, trauma, etc.) was identified, and 3/7 (43%) experienced cardiac arrest in the prehospital setting. Surviving patients were ultimately treated with resection of the AVM in 42/50 (84%) of cases. CONCLUSIONS Children who present with hemorrhage from a previously undiagnosed intracranial AVM had a 12% chance of sudden death in our single-institution series of pediatric cerebrovascular cases. Clinical triggers of hemorrhage are unpredictable, but subsequent radiographic evidence of a posterior fossa AVM was present in 57% of fatal cases, and all fatal cases were in locations with high risk of potential herniation. These data support a proactive, aggressive approach toward definitive treatment of AVMs in children.

Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial.

PubMed

Heran, Balraj S; Allan, G Michael; Green, Lee; Korownyk, Christina; Kolber, Michael; Olivier, Nicole; Flesher, Mary; Garrison, Scott

2016-08-04

Warfarin is an oral anticoagulant medication that disrupts the liver's production of clotting factors. While this medication is highly effective for the prevention of thromboembolic events, it also has a narrow therapeutic range and a vulnerability to interactions with other drugs and vitamin K-containing foods. Warfarin is commonly ingested at dinnertime, the same time of day that dietary vitamin K consumption (found largely in green leafy vegetables) is most variable. While the long half-life of warfarin might make this irrelevant, the ultra short half-life of vitamin K and the possibility of a hepatic first-pass effect for warfarin make it worth evaluating whether morning ingestion of warfarin, when vitamin K levels are consistently low, leads to greater stability of its anticoagulant effect. An examination of the timing of administration on the effectiveness of warfarin has never before been conducted. This is a 7-month Prospective Randomized Open Blinded End-point (PROBE) study in which established evening warfarin users (primary care managed Canadian outpatients in the provinces of British Columbia and Alberta) will be randomized to either switch to morning ingestion of warfarin (the intervention) or to continue with evening use (the control). The primary outcome is the percent change in the proportion of time spent outside the therapeutic range of the international normalized ratio (INR) blood test. Secondary outcomes include change in proportion of time spent within the therapeutic INR range (TTR), percentage of patients with TTR >75 %, percentage of patients with TTR <60 %, and major warfarin-related cardiovascular events (including all-cause mortality, hospitalization for stroke, hospitalization for GI bleeding, and deep venous thrombosis/pulmonary embolism). We will also compare whether day-to-day variability in the consumption of high vitamin K-containing foods at baseline affects the baseline TTR in this cohort of evening warfarin users. This study

Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model

PubMed Central

Koskimäki, Janne; Tarkia, Miikka; Ahtola-Sätilä, Tuula; Saloranta, Lasse; Laakso, Aki; Frantzén, Janek

2015-01-01

Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant. PMID:25685803

Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention?

PubMed

Kuo, Ling; Chao, Tze-Fan; Liu, Chia-Jen; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Lip, Gregory Y H; Chen, Shih-Ann

2017-06-23

Patients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation. This study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ≥20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHA 2 DS 2 -VASc score ≥2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, P =0.046) and intracranial hemorrhage (hazard ratio=1.20, P =0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88-1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58-0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy. For atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial.

PubMed

Wallentin, Lars; Yusuf, Salim; Ezekowitz, Michael D; Alings, Marco; Flather, Marcus; Franzosi, Maria Grazia; Pais, Prem; Dans, Antonio; Eikelboom, John; Oldgren, Jonas; Pogue, Janice; Reilly, Paul A; Yang, Sean; Connolly, Stuart J

2010-09-18

Effectiveness and safety of warfarin is associated with the time in therapeutic range (TTR) with an international normalised ratio (INR) of 2·0-3·0. In the Randomised Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, dabigatran versus warfarin reduced both stroke and haemorrhage. We aimed to investigate the primary and secondary outcomes of the RE-LY trial in relation to each centre's mean TTR (cTTR) in the warfarin population. In the RE-LY trial, 18 113 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to INR 2·0-3·0. Median follow-up was 2·0 years. For 18 024 patients at 906 sites, the cTTR was estimated by averaging TTR for individual warfarin-treated patients calculated by the Rosendaal method. We compared the outcomes of RE-LY across the three treatment groups within four groups defined by the quartiles of cTTR. RE-LY is registered with ClinicalTrials.gov, number NCT00262600. The quartiles of cTTR for patients in the warfarin group were: less than 57·1%, 57·1-65·5%, 65·5-72·6%, and greater than 72·6%. There were no significant interactions between cTTR and prevention of stroke and systemic embolism with either 110 mg dabigatran (interaction p=0·89) or 150 mg dabigatran (interaction p=0·20) versus warfarin. Neither were any significant interactions recorded with cTTR with regards to intracranial bleeding with 110 mg dabigatran (interaction p=0·71) or 150 mg dabigatran (interaction p=0·89) versus warfarin. There was a significant interaction between cTTR and major bleeding when comparing 150 mg dabigatran with warfarin (interaction p=0·03), with less bleeding events at lower cTTR but similar events at higher cTTR, whereas rates of major bleeding were lower with 110 mg dabigatran than with warfarin irrespective of cTTR. There were significant interactions between cTTR and effects of both 110 mg and 150 mg dabigatran versus warfarin on the composite of all

Intravascular ultrasound for intracranial angioplasty and stent placement: technical case report.

PubMed

Wehman, J Christopher; Holmes, David R; Hanel, Ricardo A; Levy, Elad I; Hopkins, L Nelson

2006-10-01

Intravascular ultrasound (IVUS) imaging has been used extensively in coronary artery interventions and has provided invaluable information for the understanding and treatment of coronary arterial disease. We present here the first description, to our knowledge, of IVUS-guided intracranial arterial interventions in the clinical setting. Two patients underwent intracranial angioplasty and stent placement with the assistance of IVUS for the evaluation of their lesions. One patient underwent stenting to treat an occlusive dissection of the left internal carotid artery that occurred during arteriovenous malformation embolization. Another patient underwent angioplasty and stenting for high-grade restenosis of a basilar artery atherosclerotic lesion. Both patients underwent successful revascularization procedures. The patient with the dissection had a small intraventricular and parenchymal hemorrhage documented by computed tomography 4 hours after treatment, but did not develop hydrocephalus or further hemorrhage. Both patients did well clinically and had no permanent neurological deficits. IVUS provided important information in terms of lesion evaluation, stent selection, and stent placement in each case. IVUS of the intracranial circulation may assist the performance of intracranial angioplasty and stenting. It provides useful information that can affect clinical decisions. It may prove to be a valuable tool in clinical use and enhance our understanding of vascular disease of the intracranial circulation, as it has in the coronary circulation.

Determinants and Prognostic Significance of Hematoma Sedimentation Levels in Acute Intracerebral Hemorrhage.

PubMed

Sato, Shoichiro; Delcourt, Candice; Zhang, Shihong; Arima, Hisatomi; Heeley, Emma; Zheng, Danni; Al-Shahi Salman, Rustam; Stapf, Christian; Tzourio, Christophe; Robinson, Thompson; Lindley, Richard I; Chalmers, John; Anderson, Craig S

2016-01-01

This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH. © 2015 S. Karger AG, Basel.

Nontraumatic Retroperitoneal Hematoma After Warfarin Administration: Fatal Case Report and Review of the Literature.

PubMed

Hosseini, Marzieh; Hosseinzadeh, Amin; Raufian, Kasra; Hedjazi, Arya

2015-12-01

Spontaneous retroperitoneal hematoma after warfarin therapy is an extremely rare event. Here, we report a 25-year-old man who was brought in to the emergency service with confusion. On arrival, the patient had hypotension, tachycardia, tachypnea, low-grade fever, and Glasgow Coma Scale score of 12. Abdominal examination revealed distention and mild tenderness in the right upper quadrant of the abdomen. The patient had a history of aortic valve replacement surgery and was on warfarin treatment at an international normalized ratio of 2.4. Our patient progressed to cardiorespiratory arrest. The resuscitation was initiated promptly. Despite all resuscitation measures, including transfusion and administration of high doses of catecholamine, the patient died of hypovolemic shock 3 hours after admission. At autopsy, the external surface of the abdominal great vessels (descending aorta and mesenteric vessels) showed scattered petechial hemorrhages without any visible site of perforation. After comprehensive exploration of the abdomen, no evidence of traumatic event was identified and the cause of internal blood loss was noted as warfarin adverse effect.

Focal Low and Global High Permeability Predict the Possibility, Risk, and Location of Hemorrhagic Transformation following Intra-Arterial Thrombolysis Therapy in Acute Stroke.

PubMed

Li, Y; Xia, Y; Chen, H; Liu, N; Jackson, A; Wintermark, M; Zhang, Y; Hu, J; Wu, B; Zhang, W; Tu, J; Su, Z; Zhu, G

2017-09-01

The contrast volume transfer coefficient ( K trans ), which reflects blood-brain barrier permeability, is influenced by circulation and measurement conditions. We hypothesized that focal low BBB permeability values can predict the spatial distribution of hemorrhagic transformation and global high BBB permeability values can predict the likelihood of hemorrhagic transformation. We retrospectively enrolled 106 patients with hemispheric stroke who received intra-arterial thrombolytic treatment. K trans maps were obtained with first-pass perfusion CT data. The K trans values at the region level, obtained with the Alberta Stroke Program Early CT Score system, were compared to determine the differences between the hemorrhagic transformation and nonhemorrhagic transformation regions. The K trans values of the whole ischemic region based on baseline perfusion CT were obtained as a variable to hemorrhagic transformation possibility at the global level. Forty-eight (45.3%) patients had hemorrhagic transformation, and 21 (19.8%) had symptomatic intracranial hemorrhage. At the region level, there were 82 ROIs with hemorrhagic transformation and parenchymal hemorrhage with a mean K trans , 0.5 ± 0.5/min, which was significantly lower than that in the nonhemorrhagic transformation regions ( P < .01). The mean K trans value of 615 nonhemorrhagic transformation ROIs was 0.7 ± 0.6/min. At the global level, there was a significant difference ( P = .01) between the mean K trans values of patients with symptomatic intracranial hemorrhage (1.3 ± 0.9) and those without symptomatic intracranial hemorrhage (0.8 ± 0.4). Only a high K trans value at the global level could predict the occurrence of symptomatic intracranial hemorrhage ( P < .01; OR = 5.04; 95% CI, 2.01-12.65). Global high K trans values can predict the likelihood of hemorrhagic transformation or symptomatic intracranial hemorrhage at the patient level, whereas focal low K trans values can predict the spatial distributions

The Intracranial Volume Pressure Response in Increased Intracranial Pressure Patients: Clinical Significance of the Volume Pressure Indicator.

PubMed

Lai, Hung-Yi; Lee, Ching-Hsin; Lee, Ching-Yi

2016-01-01

For patients suffering from primary brain injury, monitoring intracranial pressure alone is not enough to reflect the dynamic intracranial condition. In our previous study, a segment of the pressure-volume curve can be expressed by the parabolic regression model with single indicator "a". The aim of this study is to evaluate if the indicator "a" can reflect intracranial conditions. Patients with traumatic brain injury, spontaneous intracranial hemorrhage, and/or hydrocephalus who had external ventricular drainage from January 2009 to February 2010 were included. The successive volume pressure response values were obtained by successive drainage of cerebral spinal fluid from intracranial pressure 20-25 mm Hg to 10 mm Hg. The relationship between withdrawn cerebral spinal fluid volume and intracranial pressure was analyzed by the parabolic regression model with single parameter "a". The overall mean for indicator "a" was 0.422 ± 0.046. The mean of "a" in hydrocephalus was 0.173 ± 0.024 and in severe intracranial mass with slender ventricle, it was 0.663 ± 0.062. The two extreme intracranial conditions had a statistical significant difference (p<0.001). The indicator "a" of a pressure-volume curve can reflect the dynamic intracranial condition and is comparable in different situations. A significantly larger indicator "a" with increased intracranial pressure is always observed in severe intracranial mass lesions with cerebral edema. A significantly smaller indicator "a" with increased intracranial pressure is observed in hydrocephalus. Brain computed tomography should be performed early if a rapid elevation of indicator "a" is detected, as it can reveal some ongoing intracranial pathology prior to clinical deterioration. Increased intracranial pressure was frequently observed in patients with intracranial pathology. The progression can be differentiated using the pattern of the volume pressure indicator.

The Intracranial Volume Pressure Response in Increased Intracranial Pressure Patients: Clinical Significance of the Volume Pressure Indicator

PubMed Central

2016-01-01

Background For patients suffering from primary brain injury, monitoring intracranial pressure alone is not enough to reflect the dynamic intracranial condition. In our previous study, a segment of the pressure-volume curve can be expressed by the parabolic regression model with single indicator “a”. The aim of this study is to evaluate if the indicator “a” can reflect intracranial conditions. Methods Patients with traumatic brain injury, spontaneous intracranial hemorrhage, and/or hydrocephalus who had external ventricular drainage from January 2009 to February 2010 were included. The successive volume pressure response values were obtained by successive drainage of cerebral spinal fluid from intracranial pressure 20–25 mm Hg to 10 mm Hg. The relationship between withdrawn cerebral spinal fluid volume and intracranial pressure was analyzed by the parabolic regression model with single parameter “a”. Results The overall mean for indicator “a” was 0.422 ± 0.046. The mean of “a” in hydrocephalus was 0.173 ± 0.024 and in severe intracranial mass with slender ventricle, it was 0.663 ± 0.062. The two extreme intracranial conditions had a statistical significant difference (p<0.001). Conclusion The indicator “a” of a pressure-volume curve can reflect the dynamic intracranial condition and is comparable in different situations. A significantly larger indicator “a” with increased intracranial pressure is always observed in severe intracranial mass lesions with cerebral edema. A significantly smaller indicator “a” with increased intracranial pressure is observed in hydrocephalus. Brain computed tomography should be performed early if a rapid elevation of indicator “a” is detected, as it can reveal some ongoing intracranial pathology prior to clinical deterioration. Increased intracranial pressure was frequently observed in patients with intracranial pathology. The progression can be differentiated using the pattern of the volume

Warfarin-induced Venous Limb Gangrene

PubMed Central

Grim Hostetler, Sarah; Sopkovich, Jennifer; Dean, Steven

2012-01-01

Warfarin is a commonly used anticoagulant that has been associated with several significant cutaneous side effects, most notably warfarin-induced skin necrosis. A lesser known adverse reaction to warfarin is warfarin-induced venous limb gangrene. Both cutaneous adverse effects share the same pathophysiology, but are clinically quite different. The majority of cases of warfarin-induced venous limb gangrene has been in patients with cancer or heparin-induced thrombocytopenia. However, other hypercoagulable disease states, such as the antiphospholipid antibody syndrome, can be associated with venous limb gangrene. In order to increase recognition of this important condition, the authors report a case of warfarin-induced venous limb gangrene in a patient with presumed antiphospholipid antibody syndrome and review the literature on warfarin-induced venous limb gangrene. PMID:23198012

Regularization design for high-quality cone-beam CT of intracranial hemorrhage using statistical reconstruction

NASA Astrophysics Data System (ADS)

Dang, H.; Stayman, J. W.; Xu, J.; Sisniega, A.; Zbijewski, W.; Wang, X.; Foos, D. H.; Aygun, N.; Koliatsos, V. E.; Siewerdsen, J. H.

2016-03-01

Intracranial hemorrhage (ICH) is associated with pathologies such as hemorrhagic stroke and traumatic brain injury. Multi-detector CT is the current front-line imaging modality for detecting ICH (fresh blood contrast 40-80 HU, down to 1 mm). Flat-panel detector (FPD) cone-beam CT (CBCT) offers a potential alternative with a smaller scanner footprint, greater portability, and lower cost potentially well suited to deployment at the point of care outside standard diagnostic radiology and emergency room settings. Previous studies have suggested reliable detection of ICH down to 3 mm in CBCT using high-fidelity artifact correction and penalized weighted least-squared (PWLS) image reconstruction with a post-artifact-correction noise model. However, ICH reconstructed by traditional image regularization exhibits nonuniform spatial resolution and noise due to interaction between the statistical weights and regularization, which potentially degrades the detectability of ICH. In this work, we propose three regularization methods designed to overcome these challenges. The first two compute spatially varying certainty for uniform spatial resolution and noise, respectively. The third computes spatially varying regularization strength to achieve uniform "detectability," combining both spatial resolution and noise in a manner analogous to a delta-function detection task. Experiments were conducted on a CBCT test-bench, and image quality was evaluated for simulated ICH in different regions of an anthropomorphic head. The first two methods improved the uniformity in spatial resolution and noise compared to traditional regularization. The third exhibited the highest uniformity in detectability among all methods and best overall image quality. The proposed regularization provides a valuable means to achieve uniform image quality in CBCT of ICH and is being incorporated in a CBCT prototype for ICH imaging.

Delayed Vasospasm after Aneurysmal Subarachnoid Hemorrhage in Behcet Syndrome.

PubMed

Kim, Jun Hak; Lee, Si-Un; Huh, Choonwoong; Oh, Chang Wan; Bang, Jae Seung; Kim, Tackeun

2016-03-01

A man visited the emergency room with a headache. Brain computed tomography showed aneurysmal subarachnoid hemorrhage (SAH) and multiple aneurysms. After aneurysm clipping surgery, the patient was discharged. After 5 days, he was admitted to the hospital with skin ulceration and was diagnosed with Behcet syndrome. An angiogram taken 7 weeks after aneurysmal SAH showed intracranial vasospasm. Because inflammation in Behcet syndrome may aggravate intracranial vasospasm, intracranial vasospasm after aneurysmal SAH in Behcet syndrome should be monitored for longer compared to general aneurysmal SAH.

Delayed Vasospasm after Aneurysmal Subarachnoid Hemorrhage in Behcet Syndrome

PubMed Central

Kim, Jun Hak; Lee, Si-Un; Huh, Choonwoong; Oh, Chang Wan; Bang, Jae Seung

2016-01-01

A man visited the emergency room with a headache. Brain computed tomography showed aneurysmal subarachnoid hemorrhage (SAH) and multiple aneurysms. After aneurysm clipping surgery, the patient was discharged. After 5 days, he was admitted to the hospital with skin ulceration and was diagnosed with Behcet syndrome. An angiogram taken 7 weeks after aneurysmal SAH showed intracranial vasospasm. Because inflammation in Behcet syndrome may aggravate intracranial vasospasm, intracranial vasospasm after aneurysmal SAH in Behcet syndrome should be monitored for longer compared to general aneurysmal SAH. PMID:27114963

Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement.

PubMed

Wang, Jian-tang; Dong, Ming-feng; Song, Guang-min; Ma, Zeng-shan; Ma, Sheng-jun

2014-12-01

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Intracranial hemorrhage after blunt head trauma in children with bleeding disorders.

PubMed

Lee, Lois K; Dayan, Peter S; Gerardi, Michael J; Borgialli, Dominic A; Badawy, Mohamed K; Callahan, James M; Lillis, Kathleen A; Stanley, Rachel M; Gorelick, Marc H; Dong, Li; Zuspan, Sally Jo; Holmes, James F; Kuppermann, Nathan

2011-06-01

To determine computerized tomography (CT) use and prevalence of traumatic intracranial hemorrhage (ICH) in children with and without congenital and acquired bleeding disorders. We compared CT use and ICH prevalence in children with and without bleeding disorders in a multicenter cohort study of 43 904 children <18 years old with blunt head trauma evaluated in 25 emergency departments. A total of 230 children had bleeding disorders; all had Glasgow Coma Scale (GCS) scores of 14 to 15. These children had higher CT rates than children without bleeding disorders and GCS scores of 14 to 15 (risk ratio, 2.29; 95% CI, 2.15 to 2.44). Of the children who underwent imaging with CT, 2 of 186 children with bleeding disorders had ICH (1.1%; 95% CI, 0.1 to 3.8) , compared with 655 of 14 969 children without bleeding disorders (4.4%; 95% CI, 4.1-4.7; rate ratio, 0.25; 95% CI, 0.06 to 0.98). Both children with bleeding disorders and ICHs had symptoms; none of the children required neurosurgery. In children with head trauma, CTs are obtained twice as often in children with bleeding disorders, although ICHs occurred in only 1.1%, and these patients had symptoms. Routine CT imaging after head trauma may not be required in children without symptoms who have congenital and acquired bleeding disorders. Copyright © 2011 Mosby, Inc. All rights reserved.

Thrombolytic therapy for massive pulmonary embolism in a patient with a known intracranial tumor.

PubMed

Han, Steve; Chaya, Craig; Hoo, Guy W Soo

2006-01-01

The objective was to describe and review the use of thrombolytic therapy in a patient with an intracranial tumor and massive pulmonary embolism. This is the first reported case of a patient with a known glioblastoma multiforme and massive pulmonary embolism who was successfully treated with alteplase. Pulmonary embolism was demonstrated by a ventilation-perfusion scan and transthoracic echocardiogram with repeat studies demonstrating resolution of the thromboembolism and reperfusion of pulmonary vasculature. A review of the literature revealed that the incidence of intracranial hemorrhage with thrombolysis is <3% and compares favorably with the much higher mortality rate of 25% to >/=50% in patients with hemodynamically unstable pulmonary emboli. The benefit of thrombolysis may outweigh the risks of intracranial hemorrhage in these patients, and careful consideration for its use in these patients is warranted.

Comparing the Cost Effectiveness of Non-vitamin K Antagonist Oral Anticoagulants with Well-Managed Warfarin for Stroke Prevention in Atrial Fibrillation Patients at High Risk of Bleeding.

PubMed

Hospodar, Alexa R; Smith, Kenneth J; Zhang, Yuting; Hernandez, Inmaculada

2018-05-09

Several studies have compared the cost effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin using results from clinical trials evaluating NOACs. However, the time in therapeutic range (TTR) of warfarin groups ranged across clinical trials, and all were below the therapeutic goal of 70%. We compared the cost effectiveness of edoxaban 60 mg, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, rivaroxaban 20 mg, and well-managed warfarin with a TTR of 70% in preventing stroke among patients with atrial fibrillation at high risk of bleeding. For the six treatments, we used a Markov state-transition model to quantify lifetime costs in $US and effectiveness in quality-adjusted life-years (QALYs). We simulated relative risk ratios of clinical events with each NOAC versus warfarin with a TTR of 70% using published regression models that predict how the incidence of thrombotic or hemorrhagic events changes for each unit change in TTR. We re-ran our analysis for two other estimates of TTR: 65 and 75%. Treatment with edoxaban 60 mg cost $US127,520/QALY gained compared with warfarin with a TTR of 70% and cost $US41,860/QALY gained compared with warfarin with a TTR of 65%. However, warfarin with a TTR of 75% was more effective and less expensive than all NOACs. For three levels of TTR, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, and rivaroxaban 20 mg were dominated strategies. The comparative cost effectiveness of edoxaban and warfarin is highly sensitive to TTR. At the $US100,000/QALY willingness-to-pay threshold, our results suggest that warfarin is the most cost-effective treatment for patients who can achieve a TTR of 70%.

Antioxidant status and alpha1-antiproteinase activity in subarachnoid hemorrhage patients.

PubMed

Marzatico, F; Gaetani, P; Tartara, F; Bertorelli, L; Feletti, F; Adinolfi, D; Tancioni, F; Rodriguez y Baena, R

1998-01-01

The antiproteasic activity of alpha1-antitrypsin (alpha1-AT) is reduced in cases of subarachnoid hemorrhage from ruptured intracranial aneurysm and particularly in patients currently smoking; alpha1-AT is very sensitive to oxidant agents. About 50% of physiological anti-oxidant systemic capacity is represented by Vitamin A, E and C. Plasmatic amounts of alpha1-AT, alpha1-AT Collagenase Inhibitory Capacity (CIC) and levels of vitamin A, vitamin E and vitamin C were analyzed in 39 patients, 26 women and 13 men, operated for intracranial aneurysm; 11 patients with unruptured intracranial aneurysm were considered as controls while 28 patients were included within 12 hours from subarachnoid hemorrhage (SAH). Plasmatic levels of vitamin A and vitamin E were significantly lower (p=0.038 and p=0.0158) in patients suffering SAH than in controls, while no statistically significant differences were found in mean plasmatic vitamin C levels. Level of alpha1-AT was not statistically different in controls and in patients with SAH; however, the activity of alpha1-AT, evaluated as CIC, is significantly reduced in patients with SAH (p=0.019). We have observed that systemic plasmatic levels of vitamins did not significantly differ in relation to smoking habit. Vitamin A and E represent an important defensive system against free radicals reactions. Particularly, vitamin E acts as an antioxidant by scavenging free-radicals. A reduced anti-oxidant status might be related to the higher sensibility of alpha1-AT to oxidative reactions and the activity of alpha1-AT is dependent on the antioxidant capacity of liposoluble vitamins. We can speculate that an acute systemic oxidative stress condition might influence the rupture of intracranial aneurysms.

Monitoring of Intracranial Pressure in Patients with Traumatic Brain Injury

PubMed Central

Hawthorne, Christopher; Piper, Ian

2014-01-01

Since Monro published his observations on the nature of the contents of the intracranial space in 1783, there has been investigation of the unique relationship between the contents of the skull and the intracranial pressure (ICP). This is particularly true following traumatic brain injury (TBI), where it is clear that elevated ICP due to the underlying pathological processes is associated with a poorer clinical outcome. Consequently, there is considerable interest in monitoring and manipulating ICP in patients with TBI. The two techniques most commonly used in clinical practice to monitor ICP are via an intraventricular or intraparenchymal catheter with a microtransducer system. Both of these techniques are invasive and are thus associated with complications such as hemorrhage and infection. For this reason, significant research effort has been directed toward development of a non-invasive method to measure ICP. The principle aims of ICP monitoring in TBI are to allow early detection of secondary hemorrhage and to guide therapies that limit intracranial hypertension (ICH) and optimize cerebral perfusion. However, information from the ICP value and the ICP waveform can also be used to assess the intracranial volume–pressure relationship, estimate cerebrovascular pressure reactivity, and attempt to forecast future episodes of ICH. PMID:25076934

Determination of total and unbound warfarin and warfarin alcohols in human plasma by high performance liquid chromatography with fluorescence detection.

PubMed

Lomonaco, Tommaso; Ghimenti, Silvia; Piga, Isabella; Onor, Massimo; Melai, Bernardo; Fuoco, Roger; Di Francesco, Fabio

2013-11-01

Two analytical procedures are presented for the determination of the total content and unbound fraction of both warfarin and warfarin alcohols in human plasma. Chromatographic separation was carried out in isocratic conditions at 25°C on a C-18 reversed-phase column with a mobile phase consisting of a 70% buffer phosphate 25mM at pH=7, 25% methanol and 5% acetonitrile at a flow rate of 1.2mL/min. Fluorescence detection was performed at 390nm (excitation wavelength 310nm). Neither method showed any detectable interference or matrix effect. Inter-day recovery of the total warfarin and warfarin alcohols at a concentration level of 1000ng/mL was 89±3% and 73±3%, respectively, whereas for their unbound fraction (at a concentration level of 10ng/mL) was 66±8% and 90±7%, respectively. The intra- and inter-day precision (assessed as relative standard deviation) was <10% for both methods. The limits of detection were 0.4 and 0.2ng/mL for warfarin and warfarin alcohols, respectively. The methods were successfully applied to a pooled plasma sample obtained from 69 patients undergoing warfarin therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Therapeutic implications of coexisting severe pulmonary hemorrhage and pulmonary emboli in a case of Wegener granulomatosis.

PubMed

Dreyer, Gavin; Fan, Stanley

2009-05-01

Wegener granulomatosis classically involves the renal, respiratory, and ear, nose, and throat systems. Pulmonary hemorrhage is recognized as a severe respiratory complication. Untreated, the mortality rate approaches 90% at 2 years. We describe a case of Wegener granulomatosis with coexistent severe lung hemorrhage and pulmonary and deep vein thromboses. A 31-year-old man presented with features of vasculitis, including epistaxis, fever, and acute kidney injury with an increased serum creatinine level (3.27 mg/dL). Kidney biopsy confirmed pauci-immune crescentic glomerulonephritis, and antineutrophil cytoplasmic antibody showing a cytoplasmic staining pattern was strongly positive. Standard immunosuppression therapy (prednisolone and cyclophosphamide) was started. Eleven days later, the patient developed sudden dyspnea. A computed tomographic pulmonary angiogram showed pulmonary emboli, and ultrasound of the limbs showed ileofemoral thrombi bilaterally. Subcutaneous enoxaparin and warfarin therapy was started, but 8 days later, the patient had a massive pulmonary hemorrhage. Anticoagulation therapy was stopped, and plasma exchange was started to prevent further life-threatening hemorrhage. An inferior vena cava filter was inserted to prevent further pulmonary emboli during the period when anticoagulation was withheld. Kidney function improved, and pulmonary hemorrhage resolved after 5 plasma exchanges. Reintroduction of intravenous heparin and subsequently warfarin caused no further bleeding. We discuss the difficult management dilemma this combination of disease manifestations presents and review the current literature.

Azathioprine-Induced Warfarin Resistance

PubMed Central

Vazquez, Sara R; Rondina, Matthew T; Pendleton, Robert C

2011-01-01

OBJECTIVE To describe a case of azathioprine-induced warfarin resistance, present a literature review on warfarin–azathioprine interactions, and provide recommendations on appropriate management of this clinically significant interaction. CASE SUMMARY A 29-year-old female with Cogan’s syndrome experienced thrombosis of the left internal carotid artery. She was treated with an average weekly warfarin dose of 39 mg (5.5 mg daily) prior to beginning azathioprine therapy. Three weeks following initiation of azathioprine 150 mg daily, the international normalized ratio (INR) decreased from 1.9 (prior to the medication change) to 1.0 without any change in the warfarin dose or other relevant factors. Over several weeks, the patient’s warfarin dose was titrated up to 112 mg weekly (16 mg daily) to achieve an INR of 2.5 (a 188%, or 2.9-fold dose increase). Because of elevated liver enzyme levels, the azathioprine dosage was decreased to 100 mg daily. Within 2 weeks following that decrease, warfarin requirements decreased to 105 mg weekly (15 mg daily). DISCUSSION Azathioprine was the probable causative agent of warfarin resistance according to the Naranjo probability scale, and a possible causative agent according to the Drug Interaction Probability Scale. A literature search (PubMed, 1966–December 2007) revealed 8 case reports of this drug interaction and 2 cases involving a similar effect with 6-mercaptopurine, the active metabolite of azathioprine. The exact mechanism of the interaction remains unknown. Previously published case reports point to a rapid onset and offset of the warfarin–azathioprine interaction and a dose-dependent increase of at least 2.5-fold in warfarin dose requirement with the initiation of azathioprine 75–200 mg daily. CONCLUSIONS This case report and several others point toward azathioprine as a clinically significant inducer of warfarin resistance. Providers should anticipate the need for higher warfarin doses, warfarin dose adjustment

Low free triiodothyronine levels are related to symptomatic intracranial hemorrhage and poor functional outcomes after intravenous thrombolysis in acute ischemic stroke patients.

PubMed

Liu, Junfeng; Wang, Deren; Xiong, Yao; Yuan, Ruozhen; Tao, Wendan; Liu, Ming

2016-05-01

Low free triiodothyronine (fT3) levels have been associated with increased mortality and poor functional outcomes in patients with stroke. However, the research of relationship between fT3 levels and acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT) is scarce. We aimed to investigate the association of fT3 levels with symptomatic intracranial hemorrhage (sICH) and functional outcomes at discharge in AIS patients with IVT. Patients with AIS admitted to West China hospital, Sichuan University, who had underwent IVT treatment, were consecutively and retrospectively included. Demographic and clinical information were collected and analyzed according to the levels of fT3. We used logistic regression analysis to estimate the multivariable adjusted association of fT3 levels and post-IVT sICH, and functional outcomes at discharge. Among the 46 patients (26 males; mean age, 63.6 years) in the final analysis, 17 patients (37.0%) had fT3 levels lower than the reference range. After adjustment for age, gender, and statistically important variables (NIHSS on admission, urea levels and creatinine levels), low fT3 levels were significantly associated with post-IVT sICH (p = 0.01, OR = 0.27, 95% CI 0.10-0.77) and poor functional outcomes at discharge (p = 0.04 OR = 2.58, 95% CI 1.05-6.35). We found that lower free T3 levels are independently related to post-IVT sICH and poor functional outcomes at discharge in AIS patients with IVT, which should be verified and extended in large cohorts in the future.

[The current role of warfarin].

PubMed

Michalcová, Jana; Buliková, Alena; Zavřelová, Jiřina; Prudková, Marie; Penka, Miroslav

Well-managed warfarin therapy remains an important method of anticoagulation in the 21st century, despite the introduction of new antithrombotics into the clinical practice. The main advantages of warfarin are decades of treatment experience, the possibility to monitor its anticoagulant effect using the INR and the last, but not least, the low cost. Currently, approximately 75 % of anticoagulated patients in the Czech Republic are treated with warfarin and warfarin remains the only option for oral anticoagulant therapy in certain clinical conditions (particularly in patients with valvular atrial fibrillation or mechanical heart valves). For physicians across specialties it is still indispensable to master the basics of safe and effective warfarin therapy, including the management of treatment complications.Key words: anticoagulant therapy - INR - thrombosis - warfarin.

Low plasma eicosapentaenoic acid concentration as a possible risk factor for intracerebral hemorrhage.

PubMed

Ikeya, Yoshimori; Fukuyama, Naoto; Mori, Hidezo

2015-03-01

N-3 fatty acids, including eicosapentaenoic acid (EPA), prevent ischemic stroke. The preventive effect has been attributed to an antithrombic effect induced by elevated EPA and reduced arachidonic acid (AA) levels. However, the relationship between intracranial hemorrhage and N-3 fatty acids has not yet been elucidated. In this cross-sectional study, we compared common clinical and lifestyle parameters between 70 patients with intracranial hemorrhages and 66 control subjects. The parameters included blood chemistry data, smoking, alcohol intake, fish consumption, and the incidences of underlying diseases. The comparisons were performed using the Mann-Whitney U test followed by multiple logistic regression analysis. Nonparametric tests revealed that the 70 patients with intracerebral hemorrhages exhibited significantly higher diastolic blood pressures and alcohol intakes and lower body mass indices, high-density lipoprotein (HDL) cholesterol levels, EPA concentrations, EPA/AA ratios, and vegetable consumption compared with the 66 control subjects. A multiple logistic regression analysis revealed that higher diastolic blood pressure and alcohol intake and lower body mass index, HDL cholesterol, EPA/AA ratio, and vegetable consumption were relative risk factors for intracerebral hemorrhage. High HDL cholesterol was a common risk factor in both of the sex-segregated subgroups and the <65-year-old subgroup. However, neither EPA nor the EPA/AA ratio was a risk factor in these subgroups. Eicosapentaenoic acid was relative risk factor only in the ≥65-year-old subgroup. Rather than higher EPA levels, lower EPA concentrations and EPA/AA ratios were found to be risk factors for intracerebral hemorrhage in addition to previously known risk factors such as blood pressure, alcohol consumption, and lifestyle. Copyright © 2015 Elsevier Inc. All rights reserved.

Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation.

PubMed

Yao, Xiaoxi; Abraham, Neena S; Sangaralingham, Lindsey R; Bellolio, M Fernanda; McBane, Robert D; Shah, Nilay D; Noseworthy, Peter A

2016-06-13

The introduction of non-vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin. Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46-0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76-1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72-1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34-0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67-0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90-1.20], P=0.60). All non-vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding. In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial.

PubMed

Halvorsen, Sigrun; Atar, Dan; Yang, Hongqiu; De Caterina, Raffaele; Erol, Cetin; Garcia, David; Granger, Christopher B; Hanna, Michael; Held, Claes; Husted, Steen; Hylek, Elaine M; Jansky, Petr; Lopes, Renato D; Ruzyllo, Witold; Thomas, Laine; Wallentin, Lars

2014-07-21

The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial

PubMed Central

Halvorsen, Sigrun; Atar, Dan; Yang, Hongqiu; De Caterina, Raffaele; Erol, Cetin; Garcia, David; Granger, Christopher B.; Hanna, Michael; Held, Claes; Husted, Steen; Hylek, Elaine M.; Jansky, Petr; Lopes, Renato D.; Ruzyllo, Witold; Thomas, Laine; Wallentin, Lars

2014-01-01

Aims The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. Methods and results A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. Conclusion The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly. PMID:24561548

Warfarin-induced eosinophilic pleurisy.

PubMed

Kuwahara, T; Hamada, M; Inoue, Y; Aono, S; Hiwada, K

1995-08-01

A 51-year-old man was admitted to our hospital because of dry cough and low grade fever with right-sided pleural fluid and blood eosinophilia. Warfarin had been prescribed following coronary artery bypass grafting. After the discontinuation of warfarin the clinical and chest X-ray findings improved; readministration of the drug caused recurrent blood eosinophilia and pleural effusion in the other lung. Since no other specific etiologies for eosinophilia and pleural effusion were determined by extensive evaluation, warfarin seemed to be associated with his illness. This is the first report of warfarin-induced eosinophilic pleurisy.

Warfarin therapy: in need of improvement after all these years

PubMed Central

Kimmel, Stephen E

2010-01-01

Background Warfarin therapy has been used clinically for over 60 years, yet continues to be problematic because of its narrow therapeutic index and large inter-individual variability in patient response. As a result, warfarin is a leading cause of serious medication-related adverse events, and its efficacy is also suboptimal. Objective To review factors that are responsible for variable response to warfarin, including clinical, environmental, and genetic factors, and to explore some possible approaches to improving warfarin therapy. Results Recent efforts have focused on developing dosing algorithms that included genetic information to try to improve warfarin dosing. These dosing algorithms hold promise, but have not been fully validated or tested in rigorous clinical trials. Perhaps equally importantly, adherence to warfarin is a major problem that should be addressed with innovative and cost-effective interventions. Conclusion Additional research is needed to further test whether interventions can be used to improve warfarin dosing and outcomes. PMID:18345947

Acute dysphonia secondary to vocal fold hemorrhage after vardenafil use.

PubMed

Singh, Vikas; Cohen, Seth M; Rousseau, Bernard; Noordzij, J Pieter; Garrett, C Gaelyn; Ossoff, Robert H

2010-06-01

Owing to their vasodilatory effects, the phosphodiesterase-5 inhibitors have become widely used for the treatment of erectile dysfunction. Among the reported adverse events of these agents are epistaxis, variceal bleeding, intracranial hemorrhage, and hemorrhoidal bleeding. We report a case of vocal fold hemorrhage that occurred after vardenafil use in a 31-year-old man who was a professional singer.

Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Goto, Shinya; Zhu, Jun; Liu, Lisheng; Oh, Byung-Hee; Wojdyla, Daniel M; Aylward, Philip; Bahit, M Cecilia; Gersh, Bernard J; Hanna, Michael; Horowitz, John; Lopes, Renato D; Wallentin, Lars; Xavier, Denis; Alexander, John H

2014-09-01

The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non-East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non-East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin in East Asian (HR 0.49, 95% CI 0.35-0.67) than in non-East Asian (HR 0.71, 95% CI 0.63-0.79) patients (interaction P = .03). Numerically higher rates of intracranial bleeding were seen in East Asian patients with warfarin but not with apixaban. Apixaban resulted in similar reductions in stroke or systemic embolism and major bleeding and greater reductions in major or clinically relevant nonmajor bleeding in patients from East Asia. Warfarin is associated with more intracranial bleeding, particularly in patients from East Asia. Copyright © 2014 Mosby, Inc. All rights reserved.

Small Intracranial Aneurysm Treatment Using Target (®) Ultrasoft (™) Coils.

PubMed

Jindal, Gaurav; Miller, Timothy; Iyohe, Moronke; Shivashankar, Ravi; Prasad, Vikram; Gandhi, Dheeraj

2016-06-01

The introduction of small, soft, complex-shaped microcoils has helped facilitate the endovascular treatment of small intracranial aneurysms (IAs) over the last several years. Here, we evaluate the initial safety and efficacy of treating small IAs using only Target(®) Ultrasoft(™) coils. A retrospective review of a prospectively maintained clinical database at a single, high volume, teaching hospital was performed from September 2011 to May 2015. IAs smaller than or equal to 5.0 mm in maximal dimension treated with only Target(®) Ultrasoft(™) coils were included. A total of 50 patients with 50 intracranial aneurysms were included. Subarachnoid hemorrhage from index aneurysm rupture was the indication for treatment in 23 of 50 (46%) cases, and prior subarachnoid hemorrhage (SAH) from another aneurysm was the indication for treatment in eight of 50 (16%) cases. The complete aneurysm occlusion rate was 70% (35/50), the minimal residual aneurysm rate was 14% (7/50), and residual aneurysm rate was 16% (8/50). One intraoperative aneurysm rupture occurred. Three patients died during hospitalization from clinical sequelae of subarachnoid hemorrhage. Follow-up at a mean of 13.6 months demonstrated complete aneurysm occlusion in 75% (30/40) of cases, near complete occlusion in 15% (6/40) of cases, and residual aneurysm in 10% (4/40) of cases, all four of which were retreated. Our initial results using only Target(®) Ultrasoft(™) coils for the endovascular treatment of small intracranial aneurysms demonstrate initial excellent safety and efficacy profiles.

Evidence for Decreased Brain Parenchymal Volume After Large Intracerebral Hemorrhages: a Potential Mechanism Limiting Intracranial Pressure Rises.

PubMed

Williamson, Michael R; Colbourne, Frederick

2017-08-01

Potentially fatal intracranial pressure (ICP) rises commonly occur after large intracerebral hemorrhages (ICH). We monitored ICP after infusing 100-160 μL of autologous blood (vs. 0 μL control) into the striatum of rats in order to test the validity of this common model with regard to ICP elevations. Other endpoints included body temperature, behavioral impairment, lesion volume, and edema. Also, we evaluated hippocampal CA1 sector and somatosensory cortical neuron morphology to assess whether global ischemic injury occurred. Despite massive blood infusions, ICP only modestly increased (160 μL 10.8 ± 2.1 mmHg for <36 h vs. control 3.4 ± 0.5 mmHg), with little peri-hematoma edema at 3 days. Body temperature was not affected. Behavioral deficits and tissue loss were infusion volume-dependent. There was no histological evidence of hippocampal or cortical injury, indicating that cell death was confined to the hematoma and closely surrounding tissue. Surprisingly, the most severe hemorrhages significantly increased cell density (~15-20%) and reduced cell body size (~30%) in regions outside the injury site. Additionally, decreased cell size and increased density were observed after collagenase-induced ICH. Parenchymal volume is seemingly reduced after large ICH. Thus, in addition to well-known compliance mechanisms (e.g., displacement of cerebrospinal fluid and cerebral blood), reduced brain parenchymal volume appears to limit ICP rises in rodents with very large mass lesions.

Treatment of the superior sagittal sinus and transverse sinus thrombosis associated with intracranial hemorrhage with the mechanical thrombectomy and thrombolytics: Case report.

PubMed

Liu, Yuchun; Li, Keqin; Huang, Yi; Sun, Jie; Gao, Xiang

2017-12-01

The superior sagittal sinus (SSS) and transverse sinus are the major dural sinuses that receive a considerable amount of venous drainage. The occlusion of them has been suggested to cause intracranial hypertension, hemorrhage, and lead to potentially fatal consequences. We reported a 35-year-old woman with headache presented to our emergency department with a decreased level of consciousness and epileptic seizures. The examination of speech, higher mental function, and cranial nerve were normal. Computed tomography (CT) demonstrated both subarachnoid and intraparenchymal hemorrhage and brain edema at the right temporal lobe accompanied by high density shadow in the right transverse sinus. Digital subtraction angiography (DSA) revealed extensive thrombosis of the SSS and bilateral transverse sinus. The SSS and transverse sinus thrombosis, accompanied by right temporal lobe hemorrhage, subarachnoid hemorrhage (SAH). An emergent mechanical thrombectomy by placed Solitair AB stent in the SSS, respectively, passed left and right sigmoid sinus-transverse sinus route. We removed the most clots, DSA revealed recanalization of the SSS and left transverse sinus was seen with normalization of the venous outflow, the occlusion of right transverse sinus was still present. There were 4 hours after patient back to neurosurgical intensive care unit (NICU), patient appeared anisocoria (R/L:4.0/2.5 mm), bilateral light reflexes disappeared, then we took a CT reexamination revealed intraparenchymal hemorrhage increased, brain edema was aggravated at the left temporal lobe, and mild midline shift. Subsequently, we performed decompressive hemicraniectomy and puncture the hematoma supplemented by B ultrasonic. Anticoagulation treatment was initiated 24 hours after surgery, and follow-up DSA showed gradually improved patency in the SSS and bilateral transverse sinus. Despite occlusion of the SSS and bilateral transverse sinus, patient's symptoms resolved after the operations and he

New high-performance liquid chromatography method for the determination of (R)-warfarin and (S)-warfarin using chiral separation on a glycopeptide-based stationary phase.

PubMed

Malakova, Jana; Pavek, Petr; Svecova, Lucie; Jokesova, Iveta; Zivny, Pavel; Palicka, Vladimir

2009-10-01

Warfarin is a well-known anticoagulant agent that occurs in two enantiomers, (R)-(+)-warfarin and (S)-(-)-warfarin. A new liquid chromatography method for the determination of both enantiomers was developed, validated and applied in in vitro studies with the aim of evaluating the accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line. OptiMEM cell cultivation medium samples and cellular lysates were purified using Waters Oasis MAX extraction cartridges. The chiral separation of warfarin and the internal standard p-chlorowarfarin enantiomers was performed on an Astec Chirobiotic V2 column at a flow rate of 1.2mL/min. The mobile phase was composed of 31% acetonitrile, 5% of methanol and 64% of ammonium acetate buffer (10mmol/L, pH 4.1). The enantiomers were quantified using a fluorescence detector (lambda(excit)=320nm, lambda(emiss)=415nm). The limit of detection was found to be 0.121micromol/L of (S)-warfarin and 0.109micromol/L of (R)-warfarin. The range of applicability and linearity was estimated from 0.25 to 100micromol/L. The precision ranged from 1.3% to 12.2% of the relative standard deviation, and the accuracy reached acceptable values from 95.5% to 108.4%. The new bioanalytical method confirmed the same accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line.

Hospital length of stay in patients initiated on direct oral anticoagulants versus warfarin for venous thromboembolism: a real-world single-center study.

PubMed

Badreldin, Hisham

2018-07-01

This study was conducted to describe the real-world hospital length of stay in patients treated with all of the U.S. Food and Drug Administration approved direct oral anticoagulants (DOACs) versus warfarin for new-onset venous thromboembolism (VTE) at a large, tertiary, academic medical center. A retrospective cohort analysis of all adult patients diagnosed with acute onset VTE was conducted. Of the 441 patients included, 261 (57%) patients received DOACs versus 180 (41%) patients received warfarin. In the DOAC group, a total of 92 (35%) patients received rivaroxaban, followed by 83 (32%) patients received apixaban, 50 (19%) patients received dabigatran, and 36 (14%) patients received edoxaban. Patients initiated on DOACs had a statistically significant shorter hospital length of stay compared to patients initiated on warfarin (median 3 days, [IQR 0-5] vs. 8 days [IQR 5-11], P < 0.05). Despite the shorter hospital length of stay in patients receiving DOACs, the overall reported differences between the DOACs group and the warfarin group in terms of recurrent VTE, major bleeding, intracranial bleeding, and gastrointestinal bleeding at 3 and 6 months were deemed to be statistically insignificant.

Quality of Anticoagulation Control in Preventing Adverse Events in Heart Failure Patients in Sinus Rhythm: A Warfarin Aspirin Reduced Cardiac Ejection Fraction Trial (WARCEF) Substudy

PubMed Central

Homma, Shunichi; Thompson, John L.P.; Qian, Min; Ye, Siqin; Di Tullio, Marco R.; Lip, Gregory Y.H.; Mann, Douglas L.; Sacco, Ralph L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Graham, Susan; Mohr, J.P.; Labovitz, Arthur J.; Buchsbaum, Richard; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

2015-01-01

Background The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938. PMID:25850425

Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial.

PubMed

Held, Claes; Hylek, Elaine M; Alexander, John H; Hanna, Michael; Lopes, Renato D; Wojdyla, Daniel M; Thomas, Laine; Al-Khalidi, Hussein; Alings, Marco; Xavier, Dennis; Ansell, Jack; Goto, Shinya; Ruzyllo, Witold; Rosenqvist, Mårten; Verheugt, Freek W A; Zhu, Jun; Granger, Christopher B; Wallentin, Lars

2015-05-21

In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI. Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the

[Neuro-critical management of glycemia in spontaneous intracerebral hemorrhage: review of the literature].

PubMed

Navas-Marrugo, Sandy Zuleica; Alvis-Miranda, Hernando Raphael; Moscote-Salazar, Luis Rafael

2014-01-01

Spontaneous cerebral hemorrhage or intracranial hemorrhage represents between 10 and 15% of all cerebrovascular events. Intracerebral hemorrhage is far less frequent than ischemic stroke, but leads to increased morbidity and mortality, one of the leading causes of severe disability. Several changes have been identified in the field of intracerebral hemorrhage, including endocrine. These stress-mediated mechanisms exacerbate secondary injury. Deep knowledge of the injuries that are directly involved in the alterations of glucose in the context of an intracerebral hemorrhage, offers a vision of how the cytotoxicity, neuronal death and metabolic disturbances alter the prognosis of patients with spontaneous intracerebral hemorrhage.

Sudden Death From Ruptured Intracranial Vascular Malformations During Mechanical Asphyxia: A Domestic Violence Case Report.

PubMed

Wu, Xue-Mei; Zhang, Xu-Dong; Yun, Li-Bing; Liu, Min; Yi, Xu-Fu

2017-03-01

Smothering and manual strangulation are not uncommon in domestic violence against women; however, no report on the combination of mechanical asphyxia and intracranial vascular malformations has been previously published. We report a middle-aged woman who was smothered and manually strangled by her husband and subsequently died from subarachnoid hemorrhage due to ruptured intracranial vascular malformations, rather than direct mechanical asphyxiation. Smothering and manual strangulation are considered provocative conditions for rupture and contributory causes of death. In this case study, we underline the importance of meticulous autopsy in cases of mechanical asphyxia and intracranial hemorrhage. Exclusion of underlying diseases that may have caused or contributed to death is also required, despite serious asphyxiation signs and neck injuries. Postmortem angiography is a valuable complement to autopsy to detect vascular pathology, with good prospects for further development in China.

Use of Risk Assessment Tool for Inpatient Traumatic Intracranial Hemorrhage after Falls in Acute Care Hospital Setting

PubMed Central

Toyabe, Shin-ichi

2012-01-01

Severe injuries such as intracranial hemorrhage (ICH) are the most serious problem after falls in hospital, but they have not been considered in risk assessment scores for falls. We tried to determine the risk factors for ICH after falls in 20,320 inpatients (696,364 patient-days) aged from 40 to 90 years who were admitted to a tertiary-care university hospital. Possible risk factors including STRATIFY risk score for falls and FRAX™ risk score for fractures were analyzed by univariate and multivariate analyses. Fallers accounted for 3.2% of the patients, and 5.0% of the fallers suffered major injuries, including peripheral bone fracture (59.6%) and ICH (23.4%). In addition to STRATIFY, FRAX™ was significantly associated not only with bone fractures but also ICH. Concomitant use of risk score for falls and risk score for fractures might be useful for the prediction of major injuries such as ICH after falls. PMID:22980233

Surgery of intracranial aneurysms at Yonsei University: 780 cases.

PubMed

Lee, K C

1991-03-01

Seven hundred and eighty patients with intracranial aneurysm, which were surgically treated by the author since 1976, were analyzed. Strategies important for intracranial aneurysm surgery were the timing of surgery, preoperative preparation and intraoperative management. The best management outcome could be achieved by early operation, removal of subarachnoid blood clot, maintenance of circulating blood volume, administration of nimodipine, and meticulous surgical tactics to avoid pitfalls. Indications for aneurysm surgery in the acute phase were determined by intracerebral hematoma, angiographic findings, clinical grade, general physical status and readiness of the surgical team. Important goals to be considered during the operation were obtaining a slack brain, preparation of proximal control, protection of the brain, awareness of microsurgical anatomy, and complete dissection of the sac. The morbidity and mortality were 2.7% and 4.0%, respectively. The mortality was attributed to intracranial causes in 20 cases (poor grade, delayed ischemic deficits, rebleeding, postoperative infarction, and postoperative epidural hematoma), extracranial causes in 7 cases (pulmonary embolism, heparin induced intracerebral hemorrhage, hepatic failure, myocardial infarction, and gastrointestinal bleeding), and unknown problems in 5 cases. The postoperative intracerebral hemorrhage occurred in 16 cases and seemed to be caused by one or more of the following events: cerebral infarction developed during the preoperative period, occlusion of the cerebral veins during the Sylvian dissection, cerebral retraction and/or sudden change of intracranial hemodynamics. Hydrocephalus, almost always a communicating type as confirmed by isotope cisternography, was managed by lumboperitoneal shunt.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs.

PubMed

Shen, Chenlin; Huang, Xiaohui; Li, Jun; Zhang, Ping; Li, Lin; Zhang, Wei; Hu, Tingting; Pappoe, Faustina; Huang, Jihan; Tang, Haiqin

2016-01-01

1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients.

Repeat neuroimaging of mild traumatic brain-injured patients with acute traumatic intracranial hemorrhage: clinical outcomes and radiographic features.

PubMed

Kreitzer, Natalie; Lyons, Michael S; Hart, Kim; Lindsell, Cristopher J; Chung, Sora; Yick, Andrew; Bonomo, Jordan

2014-10-01

Emergency department (ED) management of mild traumatic brain injury (TBI) patients with any form of traumatic intracranial hemorrhage (ICH) is variable. Since 2000, our center's standard practice has been to obtain a repeat head computed tomography (CT) at least 6 hours after initial imaging. Patients are eligible for discharge if clinical and CT findings are stable. Whether this practice is safe is unknown. This study characterized clinical outcomes in mild TBI patients with acute traumatic ICH seen on initial ED neuroimaging. This retrospective cohort study included patients presenting to the ED with blunt mild TBI with Glasgow Coma Scale (GCS) scores of 14 or 15 and stable vital signs, during the period from January 2001 to January 2010. Patients with any ICH on initial head CT and repeat head CT within 24 hours were eligible. Cases were excluded for initial GCS < 14, injury > 24 hours old, pregnancy, concomitant nonminor injuries, and coagulopathy. A single investigator abstracted data from records using a standardized case report form and data dictionary. Primary endpoints included death, neurosurgical procedures, and for discharged patients, return to the ED within 7 days. Differences in proportions were computed with 95% confidence intervals (CIs). Of 1,011 patients who presented to the ED and had two head CTs within 24 hours, 323 (32%) met inclusion criteria. The median time between CT scans was 6 hours (interquartile range = 5 to 7 hours). A total of 153 (47%) patients had subarachnoid hemorrhage, 132 (41%) patients had subdural hemorrhage, 11 (3%) patients had epidural hemorrhage, 78 (24%) patients had cerebral contusions, and 59 (18%) patients had intraparenchymal hemorrhage. Four of 323 (1.2%, 95% CI = 0.3% to 3.2%) patients died within 2 weeks of injury. Three of the patients who died had been admitted from the ED on their initial visits, and one had been discharged home. There were 206 patients (64%) discharged from the ED, 28 (13.6%) of whom returned

Warfarin Initiation, Atrial Fibrillation, and Kidney Function: Comparative Effectiveness and Safety of Warfarin in Older Adults With Newly Diagnosed Atrial Fibrillation.

PubMed

Jun, Min; James, Matthew T; Ma, Zhihai; Zhang, Jianguo; Tonelli, Marcello; McAlister, Finlay A; Manns, Braden J; Ravani, Pietro; Quinn, Robert R; Wiebe, Natasha; Perkovic, Vlado; Wilton, Stephen B; Winkelmayer, Wolfgang C; Hemmelgarn, Brenda R

2017-06-01

The effectiveness and safety of warfarin use among patients with atrial fibrillation (AF) and reduced kidney function are uncertain. Community-based retrospective cohort study (May 1, 2003, to March 31, 2012) using province-wide laboratory and administrative data in Alberta, Canada. 14,892 adults 66 years or older with new AF and a measurement of kidney function. Long-term dialysis patients or kidney transplant recipients were excluded. Propensity scores were used to construct a matched-pairs cohort of patients with AF who did and did not have a warfarin prescription within a 60-day period surrounding their AF diagnosis. Within 1 year of initiating warfarin therapy (or the matched date for nonusers): (1) the composite of all-cause death, ischemic stroke, or transient ischemic attack (also assessed as separate end points) and (2) first hospitalization or emergency department visit for a major bleeding episode defined as an intracranial, upper or lower gastrointestinal, or other bleeding. Baseline glomerular filtration rate (GFR) was estimated using the CKD-EPI creatinine equation. Patients were matched within estimated GFR (eGFR) categories: ≥90, 60 to 89, 45 to 59, 30 to 44, and <30mL/min/1.73m 2 . Information for baseline characteristics (sociodemographics, comorbid conditions, and prescription drug use) was obtained. Across eGFR categories, warfarin therapy initiation was associated with lower risk for the composite outcome compared to nonuse (adjusted HRs [95% CI] for eGFR categories ≥ 90, 60-89, 45-59, 30-44, and <30mL/min/1.73m 2 : 0.59 [0.35-1.01], 0.61 [0.54-0.70], 0.55 [0.47-0.65], 0.54 [0.44-0.67], and 0.64 [0.47-0.87] mL/min/1.73m 2 , respectively). Compared to nonuse, warfarin therapy was not associated with higher risk for major bleeding except for those with eGFRs of 60 to 89mL/min/1.73m 2 (HR, 1.36; 95% CI, 1.13-1.64). Selection bias. Among older adults with AF, warfarin therapy initiation was associated with a significantly lower 1-year risk

Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type

PubMed Central

Wilson, Duncan; Charidimou, Andreas; Shakeshaft, Clare; Ambler, Gareth; White, Mark; Cohen, Hannah; Yousry, Tarek; Al-Shahi Salman, Rustam; Lip, Gregory Y.H.; Brown, Martin M.; Jäger, Hans Rolf

2016-01-01

Objective: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non–vitamin K oral anticoagulants (NOAC)–associated ICH to warfarin-associated ICH. Methods: In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. Results: We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3–5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0–21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037). Conclusions: In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH. PMID:26718576

Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type.

PubMed

Wilson, Duncan; Charidimou, Andreas; Shakeshaft, Clare; Ambler, Gareth; White, Mark; Cohen, Hannah; Yousry, Tarek; Al-Shahi Salman, Rustam; Lip, Gregory Y H; Brown, Martin M; Jäger, Hans Rolf; Werring, David J

2016-01-26

To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH. In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037). In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH. © 2015 American Academy of Neurology.

Acquired absolute vitamin K deficiency in a patient undergoing warfarin therapy.

PubMed

Takada, Hiroaki; Toru, Hifumi; Bunya, Naofumi; Kiriu, Nobuaki; Kato, Hiroshi; Koido, Yuichi; Yasuhiro, Kuroda

2014-06-01

We report a case of absolute vitamin K deficiency (VKD) diagnosed by measuring serum VK levels in an elderly woman undergoing warfarin therapy. A 78-year-old woman was admitted to our hospital because of dyspnea and sore throat diagnosed as pharyngitis 1 week before admission. On admission, the sore throat had exacerbated and dyspnea developed. She had history of atrial fibrillation, for which warfarin 1.5 mg/d was started approximately 10 years prior and her international normalized ratio (INR) had been maintained at an acceptable therapeutic level. Blood results revealed unmeasurable INR and abnormally prolonged activated partial thromboplastin time (APTT). She was diagnosed with adenoiditis and warfarin-related coagulopathy and administered intravenous VK (20 mg) and fresh frozen plasma (FFP; 4 U), which improved INR and APTT. Since the coagulopathy responded to intravenous VK administration, the patient was clinically diagnosed with warfarin-related relative VKD. Approximately 1 month later, she returned with complaints of sore throat. Blood results indicated abnormal INR (7.22) and APTT (N80.0 s). She was diagnosed with recurrent adenoiditis and VK deficient coagulopathy. The patient’s serum VK levels were low (VK1 level, 0.13 ng/mL; VK2 levels, 0.85 ng/mL). Initial treatment of VK (20 mg) and FFP followed by intravenous VK (20 mg/d) for 6 days, her symptoms dissipated. Warfarin was suspected to have caused absolute VKD. Severe coagulopathy in patients undergoing warfarin therapy is primarily caused by, relative VKD. However, the possibility of warfarin-related absolute VKD should be suspected when INRis not sufficiently improved by intravenous VK administration.

Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage: News Update.

PubMed

Ji, Chengyuan; Chen, Gang

2016-01-01

The annual incidence of subarachnoid hemorrhage (SAH) caused by intracranial aneurysm rupture is approximately 10.5/10 million people in China, making SAH the third most frequently occurring hemorrhage of the intracranial type after cerebral embolism and hypertensive intracerebral hemorrhage. SAH caused by ruptured aneurysm leads to a mortality rate as high as 67 %, and, because of the sudden onset of this disease, approximately 12-15 % of patients die before they can receive effective treatment. Early brain injury (EBI) is the brain damage occurring within the first 72 h after SAH. Two-thirds of mortality caused by SAH occurs within 48 h, mainly as a result of EBI. With the development of molecular biology and medicine microscopy techniques, various signaling pathways involved in EBI after SAH have been revealed. Understanding these signaling pathways may help clinicians treat EBI after SAH and improve long-term prognosis of SAH patients. This chapter summarizes several important signaling pathways implicated in EBI caused by SAH.

Comparative effectiveness of rivaroxaban versus warfarin or dabigatran for the treatment of patients with non-valvular atrial fibrillation.

PubMed

Norby, Faye L; Bengtson, Lindsay G S; Lutsey, Pamela L; Chen, Lin Y; MacLehose, Richard F; Chamberlain, Alanna M; Rapson, Ian; Alonso, Alvaro

2017-09-06

Rivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population. We selected NVAF patients initiating oral anticoagulant use in 2010-2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes. The analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups. In this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis.

PubMed

Mendoza-Sanchez, Jose; Silva, Federico; Rangel, Lady; Jaramillo, Linda; Mendoza, Leidy; Garzon, Jenny; Quiroga, Andrea

2018-01-01

Warfarin and new oral anticoagulants are effective in reducing stroke in atrial fibrillation; however, the benefits and risks rates in clinical trials show heterogeneity for each anticoagulant, and is unknown the cost influence on a model considering most of the treatment consequences. We designed a benefit-risk and cost assessment of oral anticoagulants. We followed the roadmap proposed by IMI-PROTECT and the considerations of emerged good practice to perform Multi-Criteria Decision Analysis (MCDA). The roadmap defines the following steps: (1) planning, (2) evidence gathering and data preparation, (3) analyses, (4) explorations, and (5) conclusions. We defined two reference points (0-100) to allocate numerical values for scores and weights, and used an analogue numeric scale to assess physicians' preferences. As benefits of the anticoagulant therapy, we included reductions in stroke and all-cause mortality; intracranial haemorrhage, gastrointestinal haemorrhage, minor bleeding and myocardial infarction were considered risks. We also made an estimation of the annual drug cost per person. The scores were: Apixaban 33, Dabigatrán 25, warfarin 18 and Rivaroxaban 14 this score reveals the most preferred up to the less preferred option, considering the benefit-risk ratio and drug costs altogether. The relative model weights were: 51.1% for risks, 40.4% for benefits and 8.5% for cost. The sensitivity analysis confirms the model robustness. From this analysis, apixaban should be considered as the preferred anticoagulant option -due to a better benefit-risk balance and a minor cost influence- followed by dabigatran, warfarin and rivaroxaban.

Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with intracranial vascular anomalies.

PubMed

Teo, Mario; Johnson, Jeremiah N; Bell-Stephens, Teresa E; Marks, Michael P; Do, Huy M; Dodd, Robert L; Bober, Michael B; Steinberg, Gary K

2016-12-01

OBJECTIVE Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a rare genetic disorder. Features of it include extremely small stature, severe microcephaly, and normal or near-normal intelligence. Previous studies have found that more than 50% of patients with MOPD II have intracranial vascular anomalies, but few successful surgical revascularization or aneurysm-clipping cases have been reported because of the diminutive arteries and narrow surgical corridors in these patients. Here, the authors report on a large series of patients with MOPD II who underwent surgery for an intracranial vascular anomaly. METHODS In conjunction with an approved prospective registry of patients with MOPD II, a prospectively collected institutional surgical database of children with MOPD II and intracranial vascular anomalies who underwent surgery was analyzed retrospectively to establish long-term outcomes. RESULTS Ten patients with MOPD II underwent surgery between 2005 and 2012; 5 patients had moyamoya disease (MMD), 2 had intracranial aneurysms, and 3 had both MMD and aneurysms. Patients presented with transient ischemic attack (TIA) (n = 2), ischemic stroke (n = 2), intraparenchymal hemorrhage from MMD (n = 1), and aneurysmal subarachnoid hemorrhage (n = 1), and 4 were diagnosed on screening. The mean age of the 8 patients with MMD, all of whom underwent extracranial-intracranial revascularization (14 indirect, 1 direct) was 9 years (range 1-17 years). The mean age of the 5 patients with aneurysms was 15.5 years (range 9-18 years). Two patients experienced postoperative complications (1 transient weakness after clipping, 1 femoral thrombosis that required surgical repair). During a mean follow-up of 5.9 years (range 3-10 years), 3 patients died (1 of subarachnoid hemorrhage, 1 of myocardial infarct, and 1 of respiratory failure), and 1 patient had continued TIAs. All of the surviving patients recovered to their neurological baseline. CONCLUSIONS Patients with MMD

Evaluation of a computer-aided detection algorithm for timely diagnosis of small acute intracranial hemorrhage on computed tomography in a critical care environment

NASA Astrophysics Data System (ADS)

Lee, Joon K.; Chan, Tao; Liu, Brent J.; Huang, H. K.

2009-02-01

Detection of acute intracranial hemorrhage (AIH) is a primary task in the interpretation of computed tomography (CT) brain scans of patients suffering from acute neurological disturbances or after head trauma. Interpretation can be difficult especially when the lesion is inconspicuous or the reader is inexperienced. We have previously developed a computeraided detection (CAD) algorithm to detect small AIH. One hundred and thirty five small AIH CT studies from the Los Angeles County (LAC) + USC Hospital were identified and matched by age and sex with one hundred and thirty five normal studies. These cases were then processed using our AIH CAD system to evaluate the efficacy and constraints of the algorithm.

Pharmacogenetics of warfarin: challenges and opportunities

PubMed Central

Ta Michael Lee, Ming; Klein, Teri E

2014-01-01

Since the introduction in the 1950s, warfarin has become the commonly used oral anticoagulant for the prevention of thromboembolism in patients with deep vein thrombosis, atrial fibrillation or prosthetic heart valve replacement. Warfarin is highly efficacious; however, achieving the desired anticoagulation is difficult because of its narrow therapeutic window and highly variable dose response among individuals. Bleeding is often associated with overdose of warfarin. There is overwhelming evidence that an individual's warfarin maintenance is associated with clinical factors and genetic variations, most notably polymorphisms in cytochrome P450 2C9 and vitamin K epoxide reductase subunit 1. Numerous dose-prediction algorithms incorporating both genetic and clinical factors have been developed and tested clinically. However, results from major clinical trials are not available yet. This review aims to provide an overview of the field of warfarin which includes information about the drug, genetics of warfarin dose requirements, dosing algorithms developed and the challenges for the clinical implementation of warfarin pharmacogenetics. PMID:23657428

Improving Warfarin Management Within the Medical Home: A Health-System Approach.

PubMed

Rose, Anne E; Robinson, Erin N; Premo, Joan A; Hauschild, Lori J; Trapskin, Philip J; McBride, Ann M

2017-03-01

Anticoagulation clinics have been considered the optimal strategy for warfarin management with demonstrated improved patient outcomes through increased time in therapeutic international normalized ratio (INR) range, decreased critical INR values, and decreased anticoagulation-related adverse events. However, not all health systems are able to support a specialized anticoagulation clinic or may see patient volume exceed available anticoagulation clinic resources. The purpose of this study was to utilize an anticoagulation clinic model to standardize warfarin management in a primary care clinic setting. A warfarin management program was developed that included standardized patient assessment, protocolized warfarin-dosing algorithm, and electronic documentation and reporting tools. Primary care clinics were targeted for training and implementation of this program. The warfarin management program was applied to over 2000 patients and implemented at 39 clinic sites. A total of 160 nurses and 15 pharmacists were trained on the program. Documentation of warfarin dose and date of the next INR increased from 70% to 90% (P <.0001), documentation occurring within 24 hours of the INR result increased from 75% to 87% (P <.0001), and monitoring the INR at least every 4 weeks increased from 71% to 83% (P <.0001) per patient encounter. Time in therapeutic INR range improved from 65% to 75%. Incorporating a standardized approach to warfarin management in the primary care setting significantly improves warfarin-related documentation and time in therapeutic INR range. Copyright © 2016 Elsevier Inc. All rights reserved.

Visual Aid Tool to Improve Decision Making in Anticoagulation for Stroke Prevention.

PubMed

Saposnik, Gustavo; Joundi, Raed A

2016-10-01

The management of stroke prevention among patients with atrial fibrillation (AF) has changed in the last few years. Despite the benefits of new oral anticoagulants (NOACs), decisions about the optimal agent remain a challenge. We provide a visual aid tool to guide clinicians and patients in the decision process of selecting oral anticoagulants for stroke prevention. We created visual plots representing benefits of warfarin versus NOACs from a meta-analysis comprising 58,541 participants. Visual plots (Cates plots) were created using software available at nntonline.net. The primary outcome was stroke or systemic embolism during the study period. In the chosen meta-analysis, 29,312 participants received a NOAC and 29,229 participants received warfarin. For every 1000 patients with AF, 38 would have a stroke or systemic embolic event in the warfarin group compared to 31 in the NOAC group (RR .81; 95% CI .73-.91). Fifteen patients would develop an intracranial hemorrhage in the warfarin group compared to 7 in the NOAC group (RR .48; 95% CI .39-.59). Conversely, 25 patients would develop gastrointestinal bleeding in the NOAC group compared to 20 in the warfarin group (RR 1.25; 95% CI 1.01-1.55). For every 1000 treated individuals with AF, NOACs would prevent stroke or systemic embolism in 7 additional patients and cerebral hemorrhage in 8 additional patients compared to warfarin. On the other hand, 5 more patients would develop gastrointestinal bleeding with NOACs compared to warfarin. These data are visually shown in Cates plots, facilitating conversations with patients regarding anticoagulation decisions. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Pipeline embolization device for intracranial aneurysm: a systematic review.

PubMed

Leung, G K K; Tsang, A C O; Lui, W M

2012-12-01

The pipeline embolization device (PED) is a new endovascular stent designed for the treatment of challenging intracranial aneurysms (IAs). Its use has been extended to nonruptured and ruptured IAs of a variety of configurations and etiologies in both the anterior and posterior circulations. We conducted a systematic review of ten eligible reports on its clinical efficacy and safety. There were 414 patients with 448 IAs. The majority of the IAs were large (40.2 %), saccular or blister-like (78.3 %), and were located mostly in the anterior circulation (83.5 %). The regimens of antiplatelet therapy varied greatly between and within studies. The mean number of the PED used was 2.0 per IA. Deployment was successful in around 95 % of procedures. Aneurysm obliteration was achieved in 82.9 % of IAs at 6-month. The overall incidences of periprocedural intracranial vascular complication rate and mortality rate were 6.3 and 1.5 %, respectively. The PED is a safe and effective treatment for nonruptured IAs. Its use in the context of acute subarachnoid hemorrhage (SAH) should be cautioned. Its main limitations include the need for prolonged antiplatelet therapy, as well as the potential risks of IA rupture and non-IA-related intracerebral hemorrhages (ICH). Future studies should aim at identifying factors that predispose to incomplete obliteration, delayed rupture, and thromboembolic complications.

Intracranial mapping of auditory perception: event-related responses and electrocortical stimulation.

PubMed

Sinai, A; Crone, N E; Wied, H M; Franaszczuk, P J; Miglioretti, D; Boatman-Reich, D

2009-01-01

We compared intracranial recordings of auditory event-related responses with electrocortical stimulation mapping (ESM) to determine their functional relationship. Intracranial recordings and ESM were performed, using speech and tones, in adult epilepsy patients with subdural electrodes implanted over lateral left cortex. Evoked N1 responses and induced spectral power changes were obtained by trial averaging and time-frequency analysis. ESM impaired perception and comprehension of speech, not tones, at electrode sites in the posterior temporal lobe. There was high spatial concordance between ESM sites critical for speech perception and the largest spectral power (100% concordance) and N1 (83%) responses to speech. N1 responses showed good sensitivity (0.75) and specificity (0.82), but poor positive predictive value (0.32). Conversely, increased high-frequency power (>60Hz) showed high specificity (0.98), but poorer sensitivity (0.67) and positive predictive value (0.67). Stimulus-related differences were observed in the spatial-temporal patterns of event-related responses. Intracranial auditory event-related responses to speech were associated with cortical sites critical for auditory perception and comprehension of speech. These results suggest that the distribution and magnitude of intracranial auditory event-related responses to speech reflect the functional significance of the underlying cortical regions and may be useful for pre-surgical functional mapping.

Stroke in Heart Failure in Sinus Rhythm: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial

PubMed Central

Pullicino, Patrick M.; Thompson, John L.P.; Sacco, Ralph L.; Sanford, Alexandra R.; Qian, Min; Teerlink, John R.; Haddad, Haissam; Diek, Monika; Freudenberger, Ronald S.; Labovitz, Arthur J.; Di Tullio, Marco R.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Graham, Susan; Mann, Douglas L.; Mohr, J.P.; Homma, Shunichi

2014-01-01

Background The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses. Methods We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran-Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions. Results Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mRS, mRS 90 days after IIS, and change from baseline to post-IIS mRS. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mRS 3–5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-IIS mRS (p = 0.948) between cardioembolic

Stroke in heart failure in sinus rhythm: the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial.

PubMed

Pullicino, Patrick M; Thompson, John L P; Sacco, Ralph L; Sanford, Alexandra R; Qian, Min; Teerlink, John R; Haddad, Haissam; Diek, Monika; Freudenberger, Ronald S; Labovitz, Arthur J; Di Tullio, Marco R; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Graham, Susan; Mann, Douglas L; Mohr, J P; Homma, Shunichi

2013-01-01

The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses. We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran-Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions. Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mRS, mRS 90 days after IIS, and change from baseline to post-IIS mRS. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mRS 3-5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-IIS mRS (p = 0.948) between cardioembolic, possible cardioembolic and

Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses.

PubMed

Chung, Jee-Eun; Lee, Kyung Eun; Chang, Byung Chul; Gwak, Hye Sun

2018-01-30

The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A>G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02±1.56 vs. 5.96±2.01mg; p=0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses. Copyright © 2017. Published by Elsevier B.V.

F2-isoprostanes and F4-neuroprostanes as markers of intracranial aneurysm development.

PubMed

Syta-Krzyżanowska, Anna; Jarocka-Karpowicz, Iwona; Kochanowicz, Jan; Turek, Grzegorz; Rutkowski, Robert; Gorbacz, Krzysztof; Mariak, Zenon; Skrzydlewska, Elżbieta

2018-04-24

Intracranial aneurysms are common, occurring in about 1-2% of the population. Saccular aneurysm is a pouch-like pathological dilatation of an intracranial artery that develops when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. The aim of this study was to determine whether the development of intracranial aneurysms and subarachnoid hemorrhage (SAH) affects neuronal phospholipid metabolism, and what influence different invasive treatments have on brain free radical phospholipid metabolism. The level of polyunsaturated fatty acid (PUFA) cyclization products - F2-isoprostanes and F4-neuroprostanes - was examined using liquid chromatography - mass spectrometry (LC-MS) in the plasma of patients with brain aneurysm and resulting subarachnoid hemorrhage. It was revealed that an aneurysm leads to the enhancement of lipid peroxidation with a significant increase in plasma F2-isoprostanes and F4-neuroprostanes (more than 3-fold and 11-fold, respectively) in comparison to healthy subjects. The rupture of an aneurysm results in hemorrhage and an additional increase in examined prostaglandin derivatives. The embolization and clipping of aneurysms contribute to a gradual restoration of metabolic homeostasis in brain cells, which is visible in the decrease in PUFA cyclization products. The results indicate that aneurysm development is associated with enhanced inflammation and oxidative stress, factors which favor lipid peroxidation, particularly in neurons, whose membranes are rich in docosahexaenoic acid, a precursor of F4-neuroprostanes.

Comparison of warfarin therapy clinical outcomes following implementation of an automated mobile phone-based critical laboratory value text alert system.

PubMed

Lin, Shu-Wen; Kang, Wen-Yi; Lin, Dong-Tsamn; Lee, James; Wu, Fe-Lin; Chen, Chuen-Liang; Tseng, Yufeng J

2014-01-01

Computerized alert and reminder systems have been widely accepted and applied to various patient care settings, with increasing numbers of clinical laboratories communicating critical laboratory test values to professionals via either manual notification or automated alerting systems/computerized reminders. Warfarin, an oral anticoagulant, exhibits narrow therapeutic range between treatment response and adverse events. It requires close monitoring of prothrombin time (PT)/international normalized ratio (INR) to ensure patient safety. This study was aimed to evaluate clinical outcomes of patients on warfarin therapy following implementation of a Personal Handy-phone System-based (PHS) alert system capable of generating and delivering text messages to communicate critical PT/INR laboratory results to practitioners' mobile phones in a large tertiary teaching hospital. A retrospective analysis was performed comparing patient clinical outcomes and physician prescribing behavior following conversion from a manual laboratory result alert system to an automated system. Clinical outcomes and practitioner responses to both alert systems were compared. Complications to warfarin therapy, warfarin utilization, and PT/INR results were evaluated for both systems, as well as clinician time to read alert messages, time to warfarin therapy modification, and monitoring frequency. No significant differences were detected in major hemorrhage and thromboembolism, warfarin prescribing patterns, PT/INR results, warfarin therapy modification, or monitoring frequency following implementation of the PHS text alert system. In both study periods, approximately 80% of critical results led to warfarin discontinuation or dose reduction. Senior physicians' follow-up response time to critical results was significantly decreased in the PHS alert study period (46.3% responded within 1 day) compared to the manual notification study period (24.7%; P = 0.015). No difference in follow-up response time

Primary Intracranial Choriocarcinoma Located in the Suprasellar Region

PubMed Central

Li, Xiuli; Murayama, Kazuhiro; Watanabe, Ayumi; Abe, Masato; Toyama, Hiroshi

2016-01-01

A 10 year old girl was admitted to our hospital due to headache, nausea, and weight loss for about half a year. She also had visual field disorders. Suprasellar tumor was found by X-ray computed tomography, and magnetic resonance imaging showed a ring-like lobulated enhanced mass with hemorrhage and necrosis. Biopsy of this lesion showed primary intracranial choriocarcinoma on histopathological examination. The serum human chorionic gonadotropin (hCG) level was measured after the biopsy and was elevated at 71,298.2 IU/L. The patient died due to hydrocephalus caused by an increase in the size of the tumor with a larger amount of hemorrhage than the preoperative features. If young patients present with a suprasellar lobulated mass with hemorrhage, the serum hCG level should be measured before operation. PMID:27499824

Management of intracerebral hemorrhage.

PubMed

Thabet, A M; Kottapally, M; Hemphill, J Claude

2017-01-01

Intracerebral hemorrhage (ICH) is a potentially devastating neurologic injury representing 10-15% of stroke cases in the USA each year. Numerous risk factors, including age, hypertension, male gender, coagulopathy, genetic susceptibility, and ethnic descent, have been identified. Timely identification, workup, and management of this condition remain a challenge for clinicians as numerous factors can present obstacles to achieving good functional outcomes. Several large clinical trials have been conducted over the prior decade regarding medical and surgical interventions. However, no specific treatment has shown a major impact on clinical outcome. Current management guidelines do exist based on medical evidence and consensus and these provide a framework for care. While management of hypertension and coagulopathy are generally considered basic tenets of ICH management, a variety of measures for surgical hematoma evacuation, intracranial pressure control, and intraventricular hemorrhage can be further pursued in the emergent setting for selected patients. The complexity of management in parenchymal cerebral hemorrhage remains challenging and offers many areas for further investigation. A systematic approach to the background, pathology, and early management of spontaneous parenchymal hemorrhage is provided. © 2017 Elsevier B.V. All rights reserved.

Intracranial mapping of auditory perception: Event-related responses and electrocortical stimulation

PubMed Central

Sinai, A.; Crone, N.E.; Wied, H.M.; Franaszczuk, P.J.; Miglioretti, D.; Boatman-Reich, D.

2010-01-01

Objective We compared intracranial recordings of auditory event-related responses with electrocortical stimulation mapping (ESM) to determine their functional relationship. Methods Intracranial recordings and ESM were performed, using speech and tones, in adult epilepsy patients with subdural electrodes implanted over lateral left cortex. Evoked N1 responses and induced spectral power changes were obtained by trial averaging and time-frequency analysis. Results ESM impaired perception and comprehension of speech, not tones, at electrode sites in the posterior temporal lobe. There was high spatial concordance between ESM sites critical for speech perception and the largest spectral power (100% concordance) and N1 (83%) responses to speech. N1 responses showed good sensitivity (0.75) and specificity (0.82), but poor positive predictive value (0.32). Conversely, increased high-frequency power (>60 Hz) showed high specificity (0.98), but poorer sensitivity (0.67) and positive predictive value (0.67). Stimulus-related differences were observed in the spatial-temporal patterns of event-related responses. Conclusions Intracranial auditory event-related responses to speech were associated with cortical sites critical for auditory perception and comprehension of speech. Significance These results suggest that the distribution and magnitude of intracranial auditory event-related responses to speech reflect the functional significance of the underlying cortical regions and may be useful for pre-surgical functional mapping. PMID:19070540

Outcomes and complications of intracranial pressure monitoring in acute liver failure: a retrospective cohort study.

PubMed

Karvellas, Constantine J; Fix, Oren K; Battenhouse, Holly; Durkalski, Valerie; Sanders, Corron; Lee, William M

2014-05-01

To determine if intracranial pressure monitor placement in patients with acute liver failure is associated with significant clinical outcomes. Retrospective multicenter cohort study. Academic liver transplant centers comprising the U.S. Acute Liver Failure Study Group. Adult critically ill patients with acute liver failure presenting with grade III/IV hepatic encephalopathy (n = 629) prospectively enrolled between March 2004 and August 2011. Intracranial pressure monitored (n = 140) versus nonmonitored controls (n = 489). Intracranial pressure monitored patients were younger than controls (35 vs 43 yr, p < 0.001) and more likely to be on renal replacement therapy (52% vs 38%, p = 0.003). Of 87 intracranial pressure monitored patients with detailed information, 44 (51%) had evidence of intracranial hypertension (intracranial pressure > 25 mm Hg) and overall 21-day mortality was higher in patients with intracranial hypertension (43% vs 23%, p = 0.05). During the first 7 days, intracranial pressure monitored patients received more intracranial hypertension-directed therapies (mannitol, 56% vs 21%; hypertonic saline, 14% vs 7%; hypothermia, 24% vs 10%; p < 0.03 for each). Forty-one percent of intracranial pressure monitored patients received liver transplant (vs 18% controls; p < 0.001). Overall 21-day mortality was similar (intracranial pressure monitored 33% vs controls 38%, p = 0.24). Where data were available, hemorrhagic complications were rare in intracranial pressure monitored patients (4 of 56 [7%]; three died). When stratifying by acetaminophen status and adjusting for confounders, intracranial pressure monitor placement did not impact 21-day mortality in acetaminophen patients (p = 0.89). However, intracranial pressure monitor was associated with increased 21-day mortality in nonacetaminophen patients (odds ratio, ~ 3.04; p = 0.014). In intracranial pressure monitored patients with acute liver failure, intracranial hypertension is commonly observed. The use

Non-valvular atrial fibrillation patients with none or one additional risk factor of the CHA2DS2-VASc score. A comprehensive net clinical benefit analysis for warfarin, aspirin, or no therapy.

PubMed

Lip, Gregory Y H; Skjøth, Flemming; Nielsen, Peter B; Larsen, Torben Bjerregaard

2015-10-01

Oral anticoagulation (OAC) to prevent stroke has to be balanced against the potential harm of serious bleeding, especially intracranial haemorrhage (ICH). We determined the net clinical benefit (NCB) balancing effectiveness and safety of no antithrombotic therapy, aspirin and warfarin in AF patients with none or one stroke risk factor. Using Danish registries, we determined NCB using various definitions intrinsic to our cohort (Danish weights at 1 and 5 year follow-up), with risk weights which were derived from the hazard ratio (HR) of death following an event, relative to HR of death after ischaemic stroke. When aspirin was compared to no treatment, NCB was neutral or negative for both risk strata. For warfarin vs no treatment, NCB using Danish weights was neutral where no risk factors were present and using five years follow-up. For one stroke risk factor, NCB was positive for warfarin vs no treatment, for one year and five year follow-up. For warfarin vs aspirin use in patients with no risk factors, NCB was positive with one year follow-up, but neutral with five year follow-up. With one risk factor, NCB was generally positive for warfarin vs aspirin. In conclusion, we show a positive overall advantage (i.e. positive NCB) of effective stroke prevention with OAC, compared to no therapy or aspirin with one additional stroke risk factor, using Danish weights. 'Low risk' AF patients with no additional stroke risk factors (i.e.CHA2DS2-VASc 0 in males, 1 in females) do not derive any advantage (neutral or negative NCB) with aspirin, nor with warfarin therapy in the long run.

Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists.

PubMed

Cipriano, Alessandro; Pecori, Alessio; Bionda, Alessandra Eugenia; Bardini, Michele; Frassi, Francesca; Leoli, Francesco; Lami, Valentina; Ghiadoni, Lorenzo; Santini, Massimo

2018-03-08

Prognosis after mild traumatic brain injury (MTBI) on oral anticoagulant therapy (OAT) is uncertain. We evaluated the rate of immediate and delayed traumatic intracranial hemorrhage (ICH) comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) and the safety of a clinical management protocol. In this single-center prospective observational study, we enrolled 220 patients on OAT with MTBI. After a first negative CT scan, asymptomatic patients underwent a close neurological observation; if neurologically stable, they were discharged without a second CT scan and followed up for 1 month. Out of the 220 patients, 206 met the inclusion criteria. 23 of them (11.2%) had a positive first CT scan for ICH. Only 1 (0.5%, 95% CI 0.0-1.4%) died because of ICH; no one required neurosurgical intervention. The observed prevalence rate of immediate ICH resulted statistically higher in VKAs-treated patients compared to those treated with DOACs (15.7 vs. 4.7%, RR 3.34, 95% CI 1.18-9.46, P < 0.05). In the 1-month follow-up, 5 out of the 183 patients with a negative CT scan were lost. Out of the remaining 178 patients, only 3 showed a delayed ICH (1.7%, 95% CI 0.0-3.6%), 1 of them died (0.6%, 95% CI 0.5-1.7%) and the others did not require neurosurgical intervention. DOACs resulted safer than VKAs also in the setting of MTBI. In our observation, the rate of delayed hemorrhage was relatively low. Patients presenting with a negative first CT scan and without neurological deterioration could be safely discharged after a short period of in-ward observation with a low rate of complications and without a second CT scan.

Causes and Severity of Ischemic Stroke in Patients with Symptomatic Intracranial Arterial Stenosis

PubMed Central

Famakin, Bolanle M; Chimowitz, Marc I; Lynn, Michael J; Stern, Barney J; George, Mary G.

2009-01-01

Background and purpose There are limited data on the causes and severity of subsequent stroke in patients presenting initially with TIA or stroke attributed to intracranial arterial stenosis. Methods We evaluated the location, type (lacunar vs. non-lacunar), cause, and severity of stroke in patients who had an ischemic stroke endpoint in the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. Results Of the 569 patients enrolled in the WASID trial, 106 patients (18.6%) had an ischemic stroke during a mean follow-up of 1.8 years. Stroke occurred in the territory of the symptomatic artery in 77 (73%) of 106 patients. Among the 77 strokes in the territory, 70 (91%) were non-lacunar and 34 (44%) were disabling. Stroke out of the territory of the symptomatic artery occurred in 29 (27%) of 106 patients. Among these 29 strokes, 24 (83%) were non-lacunar, 14 (48%) were due to previously asymptomatic intracranial stenosis, and 9 (31%) were disabling. Conclusions Most subsequent strokes in patients with symptomatic intracranial artery stenosis are in the same territory and non-lacunar, and nearly half of the strokes in the territory are disabling. The most commonly identified cause of stroke out of the territory was a previously asymptomatic intracranial stenosis. Penetrating artery disease was responsible for a low number of strokes. PMID:19407228

Intracranial haemorrhage possibly related to Tipranavir in an HIV-1 patient with cryptococcal meningitis.

PubMed

Chrysos, G; Gerakari, S; Stasini, F; Kokkoris, S; Kourousis, D; Velegraki, A

2008-07-01

A 55-year-old HIV-infected patient on antiretroviral treatment with Ritonavir-boosted Tipranavir as part of HAART developed intracranial haemorrhage during the acute phase of cryptococcal meningitis. CT scan and MRI confirmed the intracranial haemorrhage. Positive cryptococcal antigen and cultures of both blood and CSF confirmed the diagnosis of meningitis caused by Cryptococcus neoformans. There was no evidence of any bleeding disorder, use of aspirin or antiplatelet agents. The patient was treated with Liposomal Amphotericin B for cryptococcal meningitis. No special treatment was needed for the intracranial haemorrhage, but Tipranavir was discontinued and replaced by Kaletra and Saquinavir. Intracranial haemorrhage could be related to Tipranavir and cryptococcal meningitis was a predisposing factor. Headache stopped 3 days after starting antifungal treatment. To the best of our knowledge, this is the first reported case of intracranial haemorrhage related to Tipranavir treatment after the end of the "RESIST" studies and the only one related to meningitis.

A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients

PubMed Central

Luo, Fang; Wang, Jin'e; Shi, Yi; Tan, Yu; Chen, Qianlong; Zhang, Yu; Hui, Rutai; Wang, Yibo

2014-01-01

Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551), warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236), the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, P<0.001). Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients. PMID:25126975

The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study

PubMed Central

Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria

2016-01-01

that the combination of VKORC1 and CYP2C9 yielded a warfarin responsive index (WRI) inversely related to the number variant alleles Conclusion Our results overall suggest that 3’-hydroxywarfarin monitoring could be of great advantage in INR monitoring respect to classical warfarin assessment showing significant contribution also in multivariate analysis. Therefore, additional active metabolites should be recognized and investigated as novel useful indicators. PMID:27606428

The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study.

PubMed

Gemmati, Donato; Burini, Francesco; Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria; Tisato, Veronica; Gaudio, Rosa Maria

2016-01-01

9 yielded a warfarin responsive index (WRI) inversely related to the number variant alleles. Our results overall suggest that 3'-hydroxywarfarin monitoring could be of great advantage in INR monitoring respect to classical warfarin assessment showing significant contribution also in multivariate analysis. Therefore, additional active metabolites should be recognized and investigated as novel useful indicators.

A Partial Least-Squares Analysis of Health-Related Quality-of-Life Outcomes After Aneurysmal Subarachnoid Hemorrhage.

PubMed

Young, Julia M; Morgan, Benjamin R; Mišić, Bratislav; Schweizer, Tom A; Ibrahim, George M; Macdonald, R Loch

2015-12-01

Individuals who have aneurysmal subarachnoid hemorrhages (SAHs) experience decreased health-related qualities of life (HRQoLs) that persist after the primary insult. To identify clinical variables that concurrently associate with HRQoL outcomes by using a partial least-squares approach, which has the distinct advantage of explaining multidimensional variance where predictor variables may be highly collinear. Data collected from the CONSCIOUS-1 trial was used to extract 29 clinical variables including SAH presentation, hospital procedures, and demographic information in addition to 5 HRQoL outcome variables for 256 individuals. A partial least-squares analysis was performed by calculating a heterogeneous correlation matrix and applying singular value decomposition to determine components that best represent the correlations between the 2 sets of variables. Bootstrapping was used to estimate statistical significance. The first 2 components accounting for 81.6% and 7.8% of the total variance revealed significant associations between clinical predictors and HRQoL outcomes. The first component identified associations between disability in self-care with longer durations of critical care stay, invasive intracranial monitoring, ventricular drain time, poorer clinical grade on presentation, greater amounts of cerebral spinal fluid drainage, and a history of hypertension. The second component identified associations between disability due to pain and discomfort as well as anxiety and depression with greater body mass index, abnormal heart rate, longer durations of deep sedation and critical care, and higher World Federation of Neurosurgical Societies and Hijdra scores. By applying a data-driven, multivariate approach, we identified robust associations between SAH clinical presentations and HRQoL outcomes. EQ-VAS, EuroQoL visual analog scaleHRQoL, health-related quality of lifeICU, intensive care unitIVH, intraventricular hemorrhagePLS, partial least squaresSAH, subarachnoid

Neurovascular Cell Sheet Transplantation in a Canine Model of Intracranial Hemorrhage

PubMed Central

Lee, Woo-Jin; Lee, Jong Young; Jung, Keun-Hwa; Lee, Soon-Tae; Kim, Hyo Yeol; Park, Dong-Kyu; Yu, Jung-Suk; Kim, So-Yun; Jeon, Daejong; Kim, Manho; Lee, Sang Kun; Roh, Jae-Kyu; Chu, Kon

2017-01-01

Cell-based therapy for intracerebral hemorrhage (ICH) has a great therapeutic potential. However, methods to effectively induce direct regeneration of the damaged neural tissue after cell transplantation have not been established, which, if done, would improve the efficacy of cell-based therapy. In this study, we aimed to develop a cell sheet with neurovasculogenic potential and evaluate its usefulness in a canine ICH model. We designed a composite cell sheet made of neural progenitors derived from human olfactory neuroepithelium and vascular progenitors from human adipose tissue-derived stromal cells. We also generated a physiologic canine ICH model by manually injecting and then infusing autologous blood under arterial pressure. We transplanted the sheet cells (cell sheet group) or saline (control group) at the cortex over the hematoma at subacute stages (2 weeks from ICH induction). At 4 weeks from the cell transplantation, cell survival, migration, and differentiation were evaluated. Hemispheric atrophy and neurobehavioral recovery were also compared between the groups. As a result, the cell sheet was rich in extracellular matrices and expressed neurotrophic factors as well as the markers for neuronal development. After transplantation, the cells successfully survived for 4 weeks, and a large portion of those migrated to the perihematomal site and differentiated into neurons and pericytes (20% and 30% of migrated stem cells, respectively). Transplantation of cell sheets alleviated hemorrhage-related hemispheric atrophy (p = 0.042) and showed tendency for improving functional recovery (p = 0.062). Therefore, we concluded that the cell sheet transplantation technique might induce direct regeneration of neural tissue and might improve outcomes of intracerebral hemorrhage. PMID:28713638

Understanding and Managing Atrial Fibrillation in Patients with Kidney Disease.

PubMed

Khouri, Yazan; Stephens, Tiona; Ayuba, Gloria; AlAmeri, Hazim; Juratli, Nour; McCullough, Peter A

2015-01-01

Chronic kidney disease (CKD) is on the rise due to the increased rate of related comorbidities such as diabetes and hypertension. Patients with CKD are at higher risk of cardiovascular events and atrial fibrillation is more common in this patient population. It is estimated that the prevalence of chronic atrial fibrillation in patients with CKD is two to three times higher than general population. Furthermore, patients with CKD are less likely to stay in sinus rhythm. Atrial fibrillation presents a major burden in this population due to difficult treatment decisions in the setting of a lack of evidence from randomized clinical trials. Patients with CKD have higher risk of stroke with more than half having a CHADS2 score ≥ 2. Anticoagulation have been shown to significantly decrease embolic stroke risk, however bleeding complications such as hemorrhagic stroke is twofold higher with warfarin. Although newer novel anticoagulation drugs have shown promise with lower intracranial hemorrhage risk in comparison to warfarin, lack clinical trial data in CKD and the unavailability of an antidote remains an issue. In this review, we discuss the treatment options available including anticoagulation and the evidence behind them in patients with chronic kidney disease suffering from atrial fibrillation.

Effectiveness and Safety of Dabigatran and Warfarin in Real‐World US Patients With Non‐Valvular Atrial Fibrillation: A Retrospective Cohort Study

PubMed Central

Lauffenburger, Julie C.; Farley, Joel F.; Gehi, Anil K.; Rhoney, Denise H.; Brookhart, M. Alan; Fang, Gang

2015-01-01

Background The recent availability of dabigatran, a novel oral anticoagulant, provided a new treatment option for stroke prevention in atrial fibrillation beyond warfarin, the main therapy for years. Little is known about their real‐world comparative effectiveness and safety, even less among patient demographic and clinical subgroups. Methods and Results Using a cohort of non‐valvular AF patients initiating anticoagulation from October 2010 to December 2012 drawn from a large US database of commercial and Medicare supplement claims, we applied propensity score weights to Cox proportional hazards regression to assess the comparative effectiveness and safety of dabigatran versus warfarin. Analyses were repeated among clinical and demographic subgroups using stratum‐specific propensity scores as an exploratory analysis. Of the 64 935 patients initiating anticoagulation, 32.5% used dabigatran. Compared with warfarin, dabigatran was associated with a lower risk of ischemic stroke or systemic embolism (composite adjusted Hazard Ratio [aHR], 95% CI: 0.86, 95% CI: 0.79 to 0.93), hemorrhagic stroke (aHR: 0.51, 0.40 to 0.65), and acute myocardial infarction (aHR: 0.88, 95% CI: 0.77 to 0.99), and no relation was seen between dabigatran and the composite harm outcome (aHR: 0.94, 95% CI: 0.87 to 1.01). However, dabigatran was associated with a higher risk of gastrointestinal bleeding (aHR: 1.11, 95% CI: 1.02 to 1.22). Estimates of effectiveness and safety appeared to be mostly similar across subgroups. Conclusions Dabigatran could be a safe and potentially more effective alternative to warfarin in patients with atrial fibrillation managed in routine practice settings. PMID:25862791

Prediction of sensitivity to warfarin based on VKORC1 and CYP2C9 polymorphisms in patients from different places in Colombia.

PubMed

Cifuentes, Ricardo A; Murillo-Rojas, Juan; Avella-Vargas, Esperanza

2016-03-03

In the search to prevent hemorrhages associated with anticoagulant therapy, a major goal is to validate predictors of sensitivity to warfarin. However, previous studies in Colombia that included polymorphisms in the VKORC1 and CYP2C9 genes as predictors reported different algorithm performances to explain dose variations, and did not evaluate the prediction of sensitivity to warfarin.  To determine the accuracy of the pharmacogenetic analysis, which includes the CYP2C9 *2 and *3 and VKORC1 1639G>A polymorphisms in predicting patients' sensitivity to warfarin at the Hospital Militar Central, a reference center for patients born in different parts of Colombia.  Demographic and clinical data were obtained from 130 patients with stable doses of warfarin for more than two months. Next, their genotypes were obtained through a melting curve analysis. After verifying the Hardy-Weinberg equilibrium of the genotypes from the polymorphisms, a statistical analysis was done, which included multivariate and predictive approaches.  A pharmacogenetic model that explained 52.8% of dose variation (p<0.001) was built, which was only 4% above the performance resulting from the same data using the International Warfarin Pharmacogenetics Consortium algorithm. The model predicting the sensitivity achieved an accuracy of 77.8% and included age (p=0.003), polymorphisms *2 and *3 (p=0.002) and polymorphism 1639G>A (p<0.001) as predictors.  These results in a mixed population support the prediction of sensitivity to warfarin based on polymorphisms in VKORC1 and CYP2C9 as a valid approach in Colombian patients.

Factors influencing warfarin response in hospitalized patients

PubMed Central

Abdel-Aziz, Mahmoud I.; Ali, Mostafa A. Sayed; Hassan, Ayman K.M.; Elfaham, Tahani H.

2015-01-01

The objective of this study was to investigate the influence of simultaneous factors that potentially keep patients far from achieving target INR range at discharge in hospitalized patients. Prospective cross-sectional observational study conducted at the Cardiology Department and Intensive Care Unit (ICU) of the Assiut University Hospitals. One-hundred and twenty patients were enrolled in the study from July 2013 to January 2014. Outcome measures were discharge INRs, bleeding and thromboembolic episodes. Bivariate analysis and multinomial logistic regression were conducted to determine independent risk factors that can keep patients outside target INR range. Patients who were newly initiated warfarin on hospital admission were given low initiation dose (2.8 mg ± 0.9). They were more likely to have INR values below 1.5 during hospital stay, 13 (27.7%) patients compared with 9 (12.3%) previously treated patients, respectively (p = .034). We found that the best predictors of achieving below target INR range relative to within target INR range were; shorter hospital stay periods (OR, 0.82 for every day increase [95% CI, 0.72–0.94]), being a male patient (OR, 2.86 [95% CI, 1.05–7.69]), concurrent infection (OR, 0.21 [95% CI, 0.07–0.59]) and new initiation of warfarin therapy on hospital admission (OR, 3.73 [95% CI, 1.28–10.9]). Gender, new initiation of warfarin therapy on hospital admission, shorter hospital stay periods and concurrent infection can have a significant effect on discharge INRs. Initiation of warfarin without giving loading doses increases the risk of having INRs below 1.5 during hospital stay and increases the likelihood of a patient to be discharged with INR below target range. Following warfarin dosing nomograms and careful monitoring of the effect of various factors on warfarin response should be greatly considered. PMID:26702259

Effects of etravirine on the pharmacokinetics and pharmacodynamics of warfarin in rats

PubMed Central

John, J; John, M; Wu, L; Hsiao, C; Abobo, CV; Liang, D

2013-01-01

Background and Purpose Warfarin is often used with etravirine (ETV) to prevent HIV-related thromboembolic events. As both warfarin and ETV bind to plasma proteins and are metabolized by hepatic cytochrome P450s, they are likely to interact. Hence, we evaluated the effect of ETV on the pharmacokinetics and blood clotting time of racemic warfarin in rats. Experimental Approach Two groups of male Sprague-Dawley rats, in which the jugular vein had been cannulated, were studied. The control group (n = 10) received 1 mg·kg−1 racemic warfarin i.v., and the test group (n = 13) 1 mg·kg−1 of racemic warfarin followed by 25 mg·kg−1 ETV i.v. Serial blood samples were collected for up to 144 h and the blood clotting time (calculated as international normalized ratio [INR]) measured in blood plasma at each sample point. Plasma concentrations of R-warfarin, S-warfarin, R-7-hydroxywarfarin and S-7-hydroxywarfarin were measured by a LC/MS/MS method using a chiral lux cellulose-1 column. Pharmacokinetic parameters were analysed using non-compartmental methods. Key Results ETV significantly increased, by threefold, the systemic clearance and volume of distribution of S-warfarin, but not those of R-warfarin. ETV decreased the total AUC of warfarin, but had no effect on its elimination half-life. ETV also increased the systemic clearance of both R-7-hydroxywarfarin and S-7-hydroxywarfarin but only increased the volume of distribution of R-7-hydroxywarfarin. Interestingly, the effect of warfarin on blood clotting time (INR) was significantly increased in the presence of etravirine. Conclusion and Implications Our data suggest that etravirine may potentiate the anticoagulant effect of warfarin and this could have clinical significance. PMID:23215758

Warfarin

MedlinePlus

... forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types ... symptoms You should know that warfarin may cause necrosis or gangrene (death of skin or other body ...

An integrated epidemiological and neural net model of the warfarin effect in managed care patients.

PubMed

Jacobs, David M; Stefanovic, Filip; Wilton, Greg; Gomez-Caminero, Andres; Schentag, Jerome J

2017-01-01

Risk assessment tools are utilized to estimate the risk for stroke and need of anticoagulation therapy for patients with atrial fibrillation (AF). These risk stratification scores are limited by the information inputted into them and a reliance on time-independent variables. The objective of this study was to develop a time-dependent neural net model to identify AF populations at high risk of poor clinical outcomes and evaluate the discriminatory ability of the model in a managed care population. We performed a longitudinal, cohort study within a health-maintenance organization from 1997 to 2008. Participants were identified with incident AF irrespective of warfarin status and followed through their duration within the database. Three clinical outcome measures were evaluated including stroke, myocardial infarction, and hemorrhage. A neural net model was developed to identify patients at high risk of clinical events and defined to be an "enriched" patient. The model defines the enrichment based on the top 10 minimum mean square error output parameters that describe the three clinical outcomes. Cox proportional hazard models were utilized to evaluate the outcome measures. Among 285 patients, the mean age was 74±12 years with a mean follow-up of 4.3±2.6 years, and 154 (54%) were treated with warfarin. After propensity score adjustment, warfarin use was associated with a slightly increased risk of adverse outcomes (including stroke, myocardial infarction, and hemorrhage), though it did not attain statistical significance (adjusted hazard ratio [aHR] =1.22; 95% confidence interval [CI] 0.75-1.97; p =0.42). Within the neural net model, subjects at high risk of adverse outcomes were identified and labeled as "enriched." Following propensity score adjustment, enriched subjects were associated with an 81% higher risk of adverse outcomes as compared to nonenriched subjects (aHR=1.81; 95% CI, 1.15-2.88; p =0.01). Enrichment methodology improves the statistical

Cost-effectiveness of pharmacogenetics-guided warfarin therapy vs. alternative anticoagulation in atrial fibrillation.

PubMed

Pink, J; Pirmohamed, M; Lane, S; Hughes, D A

2014-02-01

Pharmacogenetics-guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics-guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost-effectiveness of anticoagulation treatment options. A clinical trial simulation of S-warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta-analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost-effective options. Along the cost-effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics-guided warfarin and apixaban had incremental cost-effectiveness ratios of £13,226 and £20,671 per quality-adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost-effective treatment.

The importance of mean time in therapeutic range for complication rates in warfarin therapy of patients with atrial fibrillation: A systematic review and meta-regression analysis.

PubMed

Vestergaard, Anne Sig; Skjøth, Flemming; Larsen, Torben Bjerregaard; Ehlers, Lars Holger

2017-01-01

\\Anticoagulation is used for stroke prophylaxis in non-valvular atrial fibrillation, amongst other by use of the vitamin K antagonist, warfarin. Quality in warfarin therapy is often summarized by the time patients spend within the therapeutic range (percent time in therapeutic range, TTR). The correlation between TTR and the occurrence of complications during warfarin therapy has been established, but the influence of patient characteristics in that respect remains undetermined. The objective of the present papers was to examine the association between mean TTR and complication rates with adjustment for differences in relevant patient cohort characteristics. A systematic literature search was conducted in MEDLINE and Embase (2005-2015) to identify eligible studies reporting on use of warfarin therapy by patients with non-valvular atrial fibrillation and the occurrence of hemorrhage and thromboembolism. Both randomized controlled trials and observational cohort studies were included. The association between the reported mean TTR and major bleeding and stroke/systemic embolism was analyzed by random-effects meta-regression with and without adjustment for relevant clinical cohort characteristics. In the adjusted meta-regressions, the impact of mean TTR on the occurrence of hemorrhage was adjusted for the mean age and the proportion of populations with prior stroke or transient ischemic attack. In the adjusted analyses on thromboembolism, the proportion of females was, furthermore, included. Of 2169 papers, 35 papers met pre-specified inclusion criteria, holding relevant information on 31 patient cohorts. In univariable meta-regression, increasing mean TTR was significantly associated with a decreased rate of both major bleeding and stroke/systemic embolism. However, after adjustment mean TTR was no longer significantly associated with stroke/systemic embolism. The proportion of residual variance composed by between-study heterogeneity was substantial for all analyses

A whole-body mathematical model for intracranial pressure dynamics.

PubMed

Lakin, William D; Stevens, Scott A; Tranmer, Bruce I; Penar, Paul L

2003-04-01

Most attempts to study intracranial pressure using lumped-parameter models have adopted the classical "Kellie-Monro Doctrine," which considers the intracranial space to be a closed system that is confined within the nearly-rigid skull, conserves mass, and has equal inflow and outflow. The present work revokes this Doctrine and develops a mathematical model for the dynamics of intracranial pressures, volumes, and flows that embeds the intracranial system in extensive whole-body physiology. The new model consistently introduces compartments representing the tissues and vasculature of the extradural portions of the body, including both the thoracic region and the lower extremities. In addition to vascular connections, a spinal-subarachnoid cerebrospinal fluid (CSF) compartment bridges intracranial and extracranial physiology allowing explict buffering of intracranial pressure fluctuations by the spinal theca. The model contains cerebrovascular autoregulation, regulation of systemic vascular pressures by the sympathetic nervous system, regulation of CSF production in the choroid plexus, a lymphatic system, colloid osmotic pressure effects, and realistic descriptions of cardiac output. To validate the model in situations involving normal physiology, the model's response to a realistic pulsatile cardiac output is examined. A well-known experimentally-derived intracranial pressure-volume relationship is recovered by using the model to simulate CSF infusion tests, and the effect on cerebral blood flow of a change in body position is also examined. Cardiac arrest and hemorrhagic shock are simulated to demonstrate the predictive capabilities of the model in pathological conditions.

Reducing warfarin medication interactions: an interrupted time series evaluation.

PubMed

Feldstein, Adrianne C; Smith, David H; Perrin, Nancy; Yang, Xiuhai; Simon, Steven R; Krall, Michael; Sittig, Dean F; Ditmer, Diane; Platt, Richard; Soumerai, Stephen B

2006-05-08

Computerized decision support reduces medication errors in inpatients, but limited evidence supports its effectiveness in reducing the coprescribing of interacting medications, especially in the outpatient setting. The usefulness of academic detailing to enhance the effectiveness of medication interaction alerts also is uncertain. This study used an interrupted time series design. In a health maintenance organization with an electronic medical record, we evaluated the effectiveness of electronic medical record alerts and group academic detailing to reduce the coprescribing of warfarin and interacting medications. Participants were 239 primary care providers at 15 primary care clinics and 9910 patients taking warfarin. All 15 clinics received electronic medical record alerts for the coprescription of warfarin and 5 interacting medications: acetaminophen, nonsteroidal anti-inflammatory medications, fluconazole, metronidazole, and sulfamethoxazole. Seven clinics were randomly assigned to receive group academic detailing. The primary outcome, the interacting prescription rate (ie, the number of coprescriptions of warfarin-interacting medications per 10 000 warfarin users per month), was analyzed with segmented regression models, controlling for preintervention trends. At baseline, nearly a third of patients had an interacting prescription. Coinciding with the alerts, there was an immediate and continued reduction in the warfarin-interacting medication prescription rate (from 3294.0 to 2804.2), resulting in a 14.9% relative reduction (95% confidence interval, -19.5 to -10.2) at 12 months. Group academic detailing did not enhance alert effectiveness. This study, using a strong and quasi-experimental design in ambulatory care, found that medication interaction alerts modestly reduced the frequency of coprescribing of interacting medications. Additional efforts will be required to further reduce rates of inappropriate prescribing of warfarin with interacting drugs.

Intracranial Arterial Dissection Mimicking a Saccular Aneurysm: Clinical Image.

PubMed

Rodríguez-Hernández, Ana; Torné, Ramon; Arikan, Fuat

2017-02-01

This report portrays our pitfall in the initial diagnosis of an intracranial arterial dissection that we misinterpreted as a saccular aneurysm. Intracranial arterial dissections presenting with convexity subarachnoid hemorrhage are rare, thus being easily mistaken with mild traumatic head injuries and therefore preventing transfer to a tertiary hospital. Even in those cases where the dissection is suspected and the patient is transferred to the appropriate facility for a diagnostic angiogram, misdiagnosis is not infrequent. The typical radiographic signs such as the double lumen or "pearl and string" are scarcely present in the diagnostic angiogram. Thrombus within the dissected segment can be mistaken by vasospasm and may even reveal fake images of saccular aneurysms, thus prompting inadequate endovascular or surgical treatment. The case reported here illustrates all these likely pitfalls in the diagnosis and management of intracranial arterial dissections. Copyright © 2016 Elsevier Inc. All rights reserved.

Updates on the Clinical Evidenced Herb-Warfarin Interactions

PubMed Central

Ge, Beikang; Zhang, Zhen; Zuo, Zhong

2014-01-01

Increasing and inadvertent use of herbs makes herb-drug interactions a focus of research. Concomitant use of warfarin, a highly efficacious oral anticoagulant, and herbs causes major safety concerns due to the narrow therapeutic window of warfarin. This paper presents an update overview of clinical findings regarding herb-warfarin interaction, highlighting clinical outcomes, severity of documented interactions, and quality of clinical evidence. Among thirty-eight herbs, Cannabis, Chamomile, Cranberry, Garlic, Ginkgo, Grapefruit, Lycium, Red clover, and St. John's wort were evaluated to have major severity interaction with warfarin. Herbs were also classified on account of the likelihood of their supporting evidences for interaction. Four herbs were considered as highly probable to interact with warfarin (level I), three were estimated as probable (level II), and ten and twenty-one were possible (level III) and doubtful (level IV), respectively. The general mechanism of herb-warfarin interaction almost remains unknown, yet several pharmacokinetic and pharmacodynamic factors were estimated to influence the effectiveness of warfarin. Based on limited literature and information reported, we identified corresponding mechanisms of interactions for a small amount of “interacting herbs.” In summary, herb-warfarin interaction, especially the clinical effects of herbs on warfarin therapy should be further investigated through multicenter studies with larger sample sizes. PMID:24790635

Hemorrhagic

MedlinePlus

... Hemorrhagic diseases are caused by bleeding, or they result in bleeding (hemorrhaging). Related topics include: Primary thrombocythemia (hemorrhagic thrombocythemia) Stroke Yellow fever Bleeding disorders Ebola fever Dengue hemorrhagic ...

End-Stage Liver Disease in Patients with Intracranial Hemorrhage Is Associated with Increased Mortality: A Cohort Study.

PubMed

Lagman, Carlito; Nagasawa, Daniel T; Sheppard, John P; Jacky Chen, Cheng Hao; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Pouratian, Nader; Kaldas, Fady M; Busuttil, Ronald W; Yang, Isaac

2018-05-01

To determine if end-stage liver disease (ESLD) in patients with intracranial hemorrhage (ICH) is associated with increased mortality. This single-center, retrospective cohort study included 53 patients (33 in ESLD cohort and 20 in non-ESLD cohort) who received neurosurgical care between 2006 and 2017. ESLD was defined clinically as severely impaired liver function and at least 1 major complication of liver failure. The primary outcome was mortality. Overall, in-hospital, and 30-day mortality rates were higher in the ESLD cohort versus the non-ESLD cohort (79 vs. 30%, 79 vs. 20%, and 64 vs. 25%, all P ≤ 0.01). We identified a significant difference in overall survival between ESLD and non-ESLD cohorts on Kaplan-Meier analysis (P = 0.004 with log-rank and Wilcoxon tests). Odds of overall, in-hospital, and 30-day mortality in the ESLD cohort were 8.67 (95% confidence interval [CI], 2.44-30.84), 14.86 (95% CI, 3.75-58.90), and 5.25 (95% CI, 1.53-18.08). Other predictors of overall mortality included primary admission diagnosis of liver disease (odds ratio [OR] = 9.60; 95% CI, 3.75-58.90), higher Child-Pugh (OR = 1.64; 95% CI, 2.66-34.67) and Model for End-Stage Liver Disease (OR = 1.12; 95% CI, 1.04-1.20) scores, lower Glasgow Coma Scale score (OR = 0.73; 95% CI, 0.61-0.88), ICH that developed in the hospital (OR = 4.11; 95% CI, 1.21-13.98), and intraparenchymal hemorrhage (OR = 9.23; 95% CI, 1.72-49.56). ESLD in patients with ICH is associated with increased mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

Influence of kidney function on risk of supratherapeutic international normalized ratio-related hemorrhage in warfarin users: a prospective cohort study

USDA-ARS?s Scientific Manuscript database

Background: Anticoagulation management is difficult in chronic kidney disease, with frequent supratherapeutic international normalized ratios (INRs >/= 4) increasing hemorrhagic risk. We evaluated whether the interaction of INR and lower estimated glomerular filtration rate (eGFR) increases hemorrha...

Warfarin Poisoning with Delayed Rebound Toxicity.

PubMed

Berling, Ingrid; Mostafa, Ahmed; Grice, Jeffrey E; Roberts, Michael S; Isbister, Geoffrey K

2017-02-01

Intentional poisoning with warfarin is not the same as over-anticoagulation, for which guidelines exist. The coagulopathy resulting from a warfarin overdose is reversed with vitamin K 1 , the dose and timing of which is often guided by experience with the management of over-anticoagulation with warfarin therapy, rather than acute overdose. We report a case of a 50-year-old man who ingested an unknown amount of his warfarin, venlafaxine, and paracetamol. He presented with an international normalized ratio (INR) of 2.5, which steadily increased over 24 h to 7, despite receiving an initial 1 mg of vitamin K 1 . He was then treated with 5 mg vitamin K 1 , and once the INR returned to 4.5, 40 h post ingestion, he was discharged home. He was also treated with a full course of acetylcysteine for the paracetamol overdose. The following day his INR rebounded to 8.5 and he suffered a spontaneous epistaxis requiring readmission; he was treated with low titrated doses of vitamin K 1 . The warfarin concentration was 74.6 μg/mL 26 h post ingestion and decreased to 3.7 μg/mL over 72 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case highlights the risk of a rebound elevated INR even 3 days after acute warfarin overdose despite treatment with vitamin K 1 . Understanding the pharmacokinetics of vitamin K 1 in comparison with warfarin, repeat INR testing, and continued treatment with oral vitamin K 1 may help avoid complications of rebound coagulopathy in warfarin overdose. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Inappropriate combination of warfarin and aspirin.

PubMed

Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

2016-03-01

A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

Delayed hemorrhage after surgery and radiation in suprasellar pilocytic astrocytomas

PubMed Central

Turel, Mazda K.; Kiehl, Tim-Rasmus; Gentili, Fred

2016-01-01

Delayed intracranial hemorrhage is a rare complication of treatment for central nervous system tumors. This may be secondary to malignant transformation of the tumor or vasculopathy related to radiation therapy (RT). While most reports on radiation-induced vasculopathy in children with optic pathway gliomas are associated with ischemic complications, there are only two reports of hemorrhagic complications in these patients. In both cases, the hemorrhage was asymptomatic and remote from the site of the original tumor but within the field of irradiation. We describe a female patient who underwent surgery for an optico-chiasmatic pilocytic astrocytoma (PA) at the age of 12 followed by RT at the age of 17 for tumor progression. The patient was followed with serial magnetic resonance imaging (MRI) scans showing marginal regression and no subsequent evidence of tumor recurrence, including the most recent MRI done only 6 months before the latest presentation. She then developed a symptomatic intratumoral hemorrhage at the age of 32 for which she underwent emergent surgery. To our knowledge, this is the first report of a nonaneurysmal-delayed hemorrhage within the site of previous surgery, several years after RT for a suprasellar PA. We review literature on delayed vasculopathy following the treatment of pediatric optic pathway gliomas and discuss the possible mechanisms of hemorrhage in our case. These long-term follow-up outcomes add significant insight and have implications in patient management. PMID:27857781

Contribution of three CYP3A isoforms to metabolism of R- and S-warfarin.

PubMed

Jones, Drew R; Kim, So-Young; Boysen, Gunnar; Yun, Chul-Ho; Miller, Grover P

2010-12-01

Effective coumadin (R/S-warfarin) therapy is complicated by inter-individual variability in metabolism. Recent studies have demonstrated that CYP3A isoforms likely contribute to patient responses and clinical outcomes. Despite a significant focus on CYP3A4, little is known about CYP3A5 and CYP3A7 metabolism of warfarin. Based on our studies, recombinant CYP3A4, CYP3A5 and CYP3A7 metabolized R- and S-warfarin to 10- and 4'-hydroxywarfarin with efficiencies that depended on the individual enzymes. For R-warfarin, CYP3A4, CYP3A7, and CYP3A5 demonstrated decreasing preference for 10-hydroxylation over 4'-hydroxylation. By contrast, there was no regioselectivity toward S-warfarin. While all enzymes preferentially metabolized R-warfarin, CYP3A4 was the most efficient at metabolizing all reactions. Individuals, namely African-Americans and children, with higher relative levels of CYP3A5 and/or CYP3A7, respectively, compared to CYP3A4 may metabolize warfarin less efficiently and thus may require lower doses and be at risk for adverse drug-drug interactions related to the contributions of the respective enzymes.

A computer-aided detection (CAD) system with a 3D algorithm for small acute intracranial hemorrhage

NASA Astrophysics Data System (ADS)

Wang, Ximing; Fernandez, James; Deshpande, Ruchi; Lee, Joon K.; Chan, Tao; Liu, Brent

2012-02-01

Acute Intracranial hemorrhage (AIH) requires urgent diagnosis in the emergency setting to mitigate eventual sequelae. However, experienced radiologists may not always be available to make a timely diagnosis. This is especially true for small AIH, defined as lesion smaller than 10 mm in size. A computer-aided detection (CAD) system for the detection of small AIH would facilitate timely diagnosis. A previously developed 2D algorithm shows high false positive rates in the evaluation based on LAC/USC cases, due to the limitation of setting up correct coordinate system for the knowledge-based classification system. To achieve a higher sensitivity and specificity, a new 3D algorithm is developed. The algorithm utilizes a top-hat transformation and dynamic threshold map to detect small AIH lesions. Several key structures of brain are detected and are used to set up a 3D anatomical coordinate system. A rule-based classification of the lesion detected is applied based on the anatomical coordinate system. For convenient evaluation in clinical environment, the CAD module is integrated with a stand-alone system. The CAD is evaluated by small AIH cases and matched normal collected in LAC/USC. The result of 3D CAD and the previous 2D CAD has been compared.

Oesophageal ulcer caused by warfarin.

PubMed Central

Loft, D. E.; Stubington, S.; Clark, C.; Rees, W. D.

1989-01-01

Oesophageal injury is a well recognized complication of certain oral medications but warfarin has not been implicated previously. We present a case of an oesophageal ulcer occurring in a patient with mitral regurgitation taking warfarin, and demonstrate a delayed oesophageal tablet transit time. PMID:2594605

Warfarin use and the risk of valvular calcification.

PubMed

Lerner, R G; Aronow, W S; Sekhri, A; Palaniswamy, C; Ahn, C; Singh, T; Sandhu, R; McClung, J A

2009-12-01

Warfarin affects the synthesis and function of the matrix Gla-protein, a vitamin K-dependent protein, which is a potent inhibitor of tissue calcification. To investigate the incidence of mitral valve calcium (MVC), mitral annular calcium (MAC) and aortic valve calcium (AVC) in patients with non-valvular atrial fibrillation (AF) treated with warfarin vs. no warfarin. Of 1155 patients, mean age 74 years, with AF, 725 (63%) were treated with warfarin and 430 (37%) without warfarin. The incidence of MVC, MAC and AVC was investigated in these 1155 patients with two-dimensional echocardiograms. Unadjusted logistic regression analysis was conducted to examine the association between the use of warfarin and the incidence of MVC, MAC or AVC. Logistic regression analyses were also conducted to investigate whether the relationship stands after adjustment for confounding risk factors such as age, sex, race, ejection fraction, smoking, hypertension, diabetes, dyslipidemia, coronary artery disease (CAD), glomerular filtration rate, calcium, phosphorus, calcium-phosphorus product, alkaline phosphatase, use of aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. There was a significant association between the use of warfarin and the risk of calcification [unadjusted odds ratio = 1.71, 95% CI = (1.34-2.18)]. The association still stands after adjustment for confounding risk factors. MVC, MAC or AVC was present in 473 of 725 patients (65%) on warfarin vs. 225 of 430 patients (52%) not on warfarin (P < 0.0001). Whether this is a causal relationship remains unknown. Use of warfarin in patients with AF is associated with an increased prevalence of MVC, MAC or AVC.

Analysis of Factors Related to Hypopituitarism in Patients with Nonsellar Intracranial Tumor.

PubMed

Lu, Song-Song; Gu, Jian-Jun; Luo, Xiao-Hong; Zhang, Jian-He; Wang, Shou-Sen

2017-09-01

Previous studies have suggested that postoperative hypopituitarism in patients with nonsellar intracranial tumors is caused by traumatic surgery. However, with development of minimally invasive and precise neurosurgical techniques, the degree of injury to brain tissue has been reduced significantly, especially for parenchymal tumors. Therefore, understanding preexisting hypopituitarism and related risk factors can improve perioperative management for patients with nonsellar intracranial tumors. Chart data were collected retrospectively from 83 patients with nonsellar intracranial tumors admitted to our hospital from May 2014 to April 2015. Pituitary function of each subject was determined based on results of preoperative serum pituitary hormone analysis. Univariate and multivariate logistic regression methods were used to analyze relationships between preoperative hypopituitarism and factors including age, sex, history of hypertension and secondary epilepsy, course of disease, tumor mass effect, site of tumor, intracranial pressure (ICP), cerebrospinal fluid content, and pituitary morphology. A total of 30 patients (36.14%) presented with preoperative hypopituitarism in either 1 axis or multiple axes; 23 (27.71%) were affected in 1 axis, and 7 (8.43%) were affected in multiple axes. Univariate analysis showed that risk factors for preoperative hypopituitarism in patients with a nonsellar intracranial tumor include an acute or subacute course (≤3 months), intracranial hypertension (ICP >200 mm H 2 O), and mass effect (P < 0.05). Multivariate logistic regression analysis showed that mass effect is an independent risk factor for preoperative hypopituitarism in patients with nonsellar intracranial tumors (P < 0.05; odds ratio, 3.197). Prevalence of hypopituitarism is high in patients with nonsellar intracranial tumors. The occurrence of hypopituitarism is correlated with factors including an acute or subacute course (≤3 months), intracranial hypertension (ICP >200

Warfarin: history, tautomerism and activity

NASA Astrophysics Data System (ADS)

Porter, William R.

2010-06-01

The anticoagulant drug warfarin, normally administered as the racemate, can exist in solution in potentially as many as 40 topologically distinct tautomeric forms. Only 11 of these forms for each enantiomer can be distinguished by selected computational software commonly used to estimate octanol-water partition coefficients and/or ionization constants. The history of studies on warfarin tautomerism is reviewed, along with the implications of tautomerism to its biological properties (activity, protein binding and metabolism) and chemical properties (log P, log D, p K a). Experimental approaches to assessing warfarin tautomerism and computational results for different tautomeric forms are presented.

Effectiveness and safety of rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism.

PubMed

Coleman, Craig I; Bunz, Thomas J; Turpie, Alexander G G

2017-10-05

The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012-6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline). Patients with a claim for anticoagulation at baseline were excluded. Recurrent VTE, major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) were assessed. Differences in baseline characteristics between cohorts were adjusted for using inverse probability of treatment weights based on propensity-scores. Patients had a maximum of 12-months period of follow-up post-VTE or until endpoint occurrence, switch/discontinuation of index anticoagulation, insurance disenrollment or end-of-follow-up. Cox regression was performed and reported as hazard ratios (HRs) with 95 % confidence intervals (CIs). In total, 13,609 rivaroxaban and 32,244 warfarin users experiencing VTE were included. Rivaroxaban was associated with an 19 % (95 %CI=10-27 %) reduction in recurrent VTE and a 21 % (95 %CI=4-35 %) reduction in major bleeding hazard versus warfarin. Rivaroxaban was also associated with significantly decreased hazards of ICH (HR=0.40) and GIB (HR=0.72). Rivaroxaban appears to reduce patients' hazard of both recurrent VTE and major bleeding in routine practice. These results appear consistent with EINSTEIN and post-marketing registry studies.

Warfarin

Integrated Risk Information System (IRIS)

Warfarin ; CASRN 81 - 81 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effects )

Safety and Efficacy of Bridging With Low-Molecular-Weight Heparin During Temporary Interruptions of Warfarin: A Register-Based Cohort Study.

PubMed

Sjögren, Vilhelm; Grzymala-Lubanski, Bartosz; Renlund, Henrik; Svensson, Peter J; Själander, Anders

2017-11-01

Low-molecular-weight heparin (LMWH) is often recommended as a bridging therapy during temporary interruptions in warfarin treatment, despite lack of evidence. The aim of this study was to see whether we could find benefit from LMWH bridging. We studied all planned interruptions of warfarin within the Swedish anticoagulation register Auricula during 2006 to 2011. Low-molecular-weight heparin bridging was compared to nonbridging (control) after propensity score matching. Complications were identified in national clinical registers for 30 days following warfarin cessation, and defined as all-cause mortality, bleeding (intracranial, gastrointestinal, or other), or thrombosis (ischemic stroke or systemic embolism, venous thromboembolism, or myocardial infarction) that was fatal or required hospital care. Of the 14 556 identified warfarin interruptions, 12 659 with a known medical background had a mean age of 69 years, 61% were males, mean CHADS 2 (1 point for each of congestive heart failure, hypertension, age ≥75 years, diabetes, and 2 points for stroke or transient ischemic attack) score was 1.7, and CHA 2 DS 2 -VASc score was 3.4. The total number of LMWH bridgings was 7021. Major indications for anticoagulation were mechanical heart valve prostheses 4331, atrial fibrillation 1097, and venous thromboembolism 1331. Bridging patients had a higher rate of thrombotic events overall. Total risk of any complication did not differ significantly between bridging (1.5%) and nonbridging (1.2%). Regardless of indication for warfarin treatment, we found no benefit from bridging. The type of procedure prompting bridging was not known, and the likely reason for the observed higher risk of thrombosis with LMWH bridging is that low-risk procedures more often meant no bridging. Results from randomized trials are needed, especially for patients with mechanical heart valves.

Feasibility of implementing a comprehensive warfarin pharmacogenetics service.

PubMed

Nutescu, Edith A; Drozda, Katarzyna; Bress, Adam P; Galanter, William L; Stevenson, James; Stamos, Thomas D; Desai, Ankit A; Duarte, Julio D; Gordeuk, Victor; Peace, David; Kadkol, Shrihari S; Dodge, Carol; Saraf, Santosh; Garofalo, John; Krishnan, Jerry A; Garcia, Joe G N; Cavallari, Larisa H

2013-11-01

To determine the procedural feasibility of a pharmacist-led interdisciplinary service for providing genotype-guided warfarin dosing for hospitalized patients newly starting warfarin. Prospective observational study. A 438-bed tertiary care hospital affiliated with a large academic institution. Eighty patients who started warfarin therapy and were managed by a newly implemented pharmacogenetics service. All patients received routine warfarin genotyping and clinical pharmacogenetics consultation. The primary outcomes were percentage of genotype-guided dose recommendations available prior to the second warfarin dose and adherence of the medical staff to doses recommended by the pharmacogenetics service. Of 436 genotype orders placed during the first 6 months of the service, 190 (44%) were deemed appropriate. For the 80 patients on the service who consented to data collection, 76% of the genotypes were available prior to the second warfarin dose. The median (range) time from genotype order to genotype result was 26 hours (7-80 hrs), and the time to genotype-guided dose recommendation was 30 hours (7-80 hrs). A total of 73% of warfarin doses ordered by the medical staff were within 0.5 mg of the daily dose recommended by the pharmacogenetics consult service. Providing routine genotype-guided warfarin dosing supported by a pharmacogenetics consult service is feasible from a procedural standpoint, with most genotypes available prior to the second warfarin dose and good adherence to genotype-guided dose recommendations by the medical staff. © 2013 Pharmacotherapy Publications, Inc.

Feasibility of Implementing a Comprehensive Warfarin Pharmacogenetics Service

PubMed Central

Nutescu, Edith A.; Drozda, Katarzyna; Bress, Adam P.; Galanter, William L.; Stevenson, James; Stamos, Thomas D.; Desai, Ankit A.; Duarte, Julio D.; Gordeuk, Victor; Peace, David; Kadkol, ShriHari S.; Dodge, Carol; Saraf, Santosh; Garofalo, John; Krishnan, Jerry A.; Garcia, Joe G.N.; Cavallari, Larisa H.

2013-01-01

Objective To determine the procedural feasibility of a pharmacist-led interdisciplinary service for providing genotype-guided warfarin dosing for hospitalized patients newly starting warfarin. Design Prospective observational study Setting 483-bed hospital affiliated with a large academic institution Participants Eighty patients started on warfarin and managed by a newly implemented pharmacogenetics service. Intervention Routine warfarin genotyping and clinical pharmacogenetics consultation Measurements and Main Results The primary outcomes were percent of genotype-guided dose recommendations available prior to the second warfarin dose and adherence of the medical staff to doses recommended by the pharmacogenetics service. Of 436 genotype orders during the first 6 months of the service, 190 were deemed appropriate. For 80 patients on the service who consented to data collection, 77% of genotypes were available prior to the second warfarin dose. The median (range) time from the genotype order to the genotype result was 26 (7 to 80) hours, and the time to genotype-guided dosing recommendation was 30 (7 to 80) hours. Seventy-three percent of warfarin doses ordered by the medical staff were within 0.5 mg of the dose recommended by the pharmacogenetics consult service. Conclusions Providing routine genotype-guided warfarin dosing supported by a pharmacogenetics consult service is feasible from a procedural standpoint, with the majority of genotypes available prior to the second warfarin dose and good adherence to genotype-guided dose recommendations by the medical staff. PMID:23864527

Subarachnoid and Intracerebral Hemorrhage in Patients with Churg-Strauss Syndrome: Two Case Reports

PubMed Central

Go, Myeong Hoon; Park, Jeong Un; Kang, Jae Gyu

2012-01-01

Churg-Strauss syndrome (CSS) is a systemic necrotizing vasculitis of the small and medium vessels, associated with extravascular eosinophilic granulomas, peripheral eosinophilia, and asthma. The exact etiology of CSS is unknown. This syndrome commonly affects the lungs, peripheral nerves, skin, heart, and gastrointestinal tract, but rarely the central nervous system. Subarachnoid and intracerebral hemorrhage in CSS patients is extremely rare; however, clinicians should consider that CSS may be a cause of intracranial hemorrhage and its high rate of mortality and morbidity. The authors report on two cases of subarachnoid and intracerebral hemorrhage with CSS and discuss a brief review of CSS. PMID:23210058

Validation of Clinical Testing for Warfarin Sensitivity

PubMed Central

Langley, Michael R.; Booker, Jessica K.; Evans, James P.; McLeod, Howard L.; Weck, Karen E.

2009-01-01

Responses to warfarin (Coumadin) anticoagulation therapy are affected by genetic variability in both the CYP2C9 and VKORC1 genes. Validation of pharmacogenetic testing for warfarin responses includes demonstration of analytical validity of testing platforms and of the clinical validity of testing. We compared four platforms for determining the relevant single nucleotide polymorphisms (SNPs) in both CYP2C9 and VKORC1 that are associated with warfarin sensitivity (Third Wave Invader Plus, ParagonDx/Cepheid Smart Cycler, Idaho Technology LightCycler, and AutoGenomics Infiniti). Each method was examined for accuracy, cost, and turnaround time. All genotyping methods demonstrated greater than 95% accuracy for identifying the relevant SNPs (CYP2C9 *2 and *3; VKORC1 −1639 or 1173). The ParagonDx and Idaho Technology assays had the shortest turnaround and hands-on times. The Third Wave assay was readily scalable to higher test volumes but had the longest hands-on time. The AutoGenomics assay interrogated the largest number of SNPs but had the longest turnaround time. Four published warfarin-dosing algorithms (Washington University, UCSF, Louisville, and Newcastle) were compared for accuracy for predicting warfarin dose in a retrospective analysis of a local patient population on long-term, stable warfarin therapy. The predicted doses from both the Washington University and UCSF algorithms demonstrated the best correlation with actual warfarin doses. PMID:19324988

Inappropriate combination of warfarin and aspirin

PubMed Central

Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

2016-01-01

Objective: A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). Methods: This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Results: Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). Conclusion: The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV. (Anatol J Cardiol 2016; 16: 189-96) PMID:26467380

The pharmacokinetics and pharmacodynamics of single dose (R)- and (S)-warfarin administered separately and together: relationship to VKORC1 genotype

PubMed Central

Maddison, John; Somogyi, Andrew A; Jensen, Berit P; James, Heather M; Gentgall, Melanie; Rolan, Paul E

2013-01-01

AIMS 1) To determine the pharmacokinetics and pharmacodynamics of (R)- and (S)-warfarin given alone and in combination and 2) to determine whether the relative potency of (R)- and (S)-warfarin is dependent on VKORC1 genotype. METHODS A three way crossover study was conducted in which 17 healthy male subjects stratified by VKORC1 1173 C>T genotype and all CYP2C9 1*/1* received (R)-warfarin 80 mg, (S)-warfarin 12.5 mg and rac-warfarin sodium 25 mg. Plasma (R)- and (S)-warfarin unbound and total concentrations and prothrombin time were determined at multiple time points to 168 h. RESULTS Pharmacokinetic parameters for (R)- and (S)-warfarin were similar to the literature. (R)-warfarin 80 mg alone resulted in a mean AUCPT (0,168 h) of 3550 s h (95% CI 3220, 3880). Rac-warfarin sodium 25 mg containing (S)-warfarin 11.7 mg produced a greater effect on AUCPT (0,168 h) than (S)-warfarin 12.5 mg (mean difference 250 s.h, 95% CI 110, 380, P < 0.002) given alone. In a mixed effects model the ratio of response between (R)- and (S)-warfarin (AUCPT((R)-warfarin) : AUCPT((S)-warfarin)) was 1.21 fold higher (95% CI 1.05, 1.41, P < 0.02) in subjects of VKORC1 TT genotype compared with the CC genotype. CONCLUSIONS (R)-warfarin has a clear PD effect and contributes to the hypoprothrombinaemic effect of rac-warfarin. VKORC1 genotype is a covariate of the relative R/S potency relationship. Prediction of drug interactions with warfarin needs to consider effects on (R)-warfarin PK and VKORC1 genotype. PMID:22616655

Intracranial subdural hematomas with elevated rivaroxaban concentration and subsequently detected spinal subdural hematoma: A case report.

PubMed

Yamaguchi, Yoshitaka; Koga, Masatoshi; Matsuki, Takayuki; Hino, Tenyu; Yokota, Chiaki; Toyoda, Kazunori

2016-07-01

A 79-year-old lean man with a height of 157cm and weight of 42kg (body mass index, 17.2kg/m(2)) receiving rivaroxaban developed an intracranial subdural hematoma and was treated conservatively. Because he had a reduced creatinine clearance of 44mL/min, his dosage of rivaroxaban was reduced from 15 to 10mg daily according to official Japanese prescribing information. However, he developed bilateral intracranial subdural hematomas 2weeks later. Plasma rivaroxaban concentration on anti-factor Xa chromogenic assay was elevated at 301ng/mL, suggesting excessive accumulation. He underwent burr hole drainage and resumed anticoagulation with warfarin. Subsequently, he developed a lumbosacral hematoma. He was treated conservatively and discharged without neurological sequelae. The main cause of the increased concentration of rivaroxaban was believed to be his older age and low body weight. The etiology of the spinal hematoma was suspected to be the migration of intracranial hematoma to the spinal subdural space. Copyright © 2016 Elsevier Ltd. All rights reserved.

The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms.

PubMed

Reynolds, Matthew R; Buckley, Robert T; Indrakanti, Santoshi S; Turkmani, Ali H; Oh, Gerald; Crobeddu, Emanuela; Fargen, Kyle M; El Ahmadieh, Tarek Y; Naidech, Andrew M; Amin-Hanjani, Sepideh; Lanzino, Giuseppe; Hoh, Brian L; Bendok, Bernard R; Zipfel, Gregory J

2015-10-01

Vasopressor-induced hypertension (VIH) is an established treatment for patients with aneurysmal subarachnoid hemorrhage (SAH) who develop vasospasm and delayed cerebral ischemia (DCI). However, the safety of VIH in patients with coincident, unruptured, unprotected intracranial aneurysms is uncertain. This retrospective multiinstitutional study identified 1) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who required VIH therapy (VIH group), and 2) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who did not require VIH therapy (non-VIH group). All patients had previously undergone surgical or endovascular treatment for the presumed ruptured aneurysm. Comparisons between the VIH and non-VIH patients were made in terms of the patient characteristics, clinical and radiographic severity of SAH, total number of aneurysms, number of ruptured/unruptured aneurysms, aneurysm location/size, number of unruptured and unprotected aneurysms during VIH, severity of vasospasm, degree of hypervolemia, and degree and duration of VIH therapy. For the VIH group (n = 176), 484 aneurysms were diagnosed, 231 aneurysms were treated, and 253 unruptured aneurysms were left unprotected during 1293 total days of VIH therapy (5.12 total years of VIH therapy for unruptured, unprotected aneurysms). For the non-VIH group (n = 73), 207 aneurysms were diagnosed, 93 aneurysms were treated, and 114 unruptured aneurysms were left unprotected. For the VIH and non-VIH groups, the mean sizes of the ruptured (7.2 ± 0.3 vs 7.8 ± 0.6 mm, respectively; p = 0.27) and unruptured (3.4 ± 0.2 vs 3.2 ± 0.2 mm, respectively; p = 0.40) aneurysms did not differ. The authors observed 1 new SAH from a previously unruptured, unprotected aneurysm in each group (1 of 176 vs 1 of 73 patients; p = 0.50). Baseline patient characteristics and comorbidities were similar between groups. While the degree of hypervolemia was similar between the VIH and non-VIH patients

Extra-intracranial blood shunt mimicking aneurysm rupture: intracranial-pressure-controlled rabbit subarachnoid hemorrhage model.

PubMed

Marbacher, Serge; Sherif, Camillo; Neuschmelting, Volker; Schläppi, Janine-Ai; Takala, Jukka; Jakob, Stephan M; Fandino, Javier

2010-08-30

The achieved degree of delayed cerebral vasospasm (DCVS) in the rabbits most frequently applied cistern magna blood injection model is often mild. The aim of this study was to characterize and evaluate the feasibility of an experimental SAH technique that mimics pathophysiological mechanisms and triggers higher degrees of DCVS. SAH was induced by extracranial-intracranial (EC/IC) shunting of blood from the subclavian artery into the great cerebral cistern. Intracranial pressure (ICP), arterial blood pressure, heart rate, arterial blood gas analysis, and neurological status were monitored throughout the experiments. The magnitude of spasm was determined by comparison of pre-SAH (day 0) and post-SAH (day 3) angiograms and postmortem morphometric analysis of the basilar artery. A total of 13 experiments (SAH, n=11; controls, n=2) were performed. Two animals died after initiation of the EC/IC blood shunt in respiratory arrest. In SAH animals, ICP (baseline: 12+/-1 [mean+/-SD]; peak: 51+/-4; steady-state level: 15+/-2 mm Hg) rose to diastolic blood pressure levels (56+/-3 mm Hg) within 98+/-20s, and fell to a steady state within 186+/-41 s. SAH-induced vasoconstriction of the basilar artery was 53.1+/-2.8% on day 3 compared to baseline (P<0.05) and histology confirmed marked vasoconstriction. This novel technique of SAH induction closely mimics the pathophysiological sequelae of aneurysm rupture and triggers constant higher degrees of delayed cerebral vasospasm than previously described rabbit models. The severity of vasospasm attained offers a unique opportunity to evaluate future therapeutic treatment options. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Current management of symptomatic intracranial stenosis.

PubMed

Taylor, Robert A; Weigele, John B; Kasner, Scott E

2011-08-01

Intracranial arterial stenosis (IAS) is the cause of about 10% of all ischemic strokes in the United States, but may account for about 40% of strokes in some populations. After a stroke or transient ischemic attack due to IAS, patients face a 12% annual risk of recurrent stroke on medical therapy, with most strokes occurring in the first year. Warfarin is no better than aspirin in preventing recurrent strokes but poses a higher risk of serious bleeding and death. Groups with the highest risk of recurrent stroke are those with high-grade (≥ 70%) stenosis, those with recent symptom onset, those with symptoms precipitated by hemodynamic maneuvers, and women. Endovascular treatment of IAS is a rapidly evolving therapeutic option. Antiplatelet agents are currently recommended as the primary treatment for symptomatic IAS, with endovascular therapy reserved for appropriate high-risk cases refractory to medical therapy.

Patient satisfaction with extended-interval warfarin monitoring.

PubMed

Carris, Nicholas W; Hwang, Andrew Y; Smith, Steven M; Taylor, James R; Sando, Karen; Powell, Jason; Rosenberg, Eric I; Zumberg, Marc S; Gums, John G; Dietrich, Eric A; Anderson, Katherine Vogel

2016-11-01

Extended-interval monitoring of warfarin has been proposed to reduce follow-up burden and improve patient satisfaction. We aimed to make an initial assessment of anticoagulation satisfaction before and after an extended-interval warfarin monitoring intervention. We conducted a translational prospective single-arm pilot study of extended-interval warfarin monitoring in five pharmacist-managed anticoagulation clinics. Patients meeting CHEST guideline criteria for extended-interval warfarin monitoring began progressive extended-interval follow-up (6, 8, and 12 weeks thereafter). The Duke Anticoagulation Satisfaction Scale (DASS) was administered at baseline and at end-of-study or study removal (in patients no longer appropriate for extended interval follow-up). Forty-six patients had evaluable pre- and post-intervention DASS survey data. Mean age of patients was 66.5 years, 74 % were non-Hispanic whites, and 48 % were men. Patients completed a mean ± SD of 34 ± 22 weeks of follow-up. Mean ± SD total DASS score at baseline was 45.2 ± 14.2 versus 49.1 ± 14.9 at end-of-study (mean change, +3.9 [95 % CI -0.6-8.4; p = 0.09]), indicating no benefit-and trending toward decrement-to anticoagulation satisfaction. Change in anticoagulation satisfaction varied substantially following extended-interval monitoring, with no evidence of improved satisfaction. Plausible reasons for patients not preferring extended-interval monitoring include increased anxiety and disengagement from self-management activities, both potentially related to less frequent feedback and reassurance during extended interval-monitoring. Additional research is needed to identify who is likely to benefit most from extended-interval monitoring. Anticoagulation satisfaction should be considered with clinical factors and shared-decision making when implementing extended-interval warfarin monitoring.

[Dabigatran versus warfarin for the prevention of stroke in Chinese patients with nonvalvular atrial fibrillation: Chinese subpopulation analysis of RE-LY].

PubMed

Gao, X; Yang, Y M; Zhu, J; Dai, Y; Tan, H Q

2016-11-24

Objective: This analysis was performed to evaluate the efficacy in stroke prevention and safety of dabigatran in Chinese nonvalvular atrial fibrillation(NVAF) patients enrolled in RE-LY trial. Methods: RE-LY was an prospective, open-label, randomized, multicenter study. From March 2006 to March 2009, 541 atrial fibrillation patients at risk of stroke were recruited from 13 medical centers in China. Patients randomly received, in a blinded fashion, fixed doses of dabigatran-110 mg or 150 mg twice daily or, in an unblinded fashion, adjusted-dose warfarin. The primary efficacy endpoint was stroke or systemic embolism. The primary safety endpoint was major bleeding. Results: The incidence of stroke in the Chinese subpopulation was 1.94% per year(7 cases) in the group that received 110 mg of dabigatran (dabigatran 110) and 1.10% per year(4 cases) in the group that received 150 mg of dabigatran (dabigatran 150), as compared with 2.87% per year (10 cases) in warfarin group . Incidence of ischemic stroke was 1.11% per year(4 patients) in dabigatran 110 group, 0.82% per year(3 cases) in dabigatran 150 group and 2.01% per year(7 patients) in warfarin group. Incidence of hemorrhagic stroke was 0.28% per year(1 case) in dabigatran 110 group, 0.27% per year(1 case) in dabigatran 150 group and 0.57% per year(2 cases) in warfarin group. All-cause mortality was similar among the three treatment groups: 3.33% per year(12 cases) in dabigatran 110, 2.19% per year(8 cases) in dabigatran 150 and 2.58% per year(9 cases) in warfarin group. Incidence of major bleeding event was 0.56% per year(2 cases) in both dabigatran groups, as compared with 1.43% per year(5 cases) in warfarin group. Gastrointestinal disorders such as dyspepsia occurred in 12.8% patients of both dabigatran groups, and in 5.6% patients of warfarin group. Conclusions: Despite the descriptive statistical analysis in nature of present study due to the limited number of subjects, our subgroup analysis implies that like

Patient Attitudinal and Behavioral Factors Associated with Warfarin Non-adherence at Outpatient Anticoagulation Clinics

PubMed Central

Localio, A. Russell; Platt, Alec B.; Brensinger, Colleen M.; Christie, Jason D.; Gross, Robert; Parker, Catherine S.; Price, Maureen; Metlay, Joshua P.; Cohen, Abigail; Newcomb, Craig W.; Strom, Brian L.; Kimmel, Stephen E.

2010-01-01

Background Warfarin is an anticoagulant effective in preventing stroke, but it has a narrow therapeutic range requiring optimal adherence to achieve the most favorable effects. Purpose The goal of this study was to examine specific patient factors that might help explain warfarin non-adherence at outpatient anticoagulation clinics. Method In a prospective cohort study of 156 adults, we utilized logistic regression analyses to examine the relationship between the five Treatment Prognostics scales from the Millon Behavioral Medicine Diagnostic (MBMD), as well as three additional MBMD scales (Depression, Future Pessimism, and Social Isolation), and daily warfarin non-adherence assessed using electronic medication event monitoring systems caps over a median of 139 days. Results Four of the five Treatment Prognostic scales and greater social isolation were associated with warfarin non-adherence. When controlling for pertinent demographic and medical variables, the Information Discomfort scale remained significantly associated with warfarin non-adherence over time. Conclusion Although several factors were related to warfarin non-adherence, patients reporting a lack of receptivity to details regarding their medical illness seemed most at risk for warfarin non-adherence. This information might aid in the development of interventions to enhance warfarin adherence and perhaps reduce adverse medical events. PMID:19579066

Managing Nonoperable Intracranial Bleeding Associated With Apixaban: A Series of 2 Cases.

PubMed

Faust, Andrew C; Tran, Dang M; Lo, Catherine; Lai, Sophia; Sheperd, Lyndsay; Liu, Mary; Denetclaw, Tina

2018-02-01

To report 2 cases of nonoperable intracranial bleeding associated with apixaban managed by 3-factor prothrombin complex concentrate (PCC3). Case 1 presented with a 1.3-cm left parieto-occipital hemorrhage and a thin subdural hematoma (SDH) on the left tentorium of the brain about 6 hours after his last dose of apixaban. Case 2 presented with a 4-mm left parafalcine SDH with time of most recent apixaban dose unknown. The patients received 24.9 to 25.5 U/kg of PCC3 with none to 1 U fresh frozen plasma (FFP) and demonstrated minimal or no progression in lesions measured by repeat computed tomography (CT) after treatment. One patient was discharged to a skilled nursing facility after 8 days; the other patient was discharged to home after 18 days. Apixaban has no specific antidote. Current bleeding management strategies are based on expert opinion. The risks and benefits for differing strategies are unclear, and little clinical experience for managing apixaban-associated intracranial bleeding has been reported to date. These cases describe the clinical use of PCC3 to manage parieto-occipital and subdural hemorrhage associated with apixaban in events not requiring surgical intervention. In these 2 cases, 25 U/kg PCC3, with none to one unit FFP, ceased apixaban-associated intracranial bleeding without apparent thrombogenic complications.

CYP2C9 Genotype-Dependent Warfarin Pharmacokinetics: Impact of CYP2C9 Genotype on R- and S-Warfarin and Their Oxidative Metabolites.

PubMed

Flora, Darcy R; Rettie, Allan E; Brundage, Richard C; Tracy, Timothy S

2017-03-01

Multiple factors can impact warfarin therapy, including genetic variations in the drug-metabolizing enzyme cytochrome P450 2C9 (CYP2C9). Compared with individuals with the wild-type allele, CYP2C9*1, carriers of the common *3 variant have significantly impaired CYP2C9 metabolism. Genetic variations in CYP2C9, the primary enzyme governing the metabolic clearance of the more potent S-enantiomer of the racemic anticoagulant warfarin, may impact warfarin-drug interactions. To establish a baseline for such studies, plasma and urine concentrations of R- and S-warfarin and 10 warfarin metabolites were monitored for up to 360 hours following a 10-mg warfarin dose in healthy subjects with 4 different CYP2C9 genotypes: CYP2C9*1/*1 (n = 8), CYP2C9*1/*3 (n = 9), CYP2C9*2/*3 (n = 3), and CYP2C9*3/*3 (n = 4). Plasma clearance of S-warfarin, but not R-warfarin, decreased multiexponentially and in a CYP2C9 gene-dependent manner: 56%, 70%, and 75% for CYP2C9*1/*3, CYP2C9*2/*3, and CYP2C9*3/*3 genotypes, respectively, compared with CYP2C9*1/*1, resulting in pronounced differences in the S:R ratio that identified warfarin-sensitive genotypes. CYP2C9 was the primary P450 enzyme contributing to S-warfarin metabolism and a minor contributor to R-warfarin metabolism. In the presence of a defective CYP2C9 allele, switching of warfarin metabolism to other oxidative pathways and P450 enzymes for the metabolic elimination of S-warfarin was not observed. The 10-hydroxywarfarin metabolites, whose detailed pharmacokinetics are reported for the first time, exhibited a prolonged half-life with no evidence of renal excretion and displayed elimination rate-limited kinetics. Understanding the impact of CYP2C9 genetics on warfarin pharmacokinetics lays the foundation for future genotype-dependent warfarin-drug interaction studies. © 2016, The American College of Clinical Pharmacology.

Topical Antimycotics for Oral Candidiasis in Warfarin Users.

PubMed

Hellfritzsch, Maja; Pottegård, Anton; Pedersen, Andreas James Thestrup; Burghle, Alaa; Mouaanaki, Fatima; Hallas, Jesper; Grove, Erik Lerkevang; Damkier, Per

2017-04-01

Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical database, and obtained information on their use of topically applied miconazole and nystatin from a regional prescription register. Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. Among 17 warfarin users exposed to miconazole oral gel, the mean INR increased from 2.5 (95% CI: 2.1-2.8) to 3.8 (95% CI: 2.8-4.8) after exposure, corresponding to a mean INR increase of 1.4 (95% CI: 0.3-2.4). Among 30 warfarin users exposed to nystatin oral solution, the mean INR was 2.7 (95% CI: 2.3-3.1) before and 2.5 (95% CI: 2.2-2.9) after exposure. In conclusion, we found evidence supporting a clinically relevant drug-drug interaction between warfarin and miconazole oral gel. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Pharmacogenomics of warfarin in populations of African descent

PubMed Central

Suarez-Kurtz, Guilherme; Botton, Mariana R

2013-01-01

Warfarin is the most commonly prescribed oral anticoagulant worldwide despite its narrow therapeutic index and the notorious inter- and intra-individual variability in dose required for the target clinical effect. Pharmacogenetic polymorphisms are major determinants of warfarin pharmacokinetic and dynamics and included in several warfarin dosing algorithms. This review focuses on warfarin pharmacogenomics in sub-Saharan peoples, African Americans and admixed Brazilians. These ‘Black’ populations differ in several aspects, notably their extent of recent admixture with Europeans, a factor which impacts on the frequency distribution of pharmacogenomic polymorphisms relevant to warfarin dose requirement for the target clinical effect. Whereas a small number of polymorphisms in VKORC1 (3673G > A, rs9923231), CYP2C9 (alleles *2 and *3, rs1799853 and rs1057910, respectively) and arguably CYP4F2 (rs2108622), may capture most of the pharmacogenomic influence on warfarin dose variance in White populations, additional polymorphisms in these, and in other, genes (e.g. CALU rs339097) increase the predictive power of pharmacogenetic warfarin dosing algorithms in the Black populations examined. A personalized strategy for initiation of warfarin therapy, allowing for improved safety and cost-effectiveness for populations of African descent must take into account their pharmacogenomic diversity, as well as socio-economical, cultural and medical factors. Accounting for this heterogeneity in algorithms that are ‘friendly’ enough to be adopted by warfarin prescribers worldwide requires gathering information from trials at different population levels, but demands also a critical appraisal of racial/ethnic labels that are commonly used in the clinical pharmacology literature but do not accurately reflect genetic ancestry and population diversity. PMID:22676711

Prospective surveillance pilot of rivaroxaban safety within the US Food and Drug Administration Sentinel System.

PubMed

Chrischilles, Elizabeth A; Gagne, Joshua J; Fireman, Bruce; Nelson, Jennifer; Toh, Sengwee; Shoaibi, Azadeh; Reichman, Marsha E; Wang, Shirley; Nguyen, Michael; Zhang, Rongmei; Izem, Rima; Goulding, Margie R; Southworth, Mary Ross; Graham, David J; Fuller, Candace; Katcoff, Hannah; Woodworth, Tiffany; Rogers, Catherine; Saliga, Ryan; Lin, Nancy D; McMahill-Walraven, Cheryl N; Nair, Vinit P; Haynes, Kevin; Carnahan, Ryan M

2018-03-01

The US Food and Drug Administration's Sentinel system developed tools for sequential surveillance. In patients with non-valvular atrial fibrillation, we sequentially compared outcomes for new users of rivaroxaban versus warfarin, employing propensity score matching and Cox regression. A total of 36 173 rivaroxaban and 79 520 warfarin initiators were variable-ratio matched within 2 monitoring periods. Statistically significant signals were observed for ischemic stroke (IS) (first period) and intracranial hemorrhage (ICH) (second period) favoring rivaroxaban, and gastrointestinal bleeding (GIB) (second period) favoring warfarin. In follow-up analyses using primary position diagnoses from inpatient encounters for increased definition specificity, the hazard ratios (HR) for rivaroxaban vs warfarin new users were 0.61 (0.47, 0.79) for IS, 1.47 (1.29, 1.67) for GIB, and 0.71 (0.50, 1.01) for ICH. For GIB, the HR varied by age: <66 HR = 0.88 (0.60, 1.30) and 66+ HR = 1.49 (1.30, 1.71). This study demonstrates the capability of Sentinel to conduct prospective safety monitoring and raises no new concerns about rivaroxaban safety. Copyright © 2018 John Wiley & Sons, Ltd.

Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.

PubMed

Moyer, Thomas P; O'Kane, Dennis J; Baudhuin, Linnea M; Wiley, Carmen L; Fortini, Alexandre; Fisher, Pamela K; Dupras, Denise M; Chaudhry, Rajeev; Thapa, Prabin; Zinsmeister, Alan R; Heit, John A

2009-12-01

The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1

Scleroderma en coup de sabre with recurrent episodes of brain hemorrhage.

PubMed

Takahashi, Takehiro; Asano, Yoshihide; Oka, Tomonori; Miyagaki, Tomomitsu; Tamaki, Zenshiro; Nonaka, Senshu; Sato, Shinichi

2016-02-01

We report a 39-year-old man referred to our facility with linear sclerotic lesions along the several Blaschko's lines of the scalp. A year before the referral, he had had an episode of brain hemorrhage, although there was no evidence of vascular malformation or any other risk factors of brain hemorrhage for his young age. On the diagnosis of scleroderma en coup de sabre, prednisolone intake was initiated, and the skin lesions were well controlled. However, in the course of our follow up, he had another episode of brain hemorrhage, again without any evidence of cerebral vascular abnormalities. Organic intracranial abnormalities in this disease are well-documented, but there have been few reports on comorbid recurrent brain hemorrhages. We herein discuss the possible relationship of the skin lesions with the brain hemorrhages in our case, taking notice of the implication of developmental abnormalities behind these apparently independent phenomena inside and outside the cranium. © 2015 Japanese Dermatological Association.

Management of Major Bleeding in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice (from Phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF II]).

PubMed

Steinberg, Benjamin A; Simon, DaJuanicia N; Thomas, Laine; Ansell, Jack; Fonarow, Gregg C; Gersh, Bernard J; Kowey, Peter R; Mahaffey, Kenneth W; Peterson, Eric D; Piccini, Jonathan P

2017-05-15

Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights

Gastrointestinal Hemorrhage Related to Fluoxetine in a Patient With Stroke.

PubMed

Wee, Tze Chao

2017-11-01

We report on a patient who developed massive gastrointestinal hemorrhage related to the use of fluoxetine in combination with aspirin and clopidogrel. A 58-year-old man was admitted with a posterior circulation infarct with significant weakness in all four limbs and dysarthria. Aspirin and clopidogrel were started. Fluoxetine was started for pharmacological neurostimulation to promote motor recovery and for low mood. He developed gastrointestinal hemorrhage a week after fluoxetine was started. Fluoxetine was suspended and investigations failed to reveal the source of the bleeding. He was then restarted on fluoxetine along with dual antiplatelets, and gastrointestinal hemorrhage recurred after 1 week. He was extensively investigated for a source of gastrointestinal hemorrhage, and again no source could be identified. Eventually, fluoxetine was switched to mirtazapine with no further gastrointestinal hemorrhage. He remained on dual antiplatelets. A number of case-control and cohort studies had identified the association of gastrointestinal hemorrhage with the use of selective serotonin reuptake inhibitor (SSRI). We hope to raise awareness of this association in physical medicine and rehabilitation physicians as the use of SSRI is expected to rise.

Oral warfarin affects peripheral blood leukocyte IL-6 and TNFα production in rats.

PubMed

Popov, Aleksandra; Belij, Sandra; Subota, Vesna; Zolotarevski, Lidija; Mirkov, Ivana; Kataranovski, Dragan; Kataranovski, Milena

2013-01-01

Warfarin is a Vitamin K (VK) antagonist that affects Vitamin K-dependent (VKD) processes, including blood coagulation, as well as processes unrelated to hemostasis such as bone growth, calcification, and growth of some cell types. In addition, warfarin exerts influence on some non-VKD-related activities, including anti-tumor and immunomodulating activity. With respect to the latter, both immune stimulating and suppressive effects have been noted in different experimental systems. To explore the in vivo immunomodulatory potential of warfarin on one type of activity (i.e., cytokine production) in two different immune cell populations (i.e., mononuclear or polymorphonuclear cells), effects of subchronic oral warfarin intake in rats on pro-inflammatory cytokine (i.e., TNFα, IL-6) production by peripheral blood mononuclear and polymorphonuclear cells (granulocytes) was examined. Differential effects of warfarin intake on TNFα and IL-6 were noted, depending on the type of peripheral blood leukocytes and on the cytokine examined. Specifically, a lack of effect on TNFα and a priming of IL-6 production by mononuclear cells along with a decrease in TNFα and a lack of effect on IL-6 in polymorphonuclear cells were seen in warfarin-exposed hosts. The cell- and cytokine-dependent effects from subchronic oral warfarin intake on peripheral blood leukocytes demonstrated in this study could, possibly, differentially affect reactions mediated by these cells. Ultimately, the observed effects in rats might have implications for those humans who are on long-term/prolonged warfarin therapy.

RNA interference therapy: a new solution for intracranial atherosclerosis?

PubMed Central

Tang, Tao; Wong, Ka-Sing

2014-01-01

Intracranial atherosclerotic stenosis (ICAS) of a major intracranial artery, especially middle cerebral artery (MCA), is reported to be one leading cause of ischemic stroke throughout the world. Compared with other stroke subtypes, ICAS is associated with a higher risk of recurrent stroke despite aggressive medical therapy. Increased understanding of the pathophysiology of ICAS has highlighted several possible targets for therapeutic interventions. Both luminal stenosis and plaque components of ICAS have been found to be associated with ischemic stroke based a post-mortem study. Recent application of high-resolution magnetic resonance imaging (HRMRI) in evaluating ICAS provides new insight into the vascular biology of plaque morphology and component. High signal on T1-weighted fat-suppressed images (HST1) within MCA plaque of HRMRI, highly suggested of fresh or recent intraplaque hemorrhage, has been found to be associated with ipsilateral brain infarction. Thus, the higher prevalence of intraplaque hemorrhage and neovasculature in symptomatic patients with MCA stenosis may provide a potential target for plaque stabilization. We hypothesize that RNA interference (RNAi) therapy delivered by modified nanoparticles may achieve in vivo biomedical imaging and targeted therapy. With the rapid developments in studies about therapeutic and diagnostic nanomaterials, future studies further exploring the molecular biology of atherosclerosis may provide more drug targets for plaque stabilization. PMID:25333054

Pharmacogenomics of warfarin in populations of African descent.

PubMed

Suarez-Kurtz, Guilherme; Botton, Mariana R

2013-02-01

Warfarin is the most commonly prescribed oral anticoagulant worldwide despite its narrow therapeutic index and the notorious inter- and intra-individual variability in dose required for the target clinical effect. Pharmacogenetic polymorphisms are major determinants of warfarin pharmacokinetic and dynamics and included in several warfarin dosing algorithms. This review focuses on warfarin pharmacogenomics in sub-Saharan peoples, African Americans and admixed Brazilians. These 'Black' populations differ in several aspects, notably their extent of recent admixture with Europeans, a factor which impacts on the frequency distribution of pharmacogenomic polymorphisms relevant to warfarin dose requirement for the target clinical effect. Whereas a small number of polymorphisms in VKORC1 (3673G > A, rs9923231), CYP2C9 (alleles *2 and *3, rs1799853 and rs1057910, respectively) and arguably CYP4F2 (rs2108622), may capture most of the pharmacogenomic influence on warfarin dose variance in White populations, additional polymorphisms in these, and in other, genes (e.g. CALU rs339097) increase the predictive power of pharmacogenetic warfarin dosing algorithms in the Black populations examined. A personalized strategy for initiation of warfarin therapy, allowing for improved safety and cost-effectiveness for populations of African descent must take into account their pharmacogenomic diversity, as well as socio-economical, cultural and medical factors. Accounting for this heterogeneity in algorithms that are 'friendly' enough to be adopted by warfarin prescribers worldwide requires gathering information from trials at different population levels, but demands also a critical appraisal of racial/ethnic labels that are commonly used in the clinical pharmacology literature but do not accurately reflect genetic ancestry and population diversity. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Intracranial aneurysms: Review of current science and management.

PubMed

Toth, Gabor; Cerejo, Russell

2018-06-01

Unruptured intracranial aneurysms often have a relatively benign clinical course. Frequently, they are found incidentally during workup for an underlying, possibly related or unrelated, symptom or condition. Overall, brain aneurysms are considered to have a relatively low annual risk of rupture. However, should it occur, aneurysmal subarachnoid hemorrhage can lead to significant morbidity and mortality. Our understanding of the natural history and treatment outcomes of cerebral aneurysms has significantly increased over the last few decades, but choosing the optimal management for each patient requires the careful consideration of numerous medical, clinical and anatomic factors. The purpose of this review is to help physicians and caregivers, who may participate in the diagnosis, counseling and triage of patients with brain aneurysms, understand the basic elements of decision making. We discuss natural history, risk factors, screening, presentation, diagnosis, and their implications on aneurysm management and long-term follow-up. We also provide an overview of the risks and benefits of currently available treatment options.

Validation of clinical testing for warfarin sensitivity: comparison of CYP2C9-VKORC1 genotyping assays and warfarin-dosing algorithms.

PubMed

Langley, Michael R; Booker, Jessica K; Evans, James P; McLeod, Howard L; Weck, Karen E

2009-05-01

Responses to warfarin (Coumadin) anticoagulation therapy are affected by genetic variability in both the CYP2C9 and VKORC1 genes. Validation of pharmacogenetic testing for warfarin responses includes demonstration of analytical validity of testing platforms and of the clinical validity of testing. We compared four platforms for determining the relevant single nucleotide polymorphisms (SNPs) in both CYP2C9 and VKORC1 that are associated with warfarin sensitivity (Third Wave Invader Plus, ParagonDx/Cepheid Smart Cycler, Idaho Technology LightCycler, and AutoGenomics Infiniti). Each method was examined for accuracy, cost, and turnaround time. All genotyping methods demonstrated greater than 95% accuracy for identifying the relevant SNPs (CYP2C9 *2 and *3; VKORC1 -1639 or 1173). The ParagonDx and Idaho Technology assays had the shortest turnaround and hands-on times. The Third Wave assay was readily scalable to higher test volumes but had the longest hands-on time. The AutoGenomics assay interrogated the largest number of SNPs but had the longest turnaround time. Four published warfarin-dosing algorithms (Washington University, UCSF, Louisville, and Newcastle) were compared for accuracy for predicting warfarin dose in a retrospective analysis of a local patient population on long-term, stable warfarin therapy. The predicted doses from both the Washington University and UCSF algorithms demonstrated the best correlation with actual warfarin doses.

Comparison of Aspirin and Naoxintong Capsule () with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase.

PubMed

Wang, Huan; Zhou, Xiao-Kai; Zheng, Li-Fan; Wu, Xiao-Ying; Chen, Hui

2018-04-01

To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule (, NXT) and aspirin with adjusted-dose warfarin in Chinese elderly patients (over 65 years) with nonvalvular atrial fibrillation (NVAF) and genetic variants of vitamin K epoxide reductase (VKORC1), who are at high-risk of thromboembolism. A total of 151 patients, with NVAF and AA genotype of VKORC1-1639 (a sensitive genotype to warfarin) and a CHA 2 DS 2 -VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin (100 mg/day) and NXT (1.6 g thrice a day) or adjusted-dose warfarin [international normalized ratio 2.0-3.0). The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding (secondary event) in the combination therapy group was lower than that in the adjusted-dose warfarin group (0% vs. 7.9%, odds ratio: 0.921, 95% confidence interval: 0.862-0.984, P=0.028). Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin. (No. ChiCTR-TRC-13003596).

New Target-Specific Oral Anticoagulants and Intracranial Bleeding: Management and Outcome in a Single-Center Case Series.

PubMed

Senger, Sebastian; Keiner, Dörthe; Hendrix, Philipp; Oertel, Joachim

2016-04-01

New target-specific anticoagulants such as the direct thrombin inhibitor dabigatran and the factor Xa inhibitor rivaroxaban are used in an increasing number of patients. Several studies comparing these new oral anticoagulants with vitamin K antagonists revealed a lower risk of severe bleeding complications and reduced thromboembolic events. However, the lack of antidotes is a challenging issue in the treatment of traumatic or spontaneous intracranial hemorrhage. A retrospective analysis of patients with intracranial bleeding under new oral anticoagulants was performed; these patients were admitted to our department between January 2011 and November 2014. Treatment, reversal management of blood coagulopathy, and outcome of the patients were analyzed. Seventeen patients were included. The median age was 80.4 years. Seven patients were treated with dabigatran and 10 with rivaroxaban. Eight patients had traumatic intracranial bleeding and 9 patients had spontaneous intracranial hemorrhage. Complex perioperative hematologic treatment followed. In 9 cases, the clinical outcome was devastating with severe neurologic deficits (n = 2), comatose status (n = 4), or death (n = 3). Patients with the indication for acute surgical treatment had a high risk for a critical clinical outcome. Only a few case reports have analyzed the clinical course and the outcome after intracranial bleeding under new target-specific oral anticoagulants. Here, one of the first larger series is presented. Because of the lack of reversibility of the anticoagulative effects and the overall risks with geriatric patients, surgical treatment should be delayed as long as possible and comorbidities have to be considered. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute intracranial hemorrhage secondary to thrombocytopenia: CT appearances unaffected by absence of clot retraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierce, J.N.; Taber, K.H.; Hayman, L.A.

To describe the in vivo CT appearance of acute intracerebral blood clots formed from anemic platelet-depleted blood. Three patients with intracerebral hemorrhage secondary only to thrombocytopenia were examined with CT within 2 1/2 hours after the onset of clinical symptoms. There were no unusual CT features found in the intracerebral hemorrhages of patients with only thrombocytopenia. Specifically, a hyperdense zone(s) surrounded by areas of decreased density was identified. Clot retraction (which cannot occur in patients with severe thrombocytopenia) is not necessary for the CT appearance of acute intracerebral hemorrhage. 22 refs., 3 figs., 1 tab.

Major bleeding caused by warfarin in a genetically susceptible patient.

PubMed

Bloch, Aharon; Ben-Chetrit, Eldad; Muszkat, Mordechai; Caraco, Yoseph

2002-01-01

A 90-year-old woman was hospitalized for gastrointestinal bleeding. Although she had been receiving only warfarin 5 mg/day, her international normalized ratio (INR) was 66. Warfarin was discontinued, and her INR fell to 3.7 after transfusion of fresh-frozen plasma. However, it rose again spontaneously to 7.5. Eleven days after the last dose of warfarin had been administered, it was still detectable in the patient's plasma, indicating that impaired warfarin clearance may have caused an enhanced anticoagulation effect. Genetic analysis of the cytochrome P450 (CYP) isoenzyme 2C9, which mediates the major deactivating pathway of S-warfarin, revealed that the patient was a compound heterozygote carrying two variant alleles: CYP2C9*2 and CYP2C9*3. The patient's enhanced sensitivity to warfarin 5 mg/day can be ascribed to decreased clearance of S-warfarin secondary to genetic alteration of the gene encoding CYP2C9, resulting in a life-threatening complication.

Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in "real-world" clinical practice. A propensity-matched analysis of 76,940 patients.

PubMed

Li, Xiaoyan Shawn; Deitelzweig, Steve; Keshishian, Allison; Hamilton, Melissa; Horblyuk, Ruslan; Gupta, Kiran; Luo, Xuemei; Mardekian, Jack; Friend, Keith; Nadkarni, Anagha; Pan, Xianying; Lip, Gregory Y H

2017-06-02

The ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA 2 DS 2 -VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59-0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54-0.65) than warfarin initiators. Different types of stroke/SE and major bleeding - including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding - were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA 2 DS 2 -VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest "real-world" study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with

Factors influencing warfarin control in Australia and Singapore.

PubMed

Bernaitis, Nijole; Ching, Chi Keong; Teo, Siew Chong; Chen, Liping; Badrick, Tony; Davey, Andrew K; Crilly, Julia; Anoopkumar-Dukie, Shailendra

2017-09-01

Warfarin is widely used for patients with non-valvular atrial fibrillation (NVAF). Variations in warfarin control, as measured by time in therapeutic range (TTR), have been reported across different regions and ethnicities, particularly between Western and Asian countries. However, there is limited data on comparative factors influencing warfarin control in Caucasian and Asian patients. Therefore, the aim of this study was to determine warfarin control and potential factors influencing this in patients with NVAF in Australia and Singapore. Retrospective data was collected for patients receiving warfarin for January to June 2014 in Australia and Singapore. TTR was calculated for individuals with mean patient TTR used for analysis. Possible influential factors on TTR were analysed including age, gender, concurrent co-morbidities, and concurrent medication. The mean TTR was significantly higher in Australia (82%) than Singapore (58%). At both sites, chronic kidney disease significantly lowered this TTR. Further factors influencing control were anaemia and age<60years in Australia, and vascular disease, CHA 2 DS 2 -VASc score of 6, and concurrent platelet inhibitor therapy in Singapore. Warfarin control was significantly higher in Australia compared to Singapore, however chronic kidney disease reduced control at both sites. The different levels of control in these two countries, together with patient factors further reducing control may impact on anticoagulant choice in these countries with better outcomes from warfarin in Australia compared to Singapore. Copyright © 2017 Elsevier Ltd. All rights reserved.

Noninvasive detection of intracerebral hemorrhage using near-infrared spectroscopy (NIRS)

NASA Astrophysics Data System (ADS)

Hennes, Hans-Juergen; Lott, Carsten; Windirsch, Michael; Hanley, Daniel F.; Boor, Stephan; Brambrink, Ansgar; Dick, Wolfgang

1998-01-01

Intracerebral Hemorrhage (IH) is an important cause of secondary brain injury in neurosurgical patients. Early identification and treatment improve neurologic outcome. We have tested Near Infrared Spectroscopy (NIRS) as an alternative noninvasive diagnostic tool compared to CT-Scans to detect IH. We prospectively studied 212 patients with neurologic symptoms associated with intracranial pathology before performing a CT-scan. NIRS signals indicated pathologies in 181 cases (sensitivity 0.96; specificity 0.29). In a subgroup of subdural hematomas NIRS detected 45 of 46 hematomas (sensitivity 0.96; specificity 0.79). Identification of intracerebral hemorrhage using NIRS has the potential to allow early treatment, thus possibly avoiding further injury.

Noninvasive detection of intracerebral hemorrhage using near-infrared spectroscopy (NIRS)

NASA Astrophysics Data System (ADS)

Hennes, Hans J.; Lott, C.; Windirsch, Michael; Hanley, Daniel F.; Boor, Stephan; Brambrink, Ansgar; Dick, Wolfgang

1997-12-01

Intracerebral Hemorrhage (IH) is an important cause of secondary brain injury in neurosurgical patients. Early identification and treatment improve neurologic outcome. We have tested Near Infrared Spectroscopy (NIRS) as an alternative noninvasive diagnostic tool compared to CT-Scans to detect IH. We prospectively studied 212 patients with neurologic symptoms associated with intracranial pathology before performing a CT-scan. NIRS signals indicated pathologies in 181 cases (sensitivity 0.96; specificity 0.29). In a subgroup of subdural hematomas NIRS detected 45 of 46 hematomas (sensitivity 0.96; specificity 0.79). Identification of intracerebral hemorrhage using NIRS has the potential to allow early treatment, thus possibly avoiding further injury.

Canadian experience with the pipeline embolization device for repair of unruptured intracranial aneurysms.

PubMed

O'Kelly, C J; Spears, J; Chow, M; Wong, J; Boulton, M; Weill, A; Willinsky, R A; Kelly, M; Marotta, T R

2013-02-01

Flow-diverting stents, such as the PED, have emerged as a novel means of treating complex intracranial aneurysms. This retrospective analysis of the initial Canadian experience provides insight into technical challenges, clinical and radiographic outcomes, and complication rates after the use of flow-diverting stents for unruptured aneurysms. Cases were compiled from 7 Canadian centers between July 2008 and December 2010. Each center prospectively tracked their initial experience; these data were retrospectively updated and pooled for analysis. During the defined study period, 97 cases of unruptured aneurysm were treated with the PED, with successful stent deployment in 94 cases. The overall complete or near-complete occlusion rate was 83%, with a median follow-up at 1.25 years (range 0.25-2.5 years). Progressive occlusion was witnessed over time, with complete or near-complete occlusion in 65% of aneurysms followed through 6 months, and 90% of aneurysms followed through 1 year. Multivariate analysis found previous aneurysm treatment and female sex predictive of persistent aneurysm filling. Most patients were stable or improved (88%), with the most favorable outcomes observed in patients with cavernous carotid aneurysms. The overall mortality rate was 6%. Postprocedural aneurysm hemorrhage occurred in 3 patients (3%), while ipsilateral distal territory hemorrhage was observed in 4 patients (3.4%). Flow-diverting stents represent an important tool in the treatment of complex intracranial aneurysms. The relative efficacy and morbidity of this treatment must be considered in the context of available alternate interventions.

The Creating an Optimal Warfarin Nomogram (CROWN) Study

PubMed Central

Perlstein, Todd S.; Goldhaber, Samuel Z.; Nelson, Kerrie; Joshi, Victoria; Morgan, T. Vance; Lesko, Lawrence J.; Lee, Joo-Yeon; Gobburu, Jogarao; Schoenfeld, David; Kucherlapati, Raju; Freeman, Mason W.; Creager, Mark A.

2014-01-01

A significant proportion of warfarin dose variability is explained by variation in the genotypes of the cytochrome P450 CYP2C9 and the vitamin K epoxide reductase complex, VKORC1, enzymes that influence warfarin metabolism and sensitivity, respectively. We sought to develop an optimal pharmacogenetic warfarin dosing algorithm that incorporated clinical and genetic information. We enroled patients initiating warfarin therapy. Genotyping was performed of the VKORC1, –1639G>A, the CYP2C9*2, 430C>T, and the CYP2C9*3, 1075C>A genotypes. The initial warfarin dosing algorithm (Algorithm A) was based upon established clinical practice and published warfarin pharmacogenetic information. Subsequent dosing algorithms (Algorithms B and Algorithm C) were derived from pharmacokinetic / pharmacodynamic (PK/PD) modelling of warfarin dose, international normalised ratio (INR), clinical and genetic factors from patients treated by the preceding algorithm(s). The primary outcome was the time in the therapeutic range, considered an INR of 1.8 to 3.2. A total of 344 subjects are included in the study analyses. The mean percentage time within the therapeutic range for each subject increased progressively from Algorithm A to Algorithm C from 58.9 (22.0), to 59.7 (23.0), to 65.8 (16.9) percent (p = 0.04). Improvement also occurred in most secondary endpoints, which included the per-patient percentage of INRs outside of the therapeutic range (p = 0.004), the time to the first therapeutic INR (p = 0.07), and the time to achieve stable therapeutic anticoagulation (p < 0.001). In conclusion, warfarin pharmacogenetic dosing can be optimised in real time utilising observed PK/PD information in an adaptive fashion. Clinical Trial Registration ClinicalTrials.gov (NCT00401414) PMID:22116191

Correlations between the enantio- and regio-selective metabolisms of warfarin.

PubMed

Takahashi, Harumi; Ohara, Minami; Shibata, Soichi; Lee, Ming Ta Michael; Cavallari, Larisa H; Nutescu, Edith A; Scordo, Maria G; Pengo, Vittorio; Padrini, Roberto; Atsuda, Koichiro; Matsubara, Hajime; Chen, Yuan Tsong; Echizen, Hirotoshi

2017-01-01

To clarify whether the activities of multiple CYPs associated with warfarin metabolism would be correlated with each other. Oral clearances (CLpo) of warfarin enantiomers were estimated in 378 Chinese, Caucasians and African-Americans. The partial metabolic clearances (CLm) for 7-hydroxywarfarin enantiomers were also measured. In addition, CLpo and CLm were determined in a patient on warfarin and rifampicin. Correlations between CLpo for warfarin enantiomers existed across the three populations. In addition, there was a significant correlation between the CLm for 7-hydroxylation of warfarin enantiomers. Under induced conditions by rifampicin, there were significant correlations between the enantio- and regio-selective metabolisms of warfarin. Metabolic activities of CYP2C9, CYP1A2 and CYP3A4 may be regulated by common transcriptional mechanism(s).

Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study.

PubMed

Gulløv, A L; Koefoed, B G; Petersen, P; Pedersen, T S; Andersen, E D; Godtfredsen, J; Boysen, G

1998-07-27

Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients. The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996. We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P = .67). After 3 years, no difference among the groups was seen. Major bleeding events were rare. Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.

Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders-Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency.

PubMed

Alavi, Seyed Ezatolla Rafiee; Jalalvand, Masumeh; Assadollahi, Vahideh; Tabibian, Shadi; Dorgalaleh, Akbar

2018-04-01

Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm 3 . Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding

Unruptured intracranial aneurysms in the Familial Intracranial Aneurysm and International Study of Unruptured Intracranial Aneurysms cohorts: differences in multiplicity and location.

PubMed

Mackey, Jason; Brown, Robert D; Moomaw, Charles J; Sauerbeck, Laura; Hornung, Richard; Gandhi, Dheeraj; Woo, Daniel; Kleindorfer, Dawn; Flaherty, Matthew L; Meissner, Irene; Anderson, Craig; Connolly, E Sander; Rouleau, Guy; Kallmes, David F; Torner, James; Huston, John; Broderick, Joseph P

2012-07-01

Familial predisposition is a recognized nonmodifiable risk factor for the formation and rupture of intracranial aneurysms (IAs). However, data regarding the characteristics of familial IAs are limited. The authors sought to describe familial IAs more fully, and to compare their characteristics with a large cohort of nonfamilial IAs. The Familial Intracranial Aneurysm (FIA) study is a multicenter international study with the goal of identifying genetic and other risk factors for formation and rupture of IAs in a highly enriched population. The authors compared the FIA study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort with regard to patient demographic data, IA location, and IA multiplicity. To improve comparability, all patients in the ISUIA who had a family history of IAs or subarachnoid hemorrhage were excluded, as well as all patients in both cohorts who had a ruptured IA prior to study entry. Of 983 patients enrolled in the FIA study with definite or probable IAs, 511 met the inclusion criteria for this analysis. Of the 4059 patients in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 individuals in the analysis. Multiplicity was more common in the FIA patients (35.6% vs 27.9%, p<0.001). The FIA patients had a higher proportion of IAs located in the middle cerebral artery (28.6% vs 24.9%), whereas ISUIA patients had a higher proportion of posterior communicating artery IAs (13.7% vs 8.2%, p=0.016). Heritable structural vulnerability may account for differences in IA multiplicity and location. Important investigations into the underlying genetic mechanisms of IA formation are ongoing.

Economic Evaluation of the Combined Use of Warfarin and Low-dose Aspirin Versus Warfarin Alone in Mechanical Valve Prostheses.

PubMed

El-Hamamsy, Manal H; Elsisi, Gihan H; Eldessouki, Randa; Elmazar, Mohamed M; Taha, Ahmed S; Awad, Basma F; Elmansy, Hossam

2016-08-01

The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in Egypt. A previous Markov model cost-effectiveness study on Egyptian patients aged 50-60 years demonstrated that the combined therapy reduces the overall treatment cost. However, due to the lack of actual real-world data on cost-effectiveness and the limitation of the Markov model study to 50- to 60-year-old patients, the Egyptian medical community is still questioning whether the added benefit is worth the cost. To assess, from the perspective of the Egyptian health sector, the cost-effectiveness of the combined use of warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients with mechanical heart valve prostheses who began therapy between the age of 15 and 50 years. An economic evaluation was conducted alongside a randomized, controlled trial to assess the cost-effectiveness of the combined therapy in patients with mechanical valve prostheses. A total of 316 patients aged between 15 and 50 years were included in the study and randomly assigned to a group treated with both warfarin and aspirin or a group treated with warfarin alone. The patients in the combined therapy group exhibited a significantly longer duration of protection against the first event. Fewer primary events were observed in the patients treated with warfarin plus aspirin than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013-0.118), although this difference did not reach a conventional level of statistical significance. The total costs over a 4-year period were lower with the combined therapy (difference -US$244; 95 % CI -US$483.1 to -US$3.8), which

Lonomia obliqua venom: In vivo effects and molecular aspects associated with the hemorrhagic syndrome.

PubMed

Pinto, Antônio F M; Berger, Markus; Reck, José; Terra, Renata M S; Guimarães, Jorge A

2010-12-15

Caterpillar envenomation has been an emergent health issue. Lonomia obliqua is a medically important animal that causes a hemorrhagic syndrome that can progress to acute renal failure, intracranial hemorrhage and death. In the past few years the molecular characterization of L. obliqua venom in addition to experimental models has provided fundamental information to the understanding of the envenomation syndrome. Herein studies from several authors which characterized the complex toxic-pharmacological actions of whole venom are reviewed. Copyright © 2010 Elsevier Ltd. All rights reserved.

Risk for intracranial pressure increase related to enclosed air in post-craniotomy patients during air ambulance transport: a retrospective cohort study with simulation.

PubMed

Brändström, Helge; Sundelin, Anna; Hoseason, Daniela; Sundström, Nina; Birgander, Richard; Johansson, Göran; Winsö, Ola; Koskinen, Lars-Owe; Haney, Michael

2017-05-12

Post-craniotomy intracranial air can be present in patients scheduled for air ambulance transport to their home hospital. We aimed to assess risk for in-flight intracranial pressure (ICP) increases related to observed intracranial air volumes, hypothetical sea level pre-transport ICP, and different potential flight levels and cabin pressures. A cohort of consecutive subdural hematoma evacuation patients from one University Medical Centre was assessed with post-operative intracranial air volume measurements by computed tomography. Intracranial pressure changes related to estimated intracranial air volume effects of changing atmospheric pressure (simulating flight and cabin pressure changes up to 8000 ft) were simulated using an established model for intracranial pressure and volume relations. Approximately one third of the cohort had post-operative intracranial air. Of these, approximately one third had intracranial air volumes less than 11 ml. The simulation estimated that the expected changes in intracranial pressure during 'flight' would not result in intracranial hypertension. For intracranial air volumes above 11 ml, the simulation suggested that it was possible that intracranial hypertension could develop 'inflight' related to cabin pressure drop. Depending on the pre-flight intracranial pressure and air volume, this could occur quite early during the assent phase in the flight profile. DISCUSSION: These findings support the idea that there should be radiographic verification of the presence or absence of intracranial air after craniotomy for patients planned for long distance air transport. Very small amounts of air are clinically inconsequential. Otherwise, air transport with maintained ground-level cabin pressure should be a priority for these patients.

Factors influencing medication knowledge and beliefs on warfarin adherence among patients with atrial fibrillation in China.

PubMed

Zhao, Shujuan; Zhao, Hongwei; Wang, Xianpei; Gao, Chuanyu; Qin, Yuhua; Cai, Haixia; Chen, Boya; Cao, Jingjing

2017-01-01

Warfarin is often used for ischemic stroke prevention in patients with atrial fibrillation (AF), but the factors affecting patient adherence to warfarin therapy have not been fully understood. A cross-sectional survey was conducted in AF patients undergoing warfarin therapy at least 6 months prior to the study. The clinical data collected using questionnaires by phone interviews included the following: 1) self-reported adherence measured by the Morisky Medication Adherence Scale-8 © ; 2) beliefs about medicines surveyed by Beliefs about Medicines Questionnaire (BMQ); and 3) drug knowledge as measured by the Warfarin Related Knowledge Test (WRKT). Demographic and clinical factors associated with warfarin adherence were identified using a logistic regression model. Two hundred eighty-eight patients completed the survey and 93 (32.3%) of them were classified as nonadherent (Morisky Medication Adherence Scale-8 score <6). Major factors predicting warfarin adherence included age, cardiovascular disorders, WRKT, and BMQ; WRKT and BMQ were independently correlated with adherence to warfarin therapy by multivariate logistic regression analysis. Adherents were more likely to have greater knowledge scores and stronger beliefs in the necessity of their specific medications ([odds ratio {OR} =1.81, 95% confidence interval {CI} =1.51-2.15] and [OR =1.17, 95% CI =1.06-1.29], respectively). Patients with greater concerns about adverse reactions and more negative views of general harm were more likely to be nonadherent ([OR =0.76, 95% CI =0.69-0.84] and [OR =0.82, 95% CI =0.73-0.92], respectively). BMK and WRKT are related with patient behavior toward warfarin adherence. BMQ can be applied to identify patients at increased risk of nonadherence.

Evaluation of the effect of torsemide on warfarin dosage requirements.

PubMed

Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

2017-08-01

Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

Antihyperglycemic Agents Are Inversely Associated With Intracranial Aneurysm Rupture.

PubMed

Can, Anil; Castro, Victor M; Yu, Sheng; Dligach, Dmitriy; Finan, Sean; Gainer, Vivian S; Shadick, Nancy A; Savova, Guergana; Murphy, Shawn; Cai, Tianxi; Weiss, Scott T; Du, Rose

2018-01-01

Previous studies have suggested a protective effect of diabetes mellitus on aneurysmal subarachnoid hemorrhage risk. However, reports are inconsistent, and objective measures of hyperglycemia in these studies are lacking. Our aim was to investigate the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agent use and glycated hemoglobin levels. The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariate and multivariate logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agents and glycated hemoglobin levels. Propensity score weighting was used to account for selection bias. In both unweighted and weighted multivariate analysis, antihyperglycemic agent use was inversely and significantly associated with ruptured aneurysms (unweighted odds ratio, 0.58; 95% confidence interval, 0.39-0.87; weighted odds ratio, 0.57; 95% confidence interval, 0.34-0.96). In contrast, glycated hemoglobin levels were not significantly associated with rupture status. Antihyperglycemic agent use rather than hyperglycemia is associated with decreased risk of aneurysmal subarachnoid hemorrhage, suggesting a possible protective effect of glucose-lowering agents in the pathogenesis of aneurysm rupture. © 2017 American Heart Association, Inc.

Intraventricular Hemorrhage in Adults.

PubMed

Naff

1999-07-01

Intraventricular hemorrhage (IVH) in adults usually occurs in the setting of aneurysmal subarachnoid hemorrhage or hypertension-related intracerebral hemorrhage. Thus, the underlying cause of IVH is apparent from history and radiographic findings. If the underlying cause of IVH is not apparent, additional studies, including cerebral angiography, magnetic resonance imaging, and toxicology screening, should be performed to identify etiologic agents that may alter management of IVH. Management of IVH is thus done amidst (and must be tempered by) the multiple pharmacologic, surgical, and critical care interventions directed toward the diagnosis and treatment of the underlying cause of IVH. The most immediate threat to life posed by IVH is the development of acute obstructive hydrocephalus. If the hydrocephalus is contributing to a neurologic decline, it must be treated emergently with external ventricular drainage (EVD) through an intraventricular catheter (IVC). The patient with IVH should be evaluated and treated for deficient clotting function before an IVC is inserted. For this purpose, clotting function can be adequately assessed by prothrombin and partial thromboplastin times. Insertion of an IVC may significantly lower intracranial pressure, increasing the transmural pressure difference across the wall of a ruptured cerebral aneurysm and precipitating rerupture of the aneurysm. Therefore, with IVH secondary to a ruptured cerebral aneurysm, it is advisable to delay treatment of hydrocephalus that is not contributing to a neurologic decline until the aneurysm is repaired. Hydrocephalus contributing to significant neurologic decline in the setting of a ruptured aneurysm must be treated immediately despite the unprotected status of the aneurysm. Extreme diligence must be used to allow for the slow, controlled release of cerebrospinal fluid after IVC insertion. This will mitigate the effects of increasing the transmural pressure gradient across the wall of the

Measuring Blast-Related Intracranial Pressure Within the Human Head

DTIC Science & Technology

2011-02-01

AWARD NUMBER: W81XWH-09- 1 -0498 TITLE: Measuring Blast-Related Intracranial Pressure Within...REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour...valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1 . REPORT DATE 1 February 2011 2. REPORT TYPE Final 3. DATES

Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study.

PubMed

Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

2018-03-01

While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to 'flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a 'MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (p<0.001) and MBR factors score (p=0.013) but not ATRIA and ORBIT scores. When HAS-BLED was compared to other bleeding scores, c-indexes were significantly higher compared to MBR factors (p<0.001) and ORBIT (p=0.05) scores for major bleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all p<0.001). When NRI was performed, HAS-BLED outperformed all other bleeding risk scores for major bleeding (all p<0.001). C-indexes for ATRIA and ORBIT scores suggested no significant prediction for ICH. All contemporary bleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major

Interaction of quercetin and its metabolites with warfarin: Displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme.

PubMed

Poór, Miklós; Boda, Gabriella; Needs, Paul W; Kroon, Paul A; Lemli, Beáta; Bencsik, Tímea

2017-04-01

Flavonoids are ubiquitous molecules in nature with manifold pharmacological effects. Flavonoids interact with several proteins, and thus potentially interfere with the pharmacokinetics of various drugs. Though much is known about the protein binding characteristics of flavonoid aglycones, the behaviour of their metabolites, which are extensively formed in the human body has received little attention. In this study, the interactions of the flavonoid aglycone quercetin and its main metabolites with the albumin binding of the oral anticoagulant warfarin were investigated by fluorescence spectroscopy and ultrafiltration. Furthermore, the inhibitory effects of these flavonoids on CYP2C9 enzyme were tested because the metabolic elimination of warfarin is catalysed principally by this enzyme. Herein, we demonstrate that each tested flavonoid metabolite can bind to human serum albumin (HSA) with high affinity, some with similar or even higher affinity than quercetin itself. Quercetin metabolites are able to strongly displace warfarin from HSA suggesting that high quercetin doses can strongly interfere with warfarin therapy. On the other hand, tested flavonoids showed no or weaker inhibition of CYP2C9 compared to warfarin, making it very unlikely that quercetin or its metabolites can significantly inhibit the CYP2C9-mediated inactivation of warfarin. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Factors influencing medication knowledge and beliefs on warfarin adherence among patients with atrial fibrillation in China

PubMed Central

Zhao, Shujuan; Zhao, Hongwei; Wang, Xianpei; Gao, Chuanyu; Qin, Yuhua; Cai, Haixia; Chen, Boya; Cao, Jingjing

2017-01-01

Objectives Warfarin is often used for ischemic stroke prevention in patients with atrial fibrillation (AF), but the factors affecting patient adherence to warfarin therapy have not been fully understood. Methods A cross-sectional survey was conducted in AF patients undergoing warfarin therapy at least 6 months prior to the study. The clinical data collected using questionnaires by phone interviews included the following: 1) self-reported adherence measured by the Morisky Medication Adherence Scale-8©; 2) beliefs about medicines surveyed by Beliefs about Medicines Questionnaire (BMQ); and 3) drug knowledge as measured by the Warfarin Related Knowledge Test (WRKT). Demographic and clinical factors associated with warfarin adherence were identified using a logistic regression model. Results Two hundred eighty-eight patients completed the survey and 93 (32.3%) of them were classified as nonadherent (Morisky Medication Adherence Scale-8 score <6). Major factors predicting warfarin adherence included age, cardiovascular disorders, WRKT, and BMQ; WRKT and BMQ were independently correlated with adherence to warfarin therapy by multivariate logistic regression analysis. Adherents were more likely to have greater knowledge scores and stronger beliefs in the necessity of their specific medications ([odds ratio {OR} =1.81, 95% confidence interval {CI} =1.51–2.15] and [OR =1.17, 95% CI =1.06–1.29], respectively). Patients with greater concerns about adverse reactions and more negative views of general harm were more likely to be nonadherent ([OR =0.76, 95% CI =0.69–0.84] and [OR =0.82, 95% CI =0.73–0.92], respectively). Conclusion BMK and WRKT are related with patient behavior toward warfarin adherence. BMQ can be applied to identify patients at increased risk of nonadherence. PMID:28223782

Human Albumin Improves Long-Term Behavioral Sequelae After Subarachnoid Hemorrhage Through Neurovascular Remodeling.

PubMed

Xie, Yi; Liu, Wenhua; Zhang, Xiaohao; Wang, Liumin; Xu, Lili; Xiong, Yunyun; Yang, Lian; Sang, Hongfei; Ye, Ruidong; Liu, Xinfeng

2015-10-01

Subarachnoid hemorrhage results in significant long-lasting neurologic sequelae. Here, we investigated whether human albumin improves long-term outcomes in experimental subarachnoid hemorrhage and whether neurovascular remodeling is involved in the protection of albumin. Laboratory investigation. Hospital research laboratory. Male Sprague-Dawley rats. Rats underwent subarachnoid hemorrhage by endovascular perforation. Albumin of either 0.63 or 1.25 g/kg was injected IV immediately after the surgery. Modified Garcia test, beam-walking test, novel object recognition, and Morris water maze were employed to determine the behavioral deficits. The effects of albumin on early neurovascular dysfunction and chronic synaptic plasticity were also studied. Both doses of albumin significantly improved the sensorimotor scores (F = 31.277; p = 0.001) and cognitive performance (F = 7.982; p = 0.001 in novel object recognition test; and F = 3.431; p = 0.026 in the latency analysis of Morris water maze test) for at least 40 days after subarachnoid hemorrhage. There were remarkable microvasculature hypoperfusion, intracranial pressure rise, early vasoconstriction, neural apoptosis, and degeneration in subarachnoid hemorrhage rats, with albumin significantly attenuating such neurovascular dysfunction. Furthermore, albumin markedly prevented blood-brain barrier disruption, as indicated by less blood-brain barrier leakage, preserved blood-brain barrier-related proteins, and dampened gelatinase activities. The expressions of key synaptic elements were up-regulated with albumin supplementation in both acute and chronic phases. Accordingly, a higher dendritic spine density was observed in the prefrontal and hippocampal areas of albumin-treated subarachnoid hemorrhage animals. Albumin at low-to-moderate doses markedly improves long-term neurobehavioral sequelae after subarachnoid hemorrhage, which may involve an integrated process of neurovascular remodeling.

WE-AB-207A-03: A CBCT Head Scanner for Point-Of-Care Imaging of Intracranial Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, J; Sisniega, A; Zbijewski, W

Purpose: This work reports the design, development, and first technical assessment of a cone-beam CT (CBCT) scanner developed specifically for imaging of acute intracranial hemorrhage (ICH) at the point of care, with target applications in diagnosis and monitoring of traumatic brain injury, stroke, and postsurgical hemorrhage. Methods: System design employed a task-based image quality model to quantify the influence of factors such as additive noise and high-gain (HG) detector readout on ICH detectability. Three bowtie filters with varying bare-beam attenuation strength and curvature were designed to enable HG readout without detector saturation, and a polyenergetic gain correction was developed tomore » minimize artifacts from bowtie flood-field calibration. Image reconstruction used an iterative penalized weighted least squares (PWLS) method with artifact correction including Monte Carlo scatter estimation, Joseph-Spital beam hardening correction, and spatiotemporal deconvolution of detector glare and lag. Radiation dose was characterized for half-scan and full-scan protocols at various kV, and imaging performance was assessed in a head phantom presenting simulated ICH with diameter ranging 2–12 mm. Results: The image quality model guided system design and was validated by measurements on a CBCT imaging bench. Compared to low-gain readout without a bowtie filter, the combination of HG readout and a modest bowtie improved the contrast-to-noise ratio (CNR per unit square-root dose) by 20% in the center of the image but degraded noise performance near the periphery (20% reduction in CNR). Low-frequency bowtie artifacts (∼100 HU magnitude) were corrected by the polyenergetic gain correction. Image reconstructions on the prototype scanner demonstrate clear visibility of the smallest ICH insert (2 mm diameter) in both HG readout (with a bowtie) and dual-gain readout (without bowtie). Conclusion: Technical assessment of the prototype scanner suggests the

Systematic Review and Meta-Analysis: Is Pre-Injury Antiplatelet Therapy Associated with Traumatic Intracranial Hemorrhage?

PubMed

van den Brand, Crispijn L; Tolido, Tanya; Rambach, Anna H; Hunink, Myriam G M; Patka, Peter; Jellema, Korné

2017-01-01

The objective of this systematic review and meta-analysis is to evaluate whether the pre-injury use of antiplatelet therapy (APT) is associated with increased risk of traumatic intracranial hemorrhage (tICH) on CT scan. PubMed, Medline, Embase, Cochrane Central, reference lists, and national guidelines on traumatic brain injury were used as data sources. Eligible studies were cohort studies and case-control studies that assessed the relationship between APT and tICH. Studies without control group were not included. The primary outcome of interest was tICH on CT. Two reviewers independently selected studies, assessed methodological quality, and extracted outcome data. This search resulted in 10 eligible studies with 20,247 patients with head injury that were included in the meta-analysis. The use of APT in patients with head injury was associated with significant increased risk of tICH compared with control (odds ratio [OR] 1.87, 95% confidence interval [CI]1.27-2.74). There was significant heterogeneity in the studies (I 2 84%), although almost all showed an association between APT use and tICH. This association could not be established for patients receiving aspirin monotherapy. When considering only patients with mild traumatic brain injury (mTBI), the OR is 2.72 (95% CI 1.92-3.85). The results were robust to sensitivity analysis on study quality. In summary, APT in patients with head injury is associated with increased risk of tICH; this association is most relevant in patients with mTBI. Whether this association is the result of a causal relationship and whether this relationship also exists for patients receiving aspirin monotherapy cannot be established with the current review and meta-analysis.

Thromboembolic and Major Bleeding Events With Rivaroxaban Versus Warfarin Use in a Real-World Setting.

PubMed

Russo-Alvarez, Giavanna; Martinez, Kathryn A; Valente, Megan; Bena, James; Hu, Bo; Luxenburg, Jennifer; Chaitoff, Alexander; Ituarte, Catherine; Brateanu, Andrei; Rothberg, Michael B

2018-01-01

Although randomized trials demonstrate the noninferiority of rivaroxaban compared with warfarin in the context of nonvalvular atrial fibrillation (AF), little is known about how these drugs compare in practice. To assess the relative effectiveness and safety of rivaroxaban versus warfarin in a large health system and to evaluate this association by time in therapeutic range (TTR). We conducted a retrospective cohort study with propensity matching in the Cleveland Clinic Health System. The study included patients initiated on warfarin or rivaroxaban for thromboembolic prevention in nonvalvular AF between January 2012 and July 2016. The main outcomes were thromboembolic events and major bleeds. Analyses were stratified by warfarin patients' TTR. The cohort consisted of 472 propensity-matched pairs. The mean age was 73.6 years (SD = 11.7), and the mean CHADS 2 score was 1.8. The median TTR for warfarin patients was 64%. In the propensity-matched analysis, there was no significant difference in thromboembolic or major bleeding events between groups. Among warfarin patients with a TTR <64% and their matched rivaroxaban pairs, there was also no significant difference in thromboembolic or major bleeding events. Under real-world conditions, warfarin and rivaroxaban were associated with similar safety and effectiveness, even among those with suboptimal therapeutic control. Individualized decision making, taking into account the nontherapeutic tradeoffs associated with these medications (eg, monitoring, half-life, cost) is warranted.

Importance of a multidisciplinary approach and monitoring in fetal warfarin syndrome.

PubMed

Silveira, Daniélle B; da Rosa, Ernani B; de Mattos, Vinicius F; Goetze, Thayse B; Sleifer, Pricila; Santa Maria, Fernanda D; Rosa, Rosana C M; Rosa, Rafael F M; Zen, Paulo R G

2015-06-01

Warfarin is a synthetic oral anticoagulant that crosses the placenta and can lead to a number of congenital abnormalities known as fetal warfarin syndrome. Our aim is to report on the follow-up from birth to age 8 years of a patient with fetal warfarin syndrome. He presented significant respiratory dysfunction, as well as dental and speech and language complications. The patient was the second child of a mother who took warfarin during pregnancy due to a metallic heart valve. The patient had respiratory dysfunction at birth. On physical examination, he had a hypoplastic nose, pectus excavatum, and clubbing of the fingers. Nasal fibrobronchoscopy showed upper airway obstruction due to narrowing of the nasal cavities. He underwent surgical correction with Max Pereira graft, zetaplasty, and osteotomies for the piriform aperture. At dental evaluation, he had caries and delayed eruption of the upper incisors. Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. Auditory long latency and cognitive-related potential to auditory stimuli demonstrated functional changes in the cortical auditory pathways. We believe that the frequency of certain findings observed in our patient may be higher in fetal warfarin syndrome than is appreciated, since a significant number result in abortions, stillbirths, or children evaluated in the first year of life without a follow-up. Thus, a multidisciplinary approach and long-term monitoring of these patients may be necessary. © 2015 Wiley Periodicals, Inc.

Prescribing Warfarin Appropriately to Meet Patient Safety Goals

PubMed Central

Dharmarajan, Lekshmi; Dharmarajan, T.S.

2008-01-01

The anticoagulant warfarin is increasingly used in a variety of disorders associated with risk of thromboembolism. The drug is undoubtedly effective but is linked to numerous nutrient, disease, and drug interactions; safe use of warfarin therefore necessitates close patient monitoring, using the international normalized ratio. The predominant adverse effect is bleeding, and individuals respond to warfarin in different ways. Both high and subtherapeutic international normalized ratios warrant attention, whereas a high international normalized ratio, with or without bleeding, mandates prompt patient evaluation. The 2008 National Patient Safety Goals require medical institutions to develop processes to ensure the safe use and monitoring of anticoagulant use. Last August, the US Food and Drug Administration revised the prescribing information for warfarin to include genetic testing before initiating therapy, although this is still not covered by most health plans. PMID:25126243

Out-of-range INR values and outcomes among new warfarin patients with non-valvular atrial fibrillation.

PubMed

Nelson, Winnie W; Wang, Li; Baser, Onur; Damaraju, Chandrasekharrao V; Schein, Jeffrey R

2015-02-01

Although efficacious in stroke prevention in non-valvular atrial fibrillation, many warfarin patients are sub-optimally managed. To evaluate the association of international normalized ratio control and clinical outcomes among new warfarin patients with non-valvular atrial fibrillation. Adult non-valvular atrial fibrillation patients (≥18 years) initiating warfarin treatment were selected from the US Veterans Health Administration dataset between 10/2007 and 9/2012. Valid international normalized ratio values were examined from the warfarin initiation date through the earlier of the first clinical outcome, end of warfarin exposure or death. Each patient contributed multiple in-range and out-of-range time periods. The relative risk ratios of clinical outcomes associated with international normalized ratio control were estimated. 34,346 patients were included for analysis. During the warfarin exposure period, the incidence of events per 100 person-years was highest when patients had international normalized ratio <2:13.66 for acute coronary syndrome; 10.30 for ischemic stroke; 2.93 for transient ischemic attack; 1.81 for systemic embolism; and 4.55 for major bleeding. Poisson regression confirmed that during periods with international normalized ratio <2, patients were at increased risk of developing acute coronary syndrome (relative risk ratio: 7.9; 95 % confidence interval 6.9-9.1), ischemic stroke (relative risk ratio: 7.6; 95 % confidence interval 6.5-8.9), transient ischemic attack (relative risk ratio: 8.2; 95 % confidence interval 6.1-11.2), systemic embolism (relative risk ratio: 6.3; 95 % confidence interval 4.4-8.9) and major bleeding (relative risk ratio: 2.6; 95 % confidence interval 2.2-3.0). During time periods with international normalized ratio >3, patients had significantly increased risk of major bleeding (relative risk ratio: 1.5; 95 % confidence interval 1.2-2.0). In a Veterans Health Administration non-valvular atrial fibrillation population

Neoadjuvant Chemotherapy for Facilitating Surgical Resection of Infantile Massive Intracranial Immature Teratoma.

PubMed

Kitahara, Takahiro; Tsuji, Yoshihito; Shirase, Tomoyuki; Yukawa, Hiroyuki; Takeichi, Yasuhiro; Yamazoe, Naohiro

2016-04-01

Immature teratoma (IMT) is the most frequent histological subtype of infantile intracranial teratoma, the most common congenital brain tumor. IMT contains incompletely differentiated components resembling fetal tissues. Infantile intracranial IMT has a dismal prognosis, because it is often inoperable due to its massive size and high vascularity. Neoadjuvant chemotherapy has been shown to be effective in decreasing tumor volume and vascularity to facilitate surgical resection in other types of infantile brain tumors. However, only one recent case report described the effectiveness of neoadjuvant chemotherapy for infantile intracranial IMT in the literature, even though it is common entity with a poor prognosis in infants. Here, we describe the case of a 2-month-old male infant with a very large intracranial IMT. Maximal surgical resection was first attempted but was unsuccessful because of severe intraoperative hemorrhage. Neoadjuvant carboplatin and etoposide (CARE) chemotherapy was then administered with the aim of shrinking and devascularizing the tumor. After neoadjuvant chemotherapy, tumor size did not decrease, but intraoperative blood loss significantly decreased and near-total resection was achieved by the second and third surgery. The patient underwent adjuvant CARE chemotherapy and has been alive for 3 years after surgery without tumor regrowth. Even when neoadjuvant chemotherapy does not decrease tumor volume of infantile intracranial IMT, surgical resection should be tried because chemotherapy can facilitate surgical resection and improve clinical outcome by reducing tumor vascularity.

Can We Predict Daily Adherence to Warfarin?

PubMed Central

Platt, Alec B.; Localio, A. Russell; Brensinger, Colleen M.; Cruess, Dean G.; Christie, Jason D.; Gross, Robert; Parker, Catherine S.; Price, Maureen; Metlay, Joshua P.; Cohen, Abigail; Newcomb, Craig W.; Strom, Brian L.; Laskin, Mitchell S.

2010-01-01

Background: Warfarin is the primary therapy to prevent stroke and venous thromboembolism. Significant periods of nonadherence frequently go unreported by patients and undetected by providers. Currently, no comprehensive screening tool exists to help providers assess the risk of nonadherence at the time of initiation of warfarin therapy. Methods: This article reports on a prospective cohort study of adults initiating warfarin therapy at two anticoagulation clinics (university- and Veterans Affairs-affiliated). Nonadherence, defined by failure to record a correct daily pill bottle opening, was measured daily by electronic pill cap monitoring. A multivariable logistic regression model was used to develop a point system to predict daily nonadherence to warfarin. Results: We followed 114 subjects for a median of 141 days. Median nonadherence of the participants was 14.4% (interquartile range [IQR], 5.8-33.8). A point system, based on nine demographic, clinical, and psychosocial factors, distinguished those demonstrating low vs high levels of nonadherence: four points or fewer, median nonadherence 5.8% (IQR, 2.3-14.1); five points, 9.1% (IQR, 5.9-28.6); six points, 14.5% (IQR, 7.1-24.1); seven points, 14.7% (IQR, 7.0-34.7); and eight points or more, 29.3% (IQR, 15.5-41.9). The model produces a c-statistic of 0.66 (95% CI, 0.61-0.71), suggesting modest discriminating ability to predict day-level warfarin nonadherence. Conclusions: Poor adherence to warfarin is common. A screening tool based on nine demographic, clinical, and psychosocial factors, if further validated in other patient populations, may help to identify groups of patients at lower risk for nonadherence so that intensified efforts at increased monitoring and intervention can be focused on higher-risk patients. PMID:19903973

The Time in Therapeutic Range and Bleeding Complications of Warfarin in Different Geographic Regions of Turkey: A Subgroup Analysis of WARFARIN-TR Study.

PubMed

Kılıç, Salih; Çelik, Ahmet; Çakmak, Hüseyin Altuğ; Afşin, Abdülmecit; Tekkeşin, Ahmet İlker; Açıksarı, Gönül; Memetoğlu, Mehmet Erdem; Özpamuk Karadeniz, Fatma; Şahan, Ekrem; Alıcı, Mehmet Hayri; Dereli, Yüksel; Sinan, Ümit Yaşar; Zoghi, Mehdi

2017-08-04

The time in therapeutic range values may vary between different geographical regions of Turkey in patients vitamin K antagonist therapy. To evaluate the time in therapeutic range percentages, efficacy, safety and awareness of warfarin according to the different geographical regions in patients who participated in the WARFARIN-TR study (The Awareness, Efficacy, Safety and Time in Therapeutic Range of Warfarin in the Turkish population) in Turkey. Cross-sectional study. The WARFARIN-TR study includes 4987 patients using warfarin and involved regular international normalized ratio monitoring between January 1, 2014 and December 31, 2014. Patients attended follow-ups for 12 months. The sample size calculations were analysed according to the density of the regional population and according to Turkish Statistical Institute data. The time in therapeutic range was calculated according to F.R. Roosendaal's algorithm. Awareness was evaluated based on the patients' knowledge of the effect of warfarin and food-drug interactions with simple questions developed based on a literature review. The Turkey-wide time in therapeutic range was reported as 49.5%±22.9 in the WARFARIN-TR study. There were statistically significant differences between regions in terms of time in therapeutic range (p>0.001). The highest rate was reported in the Marmara region (54.99%±20.91) and the lowest was in the South-eastern Anatolia region (41.95±24.15) (p>0.001). Bleeding events were most frequently seen in Eastern Anatolia (41.6%), with major bleeding in the Aegean region (5.11%) and South-eastern Anatolia (5.36%). There were statistically significant differences between the regions in terms of awareness (p>0.001). Statistically significant differences were observed in terms of the efficacy, safety and awareness of warfarin therapy according to different geographical regions in Turkey.

Warfarin Toxicity and Individual Variability—Clinical Case

PubMed Central

Piatkov, Irina; Rochester, Colin; Jones, Trudi; Boyages, Steven

2010-01-01

Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives—superwarfarin anticoagulants—such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases. PMID:22069565

Safety Outcomes of Apixaban Compared With Warfarin in Patients With End-Stage Renal Disease.

PubMed

Sarratt, Stefanie C; Nesbit, Ross; Moye, Robert

2017-06-01

Current guidelines make no specific recommendations on the selection of direct oral anticoagulants for the prevention and treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) receiving hemodialysis. Based on these guidelines, warfarin remains the anticoagulant of choice in these patients. To compare bleeding rates in patients receiving apixaban or warfarin with ESRD undergoing chronic hemodialysis. This was a single-center, retrospective, institutional review board-approved cohort analysis. Patients with ESRD undergoing chronic hemodialysis and receiving anticoagulation therapy with either apixaban or warfarin were included in this study. All data were collected from paper charts and electronic medical records and included documentation of bleeding events and related interventions. The primary outcome of this study was clinically relevant major bleeding events. Secondary outcomes included clinically relevant nonmajor bleeding events and minor bleeding events. A total of 160 patients were included in this study (warfarin group, n = 120; apixaban group, n = 40). There were 7 major bleeding events in the warfarin group compared with zero in the apixaban group ( P = 0.34). There were similar rates of clinically relevant nonmajor bleeding events (12.5% vs 5.8%, P = 0.17) and minor bleeding (2.5% vs 2.5%, P = 0.74) events in patients receiving apixaban and warfarin. There were no observed differences in bleeding rates in patients receiving apixaban compared with those receiving warfarin. Apixaban may be a cautious consideration in hemodialysis patients until there is further insight into the effect of subsequent, multiple doses on drug accumulation and clinical outcomes.

Pharmacogenetic association study of warfarin safety endpoints in Puerto Ricans.

PubMed

Valentín, Isa I; Rivera, Giselle; Nieves-Plaza, Mariely; Cruz, Iadelisse; Renta, Jessica Y; Cadilla, Carmen L; Feliu, Juan F; Seip, Richard L; Ruaño, Gualberto; Duconge, Jorge

2014-09-01

This study was intended to determine the incidence rate of warfarin-related adverse events (e.g., bleeding) in Puerto Ricans and whether a genetic association between warfarin pharmacogenes and any of these adverse events was observed over the initiation period (i.e., the first 90 days of therapy). We conducted an observational, retrospective cohort study of pharmacogenetic association in 122 warfarin-treated, male, Puerto Rican patients (69.9 +/- 9.6 years) from the Veterans Affair Caribbean Healthcare System (VACHS) who consented to participate. Genotyping was performed using the CYP2C9 and VKORC1 assays by Luminex. Event-free survival curves were estimated using the Kaplan-Meier method and analyzed by log-rank test. Cox regression models were constructed and hazard ratios (HR) calculated. Carriers of functional CYP2C9 and VKORC1 polymorphisms demonstrated a higher incidence rate of multiple adverse events (i.e., 5.2 vs. 1.0 cases per 100 patient-months; RR = 4.8, p = 0.12) than did wild types. A significant association was observed between multiple adverse events and carrier status (HR = 2.5; 95% CI: 1.0-6.3, p = 0.04). However, no significant associations between genotypes and individual outcomes over the first 90 days of therapy were found. The association of CYP2C9 and VKORC1 genotypes and risks for adverse events due to exposure to warfarin was examined for the first time in Puerto Ricans. Despite a lack of association with individual events in this study population, our findings revealed a potential utility of genotyping for the prevention of multiple adverse events during warfarin therapy.

Pharmacogenetic Association Study of Warfarin Safety Endpoints in Puerto Ricans

PubMed Central

Valentín, Isa I.; Rivera, Giselle; Nieves-Plaza, Mariely; Cruz, Iadelisse; Renta, Jessica Y.; Cadilla, Carmen L.; Feliu, Juan F.; Seip, Richard L.; Ruaño, Gualberto; Duconge, Jorge

2014-01-01

Objective This study was intended to determine the incidence rate of warfarin-related adverse events (e.g., bleeding) in Puerto Ricans and whether a genetic association between warfarin pharmacogenes and any of these adverse events was observed over the initiation period (i.e., the first 90 days of therapy). Methods We conducted an observational, retrospective cohort study of pharmacogenetic association in 122 warfarin-treated, male, Puerto Rican patients (69.9 ±9.6 years) from the Veterans Affair Caribbean Healthcare System (VACHS) who consented to participate. Genotyping was performed using the CYP2C9 and VKORC 1 assays by Luminex. Event-free survival curves were estimated using the Kaplan–Meier method and analyzed by log-rank test. Cox regression models were constructed and hazard ratios (HR) calculated. Results Carriers of functional CYP2C9 and VKORC1 polymorphisms demonstrated a higher incidence rate of multiple adverse events (i.e., 5.2 vs. 1.0 cases per 100 patient-months; RR = 4.8, p = 0.12) than did wild types. A significant association was observed between multiple adverse events and carrier status (HR = 2.5; 95% CI : 1.0–6.3, p = 0.04). However, no significant associations between genotypes and individual outcomes over the first 90 days of therapy were found. Conclusion The association of CYP2C9 and VKORC1 genotypes and risks for adverse events due to exposure to warfarin was examined for the first time in Puerto Ricans. Despite a lack of association with individual events in this study population, our findings revealed a potential utility of genotyping for the prevention of multiple adverse events during warfarin therapy. PMID:25244877

Lack of effect of lacosamide on the pharmacokinetic and pharmacodynamic profiles of warfarin.

PubMed

Stockis, Armel; van Lier, Jan Jaap; Cawello, Willi; Kumke, Thomas; Eckhardt, Klaus

2013-07-01

The aim of this study was to evaluate the effect of the antiepileptic drug lacosamide on the pharmacokinetics and pharmacodynamics of the anticoagulant warfarin. In this open-label, two-treatment crossover study, 16 healthy adult male volunteers were randomized to receive a single 25-mg dose of warfarin alone in one period and lacosamide 200 mg twice daily on days 1-9 with a single 25 mg dose of warfarin coadministered on day 3 in the other period. There was a 2-week washout between treatments. Pharmacokinetic end points were area under the plasma concentration-time curve (AUC(0,last) and AUC(0,∞) ) and maximum plasma concentration (Cmax ) for S- and R-warfarin. Pharmacodynamic end points were area under the international normalized ratio (INR)-time curve (AUCINR ), maximum INR (INRmax ), maximum prothrombin time (PTmax ) and area under the PT-time curve (AUCPT ). Following warfarin and lacosamide coadministration, Cmax and AUC of S- and R-warfarin, as well as peak value and AUC of PT and INR, were equivalent to those after warfarin alone. In particular, the AUC(0,∞) ratio (90% confidence interval) for coadministration of warfarin and lacosamide versus warfarin alone was 0.97 (0.94-1.00) for S-warfarin and 1.05 (1.02-1.09) for R-warfarin, and the AUCINR ratio was 1.04 (1.01-1.06). All participants completed the study. Coadministration of lacosamide 400 mg/day did not alter the pharmacokinetics of warfarin 25 mg or the anticoagulation level. These results suggest that there is no need for dose adjustment of warfarin when coadministered with lacosamide. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

PubMed

Cha, Myung-Jin; Choi, Eue-Keun; Han, Kyung-Do; Lee, So-Ryoung; Lim, Woo-Hyun; Oh, Seil; Lip, Gregory Y H

2017-11-01

There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients. Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA 2 DS 2 -VASc score ≥2) between 2014 and 2015. NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant-naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH. In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban. © 2017 American Heart Association, Inc.

Use of warfarin therapy among residents who developed venous thromboembolism in the nursing home.

PubMed

Reardon, Gregory; Pandya, Naushira; Nutescu, Edith A; Lamori, Joyce; Damaraju, Chandrasekhar V; Schein, Jeff; Bookhart, Brahim K

2012-12-01

discontinuation. Patients in specific geographic regions who were underweight, had Alzheimer's disease/dementia or cancer, or had independent physical functioning were less likely to receive warfarin. Nonpersistence of warfarin therapy was strongly related to antipsychotic use, presence of dementia, or PVD. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Review of potential drug interaction between Oseltamivir and Warfarin and why it is important for emergency medicine physicians.

PubMed

Shah, Siddharth P; Patel, Kinner M; Subedi, Rogin; Gambhir, Harvir Singh

2017-08-01

Oseltamivir is a very commonly prescribed anti-viral medication by the Emergency Medicine (EM) physicians for the prophylactic and therapeutic treatment of Influenza infection. While the drug interaction of Warfarin with various antibiotics is known, the drug interaction between Oseltamivir and Warfarin is not common. We present a case where an 83-year female patient, on Warfarin for Pulmonary Embolism, had worsening of coagulopathy after she was started on Oseltamivir. The INR was monitored daily in our patient and Warfarin was stopped when the INR became supra-therapeutic. Our patient did not have any minor or major bleeding complication. This is the first reported case of Oseltamivir related worsening coagulopathy in patient on Warfarin to the best of our knowledge. Keeping in mind the possible interaction between the two as it was evident in our case and few other published reports, we recommend monitoring the INR closely in patients using Warfarin after they are started on Oseltamivir therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Cost-effectiveness of apixaban versus warfarin and aspirin in Sweden for stroke prevention in patients with atrial fibrillation.

PubMed

Lanitis, Tereza; Kongnakorn, Thitima; Jacobson, Lena; De Geer, Anna

2014-08-01

Atrial fibrillation (AF), one of the major risk factors for stroke, imposing a substantial burden to the Swedish health care system. Apixaban has demonstrated superiority to warfarin and aspirin in stroke prevention amongst patients with AF in two large randomised clinical trials. The aim of this study was to assess the economic implications of apixaban against warfarin and aspirin in these patients from a Swedish societal perspective. A Markov cohort model was constructed to characterise the consequences of anticoagulant treatment with regards to thromboembolic and bleeding events, as well as the associated health care costs, life-years and quality-adjusted life years (QALYs) for patients with AF treated with apixaban, warfarin or aspirin. Incremental cost-effectiveness ratios (ICERs) per QALY gained of apixaban relative to warfarin (among patients suitable for warfarin treatment) and aspirin (among patients unsuitable for warfarin treatment) were calculated. Costs (in 2011 SEKs) and QALYs were discounted at 3% per annum. The model estimated the ICER of apixaban versus warfarin amongst patients who are suitable for warfarin therapy to be SEK 33,458/QALY gained and that of apixaban versus aspirin amongst those unsuitable for warfarin therapy to be SEK 41,453/QALY gained. Probabilistic sensitivity analyses indicate that apixaban is an optimal treatment option compared with warfarin and aspirin, when the willingness-to-pay is above SEK 35,000 and SEK 45,000 per QALY, respectively. Apixaban was found to be a cost-effective alternative to warfarin and aspirin for stroke prevention in patients with AF in Sweden. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: Prospective Validation of the HeRS Score.

PubMed

Marsh, Elisabeth B; Llinas, Rafael H; Schneider, Andrea L C; Hillis, Argye E; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F

2016-01-01

Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

Response to warfarin and other oral anticoagulants: effects of disease states.

PubMed

Demirkan, K; Stephens, M A; Newman, K P; Self, T H

2000-05-01

Warfarin is associated with numerous drug and food interactions, and much attention has been appropriately focused on this subject. Because several disease states may also affect response to oral anticoagulants, we present a summary of the literature. We searched MEDLINE for original articles on the effect of disease states on response to warfarin. Liver disease and thyroid dysfunction are well-documented as affecting warfarin response. Further study is needed to establish whether febrile illness, congestive heart failure, and other disease states enhance the effect of warfarin in some patients. Careful monitoring of anticoagulant therapy in patients with diseases that have the potential to affect warfarin response could increase safety and efficacy of this important agent.

Pharmacokinetics of warfarin in rats: role of serum protein binding and tissue distribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheung, W.K.

The purpose of this study was to explore the role of serum protein binding and tissue distribution in the non-linear pharmacokinetics of warfarin in rats. The first phase of the research was an attempt to elucidate the causes of intersubject differences in serum protein binding of warfarin in rats. It was found that the distribution of S-warfarin between blood and liver, kidneys, muscle, or fatty tissue was non-linear. Based on the tissue distribution data obtained, a physiologically-based pharmacokinetic model was developed to describe the time course of S-warfarin concentrations in the serum and tissues of rats. The proposed model wasmore » able to display the dose-dependent pharmacokinetics of warfarin in rats. Namely a lower clearance and a smaller apparent volume of distribution with increasing dose, which appear to be due to the presence of capacity-limited, high-affinity binding sites for warfarin in various tissues. To determine if the binding of warfarin to the high-affinity binding sites in the liver of rats is reversible, concentrations of S-warfarin in the liver and serum of rats were monitored for a very long time after an intravenous injection of a 1 mg/kg dose. In another study in rats, non-radioactive warfarin was found to be able to displace tissue-bound C/sup 14/-warfarin which was administered about 200 hours before the i.v. injection of the non-radioactive warfarin, showing that the binding of warfarin to the high-affinity binding sites in the body is persistent and reversible.« less

Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin.

PubMed

Brekelmans, Marjolein P A; Scheres, Luuk J J; Bleker, Suzanne M; Hutten, Barbara A; Timmermans, Anne; Büller, Harry R; Middeldorp, Saskia

2017-04-03

Abnormal vaginal bleeding can complicate direct oral anticoagulant (DOAC) treatment. We aimed to investigate the characteristics of abnormal vaginal bleeding in patients with venous thromboembolism (VTE) receiving apixaban or enoxaparin/warfarin. Data were derived from the AMPLIFY trial. We compared the incidence of abnormal vaginal bleeding between patients in both treatment arms and collected information on clinical presentation, diagnostic procedures, management and outcomes. In the AMPLIFY trial, 1122 women were treated with apixaban and 1106 received enoxaparin/warfarin. A clinically relevant non-major (CRNM) vaginal bleeding occurred in 28 (2.5 %) apixaban and 24 (2.1 %) enoxaparin/warfarin recipients (odds ratio [OR] 1.2, 95 % confidence interval [CI] 0.7-2.0). Of all CRNM bleeds, 28 of 62 (45 %) and 24 of 120 (20 %) were of vaginal origin in the apixaban and enoxaparin/warfarin group, respectively (OR 3.4; 95 % CI 1.8-6.7). Premenopausal vaginal bleeds on apixaban were characterised by more prolonged bleeding (OR 2.3; 95 %CI 0.5-11). In both pre- and postmenopausal vaginal bleeds, diagnostic tests were performed in six (21 %) and in seven (29 %) apixaban and enoxaparin/warfarin treated patients, respectively. Medical treatment was deemed not necessary in 16 (57 %) apixaban and 16 (67 %) enoxaparin/warfarin recipients. The severity of clinical presentation and course of the bleeds was mild in 75 % of the cases in both groups. In conclusion, although the absolute number of vaginal bleeding events is comparable between apixaban and enoxaparin/warfarin recipients, the relative occurrence of vaginal bleeds is higher in apixaban-treated women. The characteristics and severity of bleeding episodes were comparable in both treatment arms.

Superior Prognostic Value of Cumulative Intracranial Tumor Volume Relative to Largest Intracranial Tumor Volume for Stereotactic Radiosurgery-Treated Brain Metastasis Patients.

PubMed

Hirshman, Brian R; Wilson, Bayard; Ali, Mir Amaan; Proudfoot, James A; Koiso, Takao; Nagano, Osamu; Carter, Bob S; Serizawa, Toru; Yamamoto, Masaaki; Chen, Clark C

2018-04-01

Two intracranial tumor volume variables have been shown to prognosticate survival of stereotactic-radiosurgery-treated brain metastasis patients: the largest intracranial tumor volume (LITV) and the cumulative intracranial tumor volume (CITV). To determine whether the prognostic value of the Scored Index for Radiosurgery (SIR) model can be improved by replacing one of its components-LITV-with CITV. We compared LITV and CITV in terms of their survival prognostication using a series of multivariable models that included known components of the SIR: age, Karnofsky Performance Score, status of extracranial disease, and the number of brain metastases. Models were compared using established statistical measures, including the net reclassification improvement (NRI > 0) and integrated discrimination improvement (IDI). The analysis was performed in 2 independent cohorts, each consisting of ∼3000 patients. In both cohorts, CITV was shown to be independently predictive of patient survival. Replacement of LITV with CITV in the SIR model improved the model's ability to predict 1-yr survival. In the first cohort, the CITV model showed an NRI > 0 improvement of 0.2574 (95% confidence interval [CI] 0.1890-0.3257) and IDI of 0.0088 (95% CI 0.0057-0.0119) relative to the LITV model. In the second cohort, the CITV model showed a NRI > 0 of 0.2604 (95% CI 0.1796-0.3411) and IDI of 0.0051 (95% CI 0.0029-0.0073) relative to the LITV model. After accounting for covariates within the SIR model, CITV offers superior prognostic value relative to LITV for stereotactic radiosurgery-treated brain metastasis patients.

Post-hemorrhagic hydrocephalus: Recent advances and new therapeutic insights.

PubMed

Chen, Qianwei; Feng, Zhou; Tan, Qiang; Guo, Jing; Tang, Jun; Tan, Liang; Feng, Hua; Chen, Zhi

2017-04-15

Post-hemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation, is caused by disturbances in cerebrospinal fluid (CSF) flow or absorption following hemorrhage in the brain. As one of the most serious complications of neonatal/adult intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), PHH is associated with increased morbidity and disability of these events. Common sequelae of PHH include neurocognitive impairment, motor dysfunction, and growth impairment. Non-surgical measures to reduce increased intracranial pressure (ICP) in PHH have shown little success and most patients will ultimately require surgical management, such as external ventricular drainage and shunting which mostly by inserting a CSF drainage shunt. Unfortunately, shunt complications are common and the optimum time for intervention is unclear. To date, there remains no comprehensive strategy for PHH management and it becomes imperative that to explore new therapeutic targets and methods for PHH. Over past decades, increasing evidence have indicated that hemorrhage-derived blood and subsequent metabolic products may play a key role in the development of IVH-, SAH- and TBI-associated PHH. Several intervention strategies have recently been evaluated and cross-referenced. In this review, we summarized and discussed the common aspects of hydrocephalus following IVH, SAH and TBI, relevant experimental animal models, clinical translation of in vivo experiments, and potential preventive and therapeutic targets for PHH. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical and Genetic Determinants of Warfarin Pharmacokinetics and Pharmacodynamics during Treatment Initiation

PubMed Central

Gong, Inna Y.; Schwarz, Ute I.; Crown, Natalie; Dresser, George K.; Lazo-Langner, Alejandro; Zou, GuangYong; Roden, Dan M.; Stein, C. Michael; Rodger, Marc; Wells, Philip S.; Kim, Richard B.; Tirona, Rommel G.

2011-01-01

Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (Imax) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for Imax were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of Imax during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy. PMID:22114699

Warfarin Personalized Dosage: Re-compounding for a More Suitable Therapy and Better Compliance.

PubMed

Pellagatti, Tommaso; Ternelli, Marco; Frascio, Davide; Bettini, Ruggero

2017-01-01

Warfarin is still the most prescribed oral anticoagulant prescribed for the prophylaxis and treatment of thromboembolic events such as stroke, heart attack, embolism, and deep vein thrombosis. It is administered orally in the form of sodium salt as a tablet with a typical strength of 5 mg. The molecule has a narrow therapeutic index. As a consequence, the dosage must be individualized for each patient based on the patient response in terms of time of coagulation. Thus, warfarin represents an example of a drug whose dose needs to be tailored to individual requirements that are often changing and, therefore, constitute a paramount illustration of personalized medicine. The aim of the present work was to investigate to what extent the manual division of a warfarin tablet by the patient represents an issue in terms of dose accuracy and precision. A second goal was to demonstrate that possible problems stemming from the manual division of the warfarin tablet could be overcome by compounding a solid dosage form (e.g., a capsule) starting from the commercially available warfarin product. The results of the present study put into evidence the great inhomogeneity and discrepancy from the target dose obtained when commercially available warfarin tablets are manually divided in four parts. This represents a potential source of inefficacy of the anticoagulant activity, with increased risk of either bleeding or thromboembolic events. The proposed solution is effective and yet simple and economically affordable, in particular considering the cost of the possible hospitalizations related to therapy failure. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Racial background is a determinant factor in the maintenance dosage of warfarin.

PubMed

Gan, Gin Gin; Teh, Alan; Goh, Kim Yen; Chong, Heng Thay; Pang, Kang Wah

2003-07-01

Warfarin is a drug commonly used in the prevention of thromboembolic events. There have been reports suggesting that racial background may influence warfarin dose requirements. Malaysia is a multiracial country in which there are 3 major races, Malay, Chinese, and Indian. We examined 100 patients from our hospital on stable maintenance doses of warfarin, with international normalized ratio (INR) of 2.0 to 3.5. We found that the mean warfarin dose for Indian patients (n = 19) was 6.9 mg, for Chinese patients (n = 55) was 3.6 mg, and for Malay patients (n = 26) was 3.2 mg. The results showed that the Indian patients required a statistically significantly higher warfarin dose than did patients of the other 2 races (P < .0005). Age was also found to affect the daily warfarin maintenance dose.

Lower incidence of reoperation with longer shunt survival with adult ventriculoperitoneal shunts placed for hemorrhage-related hydrocephalus.

PubMed

Hoh, Brian L; Lang, Shih-Shan; Ortiz, Michael V; Chi, Yueh-Yun; Lewis, Stephen B; Pincus, David W

2008-07-01

The incidence of reoperation for ventriculoperitoneal shunts (VPS) in adults, although lower than in pediatric patients, is not insignificant. We hypothesize that adult VPS placed for hemorrhage-related hydrocephalus have a lower incidence of reoperation than those placed for other types of hydrocephalus. We retrospectively reviewed all adult (>/= 20 yr) VPS initially placed from February 2001 to August 2006 at the University of Florida. We determined the incidence and time interval to reoperation. Follow-up was conducted by telephone interview and review of medical records. A total of 286 adult VPS were initially placed: 96 (34%) hemorrhage and 190 (66%) nonhemorrhage. A total of 15 (16%) hemorrhage patients underwent 22 shunt reoperations, compared with 50 (27%) nonhemorrhage patients who underwent 82 shunt reoperations (P = 0.0316). A Poisson regression analysis of the number of reoperations, factoring hemorrhage, age, and sex, demonstrated a significantly lower incidence of reoperation in hemorrhage patients (P = 0.0900). A Cox proportional hazards model analysis of time to first reoperation, factoring hemorrhage, age, and sex, demonstrated a significantly longer shunt survival in hemorrhage patients (P = 0.0404). Adult VPS placed for hemorrhage-related hydrocephalus have a significantly lower incidence of reoperation and significantly longer shunt survival. This result may be related to an incidence of transient shunt dependency in patients with hemorrhage-related hydrocephalus. However, the precise mechanism remains unclear.

Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

PubMed Central

Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

2015-01-01

Background VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1–1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. Material/Methods A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1–1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. Results Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1–1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1–1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). Conclusions VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

Real-World Use of Apixaban for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis.

PubMed

Proietti, Marco; Romanazzi, Imma; Romiti, Giulio Francesco; Farcomeni, Alessio; Lip, Gregory Y H

2018-01-01

The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation. We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs. From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents ( P <0.00001 for all comparisons). Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban. © 2017 American Heart Association, Inc.

Predicting prolonged dose titration in patients starting warfarin.

PubMed

Finkelman, Brian S; French, Benjamin; Bershaw, Luanne; Brensinger, Colleen M; Streiff, Michael B; Epstein, Andrew E; Kimmel, Stephen E

2016-11-01

Patients initiating warfarin therapy generally experience a dose-titration period of weeks to months, during which time they are at higher risk of both thromboembolic and bleeding events. Accurate prediction of prolonged dose titration could help clinicians determine which patients might be better treated by alternative anticoagulants that, while more costly, do not require dose titration. A prediction model was derived in a prospective cohort of patients starting warfarin (n = 390), using Cox regression, and validated in an external cohort (n = 663) from a later time period. Prolonged dose titration was defined as a dose-titration period >12 weeks. Predictor variables were selected using a modified best subsets algorithm, using leave-one-out cross-validation to reduce overfitting. The final model had five variables: warfarin indication, insurance status, number of doctor's visits in the previous year, smoking status, and heart failure. The area under the ROC curve (AUC) in the derivation cohort was 0.66 (95%CI 0.60, 0.74) using leave-one-out cross-validation, but only 0.59 (95%CI 0.54, 0.64) in the external validation cohort, and varied across clinics. Including genetic factors in the model did not improve the area under the ROC curve (0.59; 95%CI 0.54, 0.65). Relative utility curves indicated that the model was unlikely to provide a clinically meaningful benefit compared with no prediction. Our results suggest that prolonged dose titration cannot be accurately predicted in warfarin patients using traditional clinical, social, and genetic predictors, and that accurate prediction will need to accommodate heterogeneities across clinical sites and over time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Serious hemorrhages after ischemic stroke or TIA - Incidence, mortality, and predictors.

PubMed

Ögren, Joachim; Irewall, Anna-Lotta; Söderström, Lars; Mooe, Thomas

2018-01-01

Data are lacking on the risk and impact of a serious hemorrhage on the prognosis after ischemic stroke (IS) or transient ischemic attack (TIA). We aimed to estimate the incidence of serious hemorrhage, analyze the impact on mortality, and identify predictors of hemorrhage after discharge from IS or TIA. All patients admitted to Östersund Hospital for an IS or TIA in 2010-2013 were included (n = 1528, mean age: 75.1 years). Serious hemorrhages were identified until 31st December 2015. Incidence rates were calculated. The impact on mortality (stratified by functional level) was determined with Kaplan-Meier analysis. Non-parametric estimation under the assumption of competing risk was performed to assess the cumulative incidence and predictors of serious hemorrhages. The incidence rates of serious (n = 113) and intracranial hemorrhages (n = 45) after discharge from IS and TIA were 2.48% and 0.96% per year at risk, respectively. Patients with modified Rankin Scale (mRS) scores of 3-5 exhibited 58.9% mortality during follow-up and those with mRS scores of 0-2 exhibited 18.4% mortality. A serious hemorrhage did not affect mortality in patients with impaired functional status, but it increased the risk of death in patients with mRS scores of 0-2. Hypertension was associated with increased risk of serious hemorrhage. We found that, after discharge from an IS or TIA, serious hemorrhages were fairly common. Impairments in function were associated with high mortality, but serious hemorrhages only increased the risk of mortality in patients with no or slight disability. Improved hypertension treatment may decrease the risk of serious hemorrhage, but in patients with low functional status, poor survival makes secondary prevention challenging.

Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Granger, Christopher B; Lopes, Renato D; Hanna, Michael; Ansell, Jack; Hylek, Elaine M; Alexander, John H; Thomas, Laine; Wang, Junyuan; Bahit, M Cecilia; Verheugt, Freek; Lawrence, Jack; Xavier, Denis; Wallentin, Lars

2015-01-01

We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE. At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug. Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial. The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether ≥2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation. Copyright © 2014 Elsevier Inc. All rights reserved.

Educating patients about warfarin therapy using information technology: A survey on healthcare professionals’ perspectives

PubMed Central

Nasser, Sayeed; Mullan, Judy; Bajorek, Beata

Objective To explore healthcare professionals' views about the benefits and challenges of using information technology (IT) resources for educating patients about their warfarin therapy. Methods A cross-sectional survey of both community and hospital-based healthcare professionals (e.g., doctors, pharmacists and nurses) involved using a purpose-designed questionnaire. The questionnaires were distributed using a multi-modal approach to maximise response rates. Results Of the total 300 questionnaires distributed, 109 completed surveys were received (43.3% response rate). Over half (53.2%) of the healthcare participants were aged between 40-59 years, the majority (59.5%) of whom were female. Fifty nine (54.1%) participants reported having had no access to warfarin-specific IT-based patient education resources, and a further 19 (38.0%) of the participants who had IT-access reported that they never used such resources. According to the healthcare participants, the main challenges associated with educating their patients about warfarin therapy included: patient-related factors, such as older age, language barriers, cognitive impairments and/or ethnic backgrounds or healthcare professional factors, such as time constraints. The healthcare professionals reported that there were several aspects about warfarin therapy which they found difficult to educate their patients about which is why they identified computers and interactive touch screen kiosks as preferred IT devices to deliver warfarin education resources in general practices, hospital-based clinics and community pharmacies. At the same time, the healthcare professionals also identified a number of facilitators (e.g., to reinforce warfarin education, to offer reliable and easily comprehensible information) and barriers (e.g., time and costs of using IT resources, difficulty in operating the resources) that could impact on the effective implementation of these devices in educating patients about their warfarin therapy

[Subarachnoid hemorrhage: epidemiology, social impact and a multidisciplinary approach].

PubMed

Ingelmo Ingelmo, I; Fàbregas Julià, N; Rama-Maceiras, P; Hernández-Palazón, J; Rubio Romero, R; Carmona Aurioles, J

2010-12-01

Cerebrovascular disease, whether ischemic or hemorrhagic, is a worldwide problem, representing personal tragedy, great social and economic consequences, and a heavy burden on the health care system. Estimated to be responsible for up to 10% of mortality in industrialized countries, cerebrovascular disease also affects individuals who are still in the workforce, with consequent loss of productive years. Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident that leads to around 5% of all strokes. SAH is most often due to trauma but may also be spontaneous, in which case the cause may be a ruptured intracranial aneurysm (80%) or arteriovenous malformation or any other abnormality of the blood or vessels (20%). Although both the diagnosis and treatment of aneurysmal SAH has improved in recent years, related morbidity and mortality remains high: 50% of patients die from the initial hemorrhage or later complications. If patients whose brain function is permanently damaged are added to the count, the percentage of cases leading to severe consequences rises to 70%. The burden of care of patients who are left incapacitated by SAH falls to the family or to private and public institutions. The economic cost is considerable and the loss of quality of life for both the patient and the family is great. Given the magnitude of this problem, the provision of adequate prophylaxis is essential; also needed are organizational models that aim to reduce mortality as well as related complications. Aneurysmal SAH is a condition which must be approached in a coordinated, multidisciplinary way both during the acute phase and throughout rehabilitation in order to lower the risk of unwanted outcomes.

Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

PubMed Central

Shahin, Mohamed H.A.; Johnson, Julie A.

2013-01-01

Purpose of review To review the most promising genetic markers associated with the variability in the safety or efficacy of warfarin and clopidogrel and highlight the verification and validation initiatives for translating clopidogrel and warfarin pharmacogenetic tests to clinical practice. Recent findings Rapid advances in pharmacogenetics, continuous decrease in genotyping cost, development of point-of-care devices and the newly established clinical genotyping programs at several institutions hold the promise of individualizing clopidogrel and warfarin based on genotype. Guidelines have been established to assist clinicians in prescribing clopidogrel or warfarin dose based on genotype. However, the clinical utility of clopidogrel and warfarin is still limited. Accordingly, large randomized clinical trials are underway to define the role of clopidogrel and warfarin pharmacogenetics in clinical practice. Summary Pharmacogenetics has offered compelling evidence toward the individualization of clopidogrel and warfarin therapies. The rapid advances in technology make the clinical implementation of clopidogrel and warfarin pharmacogenetics possible. The clinical genotyping programs and the ongoing clinical trials will help in overcoming some of the barriers facing the clinical implementation of clopidogrel and warfarin pharmacogenetics. PMID:23478884

Prospective assessment of concomitant lumbar and chronic subdural hematoma: is migration from the intracranial space involved in their manifestation?

PubMed

Kokubo, Rinko; Kim, Kyongsong; Mishina, Masahiro; Isu, Toyohiko; Kobayashi, Shiro; Yoshida, Daizo; Morita, Akio

2014-02-01

Spinal subdural hematomas (SDHs) are rare and some are concomitant with intracranial SDH. Their pathogenesis and etiology remain to be elucidated although their migration from the intracranial space has been suggested. The authors postulated that if migration plays a major role, patients with intracranial SDH may harbor asymptomatic lumbar SDH. The authors performed a prospective study on the incidence of spinal SDH in patients with intracranial SDH to determine whether migration is a key factor in their concomitance. The authors evaluated lumbar MR images obtained in 168 patients (125 males, 43 females, mean age 75.6 years) with intracranial chronic SDH to identify cases of concomitant lumbar SDH. In all cases, the lumbar MRI studies were performed within the 1st week after surgical irrigation of the intracranial SDH. Of the 168 patients, 2 (1.2%) harbored a concomitant lumbar SDH; both had a history of trauma to both the head and the hip and/or lumbar area. One was an 83-year-old man with prostate cancer and myelodysplastic syndrome who suffered trauma to his head and lumbar area in a fall from his bed. The other was a 70-year-old man who had hit his head and lumbar area in a fall. Neither patient manifested neurological deficits and their hematomas disappeared under observation. None of the patients with concomitant lumbar SDH had sustained head trauma only, indicating that trauma to the hip or lumbar region is significantly related to the concomitance of SDH (p < 0.05). As the incidence of concomitant lumbar and intracranial chronic SDH is rare and both patients in this study had sustained a direct impact to the head and hips, the authors suggest that the major mechanism underlying their concomitant SDH was double trauma. Another possible explanation is hemorrhagic diathesis and low CSF syndrome.

Evaluation of the clinical and economic impact of a brand name-to-generic warfarin sodium conversion program.

PubMed

Witt, Daniel M; Tillman, Donald J; Evans, Christy M; Plotkin, Tatyana V; Sadler, Melanie A

2003-03-01

anticoagulation-related adverse events. Most of these patients were successfully switched from brand name to generic warfarin. However, supplemental INR monitoring is warranted when one warfarin product is substituted for another to allow timely detection of those patients who experience significant changes in anticoagulation response.

[A case of Churg-Strauss syndrome with subarachnoid hemorrhage].

PubMed

Ito, Miiko; Kato, Naoki; Su, Ching-Chan; Kayama, Takamasa

2014-03-01

Churg-Strauss syndrome (CSS) is a vasculitis syndromes and is only rarely complicated by subarachnoid hemorrhage. In the current report, we describe a case of CSS with subarachnoid hemorrhage, which showed a favorable outcome following conservative treatment. A 68-year-old man with CSS on maintenance steroid therapy underwent MRI/A during tinnitus aggravation, and showed dilation of the left middle cerebral artery and stenosis of the peripheral area of the right vertebral artery. After 2 months, he presented sudden pain in the occipitocervical area, and CT revealed subarachnoid hemorrhage. Intracranial 3D CT-A and MRI/A showed the development of a protrusion at the base of the left anterior cerebral artery. Although both findings suggested cerebral artery dissection, the source of hemorrhage could not be identified. The 2009 Japanese Guidelines for the Management of Stroke recommends early diagnosis and treatment of hemorrhagic cerebral artery dissection because of the high risk of re-bleeding. However, considering the risks of vasculitis aggravation, development of systemic complications, and recurrence, conservative treatment was selected. In addition, owing to the risk of complications associated with the frequent use of iodinated contrast agents and angiography procedures, patient was followed up using MRI. His course was favorable, and he was discharged despite mild right abducens paralysis. When patients with hemorrhagic cerebral artery dissection have a history of allergic diseases, CCS should be considered; conservative treatment consisting of rest, strict blood pressure control, and steroid therapy may be the most appropriate option for certain patients.

Ezetimibe enhances and stabilizes anticoagulant effect of warfarin.

PubMed

Hashikata, Takehiro; Yamaoka-Tojo, Minako; Kakizaki, Ryota; Nemoto, Teruyoshi; Fujiyoshi, Kazuhiro; Namba, Sayaka; Kitasato, Lisa; Hashimoto, Takuya; Ishii, Shunsuke; Kameda, Ryo; Shimohama, Takao; Tojo, Taiki; Ako, Junya

2017-01-01

Ezetimibe reduces plasma levels of low-density lipoprotein cholesterol by inhibiting Niemann-Pick C1-like protein 1 (NPC1L1). A recent study demonstrated that NPC1L1 plays an important role in absorption of fat-soluble vitamins including vitamin K. We evaluated whether the add-on treatment of ezetimibe affects anticoagulation in patients taking warfarin. Between October 2007 and March 2015, the administration of ezetimibe was started to a total of 101 outpatients who were already on oral anticoagulation with warfarin. We retrospectively analyzed blood lipid levels, prothrombin time international normalized ratio (PT-INR) and time in therapeutic INR range (TTR). Seventy-one patients (70 %) showed increase in PT-INR after ezetimibe treatment (1.96 ± 0.45 to 2.20 ± 0.61, p < 0.001). It was necessary to reduce the warfarin dose in 9 of 101 patients for clinical indication. There was a significant positive correlation between change in PT-INR and statin usage at baseline (p = 0.03). The mean value of changes in PT-INR of patients with taking statin was significantly larger than that of patients without taking statin (0.34 ± 0.54 vs. 0.06 ± 0.36, p = 0.03). There was an increase in the TTR (52 ± 26 to 61 ± 23 %, p < 0.0001) and a decrease in the frequency to change the dose of warfarin after the ezetimibe treatment [45 times of 735 examination days (6 %) to 20 times of 695 examination days (3 %), p = 0.02]. Our data suggest possible drug interaction between warfarin and ezetimibe. Ezetimibe may increase and stabilize the anticoagulant effect of warfarin, especially in patients taking statins.

Interaction between gemfibrozil and warfarin: case report and review of the literature.

PubMed

Dixon, Dave L; Williams, Virginia G

2009-06-01

Possible procoagulant effects can occur when lipid-lowering fibric acid derivatives, such as gemfibrozil and fenofibrate, are taken concomitantly with warfarin. Although there are several detailed reports of fenofibrate potentiating the anticoagulant effects of warfarin, few case reports have been published regarding an interaction between gemfibrozil and warfarin. We describe a 62-year-old man who was taking warfarin for paroxysmal atrial fibrillation and came to the anticoagulation clinic for a routine follow-up. For 9 months, the patient's international normalized ratio (INR) had been stable (target range 2.0-3.0) with warfarin 45 mg/week. At this clinic visit, however, his INR was supratherapeutic at 5.8; the only identified change in his drug therapy was the addition of gemfibrozil 600 mg twice/day, started 3 weeks earlier. The patient denied any changes in his dietary intake of vitamin K, alcohol use, or addition of nonprescription or herbal agents. Recent laboratory tests revealed no signs of thyroid abnormalities and only an insignificant elevation in his alanine aminotransferase level. His warfarin dose was decreased to 35-37.5 mg/week (a 22% reduction), and a therapeutic INR was maintained until gemfibrozil was later discontinued because of myalgia. After consecutive subtherapeutic INRs, his warfarin dose was increased to 45 mg/week and a therapeutic INR was maintained. Use of the Drug Interaction Probability Scale indicated that the likelihood of the gemfibrozil-warfarin interaction was probable. The exact mechanism of the proposed interactions between fibric acid derivatives and warfarin remains unknown but may be multifactorial through inhibition of cytochrome P450 isoenzymes, displacement from protein binding sites, or changes in coagulation factor synthesis. Regardless of the fibric acid derivative chosen, an empiric dosage reduction of 20% and close INR monitoring are warranted in patients receiving warfarin.

Risk Factors of Subacute Thrombosis After Intracranial Stenting for Symptomatic Intracranial Arterial Stenosis.

PubMed

Sun, Xuan; Tong, Xu; Lo, Wai Ting; Mo, Dapeng; Gao, Feng; Ma, Ning; Wang, Bo; Miao, Zhongrong

2017-03-01

We aimed to explore the risk factors of subacute thrombosis (SAT) after intracranial stenting for patients with symptomatic intracranial arterial stenosis. From January to December 2013, all symptomatic intracranial arterial stenosis patients who underwent intracranial stenting in Beijing Tiantan Hospital were prospectively registered into this study. Baseline clinical features and operative data were compared in patients who developed SAT with those who did not. Binary logistic regression model was used to determine the risk factors associated with SAT. Of the 221 patients enrolled, 9 (4.1%) cases had SAT 2 to 8 days after stenting. Binary logistic analysis showed that SAT was related with tandem stenting (odds ratio [OR], 11.278; 95% confidence interval [CI], 2.422-52.519) and antiplatelet resistance (aspirin resistance: OR, 6.267; 95% CI, 1.574-24.952; clopidogrel resistance: OR, 15.526; 95% CI, 3.105-77.626; aspirin and clopidogrel resistance: OR, 12.246; 95% CI, 2.932-51.147; and aspirin or clopidogrel resistance: OR, 11.340; 95% CI, 2.282-56.344). Tandem stenting and antiplatelet resistance might contribute to the development of SAT after intracranial stenting in patients with symptomatic intracranial arterial stenosis. © 2017 American Heart Association, Inc.

Spontaneous acute subdural hematoma: A rare presentation of a dural intracranial fistula.

PubMed

de Aguiar, Guilherme Brasileiro; Veiga, José Carlos Esteves; Silva, João Miguel de Almeida; Conti, Mario Luiz Marques

2016-03-01

Dural arteriovenous fistulas are acquired lesions between the meningeal arteries and their associated draining veins. They may have highly variable clinical presentations and evolution, from severe neurological deficit to no or trivial symptoms. Intracranial hemorrhage occurs in less than 24% of all dural fistulas, and the bleeding is usually subarachnoid, more infrequently intracerebral, and rarely in the subdural space. Here, we present a rare case of a patient who presented with a subdural spontaneous hemorrhage. After investigation by cerebral angiography, the diagnosis of a dural arteriovenous fistula was made. The patient underwent uneventful endovascular treatment. As there are with only a few reports in the literature of such a presentation, we present this patient and perform a brief review of the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of antithrombotic therapy after cardioembolic stroke due to atrial fibrillation or flutter.

PubMed

Peterson, Evan J; Reaves, Anne B; Smith, Jennifer L; Oliphant, Carrie S

2013-02-01

Guidelines recommend that all patients with atrial fibrillation and a history of ischemic stroke should receive an anticoagulant. Prior analyses show that warfarin is underutilized in most populations. To examine the use of antithrombotic and anticoagulant therapy in patients with atrial fibrillation or flutter during the index hospitalization for acute, ischemic stroke. Retrospective electronic medical record review of 200 patients treated at a tertiary care hospital with a primary ICD-9 code for ischemic stroke and a secondary ICD-9 code for atrial fibrillation or flutter. Exclusion criteria were active bleeding, pregnancy, age less than 18, pre-existing warfarin allergy, or dabigatran use. Fifty-two percent of patients received at least one dose of warfarin during the index hospitalization. There was no relationship between CHADS2 score and likelihood of receiving warfarin (P > .05). There was no significant difference in adverse event rate in patients receiving warfarin compared to those receiving aspirin (3.8% vs 9.1%; P = .14), but the rate of hemorrhagic transformation was lower in patients receiving warfarin (1% vs 7%; P = .03). The composite of hemorrhagic stroke or hemorrhagic transformation was significantly lower in patients receiving bridging therapy (0% vs 11%; P = .03). Sixteen patients were readmitted for stroke within 3 months of discharge. Ten were readmitted for ischemic stroke, 3 for hemorrhagic stroke or hemorrhagic transformation, and 3 for systemic bleeding. Ten patients (62.5%) were receiving warfarin at readmission, but only one of these patients had a therapeutic INR. Warfarin was underutilized as secondary stroke prophylaxis in these high-risk patients. Bridging therapy appeared to be safe and was not associated with an increase in adverse events.

Financial Impact of Direct-Acting Oral Anticoagulants in Medicaid: Budgetary Assessment Based on Number Needed to Treat.

PubMed

Fairman, Kathleen A; Davis, Lindsay E; Kruse, Courtney R; Sclar, David A

2017-04-01

Faced with rising healthcare costs, state Medicaid programs need short-term, easily calculated budgetary estimates for new drugs, accounting for medical cost offsets due to clinical advantages. To estimate the budgetary impact of direct-acting oral anticoagulants (DOACs) compared with warfarin, an older, lower-cost vitamin K antagonist, on 12-month Medicaid expenditures for nonvalvular atrial fibrillation (NVAF) using number needed to treat (NNT). Medicaid utilization files, 2009 through second quarter 2015, were used to estimate OAC cost accounting for generic/brand statutory minimum (13/23%) and assumed maximum (13/50%) manufacturer rebates. NNTs were calculated from clinical trial reports to estimate avoided medical events for a hypothetical population of 500,000 enrollees (approximate NVAF prevalence × Medicaid enrollment) under two DOAC market share scenarios: 2015 actual and 50% increase. Medical service costs were based on published sources. Costs were inflation-adjusted (2015 US$). From 2009-2015, OAC reimbursement per claim increased by 173 and 279% under maximum and minimum rebate scenarios, respectively, while DOAC market share increased from 0 to 21%. Compared with a warfarin-only counterfactual, counts of ischemic strokes, intracranial hemorrhages, and systemic embolisms declined by 36, 280, and 111, respectively; counts of gastrointestinal hemorrhages increased by 794. Avoided events and reduced monitoring, respectively, offset 3-5% and 15-24% of increased drug cost. Net of offsets, DOAC-related cost increases were US$258-US$464 per patient per year (PPPY) in 2015 and US$309-US$579 PPPY after market share increase. Avoided medical events offset a small portion of DOAC-related drug cost increase. NNT-based calculations provide a transparent source of budgetary-impact information for new medications.

Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of racemic warfarin in healthy subjects

PubMed Central

Lilja, Jari J; Backman, Janne T; Neuvonen, Pertti J

2005-01-01

Aims Case reports suggest that gemfobrozil can increase the anticoagulant effect of warfarin. Because gemfibrozil inhibits CYP2C9 in vitro, we studied its effects on the pharmacokinetics and pharmacodynamics of racemic warfarin. Methods In a randomized cross-over study, 10 healthy subjects ingested 600 mg gemfibrozil or placebo twice daily for 8 days. On day 3, they were administered a single dose of 10 mg racemic R-S-warfarin orally. The concentrations of R- and S-warfarin in plasma and thromboplastin time were monitored up to 168 h. Results Gemfibrozil decreased the mean (±SD) area under the plasma concentration-time curve [AUC(0–∞)] of S-warfarin by 11%, from 19.9 ± 5.2 mg l−1 h to 17.6 ± 4.7 mg l−1 h (95% CI on the difference −3.7, −0.78; P < 0.01) and that of R-warfarin by 6% from 31.3 ± 7.5 mg l−1 h during the gemfibrozil phase to 29.5 ± 6.9 mg l−1 h during the placebo phase (95% CI −3.3, −0.33; P < 0.05). There were no significant differences in the elimination half-lives of S- or R-warfarin between the phases. Gemfibrozil did not alter the anticoagulant effect of warfarin. Conclusion Unexpectedly, gemfibrozil slightly decreased the plasma concentrations of R- and S-warfarin. Displacement of warfarin from plasma albumin by gemfibrozil or its interference with the absorption of warfarin could explain the present findings. Usual therapeutic doses of gemfibrozil seem to have limited effects on the pharmacokinetics and pharmacodynamics of single dose warfarin in healthy subjects. PMID:15801938

The incidence of postoperative thromboembolic complications following surgical resection of intracranial meningioma. A retrospective study of a large single center patient cohort.

PubMed

Hoefnagel, Daphna; Kwee, Lesley E; van Putten, Erik H P; Kros, Johan M; Dirven, Clemens M F; Dammers, Ruben

2014-08-01

Patients with meningiomas carry an increased risk for postoperative venous thromboembolic complications (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE). In the present retrospective study we investigated the incidence of VTE and the risk factors involved, in a large cohort of patients surgically treated for an intracranial meningioma at our institution. During the period from January 1997 to January 2009, 581 consecutive patients underwent craniotomy for intracranial meningioma. All patients received low-molecular weight heparins as thromboembolism prophylaxis. Patient demographics and tumor characteristics were gathered via retrospective chart review. Postoperative VTE and hemorrhages were noted. Backward stepwise logistic regression was used to determine the risk factors. 80.6% of meningiomas were WHO grade 1; 15.1% WHO grade 2; 4.3% WHO grade 3. Postoperative VTE were observed in 41 patients (7.2%). Of these, DVT was seen in 20 (3.5%) and PE in 26 patients (4.6%). The thromboembolic complication appeared on average 21.1±29.2 days post surgery. The 90-day mortality rate after VTE was 11.2% (23.1% for PE and 5.0% for DVT). Postoperative hemorrhages requiring surgical treatment were found in 2.9% of patients. Risk factors for VTE were body mass index (p=0.015) for DVT; weight (p=0.001) and bedridden postoperatively (p=0.001) for PE; and weight (p=0.004) and bedridden postoperatively (p=0.003) for VTE in general. There was no relation between tumor grade and thromboembolic complications. The major risk factors for postoperative VTE found in our single center study are patient weight and a bedridden status postoperatively. Prophylactic intervention for this potentially fatal complication should be evaluated against the relative lower risk of postoperative hemorrhages. Copyright © 2014 Elsevier B.V. All rights reserved.

Convexity Subarachnoid Hemorrhage Due to Cardioembolic Stroke in a Woman with Thyrotoxicosis: Α Case Report.

PubMed

Spanou, Ioanna; Vassilopoulou, Sophia; Koroboki, Eleni; Tountopoulou, Argyro; Velonakis, Georgios; Mitsikostas, Dimos Dimitrios

2017-10-01

Non-traumatic convexity subarachnoid hemorrhage (cSAH) is a rarely reported condition with a wide spectrum of etiologies. Cerebral ischemia secondary to extracranial or intracranial atherosclerotic disease has been identified as a relatively uncommon cause of cSAH. We report a case of cSAH caused by cardioembolic stroke. A 69-year old female patient developed suddenly left-sided face and body weakness and numbness and visual neglect on the left. She was newly detected with paroxysmal atrial fibrillation on the ground of thyrotoxicosis. Brain magnetic resonance imaging revealed ischemia of embolic pattern with cSAH. Further evaluation excluded other cause of hemorrhage. Dilation of leptomeningeal collateral vessels and rupture of pial vessels in distal cortical arteries may caused cSAH. Full anticoagulation was initiated. After one month, her condition improved significantly (NIHSS from 6 to 2). cSAH may be a rare complication of cardioembolic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Edoxaban versus warfarin in patients with atrial fibrillation.

PubMed

Giugliano, Robert P; Ruff, Christian T; Braunwald, Eugene; Murphy, Sabina A; Wiviott, Stephen D; Halperin, Jonathan L; Waldo, Albert L; Ezekowitz, Michael D; Weitz, Jeffrey I; Špinar, Jindřich; Ruzyllo, Witold; Ruda, Mikhail; Koretsune, Yukihiro; Betcher, Joshua; Shi, Minggao; Grip, Laura T; Patel, Shirali P; Patel, Indravadan; Hanyok, James J; Mercuri, Michele; Antman, Elliott M

2013-11-28

Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P

Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population [ISRCTN89345269

PubMed Central

Mant, Jonathan WF; Richards, Suzanne H; Hobbs, FD Richard; Fitzmaurice, David; Lip, Gregory YH; Murray, Ellen; Banting, Miriam; Fletcher, Kate; Rahman, Joy; Allan, Teresa; Raftery, James; Bryan, Stirling

2003-01-01

Background Atrial fibrillation (AF) is an important independent risk factor for stroke. Randomised controlled trials have shown that this risk can be reduced substantially by treatment with warfarin or more modestly by treatment with aspirin. Existing trial data for the effectiveness of warfarin are drawn largely from studies in selected secondary care populations that under-represent the elderly. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study will provide evidence of the risks and benefits of warfarin versus aspirin for the prevention of stroke for older people with AF in a primary care setting. Study design A randomised controlled trial where older patients with AF are randomised to receive adjusted dose warfarin or aspirin. Patients will be followed up at three months post-randomisation, then at six monthly intervals there after for an average of three years by their general practitioner. Patients will also receive an annual health questionnaire. 1240 patients will be recruited from over 200 practices in England. Patients must be aged 75 years or over and have AF. Patients will be excluded if they have a history of any of the following conditions: rheumatic heart disease; major non-traumatic haemorrhage; intra-cranial haemorrhage; oesophageal varices; active endoscopically proven peptic ulcer disease; allergic hypersensitivity to warfarin or aspirin; or terminal illness. Patients will also be excluded if the GP considers that there are clinical reasons to treat a patient with warfarin in preference to aspirin (or vice versa). The primary end-point is fatal or non-fatal disabling stroke (ischaemic or haemorrhagic) or significant arterial embolism. Secondary outcomes include major extra-cranial haemorrhage, death (all cause, vascular), hospital admissions (all cause, vascular), cognition, quality of life, disability and compliance with study medication. PMID:12939169

Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control.

PubMed

Janzic, Andrej; Kos, Mitja

2015-04-01

Vitamin K antagonists, such as warfarin, are standard treatments for stroke prophylaxis in patients with atrial fibrillation. Patient outcomes depend on quality of warfarin management, which includes regular monitoring and dose adjustments. Recently, novel oral anticoagulants (NOACs) that do not require regular monitoring offer an alternative to warfarin. The aim of this study was to evaluate whether cost effectiveness of NOACs for stroke prevention in atrial fibrillation depends on the quality of warfarin control. We developed a Markov decision model to simulate warfarin treatment outcomes in relation to the quality of anticoagulation control, expressed as percentage of time in the therapeutic range (TTR). Standard treatment with adjusted-dose warfarin and improved anticoagulation control by genotype-guided dosing were compared with dabigatran, rivaroxaban, apixaban and edoxaban. The analysis was performed from the Slovenian healthcare payer perspective using 2014 costs. In the base case, the incremental cost-effectiveness ratio for apixaban, dabigatran and edoxaban was below the threshold of €25,000 per quality-adjusted life-years compared with adjusted-dose warfarin with a TTR of 60%. The probability that warfarin was a cost-effective option was around 1%. This percentage rises as the quality of anticoagulation control improves. At a TTR of 70%, warfarin was the preferred treatment in half the iterations. The cost effectiveness of NOACs for stroke prevention in patients with nonvalvular atrial fibrillation who are at increased risk for stroke is highly sensitive to warfarin anticoagulation control. NOACs are more likely to be cost-effective options in settings with poor warfarin management than in settings with better anticoagulation control, where they may not represent good value for money.

Healthcare utilization and costs for patients initiating Dabigatran or Warfarin.

PubMed

Reynolds, Shannon L; Ghate, Sameer R; Sheer, Richard; Gandhi, Pranav K; Moretz, Chad; Wang, Cheng; Sander, Stephen; Costantino, Mary E; Annavarapu, Srinivas; Andrews, George

2017-06-21

Novel oral anticoagulants (NOAC) such as dabigatran, when compared to warfarin, have been shown to potentially reduce the risk of stroke in patients with non-valvular atrial fibrillation (NVAF) together with lower healthcare resource utilization (HCRU) and similar total costs. This study expands on previous work by comparing HCRU and costs for patients newly diagnosed with NVAF and newly initiated on dabigatran or warfarin, and is the first study specifically in a Medicare population. A retrospective matched-cohort study was conducted using data from administrative health care claims during the study period 01/01/2010-12/31/2012. Cox regression analyses were used to compare all-cause risk of first hospitalizations and emergency room (ER) visits. Medical, pharmacy, and total costs per-patient-per-month (PPPM) were compared between dabigatran and warfarin users. A total of 1110 patients initiated on dabigatran were propensity score-matched with corresponding patients initiated on warfarin. The mean number of hospitalizations (0.92 vs. 1.13, P = 0.012), ER visits (1.32 vs. 1.56, P < 0.01), office visits (21.43 vs. 29.41; P < 0.01), and outpatient visits (10.86 vs. 22.02; P < 0.01) were lower among dabigatran compared to warfarin users. Patients initiated on dabigatran had significantly lower risk of first all-cause ER visits [hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.73-0.98] compared to those initiated on warfarin. Adjusted mean pharmacy costs PPPM were significantly greater for dabigatran users ($510 vs. $250, P < 0.001); however, mean medical costs PPPM ($1912 vs. $1956, P = 0.55) and mean total costs PPPM ($2381 vs. $2183, P = 0.10) were not significantly different compared to warfarin users. Dabigatran users had significantly lower HCRU compared to warfarin users. In addition, dabigatran users had lower risk of all-cause ER visits. Despite higher pharmacy costs, the two cohorts did not differ significantly in medical or total all

Health literacy and knowledge in a cohort of Australian patients taking warfarin.

PubMed

Yiu, Angela W; Bajorek, Beata V

2018-01-01

To 1) characterise older patients taking warfarin, 2) assess these patients' level of warfarin knowledge, and 3) describe their strengths and limitations in health literacy, and 4) explore relationships between participants' characteristics, warfarin knowledge and health literacy. A warfarin knowledge questionnaire and Health Literacy Questionnaire (HLQ) were administered to older patients (aged >65 years, N=34) taking warfarin in an Australian general practice setting. Key gaps in participant knowledge pertained to the consequences of an international normalized ratio (INR) being below the target INR range and safety issues such as when to seek medical attention. A limitation for participants with a lower level of health literacy was the ability to appraise health information. Patients who needed assistance in completing the HLQs had significantly lower warfarin knowledge scores (p=0.03). Overseas-born participants and those taking 5 or more long-term medications had lower HLQ scores for specific scales (p<0.05). In this study warfarin knowledge gaps and a limitation of health literacy amongst a small sample of older patients were identified. The findings suggest that education and resources may need to be tailored to the needs of older patients taking warfarin and their carers to address these knowledge gaps and limitations in health literacy. Patients who may need greater support include those that need assistance in completing the HLQ, are overseas-born, or are taking 5 or more long-term medications.

Cannabis can augment thrombolytic properties of rtPA: Intracranial hemorrhage in a heavy cannabis user.

PubMed

Shere, Amar; Goyal, Hemant

2017-12-01

Cannabis is one of the most commonly used illicit drugs in the United States and is considered to have several adverse health effects. There is evidence suggesting that its recreational use is associated with both increased cardio- and cerebrovascular events. Recently, multiple cases of ischemic and hemorrhagic strokes associated with cannabis use were reported in the literature (Goyal et al., 2017). It has been suggested that cannabis can affect cerebral auto-regulation and vascular tone leading to vasoconstriction and acute ischemic stroke. However, hemorrhagic strokes, which are often seen with sympathomimetic illicit drugs (e.g. cocaine and amphetamines), have rarely been reported due to cannabis. Many cellular mechanisms within non-ischemic tissue post stroke may be augmented by heavy cannabis use. Here, we describe a rapid development of hemorrhage following thrombolytic therapy in a patient with heavy cannabis use with an ischemic stroke. Copyright © 2017 Elsevier Inc. All rights reserved.