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Background: Patients with atrial fibrillation (AF) are at higher risk for developing dementia. Warfarin is a common therapy for the prevention of thromboembolism in AF, valve replacement, and thrombosis patients. The extent to which AF itself increases dementia risk remains unknown., Methods: A total 6030 patients with no history of dementia and chronically anticoagulated with warfarin were studied. Warfarin management was provided through a Clinical Pharmacy Anticoagulation Service. Patients were stratified by warfarin indication of AF (n=3015) and non-AF (n=3015) and matched by propensity score (±0.01). Patients were stratified by the congestive heart failure, hypertension, age >75 years, diabetes, stroke (CHADS 2 ) score calculated at the time of warfarin initiation and followed for incident dementia., Results: The average age of the AF cohort was 69.3±11.2 years, and 52.7% were male; average age of non-AF cohort was 69.3±10.9 years, and 51.5% were male. Increasing CHADS 2 score was associated with increased dementia incidence, P trend=.004. When stratified by warfarin indication, AF patients had an increased risk of dementia incidence. After multivariable adjustment, AF patients continued to display a significantly increased risk of dementia when compared with non-AF patients across all CHADS 2 scores strata., Conclusions: In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS 2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS 2 score strata. These data suggest that AF contributes to the risk of dementia and that this risk is not solely attributable to anticoagulant use. Dementia may be an end manifestation of a systemic disease state, and AF likely contributes to its progression., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itself increases dementia risk, in addition to long-term anticoagulation exposure., Methods and Results: A total of 10 537 patients anticoagulated with warfarin (target INR 2-3), managed by the Clinical Pharmacist Anticoagulation Service with no history of dementia were included. Warfarin indication was for AF (n=4460), thromboembolism (n=5868), and mechanical heart valve(s) (n=209). Patients in the latter 2 categories were included only if they had no prior history of AF. The primary outcome was dementia. Patients with AF were older and had higher rates of hypertension, diabetes, heart failure, and stroke. AF patients experienced higher rates of total dementia (5.8% versus 1.6%, P<0.0001), Alzheimer disease (2.8% versus 0.9%, P<0.0001), and vascular dementia (1.0% versus 0.2%, P<0.0001). A propensity analysis of 6030 patients was performed to account for baseline demographics differences. Long-term risk of dementia remained significant in AF patients compared with matched non-AF patients (total dementia: hazard ratio [HR]=2.42 [1.85-3.18], P<0.0001; Alzheimer: HR=2.04 [1.40-2.98], P<0.0001; senile: HR=2.46 [1.58-3.86], P<0.0001). Low percent therapeutic range compared with a higher percent therapeutic range was associated with dementia risk in both AF (26-50% versus >75%: HR=2.51, P=0.005) and non-AF groups (≤25% versus >75%: HR=3.92, P<0.0001)., Conclusions: The presence of AF significantly increases risk of dementia, including Alzheimer's disease, compared with matched patients receiving warfarin anticoagulation for other reasons. Quality of anticoagulation management remains an important risk factor for dementia in all patients., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

The American College of Chest Physicians (CHEST) Antithrombotic Therapy for Venous Thromboembolism Disease evidence-based guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guidelines and two subsequent updates have not been gathered into a single source. An international panel of experts with experience in prior antithrombotic therapy guideline development reviewed the 2012 CHEST antithrombotic therapy guidelines and its two subsequent updates. All guideline statements and their associated patient, intervention, comparator, and outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified Grading of Recommendations, Assessment, Development, and Evaluations (ie, GRADE) format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments after statements deemed as relevant, including suggesting that statements be updated in future guidelines because of interval evidence. We include 58 guidance statements from prior versions of the antithrombotic therapy guidelines, with updated phrasing as needed to adhere to contemporary nomenclature. Statements were classified as strong or weak recommendations based on high-certainty, moderate-certainty, and low-certainty evidence using GRADE methodology. The panel suggested that five statements are no longer relevant to current practice. As CHEST continues to update guidance statements relevant to antithrombotic therapy for VTE disease, this article serves as a unified collection of currenrtly relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications. [ABSTRACT FROM AUTHOR]

BackgroundThe clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.MethodsWe randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy.ResultsAt 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.ConclusionsGenotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).

Many patients with impaired renal function have concurrent indications for anticoagulant therapy, including atrial fibrillation and venous thromboembolism. For mild chronic kidney disease, data from clinical trials and existing guidelines can be applied to clinical management. The benefits and harms of anticoagulation therapy in patients with more advanced renal impairment are nuanced, as both thrombotic and bleeding risk are increased. Until recently, data regarding anticoagulants in severe renal impairment were primarily observational, but emerging evidence includes a few small clinical trials and the emergence of novel agents hypothesized to have improved efficacy and safety in this population. In this review, we summarize existing data on anticoagulation in patients with chronic kidney disease. We suggest a framework for anticoagulation decision-making in the burgeoning worldwide population of patients with chronic kidney disease. • Chronic kidney disease (CKD) increases thrombosis and bleeding risk. • Existing evidence and guidelines can be applied patients with mild CKD. • Appropriately dosed DOACs are appropriate for mild or moderate CKD. • Data are limited in severe CKD, with ongoing clinical trials. • Severe CKD merits individualized decisions informed by patient preferences. [ABSTRACT FROM AUTHOR]

Real-time identification of venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) and pulmonary embolism (PE), can inform a healthcare organization's understanding of these events and be used to improve care. In a former publication, we reported the performance of an electronic medical record (EMR) interrogation tool that employs natural language processing (NLP) of imaging studies for the diagnosis of venous thromboembolism. Because we transitioned from the legacy electronic medical record to the Cerner product, iCentra, we now report the operating characteristics of the NLP EMR interrogation tool in the new EMR environment. Two hundred randomly selected patient encounters for which the imaging report assessed by NLP that revealed VTE was present were reviewed. These included one hundred imaging studies for which PE was identified. These included computed tomography pulmonary angiography—CTPA, ventilation perfusion—V/Q scan, and CT angiography of the chest/ abdomen/pelvis. One hundred randomly selected comprehensive ultrasound (CUS) that identified DVT were also obtained. For comparison, one hundred patient encounters in which PE was suspected and imaging was negative for PE (CTPA or V/Q) and 100 cases of suspected DVT with negative CUS as reported by NLP were also selected. Manual chart review of the 400 charts was performed and we report the sensitivity, specificity, positive and negative predictive values of NLP compared with manual chart review. NLP and manual review agreed on the presence of PE in 99 of 100 cases, the presence of DVT in 96 of 100 cases, the absence of PE in 99 of 100 cases and the absence of DVT in all 100 cases. When compared with manual chart review, NLP interrogation of CUS, CTPA, CT angiography of the chest, and V/Q scan yielded a sensitivity = 93.3%, specificity = 99.6%, positive predictive value = 97.1%, and negative predictive value = 99%. [ABSTRACT FROM AUTHOR]

Source Citation: Meaidi A, Mascolo A, Sessa M, et al. Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study. BMJ. 2023;382:e074450. 37673431 Clinical Impact Ratings: GIM/FP/GP: Hematology: [ABSTRACT FROM AUTHOR]

Patients with acute pulmonary embolism (PE) are often tested for thrombophilias, which are hereditary and acquired conditions that predispose to thrombosis. If a hereditary condition is identified, then testing is often performed on members of the patient's family. Testing for these conditions can be complex, as the presence of acute thrombosis and antithrombotic therapies can make the results of many tests unreliable. Many risk factors for thrombosis exist that are not routinely assessed by laboratory testing, and it is likely that many hereditary thrombophilia conditions remain to be discovered. Also, various risk factors for thrombosis interact with one another. Therefore, the results of a laboratory thrombophilia evaluation provide a limited ability to assess a patient or family members' risk for future thrombosis, and such testing usually does not provide information that improves a management decision. Thrombophilia testing is expensive and carries potential risks. This article reviews common thrombophilias, their epidemiology and classification, and timing and technical aspects of accurate testing and provides rational suggestions for the use of thrombophilia testing in five clinical situations: (1) following provoked PE (or other venous thromboembolism), (2) following unprovoked venous thromboembolism, (3) in relatives of patients with thrombosis, (4) in female relatives of patients with thrombosis considering estrogen use, and (5) in female relatives of patients with thrombosis who are considering pregnancy. Published guidelines and guidance statements from professional societies and other groups are also reviewed. Clinicians should carefully consider the relevant risks and benefits before testing patients for thrombophilia. When performed, testing should be timed correctly and care should be taken to properly interpret results. New models that incorporate multiple genetic and clinical markers may improve the utility of testing, but these await further research. [ABSTRACT FROM AUTHOR]

The article offers information on a study which examined the danger of venous thromboembolism following withholding anticoagulation in patients with suspected lower extremity deep vein thrombosis (DVT) after a single negative whole-leg compression ultrasound (CUS) result. Databases analyzed by the researchers include MEDLINE, EMBASE and Cochrane, among others. Information on the data extraction conducted by two authors is offered. Presented in details are the research findings. It concludes that withholding anticoagulation after a single negative whole-leg CUS finding was linked with a low risk of venous thromboembolism within 3-month follow-up.

Suspected deep venous thrombosis (DVT) is difficult to refute without complex diagnostic algorithms and expensive testing. We analysed five d-dimer assays’ utility for exclusion of suspected DVT during a prospective clinical cohort trial, choosing a highly sensitive cut-off value at which to compare the assays. Assays were performed on 436 consecutive patients who were referred with symptoms that suggested a first episode of DVT. Venous thromboembolism (VTE) was defined as positive findings on comprehensive duplex ultrasonography or any episode, or complication of VTE detected during 3 months of clinical follow-up. All five assays were performed in 377 patients. At a highly sensitive cut-off value, all five assays reliably excluded DVT in the study population. While the choice of a highly sensitive cut-off value reduced the specificity of all the assays, the change in specificity differed between tests. Our findings suggest that a second-generation d-dimer assay could be used as a stand-alone test to rule out suspected DVT when a highly sensitive cut-off value is chosen. These findings should be subjected to a prospective management study, as a small reduction in sensitivity from our findings could result in a clinically relevant decrease in negative predictive value. [ABSTRACT FROM AUTHOR]

Abstract Background Central venous catheters (CVC) and peripherally inserted central catheters (PICCs) are central vascular access devices (CVADs) that facilitate administration of medications among critically ill patients. Both are associated with risk of venous thromboembolism (VTE). The relative risk of VTE between these catheter types is not well defined. We report the rate of VTE in intensive care unit (ICU) medical patients receiving PICC, CVC, both, or neither. Methods We conducted a single-center, retrospective cohort study of medical-ICU patients between November 2007 and November 2013 grouped by receipt of CVC, PICC, both, or neither. The primary outcome was the rate of 30-day symptomatic venous thrombosis (upper and lower deep vein thrombosis and pulmonary embolism). Cox modeling was used to analyze this population and adjust for comorbidities which could contribute to VTE. Secondary outcomes included VTE location, major bleeding, and all-cause mortality among patients with and without CVADs. Results We analyzed 5788 patients. CVADs were placed in 2403 (42%) patients (PICC, n = 816; CVC, n = 1153; both, n = 434). Compared with no CVAD, the hazard ratio (HR) for 30-day VTE was 1.81 (95% CI 1.52–2.17) for any CVAD, 1.90 (95% CI 1.52–2.37) for PICC, 1.57 (95% CI 1.26–1.96) for CVC, and 2.70 (95% CI 2.09–3.47) for both. PICCs had a non-significantly higher HR for VTE compared with CVC (1.21; 95% CI 0.94–1.55). For patients with both a CVC and PICC the HR for VTE was 1.72 times that of solitary CVAD (95% CI 1.32–2.23). Conclusions Among critically ill medical patients, PICCs and CVCs were associated with increased risk of VTE. Placement of both conferred higher risk of VTE compared with either alone. Highlights • Peripheral and central venous lines increase hazard for venous thrombosis in ICU. • When both lines have been used in one patient clot hazard is even higher. • Hazard ratio for lower extremity clots was increased despite upper body lines. • Non-Significant Trend toward higher risk of clot with peripheral line over central. [ABSTRACT FROM AUTHOR]

The author comments on the study which examines the effectiveness of idraparinux in treating patients with deep venous thrombosis (DVT) or pulmonary embolism (PE). According to the author, the study provides valuable insight into the benefits and limitations of idraparinux. However, the coagulation cascade presents opportunities to intervene.

A response from the authors of the article "Optimal Duration Study Investigators. D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study" in a 2014 issue of the periodical is presented.

Post-hospitalization thromboprophylaxis can reduce venous thromboembolism (VTE) risk for non-surgical patients but may carry bleeding risks. We aimed to externally validate the Intermountain Risk Scores for hospital-associated venous thromboembolism (HA-VTE IMRS) and major bleeding (HA-MB IMRS) for VTE and bleeding outcomes. Retrospective cohort study of adult patients discharged alive from medical services between 2015 and 2019. HA-VTE IMRS and HA-MB IMRS were calculated at the time of hospital discharge and dichotomized as high- or low-risk as described in the derivation manuscript. 90-day post-discharge VTE outcomes were assessed from diagnostic radiology reports, and bleeding outcomes were assessed using ICD-10 codes and blood bank transfusion records. Among 113,578 patients in the study, 66,340 patients (58.4 %) had a low-risk HA-VTE IMRS <7, versus 47,238 (41.6 %) high-risk ≥7. For bleed prediction, 71,576 patients (63 %) had a low-risk HA-MB IMRS <8, versus 42,002 (37 %) high-risk ≥8. VTE incidence was 1.1 % and 0.6 % while major bleeding incidence was 1.3 % and 0.1 % in high-risk versus low-risk cohorts, respectively. AUCs for VTE and bleed outcome discrimination were 0.59 and 0.78, respectively. Patients with a combined high-risk VTE score and low-risk bleeding score comprised 14.5 % of the population. In this external validation study, the HA-VTE IMRS had poor discrimination for VTE but the HA-MB IMRS had good discriminatory ability for major bleeding events. A sizable minority of patients were categorized as high VTE risk with low bleed risk, a population which may have an optimal risk-benefit profile for post-hospital thromboprophylaxis. • The Intermountain Risk Scores use age and common laboratory studies to estimate the risk of post-hospital venous thromboembolism (VTE) and bleeding • Overall discrimination of the Intermountain Risk Scores was modest in this external validation cohort of 113,578 patients • Approximately 15% of patients were at increased risk of VTE but at low risk of bleeding following hospitalization [ABSTRACT FROM AUTHOR]

The authors' comment on the prognosis study that states that concomitant venous thromboembolism (VTE) increased risks for mortality and hemorrhage in older patients with cancer with risk varying by cancer type. They argue that although we know that the risk for both thrombosis and hemorrhage is higher in older cancer patients than in patients without cancer, we still lack clear guidance on balancing these risks.

It is uncertain whether antiphospholipid antibodies (APAs) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti-β2 glycoprotein 1 antibodies, and lupus anticoagulant on 2 occasions ~6 months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APAs were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results. Compared with those without an APA, the hazard ratios for recurrent VTE were 1.8 (95% confidence interval [CI], 0.9-3.7; P=.09) in the 25.9% of patients with an APA on ≥1 occasions, 2.7 (95% CI, 1.1-.7; P=.03) in the 9.0% of patients with the same APA on 2 occasions, and 4.5 (95% CI, 1.5-13.0; P=.006) in the 3.8% of patients with 2 or 3 different APA types on either the same or different occasions. There was no association between having an APA and D-dimer levels. We conclude that having the same type of APA on 2 occasions or having >1 type of APAon the same or different occasions is associated with recurrent thrombosis in patients with a first unprovoked VTE who stop anticoagulant therapy in response to negative D-dimer tests. APA and D-dimer levels seem to be independent predictors of recurrence in patients with an unprovoked VTE. [ABSTRACT FROM AUTHOR]