Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Assessment of a venous thromboembolism prophylaxis shared decision-making intervention (DASH-TOP) using the decisional conflict scale: a mixed-method study.

BACKGROUND: Venous thromboembolism (VTE) in pregnancy is a major cause of maternal morbidity and death. The use of low-molecular-weight heparin (LMWH), despite being the standard of care to prevent VTE, comes with some challenges. Shared decision-making (SDM) interventions are recommended to support patients and clinicians in making preference-sensitive decisions. The quality of the SDM process has been widely assessed with the decisional conflict scale (DCS). Our aim is to report participants' perspectives of each of the components of an SDM intervention (DASH-TOP) in relation to the different subscales of the DCS. METHODS: Design: A convergent, parallel, mixed-methods design. PARTICIPANTS: The sample consisted of 22 health care professionals, students of an Applied Clinical Research in Health Sciences (ICACS) master program. INTERVENTION: We randomly divided the participants in three groups: Group 1 received one component (evidence -based information), Group 2 received two components (first component and value elicitation exercises), and Group 3 received all three components (the first two and a decision analysis recommendation) of the SDM intervention. ANALYSIS: For the quantitative strand, we used a non-parametric test to analyze the differences in the DCS subscales between the three groups. For the qualitative strand, we conducted a content analysis using the decisional conflict domains to deductively categorize the responses. RESULTS: Groups that received more intervention components experienced less conflict and better decision-making quality, although the differences between groups were not statistically significant. The decision analysis recommendation improved the efficacy with the decision-making process, however there are some challenges when implementing it in clinical practice. The uncertainty subscale showed a high decisional conflict for all three groups; contributing factors included low certainty of the evidence-based information provided and a perceived small effect of the drug to reduce the risk of a VTE event. CONCLUSIONS: The DASH-TOP intervention reduced decisional conflict in the decision -making process, with decision analysis being the most effective component to improve the quality of the decision. There is a need for more implementation research to improve the delivery of SDM interventions in the clinical encounter.

Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability.

BACKGROUND: Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP. METHODS: We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism. RESULTS: A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9). CONCLUSIONS: A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.).

Pulmonary Embolism in Pregnancy.

Even though venous thromboembolism is a leading cause of maternal mortality in high-income countries, there are limited high-quality data to assist clinicians with the management of pulmonary embolism in this patient population. Diagnosis, prevention, and treatment of pregnancy-associated pulmonary embolism are complicated by the need to consider fetal, as well as maternal, well-being. Recent studies suggest that clinical prediction rules and D-dimer testing can reduce the need for diagnostic imaging in a subset of patients. Low-molecular-weight heparin is the preferred anticoagulant for both prophylaxis and treatment in this setting. Direct oral anticoagulants are contraindicated during pregnancy and in breastfeeding women. Thrombolysis or embolectomy should be considered for pregnant women with pulmonary embolism complicated by hemodynamic instability. Treatment of pregnancy-associated pulmonary embolism should be continued for at least 3 months, including 6 weeks postpartum. Management of anticoagulants at the time of delivery should involve a multidisciplinary individualized approach that uses shared decision making to take patient and caregiver values and preferences into account.

Rivaroxaban Compared to Placebo for the Treatment of Leg Superficial Vein Thrombosis: A Randomized Trial.

The role of rivaroxaban in the treatment of leg superficial venous thrombosis (SVT) is uncertain. This article aims to determine if rivaroxaban is an effective and safe treatment for leg SVT. Patients with symptomatic leg SVT of at least 5 cm length were randomized to 45 days of rivaroxaban 10 mg daily or to placebo, and followed for a total of 90 days. Treatment failure (required a nonstudy anticoagulant; had proximal deep vein thrombosis or pulmonary embolism; or had surgery for SVT) at 90 days was the primary efficacy outcome. Secondary efficacy outcomes included leg pain severity, and venous disease-specific and general health-related quality of life over 90 days. Major bleeding at 90 days was the primary safety outcome. Poor enrollment led to the trial being stopped after 85 of the planned 600 patients were randomized to rivaroxaban (n = 43) or placebo (n = 42). One rivaroxaban and five placebo patients had a treatment failure by 90 days (absolute risk reduction = 9.0%, 95% confidence interval: -22 to 5.9%). Leg pain improvement did not differ at 7 (p = 0.16) or 45 days (p = 0.89), but was greater with rivaroxaban at 90 days (p = 0.011). There was no difference in venous disease-specific (p = 0.99) or general health-related (p = 0.37) quality of life over 45 days. There were no major bleeds or deaths in either group. There were no identifiable differences in efficacy or safety between rivaroxaban and placebo in patients with symptomatic SVT but comparisons were undermined by a much smaller than planned sample size (NCT1499953).

How I treat heavy menstrual bleeding associated with anticoagulants.

Anticoagulant-associated heavy menstrual bleeding (HMB) is an underrecognized but not uncommon problem in clinical practice. Premenopausal women should be advised of the potential effect of anticoagulant therapy on menstrual bleeding at the time of treatment initiation. Consequences of HMB should be assessed and treated on an ongoing basis. In the acute setting, the decision to withhold anticoagulants is based on an individual patient's risk of thrombosis and the severity of the bleeding. For women who require long-term anticoagulation, a levonorgestrel intrauterine system, tranexamic acid (during menstrual flow), high-dose progestin-only therapy, or combined hormonal contraceptives are effective for controlling HMB. The risk of thrombosis during anticoagulant therapy with these treatments is not well studied but is likely to be low. Selection of type of hormonal therapy is based on patient preference, other indications for and contraindications to therapy, adverse effect profile, and ongoing thrombotic risk factors. Women who do not respond to medical treatment or who do not wish to retain their fertility should be considered for surgical management.

The Society for Obstetric Anesthesia and Perinatology Consensus Statement on the Anesthetic Management of Pregnant and Postpartum Women Receiving Thromboprophylaxis or Higher Dose Anticoagulants.

Venous thromboembolism is recognized as a leading cause of maternal death in the United States. Thromboprophylaxis has been highlighted as a key preventive measure to reduce venous thromboembolism-related maternal deaths. However, the expanded use of thromboprophylaxis in obstetrics will have a major impact on the use and timing of neuraxial analgesia and anesthesia for women undergoing vaginal or cesarean delivery and other obstetric surgeries. Experts from the Society of Obstetric Anesthesia and Perinatology, the American Society of Regional Anesthesia, and hematology have collaborated to develop this comprehensive, pregnancy-specific consensus statement on neuraxial procedures in obstetric patients receiving thromboprophylaxis or higher dose anticoagulants. To date, none of the existing anesthesia societies' recommendations have weighed the potential risks of neuraxial procedures in the presence of thromboprophylaxis, with the competing risks of general anesthesia with a potentially difficult airway, or maternal or fetal harm from avoidance or delayed neuraxial anesthesia. Furthermore, existing guidelines have not integrated the pharmacokinetics and pharmacodynamics of anticoagulants in the obstetric population. The goal of this consensus statement is to provide a practical guide of how to appropriately identify, prepare, and manage pregnant women receiving thromboprophylaxis or higher dose anticoagulants during the ante-, intra-, and postpartum periods. The tactics to facilitate multidisciplinary communication, evidence-based pharmacokinetic and spinal epidural hematoma data, and Decision Aids should help inform risk-benefit discussions with patients and facilitate shared decision making.

Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials.

BACKGROUND: Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and birth of a small-for-gestational-age (SGA) neonate. These complications are leading causes of maternal, fetal, and neonatal morbidity and mortality in high-income countries. Affected women are at high risk of recurrence in subsequent pregnancies; however, effective strategies to prevent recurrence are absent. Findings from our previous study-level meta-analysis suggested that low-molecular-weight heparin reduced the risk of recurrent placenta-mediated pregnancy complications. However, we identified significant heterogeneity in the results, possibly due to trial design or inclusion criteria. To identify which patients benefit from, and which outcomes are prevented by, low-molecular-weight heparin, we did an individual patient data meta-analysis. METHODS: We did a systematic review in May, 2013, which identified eight eligible randomised trials done between 2000 and 2013 of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. We excluded studies on the basis of the wrong population, the study being ongoing, inability to confirm eligibility of participants, intervention stopped too early, and no response from the principal investigator. We requested individual patient data from the study authors for eligible women (women pregnant at the time of the study with a history of previous pregnancy that had been complicated by one or more of the following: pre-eclampsia, placental abruption, birth of an SGA neonate [<10th percentile], pregnancy loss after 16 weeks' gestation, or two losses after 12 weeks' gestation) and recoded, combined, and analysed the data for our meta-analysis. The primary outcome was a composite of early-onset (<34 weeks) or severe pre-eclampsia, birth of an SGA neonate (<5th percentile), late pregnancy loss (≥20 weeks' gestation), or placental abruption leading to delivery, assessed on an intention-to-treat basis. We assessed risk of bias with the Cochrane Risk of Bias tool. This study is registered with PROSPERO, number CRD42013006249. FINDINGS: We analysed data from 963 eligible women in eight trials: 480 randomly assigned to low-molecular-weight heparin and 483 randomly assigned to no low-molecular-weight heparin. Overall, the risk of bias was not substantial enough to affect decisions regarding trial inclusion. Participants were mostly white (795/905; 88%) with a mean age of 30·9 years (SD 5·0) and 403/963 (42%) had thrombophilia. In the primary analysis, low-molecular-weight heparin did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications (low-molecular-weight heparin 62/444 [14%] versus no low-molecular-weight heparin 95/443 (22%) absolute difference -8%, 95% CI -17·3 to 1·4, p=0·09; relative risk 0·64, 95% CI 0·36-1·11, p=0·11). We noted significant heterogeneity between single-centre and multicentre trials. In subgroup analyses, low-molecular-weight heparin in multicentre trials reduced the primary outcome in women with previous abruption (p=0·006) but not in any of the other subgroups of previous complications. INTERPRETATION: Low-molecular-weight heparin does not seem to reduce the risk of recurrent placenta-mediated pregnancy complications in at-risk women. However, some decreases in event rates might have been too small for the power of our study to explore. FUNDING: Canadian Institutes of Health Research.

Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study.

Rapid exclusion of heparin-induced thrombocytopenia (HIT) is needed to determine which patients can continue to receive heparin. In this prospective management study, 526 participants had a 4Ts score, rapid particle gel immunoassay (platelet factor 4/heparin [PF4/H]-PaGIA), and serotonin-release assay (SRA) performed. While awaiting SRA results, participants with a low 4Ts score (irrespective of PF4/H-PaGIA result) or intermediate 4Ts score plus a negative PF4/H-PaGIA result received prophylactic doses of danaparoid or fondaparinux; all others received therapeutic doses of nonheparin anticoagulants. The primary outcome was the frequency of management failures defined as HIT-positive participants with a low 4Ts score (irrespective of PF4/H-PaGIA result) or intermediate 4Ts score plus negative PF4/H-PaGIA result. Six participants (1.1%; 95% confidence interval [CI], 0.2-2.1%) were management failures. A negative PF4/H-PaGIA result reduced the pretest probability of HIT from 1.9% to 0% (95% CI, 0-1.3%), 6.7% to 0% (95% CI, 0-2.7%), and 36.6% to 0% (95% CI, 0-14.3%) in the low, intermediate, and high score groups, respectively. A positive PF4/H-PaGIA result increased the probability of HIT in the low score group to 15.4% (95% CI, 5.9-30.5). Thus, a low or intermediate 4Ts score plus negative PaGIA result excluded HIT, whereas any other combination of results justified the use of alternative anticoagulants until HIT could be excluded. This trial was registered at www.clinicaltrials.gov as #NCT00489437.

Guidance for the treatment and prevention of obstetric-associated venous thromboembolism.

Venous thromboembolism (VTE), which may manifest as pulmonary embolism (PE) or deep vein thrombosis (DVT), is a serious and potentially fatal condition. Treatment and prevention of obstetric-related VTE is complicated by the need to consider fetal, as well as maternal, wellbeing when making management decisions. Although absolute VTE rates in this population are low, obstetric-associated VTE is an important cause of maternal morbidity and mortality. This manuscript, initiated by the Anticoagulation Forum, provides practical clinical guidance on the prevention and treatment of obstetric-associated VTE based on existing guidelines and consensus expert opinion based on available literature where guidelines are lacking.

Superficial venous thrombosis: recognizing the risk.

In this issue of Blood, Roach and colleagues show that individuals with prior superficial venous thrombosis are at increased risk of developing venous thromboembolism when exposed to acquired clinical risk factors.

Selective D-dimer testing for diagnosis of a first suspected episode of deep venous thrombosis: a randomized trial.

BACKGROUND: D-Dimer testing is sensitive but not specific for diagnosing deep venous thrombosis (DVT). Changing the use of testing and the threshold level for a positive test result on the basis of risk for DVT might improve the tradeoff between sensitivity and specificity and reduce the need for testing. OBJECTIVE: To determine whether using a selective D-dimer testing strategy based on clinical pretest probability (C-PTP) for DVT is safe and reduces diagnostic testing compared with using a single D-dimer threshold for all patients. DESIGN: Randomized, multicenter, controlled trial. Patients were allocated using a central automated system. Ultrasonographers and study adjudicators but not other study personnel were blinded to trial allocation. (ClinicalTrials.gov: NCT00157677) SETTING: 5 Canadian hospitals. PATIENTS: Consecutive symptomatic patients with a first episode of suspected DVT. INTERVENTION: Selective testing (n = 860), defined as D-dimer testing for outpatients with low or moderate C-PTP (DVT excluded at D-dimer levels <1.0 µg/mL [low C-PTP] or <0.5 µg/mL [moderate C-PTP]) and venous ultrasonography without D-dimer testing for outpatients with high C-PTP and inpatients, or uniform testing (n = 863), defined as D-dimer testing for all participants (DVT excluded at D-dimer levels <0.5 µg/mL). MEASUREMENTS: The proportion of patients not diagnosed with DVT during initial testing who had symptomatic venous thromboembolism during 3-month follow-up and the proportion of patients undergoing D-dimer testing and ultrasonography. RESULTS: The incidence of symptomatic venous thromboembolism at 3 months was 0.5% in both study groups (difference, 0.0 percentage point [95% CI, -0.8 to 0.8 percentage points]). Selective testing reduced the proportion of patients who required D-dimer testing by 21.8 percentage points (CI, 19.1 to 24.8 percentage points). It reduced the proportion who required ultrasonography by 7.6 percentage points (CI, 2.9 to 12.2 percentage points) overall and by 21.0 percentage points (CI, 14.2 to 27.6 percentage points) in outpatients with low C-PTP. LIMITATION: Results may not be generalizable to all D-dimer assays or patients with previous DVT, study personnel were not blinded, and the trial was stopped prematurely. CONCLUSION: A selective D-dimer testing strategy seems as safe as and more efficient than having everyone undergo D-dimer testing when diagnosing a first episode of suspected DVT. PRIMARY FUNDING SOURCE: Heart and Stroke Foundation of Ontario.

Oral direct Factor Xa inhibitors versus low-molecular-weight heparin to prevent venous thromboembolism in patients undergoing total hip or knee replacement: a systematic review and meta-analysis.

BACKGROUND: Thromboembolic disease is the most frequent medical complication of arthroplasty. PURPOSE: To evaluate the benefits and harms of oral direct factor Xa inhibitors versus low-molecular-weight heparin (LMWH) in patients undergoing total hip or knee replacement. DATA SOURCES: MEDLINE (1966 to December 2011), EMBASE (1980 to December 2011), and the Cochrane Central Register of Controlled Trials (up to December 2011), without language restrictions. References of reviews and abstracts of conferences were hand-searched. STUDY SELECTION: Randomized trials in patients undergoing hip or knee replacement that evaluated factor Xa inhibitors versus LMWH. DATA EXTRACTION: Two reviewers independently evaluated eligibility, abstracted the data, and assessed risk for bias. DATA SYNTHESIS: In 22 trials, high-quality evidence indicated that the absolute effect of factor Xa inhibitors and LMWH does not differ in terms of all-cause mortality (risk difference, 0 fewer deaths per 1000 patients [95% CI, 2 fewer to 1 more death]) or nonfatal pulmonary embolism (risk difference, 0 fewer events per 1000 patients [CI, 1 fewer to 2 more events]). Factor Xa inhibitors can prevent 4 instances of symptomatic deep venous thrombosis per 1000 treated patients (CI, 3 to 6 fewer events; high-quality evidence) but may increase major bleeding by 2 more events per 1000 patients (CI, 0 to 4 more events; moderate-quality evidence). High, but not lower, doses of oral factor Xa inhibitors increased bleeding compared with LMWH. LIMITATIONS: Most trials did not report outcome data for a substantial proportion of the patients. In 9 trials, the follow-up period was 14 days or less. CONCLUSION: Compared with LMWH, lower doses of oral factor Xa inhibitors can achieve a small absolute risk reduction in symptomatic deep venous thrombosis without increasing bleeding.

Multidisciplinary care of the pregnant patient with or at risk for venous thromboembolism: a recommended toolkit from the Foundation for Women and Girls with Blood Disorders Thrombosis Subcommittee.

The care of pregnant persons with/at risk of venous thromboembolism is complex and often challenging. Although guidelines have been published regarding the use of specific therapies, such as anticoagulants; in this population, none have provided guidance on how to coordinate multidisciplinary care of these patients. Here we provide an expert consensus on the role of various providers in the care of this patient population, as well as necessary resources and suggestions for best practices.

Decision Analysis in SHared decision making for Thromboprophylaxis during Pregnancy (DASH-TOP): a sequential explanatory mixed-methods pilot study.

OBJECTIVES: To gain insight into formal methods of integrating patient preferences and clinical evidence to inform treatment decisions, we explored patients' experience with a personalised decision analysis intervention, for prophylactic low-molecular-weight heparin (LMWH) in the antenatal period. DESIGN: Mixed-methods explanatory sequential pilot study. SETTING: Hospitals in Canada (n=1) and Spain (n=4 sites). Due to the COVID-19 pandemic, we conducted part of the study virtually. PARTICIPANTS: 15 individuals with a prior venous thromboembolism who were pregnant or planning pregnancy and had been referred for counselling regarding LMWH. INTERVENTION: A shared decision-making intervention that included three components: (1) direct choice exercise; (2) preference elicitation exercises and (3) personalised decision analysis. MAIN OUTCOME MEASURES: Participants completed a self-administered questionnaire to evaluate decision quality (decisional conflict, self-efficacy and satisfaction). Semistructured interviews were then conducted to explore their experience and perceptions of the decision-making process. RESULTS: Participants in the study appreciated the opportunity to use an evidence-based decision support tool that considered their personal values and preferences and reported feeling more prepared for their consultation. However, there were mixed reactions to the standard gamble and personalised treatment recommendation. Some participants could not understand how to complete the standard gamble exercises, and others highlighted the need for more informative ways of presenting results of the decision analysis. CONCLUSION: Our results highlight the challenges and opportunities for those who wish to incorporate decision analysis to support shared decision-making for clinical decisions.

D-dimer assays in diagnosis and management of thrombotic and bleeding disorders.

D-dimer is a global indicator of coagulation activation and fibrinolysis and, therefore, an indirect marker of thrombotic activity. The utility of D-dimer measurement has been evaluated in several clinical situations including the exclusion of venous thromboembolism (VTE), prediction of future risk of VTE, and the diagnosis and monitoring of disseminated intravascular coagulation (DIC). Assay standardization remains problematic and clinicians need to be aware of variability in D-dimer assay performance and the characteristics of their institution's test when making clinical decisions. This article will review the available evidence for the utilization of D-dimer antigen measurement in the management of thrombotic and bleeding disorders.

Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded.

BACKGROUND: D-dimer testing to rule out deep vein thrombosis is less useful in older patients because of a lower specificity. An age-adjusted D-dimer cut-off value increased the proportion of older patients (>50 years) in whom pulmonary embolism could be excluded. We retrospectively validated the efficacy of this cut-off combined with clinical probability for the exclusion of deep vein thrombosis. DESIGN AND METHODS: Five management study cohorts of 2818 consecutive outpatients with suspected deep vein thrombosis were used. Patients with non-high or unlikely probability of deep vein thrombosis were included in the analysis; four different D-dimer tests were used. The proportion of patients with a normal D-dimer test and the failure rates were calculated using the conventional (500 µg/L) and the age-adjusted D-dimer cut-off (patient's age x 10 µg/L in patients >50 years). RESULTS: In 1672 patients with non-high probability, deep vein thrombosis could be excluded in 850 (51%) patients with the age-adjusted cut-off value versus 707 (42%) patients with the conventional cut-off value. The failure rates were 7 (0.8; 95% confidence interval 0.3-1.7%) for the age-adjusted cut-off value and 5 (0.7%, 0.2-1.6%) for the conventional cut-off value. The absolute increase in patients in whom deep vein thrombosis could be ruled out using the age-adjusted cut-off value was largest in patients >70 years: 19% among patients with non-high probability. CONCLUSIONS: The age-adjusted cut-off of the D-dimer combined with clinical probability greatly increases the proportion of older patients in whom deep vein thrombosis can be safely excluded.

Evaluating patient values and preferences for thromboprophylaxis decision making during pregnancy: a study protocol.

BACKGROUND: Pregnant women with prior venous thromboembolism (VTE) are at risk of recurrence. Low molecular weight heparin (LWMH) reduces the risk of pregnancy-related VTE. LMWH prophylaxis is, however, inconvenient, uncomfortable, costly, medicalizes pregnancy, and may be associated with increased risks of obstetrical bleeding. Further, there is uncertainty in the estimates of both the baseline risk of pregnancy-related recurrent VTE and the effects of antepartum LMWH prophylaxis. The values and treatment preferences of pregnant women, crucial when making recommendations for prophylaxis, are currently unknown. The objective of this study is to address this gap in knowledge. METHODS: We will perform a multi-center cross-sectional interview study in Canada, USA, Norway and Finland. The study population will consist of 100 women with a history of lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and who are either pregnant, planning pregnancy, or may in the future consider pregnancy (women between 18 and 45 years). We will exclude individuals who are on full dose anticoagulation or thromboprophylaxis, who have undergone surgical sterilization, or whose partners have undergone vasectomy. We will determine each participant's willingness to receive LMWH prophylaxis during pregnancy through direct choice exercises based on real life and hypothetical scenarios, preference-elicitation using a visual analog scale ("feeling thermometer"), and a probability trade-off exercise. The primary outcome will be the minimum reduction (threshold) in VTE risk at which women change from declining to accepting LMWH prophylaxis. We will explore possible determinants of this choice, including educational attainment, the characteristics of the women's prior VTE, and prior experience with LMWH. We will determine the utilities that women place on the burden of LMWH prophylaxis, pregnancy-related DVT, pregnancy-related PE and pregnancy-related hemorrhage. We will generate a "personalized decision analysis" using participants' utilities and their personalized risk of recurrent VTE as inputs to a decision analytic model. We will compare the personalized decision analysis to the participant's stated choice. DISCUSSION: The preferences of pregnant women at risk of VTE with respect to the use of antithrombotic therapy remain unexplored. This research will provide explicit, quantitative expressions of women's valuations of health states related to recurrent VTE and its prevention with LMWH. This information will be crucial for both guideline developers and for clinicians.

More work needed on decision analysis for shared decision-making: A scoping review.

OBJECTIVE: To explore and characterize published evidence on the ways decision analysis has been used to inform shared decision-making. STUDY DESIGN AND SETTING: For this scoping review, we searched five bibliographic databases (from inception until February 2021), reference lists of included studies, trial registries, a thesis database and websites of relevant interest groups. Studies were eligible if they evaluated the application of decision analysis in a shared decision-making encounter. Pairs of reviewers independently screened and selected studies for inclusion, extracted study information using a data extraction form developed by the research team and assessed risk of bias for all studies with an experimental or quasi-experimental design. Data were narratively synthesized. RESULTS: We identified 27 studies that varied greatly with regard to their patient population, design, content and delivery. A range of outcomes were evaluated to explore the effectiveness and acceptability of decision analytic interventions, with little information about the implementation process. Most studies found that decision analysis was broadly beneficial. CONCLUSION: Despite the compelling rationale on the potential for decision analysis to support shared decision-making, rigorous randomized controlled trials are needed to confirm these interventions' effectiveness, while qualitative studies should seek to understand their potential implementation.

Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism: Rationale and design of the SERIOUS-PE study.

BACKGROUND: Sex is an important factor associated with pulmonary embolism (PE) disease presentation and outcomes, which may be related to pathobiological, social, and treatment-based differences. We are seeking to illuminate sex differences in pulmonary embolism presentation, care, and outcomes using an international registry and a national US database of people 65 years and older, the age group in which the majority of these events occur. METHODS: The Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism (SERIOUS-PE) study has been designed to address knowledge gaps in this area. This study will use data from the Registro Informatizado Enfermedad TromboEmbolica (RIETE) registry and the US Medicare Fee-For-Service beneficiaries. RIETE is a large international registry of patients with venous thromboembolism with data collected on PE presentation, risk factors, co-morbidities, drug and interventional therapies, as well as 30-day and 1-year outcomes (including recurrent VTE, major bleeding, and mortality). Data from US Medicare Fee-For-Service beneficiaries will be used to understand the sex differences in PE hospitalizations, advanced therapies, and outcomes at 30-day and 1-year follow-up. Assessment of outcomes in both databases will be performed in unadjusted models, as well as those adjusted for demographics, co-morbidities, and treatments, to understand whether the potential sex differences in outcomes are related to differences in risk factors and co-morbidities, potential disparities in treatment, or a plausible biological difference in women versus men. Linear trends will be assessed over time. RESULTS: RIETE data from March 2001 through March 2021 include 33,462 elderly patients with PE, of whom 19,294 (57.7%) were women and 14,168 (42.3%) were men. In the Medicare Fee-For-Service database, between January 2001 and December 31, 2019, 1,030,247 patients were hospitalized with a principal discharge diagnosis of PE, of whom 599,816 (58.2%) were women and 430,431 (41.8%) were men. CONCLUSIONS: Findings from the SERIOUS-PE study will help address important knowledge gaps related to sex differences in presentation and risk factors, treatment patterns, and outcomes of older adults with PE. The results may guide changes in prognostic prediction rules based on sex-specific findings, identify sex-based disparities in care delivery that should be addressed by quality improvement, or uncover potential differences in response to available therapies that warrant testing in dedicated randomized trials.