Periprocedural Anticoagulation.

Management of patients taking anticoagulants around the time of a procedure is a common and complex clinical scenario. Providing evidence-based care requires estimation of risk for thrombosis and bleeding, knowledge of commonly used medications, multidisciplinary communication and collaboration, and patient engagement and education. This review provides a standardized, evidence-based approach to periprocedural management of anticoagulation, based on current evidence and expert clinical guidelines.

In intermediate- or high-risk PE, catheter-directed thrombolysis is linked to reduced mortality vs. systemic thrombolysis or anticoagulation.

SOURCE CITATION: Planer D, Yanko S, Matok I, et al. Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis. CMAJ. 2023;195:E833-E843. 37336568.

NSAIDs and hormonal contraceptives are linked to VTE in women with no previous thrombotic disease.

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.

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR2HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions.

Excluding pregnancy-associated deep vein thrombosis with whole-leg ultrasound.

Background: Deep vein thrombosis (DVT) is common in pregnancy, yet data are limited on the best diagnostic strategies in pregnant patients suspected of DVT. Objectives: We conducted a prospective cohort study to evaluate the rate of symptomatic DVT in the 90 days after a negative whole-leg compression ultrasound (CUS) in pregnant women presenting with DVT symptoms. Methods: In this prospective cohort study, we enrolled pregnant patients suspected of DVT between 2011 and 2019 who were referred to the vascular imaging laboratory at a tertiary care center and had anticoagulation held after a negative whole-leg CUS. Primary outcome was objectively confirmed DVT or pulmonary embolism or death due to venous thromboembolism (VTE). Results: Whole-leg CUS yielded normal results in 186 patients (97.9%) and identified DVT in 4 (2.1%). The mean age was 30 and 164 were White. Among the 186 patients with a negative, initial whole-leg CUS who did not receive anticoagulation, there were 2 DVT events identified over the 90-day follow-up period, for an overall rate of 1.1% (95% CI: 0.2-3.4%). The study was terminated before full planned accrual for administrative reasons. Conclusion: The rate of symptomatic DVT is low in pregnant patients who have a single, negative whole-leg CUS and did not receive anticoagulation. Adequately powered studies should prospectively assess whole-leg CUS in a larger population alone and in combination with pre-test probability scores and/or D-dimer to determine its role in the evaluation of suspected DVT in pregnancy.

Use of patient-reported outcome measures in patients with venous thromboembolism: communication from the ISTH SSC Subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease.

Patient-reported outcome measures (PROMs) are patient-completed instruments that capture patient-perceived health status and well-being. PROMs measure disease impact and outcomes of care as reported by those who experience the disease. After pulmonary embolism or deep vein thrombosis, patients may face a broad spectrum of complications and long-term sequelae beyond the usual quality-of-care indicators of recurrent venous thromboembolism (VTE), bleeding complications, and survival. The full impact of VTE on individual patients can only be captured by assessing all relevant health outcomes from the patient's perspective in addition to the traditionally recognized complications. Defining and measuring all important outcomes will help facilitate treatment tailored to the needs and preferences of patients and may improve health outcomes. The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease endorsed the International Consortium for Health Outcomes Measurement (ICHOM) VTE project on development of a standardized set of patient-centered outcome measures for patients with VTE. In this communication, the course and result of the project are summarized, and based on these findings, we propose recommendations for the use of PROMs during clinical follow-up of patients with VTE. We describe challenges to implementation of PROMs and explore barriers and enablers.

Assessment of the Risk of Venous Thromboembolism in Nonhospitalized Patients With COVID-19.

Importance: Patients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood. Objectives: To assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE. Design, Setting, and Participants: A retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021. Exposures: Patient demographic and clinical characteristics identified from integrated electronic health records. Main Outcomes and Measures: The primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data. Results: A total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]). Conclusions and Relevance: In this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.

An Elusive Seizure.

We present a case of a healthy 62-year-old woman who developed recurrent seizures preceded by subacute cognitive slowing, ataxia, night sweats, and weight loss. She was found to have cytopenias, multifocal T2/FLAIR hyperintensities on magnetic resonance imaging (MRI), and magnetic susceptibility artifact lesions on susceptibility weighted imaging (SWI). Her symptoms, imaging and laboratory abnormalities all improved with high-doses of steroids and intravenous immunoglobulin (IVIG). But recurred several weeks after completing treatment. Despite extensive work-up, she required multiple hospitalizations and repeat diagnostic studies to arrive at a diagnosis. With an expert discussant in hematology and oncology, we review the differential diagnosis and stepwise approach of unexplained neuro-inflammatory syndromes with cytopenias and systemic symptoms. Our case highlights how time, empiric treatment response, and repeated diagnostic studies refine differential diagnoses and subsequent evaluation. After revealing the diagnosis, we discuss the heterogenous clinical manifestations of this disease process.

Long-term functional outcomes and mortality after hospitalization for extracranial hemorrhage.

BACKGROUND: The effects of extracranial hemorrhage (ECH), or bleeding outside the brain, are often considered transient. Yet, there are few data on the long-term and functional consequences of ECH. OBJECTIVE: Define the association of ECH hospitalization with functional independence and survival in a nationally representative cohort of older adults. DESIGN: Longitudinal cohort study. SETTINGS AND PARTICIPANTS: Data from the Health and Retirement Study from 1995 to 2016, a nationally representative, biennial survey of older adults. Adults aged 66 and above with Medicare linkage and at least 12 months of continuous Medicare Part A and B enrollment. INTERVENTION: Hospitalization for ECH. MAIN OUTCOMES AND MEASURES: Adjusted odds ratios and predicted likelihood of independence in all activities of daily living (ADLs), independence in all instrumental activities of daily living (IADLs) and extended nursing home stay. Adjusted hazard ratio and predicted likelihood for survival. RESULTS: In a cohort of 6719 subjects (mean age 77, 59% women) with average follow-up time of 8.3 years (55,767 person-years), 736 (11%) were hospitalized for ECH. ECH was associated with a 15% increase in ADL disability, 15% increase in IADL disability, 8% increase in nursing home stays, and 4% increase in mortality. After ECH, subjects became disabled and died at the same annual rate as pre-ECH but never recovered to pre-ECH levels of function. In conclusion, hospitalization for ECH was associated with significant and durable declines in independence and survival. Clinical and research efforts should incorporate the long-term harms of ECH into decision-making and strategies to mitigate these effects.

Venous thromboembolism (VTE) prevention and diagnosis in COVID-19: Practice patterns and outcomes at 33 hospitals.

BACKGROUND: Early reports of increased thrombosis risk with SARS-CoV-2 infection led to changes in venous thromboembolism (VTE) management. Real-world data on the prevalence, efficacy and harms of these changes informs best practices. OBJECTIVE: Define practice patterns and clinical outcomes related to VTE diagnosis, prevention, and management in hospitalized patients with coronavirus disease-19 (COVID-19) using a multi-hospital US sample. METHODS: In this retrospective cross-sectional study of 1121 patients admitted to 33 hospitals, exposure was dose of anticoagulant prescribed for VTE prophylaxis (standard, intensified, therapeutic), and primary outcome was VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]); secondary outcomes were PE, DVT, arterial thromboembolism (ATE), and bleeding events. Multivariable logistic regression models accounting for clustering by site and adjusted for risk factors were used to estimate odds ratios (ORs). Inverse probability weighting was used to account for confounding by indication. RESULTS: 1121 patients (mean age 60 ± 18, 47% female) admitted with COVID-19 between February 2, 2020 and December 31, 2020 to 33 US hospitals were included. Pharmacologic VTE prophylaxis was prescribed in 86%. Forty-seven patients (4.2%) had PE, 51 (4.6%) had DVT, and 23 (2.1%) had ATE. Forty-six patients (4.1%) had major bleeding and 46 (4.1%) had clinically relevant non-major bleeding. Compared to standard prophylaxis, adjusted odds of VTE were 0.67 (95% CI 0.21-2.1) with no prophylaxis, 1.0 (95% CI 0.06-17) with intensified, and 3.0 (95% CI 0.89-10) with therapeutic. Adjusted odds of bleeding with no prophylaxis were 5.6 (95% CI 3.0-11) and 5.3 (95% CI 3.0-10) with therapeutic (no events on intensified dosing). CONCLUSIONS: Therapeutic anticoagulation was associated with a 3-fold increased odds of VTE and 5-fold increased odds of bleeding. While higher bleeding rates with high-intensity prophylaxis were likely due to full-dose anticoagulation, we conclude that high thrombosis rates were due to clinical concern for thrombosis before formal diagnosis.

Health-related quality of life associated with warfarin and direct oral anticoagulants in venous thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE) is commonly treated with oral anticoagulants, including warfarin or direct oral anticoagulants (DOACs). Although DOACs are associated with favorable treatment satisfaction, few studies have assessed whether quality of life differs between DOAC and warfarin users. MATERIALS AND METHODS: We invited adults enrolled in two California-based integrated health care delivery systems and with a history of VTE between January 1, 2015 and June 30, 2018 to complete a survey on their experience with anticoagulants. Health-related quality of life (QOL) was assessed using the RAND 36-item Short Form Health Survey (SF-36), which measures QOL in 2 general component scores (physical and mental). We used multivariable linear regression to compare mean QOL component scores between DOAC-users and warfarin-users, adjusting for patient and clinical characteristics. RESULTS: Overall, 2230 patients (43.1 % women and 31.8 % >75 years of age) taking anticoagulants answered at least 1 question on the SF-36, 975 taking DOACs and 1255 taking warfarin. After adjustment for patient-level factors, there were no significant differences in either physical component scores (39.2 v 38.3, p = 0.24) or mental component scores (48.5 v 49.0, p = 0.42) between DOAC and warfarin users. CONCLUSIONS: Health-related QOL did not significantly differ between DOAC and warfarin users with a history of VTE.

Long-term individual and population functional outcomes in older adults with atrial fibrillation.

BACKGROUND: Older adults with atrial fibrillation (AF) have multiple risk factors for disablement. Long-term function and the contribution of strokes to disability have not been previously characterized. Our objective was to determine long-term function among older adults with AF and the relative contribution of stroke. METHODS: We used data from the nationally representative Health and Retirement Study (1992-2014) with participants ≥65 years with incident AF. We examined the association of incident stroke with three outcomes: independence with activities of daily living (ADL), instrumental activities of daily living (IADL), and residence outside a nursing home (community-dwelling). We fit logistic regression models with repeated measures adjusting for comorbidities and demographics to estimate the effect of stroke on function. We estimated the contribution of strokes to the overall population burden of disability using the method of recycled predictions. RESULTS: Among 3530 participants (median age 79 years, 53% women), 262 had a stroke over 17,396 person-years. Independent of stroke and accounting for comorbidities, annually, ADL independence decreased by 4.4%, IADL independence decreased by 3.9%, and community dwelling decreased by 1.2% (p < 0.05 for all). Accounting for comorbidities, of those who experienced a stroke, 31.9% developed new ADL dependence, 26.5% developed new IADL dependence, and 8.6% newly moved to a nursing home (p < 0.05 for all). Considering all causes of function loss, 1.7% of ADL disability-years, 1.2% of IADL disability-years, and 7.3% of nursing home years could be attributed to stroke over 7.4 years. CONCLUSION: Older adults lose substantial function over time following AF diagnosis, independent of stroke. Stroke was associated with a significant functional decline and increase in the likelihood of nursing home move, but stroke did not accelerate subsequent disability accrual. Because of the high background rate of disability, stroke was not the dominant determinant of population-level disability in older adults with AF.

Succeeding in Aging Research During the Pandemic: Strategies for Fellows and Junior Faculty.

Fellows and junior faculty conducting aging research have encountered substantial new challenges during the COVID-19 pandemic. They report that they have been uncertain how and whether to modify existing research studies, have faced difficulties with job searches, and have struggled to balance competing pressures including greater clinical obligations and increased responsibilities at home. Many have also wondered if they should shift gears and make COVID-19 the focus of their research. We asked a group of accomplished scientists and mentors to grapple with these concerns and to share their thoughts with readers of this journal.

Long-term individual and population functional outcomes in older adults with atrial fibrillation.

BACKGROUND: Older adults with atrial fibrillation (AF) have multiple risk factors for disablement. Long-term function and the contribution of strokes to disability has not been previously characterized. METHODS: We performed a longitudinal, observational study in the nationally representative Health and Retirement Study (1992-2014). We included participants ≥65 years with Medicare claims who met incident AF diagnosis claims criteria. We examined the association of incident stroke with three functional outcomes: independence with activities of daily living (ADL) and instrumental activities of daily living (IADL) and community-dwelling. We fit separate logistic regression models with repeated measures adjusting for comorbidities and demographics to estimate the effect of stroke on function. We estimate the contribution of strokes to the overall population burden of functional impairment using the method of recycled predictions. RESULTS: Among 3530 participants (median age 79 years, 53% women, median CHA 2 DS 2 -VASc 5), 262 had a stroke over 17,396 person-years. Independent of stroke and accounting for population comorbidities, annually, ADL dependence increased by 4.4%, IADL dependence increased by 3.9%, and nursing home residence increased by 1.2% (p<0.05 for all). Accounting for comorbidities, of those who experienced a stroke, 31.9% developed new ADL dependence, 26.5% developed new IADL dependence, and 8.6% newly moved to a nursing home (p<0.05 for all). Considering all causes of function loss, 1.7% of ADL disability-years, 1.2% of IADL disability-years, and 7.3% of nursing home years could be attributed to stroke over 7.4years. CONCLUSION: Older adults lose substantial function over time following AF diagnosis, independent of stroke. Stroke was associated with a significant decline in function and an increase in the likelihood of nursing home move, but stroke did not accelerate subsequent disability accrual. Because of the high background rate of functional loss, stroke was not the dominant determinant of population-level disability in older adults with AF. IMPACT STATEMENT: We certify that this work is novel. Little is known about long-term function (ADL, IADL, community-dwelling) among older adults with AF and the association with stroke. This nationally representative study finds a high rate of function loss independent of stroke, and among those who suffer a stroke, a dramatic and immediate decline in function. Because of the high rate of function loss independent of stroke and the relatively low rate of stroke, on a population level, stroke is not the dominant determinant of disability in older adults with AF.

Long-term individual and population functional outcomes in older adults with atrial fibrillation.

BACKGROUND: Older adults with atrial fibrillation (AF) have multiple risk factors for disablement. Long-term function and the contribution of strokes to disability has not been previously characterized. METHODS: We performed a longitudinal, observational study in the nationally representative Health and Retirement Study (1992-2014). We included participants ≥65 years with Medicare claims who met incident AF diagnosis claims criteria. We examined the association of incident stroke with three functional outcomes: independence with activities of daily living (ADL) and instrumental activities of daily living (IADL) and community-dwelling. We fit separate logistic regression models with repeated measures adjusting for comorbidities and demographics to estimate the effect of stroke on function. We estimate the contribution of strokes to the overall population burden of functional impairment using the method of recycled predictions. RESULTS: Among 3530 participants (median age 79 years, 53% women, median CHA2DS2-VASc 5), 262 had a stroke over 17,396 person-years. Independent of stroke and accounting for population comorbidities, annually, ADL dependence increased by 4.4%, IADL dependence increased by 3.9%, and nursing home residence increased by 1.2% (p<0.05 for all). Accounting for comorbidities, of those who experienced a stroke, 31.9% developed new ADL dependence, 26.5% developed new IADL dependence, and 8.6% newly moved to a nursing home (p<0.05 for all). Considering all causes of function loss, 1.7% of ADL disability-years, 1.2% of IADL disability-years, and 7.3% of nursing home years could be attributed to stroke over 7.4years. CONCLUSION: Older adults lose substantial function over time following AF diagnosis, independent of stroke. Stroke was associated with a significant decline in function and an increase in the likelihood of nursing home move, but stroke did not accelerate subsequent disability accrual. Because of the high background rate of functional loss, stroke was not the dominant determinant of population-level disability in older adults with AF. IMPACT STATEMENT: We certify that this work is novel. Little is known about long-term function (ADL, IADL, community-dwelling) among older adults with AF and the association with stroke. This nationally representative study finds a high rate of function loss independent of stroke, and among those who suffer a stroke, a dramatic and immediate decline in function. Because of the high rate of function loss independent of stroke and the relatively low rate of stroke, on a population level, stroke is not the dominant determinant of disability in older adults with AF.

COVID-19 coagulopathy and thrombosis: Analysis of hospital protocols in response to the rapidly evolving pandemic.

As the Coronavirus disease 2019 (COVID-19) pandemic spread to the US, so too did descriptions of an associated coagulopathy and thrombotic complications. Hospitals created institutional protocols for inpatient management of COVID-19 coagulopathy and thrombosis in response to this developing data. We collected and analyzed protocols from 21 US academic medical centers developed between January and May 2020. We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. Protocols differed regarding incorporation of D-dimer tests, dosing of VTE prophylaxis, indications for post-discharge pharmacologic VTE prophylaxis, how to evaluate for VTE, and the use of empiric therapeutic anticoagulation. These findings support ongoing efforts to establish international, evidence-based guidelines.

Blood Clots, or Thrombosis, in Patients With Cancer.

This JAMA Oncology Patient Page explains the risk, diagnosis, treatment, and prevention of thrombosis in patients with cancer.