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.

Cost-effectiveness of managing low-risk pulmonary embolism patients without hospitalization. The low-risk pulmonary embolism prospective management study.

OBJECTIVE: Evaluate the cost-effectiveness and difference in length-of-stay when patients in the ED diagnosed with low-risk pulmonary embolism (PE) are managed with early discharge or observation. METHODS: Single cohort prospective management study from January 2013 to October 2016 of patients with PE diagnosed in the ED and evaluated for a primary composite endpoint of mortality, recurrent venous thromboembolism, and/or major bleeding event at 90 days. Low-risk patients had a PE Severity Index score < 86, no evidence of proximal deep vein thrombosis on venous compression ultrasonography of both lower extremities, and no evidence of right heart strain on echocardiography. Patients were managed either in the ED or in the hospital on observation status. Primary outcomes were total length of stay, total encounter costs, and 30-day costs. RESULTS: 213 patients were enrolled. 13 were excluded per the study protocol. Of the remaining 200, 122 were managed with emergency department observation (EDO) and 78 with hospital observation (HO). One patient managed with EDO met the composite outcome due to a major bleeding event on day 61. The mean length of stay for EDO was 793.4 min (SD -169.7, 95% CI:762-823) and for HO was 1170 (SD -211.4, 95% CI:1122-1218) with a difference of 376.8 (95% CI: 430-323, p < 0.0001). Total encounter mean costs for EDO were $1982.95 and $2759.59 for HO, with a difference of $776.64 (95% CI: 972-480, p > 0.0001). 30-day total mean costs for EDO were $2864.14 and $3441.52 for HO, with a difference of $577.38 (95% CI: -1372-217, p = 0.15). CONCLUSIONS: Patients with low-risk PE managed with ED-based observation have a shorter length of stay and lower total encounter costs than patients managed with Hospital-based observation.

Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism.

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-ß2 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 APA on 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. This trial was registered at www.clinicaltrials.gov as #NCT00720915.

Effect of Low-Intensity vs Standard-Intensity Warfarin Prophylaxis on Venous Thromboembolism or Death Among Patients Undergoing Hip or Knee Arthroplasty: A Randomized Clinical Trial.

Importance: The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. Objective: To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. Design, Setting, and Participants: The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. Main Outcomes and Measures: The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Results: Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%). Conclusions and Relevance: Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01006733.

Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.

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 (CHADS2) 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 CHADS2 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 CHADS2 scores strata. CONCLUSIONS: In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS2 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.

Thrombophilic Evaluation in Patients with Acute Pulmonary Embolism.

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.

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

Importance: Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. Objective: To determine whether genotype-guided dosing improves the safety of warfarin initiation. Design, Setting, and Patients: The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. Main Outcomes and Measures: The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Results: Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51-0.99), 33 vs 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54-1.34), and there were no deaths. Conclusions and Relevance: Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Further research is needed to determine the cost-effectiveness of personalized warfarin dosing. Trial Registration: clinicaltrials.gov Identifier: NCT01006733.

A pharmacogenetic versus a clinical algorithm for warfarin dosing.

BACKGROUND: The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results. METHODS: We 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. RESULTS: At 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. CONCLUSIONS: Genotype-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.).

Guidance for the evaluation and treatment of hereditary and acquired thrombophilia.

Thrombophilias are hereditary and/or acquired conditions that predispose patients to thrombosis. Testing for thrombophilia is commonly performed in patients with venous thrombosis and their relatives; however such testing usually does not provide information that impacts management and may result in harm. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for thrombophilia testing in five clinical situations: following 1) provoked venous thromboembolism, 2) 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. Additionally, guidance is provided regarding the timing of thrombophilia testing. The role of thrombophilia testing in arterial thrombosis and for evaluation of recurrent pregnancy loss is not addressed. Statements are based on existing guidelines and consensus expert opinion where guidelines are lacking. We recommend that thrombophilia testing not be performed in most situations. When performed, it should be used in a highly selective manner, and only in circumstances where the information obtained will influence a decision important to the patient, and outweigh the potential risks of testing. Testing should not be performed during acute thrombosis or during the initial (3-month) period of anticoagulation.

D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study.

BACKGROUND: Normal D-dimer levels after withdrawal of anticoagulant therapy are associated with a reduced risk for recurrence in patients with unprovoked venous thromboembolism (VTE) and may justify stopping treatment. OBJECTIVE: To determine whether patients with a first unprovoked VTE and negative D-dimer test result who stop anticoagulant therapy have a low risk for recurrence. DESIGN: Prospective management study with blinded outcome assessment. (ClinicalTrials.gov: NCT00720915). SETTING: 13 university-affiliated clinical centers. PATIENTS: 410 adults aged 75 years or younger with a first unprovoked proximal deep venous thrombosis or pulmonary embolism who had completed 3 to 7 months of anticoagulant therapy. INTERVENTION: Anticoagulant therapy was stopped if D-dimer test results were negative and was not restarted if results were still negative after 1 month. MEASUREMENTS: Recurrent VTE during an average follow-up of 2.2 years. RESULTS: In 319 patients (78%) who had 2 negative D-dimer results and did not restart anticoagulant therapy, rates of recurrent VTE were 6.7% (95% CI, 4.8% to 9.0%) per patient-year overall (42 of 319), 9.7% (CI, 6.7% to 13.7%) per patient-year in men (33 of 180), 5.4% (CI, 2.5% to 10.2%) per patient-year in women with VTE not associated with estrogen therapy (9 of 81), and 0.0% (CI, 0.0% to 3.0%) per patient-year in women with VTE associated with estrogen therapy (0 of 58) (P = 0.001 for the 3-group comparison). LIMITATIONS: Imprecision in female subgroups. Results may not be generalizable to different D-dimer assays from the one used in the study. CONCLUSION: The risk for recurrence in patients with a first unprovoked VTE who have negative D-dimer results is not low enough to justify stopping anticoagulant therapy in men but may be low enough to justify stopping therapy in women. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Percent Time With a Supratherapeutic INR in Atrial Fibrillation Patients Also Using an Antiplatelet Agent Is Associated With Long-Term Risk of Dementia.

BACKGROUND: Patients with atrial fibrillation (AF) are at higher risk of developing dementia. AF patients treated with warfarin with poor time in therapeutic ranges are significantly more likely to develop dementia. AF patients are also frequently treated with antiplatelet agents due to coexistent vascular disease. We hypothesize that AF patients with anticoagulation and antiplatelet therapies will be at higher risk of dementia, particularly with chronic exposure to over-anticoagulation. METHODS: Chronically anticoagulated patients receiving warfarin (target INR 2-3) for AF and managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service (CPAS) on concurrent antiplatelet agents with no history of dementia or stroke/TIA were included. The primary outcome was the presence of dementia defined by neurologist determined ICD-9 codes. Percent time with an INR>3.0 was determined and then compared by 3 strata <10% (n = 340), 10-24% (n = 417), ≥25% (n = 235). Multivariable Cox hazard regression was utilized to determine dementia incidence by percent time. RESULTS: A total of 992 patients were studied. Patients with an INR>3 more than 25% of the time were 2.40 times more likely to develop dementia (P = 0.04). A comparison between < 10% group and 10-24.9% group with INR>3 indicated no difference in risk for the development of dementia (P = 0.74). The risk was significantly increased in patients using triple antithrombotic therapy, although the number of patients within this group was small. CONCLUSION: In AF patients receiving antiplatelet and anticoagulant therapies, the percent of time exposed to over-anticoagulation increased dementia risk. These data support the possibility of chronic cerebral injury from microbleeds as a mechanism underlying the association of AF and dementia.

Antithrombotic Therapy for VTE Disease: Compendium and Review of CHEST Guidelines 2012-2021.

The 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 (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 currently relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications.

A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II).

BACKGROUND: Warfarin is characterized by marked variations in individual dose requirements and a narrow therapeutic window. Pharmacogenetics (PG) could improve dosing efficiency and safety, but clinical trials evidence is meager. METHODS AND RESULTS: A Randomized and Clinical Effectiveness Trial Comparing Two Pharmacogenetic Algorithms and Standard Care for Individualizing Warfarin Dosing (CoumaGen-II) comprised 2 comparisons: (1) a blinded, randomized comparison of a modified 1-step (PG-1) with a 3-step algorithm (PG-2) (N=504), and (2) a clinical effectiveness comparison of PG guidance with use of either algorithm with standard dosing in a parallel control group (N=1866). A rapid method provided same-day CYP2C9 and VKORC1 genotyping. Primary outcomes were percentage of out-of-range international normalized ratios at 1 and 3 months and percentage of time in therapeutic range. Primary analysis was modified intention to treat. In the randomized comparison, PG-2 was noninferior but not superior to PG-1 for percentage of out-of-range international normalized ratios at 1 month and 3 months and for percentage of time in therapeutic range at 3 months. However, the combined PG cohort was superior to the parallel controls (percentage of out-of-range international normalized ratios 31% versus 42% at 1 month; 30% versus 42% at 3 months; percentage of time in therapeutic range 69% versus 58%, 71% versus 59%, respectively, all P<0.001). Differences persisted after adjustment for age, sex, and clinical indication. There were fewer percentage international normalized ratios ≥4 and ≤1.5 and serious adverse events at 3 months (4.5% versus 9.4% of patients, P<0.001) with PG guidance. CONCLUSIONS: These findings suggest that PG dosing should be considered for broader clinical application, a proposal that is being tested further in 3 major randomized trials. The simpler 1-step PG algorithm provided equivalent results and may be preferable for clinical application. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927862.

Predicting post-discharge venous thromboembolism and bleeding among medical patients: External validation of a novel risk score utilizing ubiquitous biomarkers.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Performance of a Prospective Anticoagulation Stratification Algorithm After Liver Transplantation.

Venous thromboembolism (VTE) occurs in 0.4% to 15.5% and bleeding occurs in 20% to 35% of patients after liver transplantation (LT). Balancing the risk of bleeding from therapeutic anticoagulation and risk of thrombosis in the postoperative period is challenging. Little evidence exists regarding the best treatment strategy for these patients. We hypothesized that a subset of LT patients who develop postoperative deep vein thromboses (DVTs) could be managed without therapeutic anticoagulation. We implemented a quality improvement (QI) initiative using a standardized Doppler ultrasound-based VTE risk stratification algorithm to guide parsimonious implementation of therapeutic anticoagulation with heparin drip. Methods: In a prospective management QI initiative for DVT management, we compared 87 LT historical patients (control group; January 2016-December 2017) to 182 LT patients (study group; January 2018-March 2021). We analyzed the rates of immediate therapeutic anticoagulation after DVT diagnosis within 14 d of LT, clinically significant bleeding, return to the operating room, readmission, pulmonary embolism, and death within 30 d of LT before and after the QI initiative. Results: Ten patients (11.5%) in the control group and 23 patients (12.6%; P = 0.9) in the study group developed DVTs after LT. Immediate therapeutic anticoagulation was used in 7 of 10 and 5 of 23 patients in the control and study groups, respectively (P = 0.024). The study group had lower odds of receiving immediate therapeutic anticoagulation after VTE (21.7% versus 70%; odds ratio = 0.12; 95% confidence interval, 0.019-0.587; P = 0.013) and a lower rate of postoperative bleeding (8.7% versus 40%; odds ratio = 0.14, 95% confidence interval, 0.02-0.91; P = 0.048). All other outcomes were similar. Conclusions: Implementing a risk-stratified VTE treatment algorithm for immediate post-LT patients appears to be safe and feasible. We observed a decrease in the use of therapeutic anticoagulation and a lower rate of postoperative bleeding without adverse impacts on early outcomes.

Antithrombotic management of patients with deep vein thrombosis and venous stents: an international registry.

BACKGROUND: In patients with acute deep vein thrombosis (DVT) treated with catheter-based thrombolysis and venous stenting, poststenting anticoagulant management is uncertain. OBJECTIVES: To determine the type and duration of antithrombotic therapy used in patients who have received venous stents for treatment of acute lower extremity DVT. METHODS: We created an international registry of patients with leg DVT from 2005 to 2019 who received venous stents as part of their acute management. We collected data on baseline clinical characteristics and pre-venous and post-venous stent antithrombotic therapy. RESULTS: We studied 173 patients with venous stents: 101 (58%) were aged ≤50 years, 105 (61%) were female, and 128 (74%) had risk factors for thrombotic disease. DVT was iliofemoral in 150 (87%) patients, and catheter-based treatment was given within 7 days of diagnosis in 92 (53%) patients. After venous stenting, 109 (63%) patients received anticoagulant-only therapy with a direct oral anticoagulant (29%), warfarin (22%), or low-molecular-weight heparin (10%), and 59 (34%) received anticoagulant-antiplatelet therapy. In patients taking anticoagulant-only therapy, 29% received indefinite treatment; in patients on anticoagulant-antiplatelet therapy, 19% received indefinite treatment. Factors associated with combined anticoagulant-antiplatelet therapy vs anticoagulant-only therapy were use of thrombolytic, thrombectomy, and aspiration interventions (odds ratio [OR], 5.11; 95% CI, 1.45-18.05); use of balloon angioplasty (OR, 2.62; 95% CI, 1.20-5.76); and immediate stent restenosis (OR, 7.2; 95% CI, 1.45-5.89). CONCLUSION: Anticoagulant therapy without concomitant antiplatelet therapy appears to be the most common antithrombotic strategy in patients with DVT and venous stenting. More research is needed to determine outcomes of venous stenting in relation to antithrombotic therapy.