Management and outcomes of superficial vein thrombosis: a single-center retrospective study.

Background: Guidelines suggest but cannot recommend the optimal management of superficial vein thrombosis (SVT). Objectives: To identify the prevalence of asymptomatic deep vein thrombosis (DVT) at the time of SVT diagnosis, and to report the treatment and 3-month complications of patients with only SVT more than 3 cm from deep vein junction (or unknown distance). Methods: We performed a single-center retrospective review of patients referred to the Ottawa Hospital thrombosis unit with ultrasound (US)-diagnosed SVT, and followed patients with only SVT for 3 months. Results: Three hundred sixteen patients with SVT were included. Of the 218 patients without DVT symptoms at presentation, 19 (8.7%; 95% CI, 5.7%-13.2%) were found to have asymptomatic concomitant DVT (11 proximal and 8 distal), and 45 (20.6%) had SVT within 3 cm of the saphenofemoral or saphenopopliteal junctions. Among the 192 patients diagnosed with SVT only, we observed 3-month thrombotic complications in 56 (29.2%; 95% CI, 23.2%-36.0%) patients, with a total of 69 events: 11 (5.7%) DVTs, 2 (1.0%) pulmonary embolisms, 37 (19.2%) SVT extensions, and 19 (9.8%) SVT recurrences. Eighty-two percent (9/11) of the 3-month DVT and pulmonary embolism events occurred in patients who initially received conservative management. Therapeutic treatment doses were most effective. Conclusion: At the time of SVT diagnosis, many patients had asymptomatic DVT and SVT near the deep venous system, supporting the systematic use of initial US in patients clinically diagnosed with SVT. The observed differences in 3-month complication rates, according to the treatment provided, highlight the need for large-scale randomized controlled trials to establish optimal management.

Management strategies in persons with inherited haemophilia requiring antithrombotic therapy: A scoping review.

BACKGROUND: Thromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE). METHODS: We searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis. RESULTS: We included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing. DISCUSSION: Our scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non-haemophilic patients. Prospective data are needed to inform optimal and evidence-based management strategies of CVD and VTE in persons with haemophilia.

Bleeding disorders and postpartum hemorrhage by mode of delivery: a retrospective cohort study.

Background: Pregnant persons with bleeding disorders and their potentially affected newborns are at a higher risk of peripartum bleeding complications. The safest mode of delivery for persons with bleeding disorders remains debated, leading to uncertainties in decision-making between the patient and her multidisciplinary team. Objectives: This study aimed to describe maternal outcomes for pregnant persons with bleeding disorders by mode of delivery and to examine whether postpartum hemorrhage (PPH) and neonatal hemorrhagic manifestations are associated with the mode of delivery. Methods: We collected retrospective data on pregnant persons with bleeding disorders who delivered at a single center from 2010 to 2021. Descriptive statistics, Fisher exact test, and odds ratios were used for analysis. Results: A total of 82 pregnancies in 56 subjects were included. Hemophilia A and von Willebrand disease represented the largest cohort, at 30% (17/56) each. Overall rates of primary and secondary PPH were 7.3% (6/82) and 17.4% (12/69), respectively. We did not find a statistically significant difference between mode of delivery and PPH. Upon comparing vaginal and cesarian deliveries, we found an odds ratio of 0.7 (95% CI, 0.1-3.4) for primary PPH and 2.6 (95% CI, 0.4-16.4) for secondary PPH. One male newborn with severe hemophilia A was treated for a suspected intracranial hemorrhage. Conclusion: In our cohort, high rates of PPH remained an important complication for pregnant persons with bleeding disorders. There was no significant difference in PPH based on modes of delivery. The small sample size likely limited the power of our study, and consequently, future larger studies are needed.

Deep Venous Thrombosis.

Venous thromboembolism (VTE) is the third most common cardiovascular disorder, affecting up to 5% of the population. VTE commonly manifests as lower-extremity deep venous thrombosis (DVT) or pulmonary embolism. Half of these events are associated with a transient risk factor and may be preventable with prophylaxis. Direct oral anticoagulants are effective and safe and carry a lower risk for bleeding than vitamin K antagonists. Many patients with VTE will have a chronic disease requiring long-term anticoagulation. Postthrombotic syndrome affects 25% to 40% of patients with DVT and significantly impacts function and quality of life.

Evaluation of patients' experience and related qualitative outcomes in venous thromboembolism: A scoping review.

BACKGROUND: Venous thromboembolism (VTE) is a prevalent disease with high morbidity and mortality. VTE has well-documented physical sequelae; however, the psychological and emotional impacts are seldom evaluated in randomized controlled trials. OBJECTIVE: We conducted a scoping review of published qualitative studies aiming to understand the physical, psychological, and emotional impact of VTE as reflected from patients' perspectives. This scoping review is part of a larger initiative to develop a core outcome set for VTE treatment studies. METHODS: A systematic literature search was conducted to identify qualitative studies assessing patient experience of VTE. Two authors independently screened titles and abstracts using Covidence systematic review software. Full-text reviews were conducted independently by 2 study team members. A modified method of "thematic synthesis" was used to collate themes upon reading and rereading of the publications. RESULTS: Our search strategy returned a total of 4944 citations; 28 were ultimately included in the analysis. The studies were conducted across 13 countries and representative of 436 participants including a spectrum of VTE subpopulations. There were seven major themes identified: Acute impacts: an unforeseen blow, Sustained psychological distress, Loss of self: life is changed, Challenges of thrombosis management, Balancing coping and control, Negative experience with the medical system, and VTE in the context of other conditions. CONCLUSIONS: The physical, psychological, and emotional impacts of VTE extend beyond objective outcomes typically evaluated in clinical trials. An improved understanding of the outcomes most important to patients will improve patient-centered care in VTE.

Identification of outcomes in clinical studies of interventions for venous thromboembolism in non-pregnant adults: A scoping review.

BACKGROUND: The development of a core outcome set (COS), defined as an agreed minimum set of outcome domains that should be measured and reported in all trials of a specific disease, aims to increase the relevance of study findings to stakeholder groups and improve standardization. OBJECTIVES: As the first step in developing a COS for venous thromboembolism (VTE) treatment studies, we aimed to generate an inclusive list of unique outcomes reported in previous VTE treatment studies and classify them into domains and core areas. METHODS: MEDLINE, Embase and CENTRAL were searched for prospective studies reporting on interventions for VTE in non-pregnant adults. Study selection and data extraction were performed in blocks based on publication date, starting with 2015-2020 and subsequent 1-year periods, until no new outcome was identified. Outcomes were classified into domains, which are groups of closely related outcomes, and domains into four core areas including death, pathophysiological manifestations/abnormalities, life impact, and resource use. RESULTS: Of 7100 records identified, 240 publications were included, representing 165 distinct studies. A total of 205 unique outcomes were identified that were grouped into 48 domains; 30 (13%) studies covered at least three core areas; death was included in 102 (43%), pathophysiological manifestations/abnormalities in 218 (91%), life impact in 41 (17%), and resource use in 25 (10%) studies. CONCLUSION: Most VTE treatment studies evaluated pathophysiological features of VTE, but few studies reported outcomes that measured life impact or resource use. The findings will inform next steps in the development of a COS for VTE treatment studies.

Knowledge gaps in bleeding disorders: Results from an objective structured oral examination in internal medicine residency training.

BACKGROUND: Empirical evidence for physicians' knowledge gaps in bleeding disorders is limited to self-reported surveys, yet often cited as a leading cause of diagnostic and management delays. OBJECTIVES: Our aim was to assess internal medicine (IM) residents' competence, based on their training level, in evaluating a patient with a bleeding disorder, and knowledge gaps in their clinical approach. METHODS: Content experts developed patient case presenting with abnormal bleeding, bruising, and an isolated prolonged PTT. We administered the hemostasis case as part of an objective structured clinical examination (OSCE). We performed a descriptive analysis. One-way anova was conducted to compare the effect of training level on performance. Item difficulty level for the hemostasis case was also determined. RESULTS: Sixty-seven IM residents participated in the OSCE. The hemostasis case had the highest failure rate at 41.8% with a mean score for the station of 57.96% (SD 13.04). Senior residents scored significantly higher than junior residents on this case (F(2,64) = 4.604, p = .014, ηp2  = 0.126). The item difficulty analysis demonstrated challenges in in eliciting a history of bleeding provoked by challenges, examining the bleeding site, interpreting the mixing study, requesting appropriate follow-up tests, making the diagnosis and providing acute management for a bleeding patient. Only 49.3% of residents requested a hematology consultation. CONCLUSIONS: We demonstrated important knowledge gaps in IM residents' approach to the bleeding patient. Innovative strategies for hemostasis education should be a priority to address physician-related factors in the diagnostic and management delays of patients with bleeding disorders.

Derivation of Patient-Defined Adverse Cardiovascular and Noncardiovascular Events Through a Modified Delphi Process.

Importance: There is little evidence to support patient-centered outcomes in patients with cardiovascular disease. Objective: To derive patient-defined adverse cardiovascular and noncardiovascular events (PACE) through a consensus-based process. Design, Setting, and Participants: This pan-Canadian, consensus-based, qualitative study used an iterative Delphi method to achieve consensus within a 35-member panel consisting of patients with cardiovascular diseases and their caregivers and clinicians. The process included 4 rounds of online questionnaires, followed by an in-person final consensus meeting. Data analysis was performed in September 2019. Main Outcomes and Measures: Defining PACE as a 5-item composite outcome. Results: Thirty-five potential panelists consented to participate, including 11 clinicians (8 men [73%]) and 24 patients and caregivers (13 men [54%]). Twenty-nine (83%), 28 (80%), 26 (74%), and 23 (66%) of the panelists participated in each of respective the online rounds. A shortlist of 11 patient-defined items was further refined at the in-person meeting, which 20 of the panelists attended. The PACE definition that was decided through the consensus process was a composite of severe stroke necessitating hospitalization for 14 days or longer or inpatient rehabilitation, ventilator dependence, new onset or worsening heart failure, nursing home admission, or new onset dialysis. Conclusions and Relevance: This study defined PACE as a versatile, patient-centered outcome through a consensus process with input from patients, caregivers, and clinicians. Given the paucity of patient-centered outcomes in cardiovascular research, PACE may be considered as a potential outcome after methodological evaluation of its reliability.

Pulmonary embolism: update on management and controversies.

Pulmonary embolism is a common and potentially fatal cardiovascular disorder that must be promptly diagnosed and treated. The diagnosis, risk assessment, and management of pulmonary embolism have evolved with a better understanding of efficient use of diagnostic and therapeutic options. The use of either clinical probability adjusted or age adjusted D-dimer interpretation has led to a reduction in diagnostic imaging to exclude pulmonary embolism. Direct oral anticoagulation therapies are safe, effective, and convenient treatments for most patients with acute venous thromboembolism, with a lower risk of bleeding than vitamin K antagonists. These oral therapeutic options have opened up opportunities for safe outpatient management of pulmonary embolism in selected patients. Recent clinical trials exploring the use of systemic thrombolysis in intermediate to high risk pulmonary embolism suggest that this therapy should be reserved for patients with evidence of hemodynamic compromise. The role of low dose systemic or catheter directed thrombolysis in other patient subgroups is uncertain. After a diagnosis of pulmonary embolism, all patients should be assessed for risk of recurrent venous thromboembolism to guide duration of anticoagulation. Patients with a venous thromboembolism associated with a strong, transient, provoking risk factor can safely discontinue anticoagulation after three months of treatment. Patients with an ongoing strong risk factor, such as cancer, or unprovoked events are at increased risk of recurrent events and should be considered for extended treatment. The use of a risk prediction score can help to identify patients with unprovoked venous thromboembolism who can benefit from extended duration therapy. Despite major advances in the management of pulmonary embolism, up to half of patients report chronic functional limitations. Such patients should be screened for chronic thromboembolic pulmonary hypertension, but only a small proportion will have this as the explanation of their symptoms. In the remaining patients, future studies are needed to understand the pathophysiology and explore interventions to improve quality of life.

Treatment of Superficial Vein Thrombosis: A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal first line treatment for patients with isolated superficial venous thrombosis (SVT) of the lower extremity is unknown. OBJECTIVE: This article reports estimates of the rate of venous thromboembolic complications among patients with SVT according to treatment. MATERIALS AND METHODS: A systematic review and meta-analysis was performed using unrestricted searches of electronic databases. Reported events were transformed to event per 100 patient-years of follow-up and a random effects model was used to calculate pooled rates according to pre-specified treatment categories. The primary outcome was the occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE) during the study follow-up period. RESULTS: Seventeen articles, including 6,862 patients, were included in the meta-analysis. Fondaparinux had the lowest event rate with 1.4 events per 100 patient-years of follow-up (95% confidence interval [CI], 0.5-2.8, I 2 = 18%). Pooled event rates for DVT or PE ranged from 9.3 to 16.6 events per 100 patient-years across other treatment categories, and the pooled event rate for no treatment/placebo was 10.5 events per 100 patient-years (95% CI, 3.0-22.0). Major bleeding was low and similar across all treatment categories. Heterogeneity was moderate to high for most pooled estimates. CONCLUSION: While pooled event rates suggest that fondaparinux achieves the lowest rate of DVT or PE, low-quality evidence for other treatments prevents firm conclusions about the optimal treatment for SVT.

The prevalence of patient engagement in published trials: a systematic review.

Plain English summary: With the growing movement to engage patients in research, questions are being asked about who is engaging patients and how they are being engaged. Internationally, research groups are supporting and funding patient-oriented research studies that engage patients in the identification of research priorities and the design, conduct and uptake of research. As we move forward, we need to know what meaningful patient engagement looks like, how it benefits research and clinical practice, and what are the barriers to patient engagement?We conducted a review of the published literature looking for trials that report engaging patients in the research. We included both randomized controlled trials and non-randomized comparative trials. We looked at these trials for important study characteristics, including how patients were engaged, to better understand the practices used in trials. Importantly, we also discuss the number of trials reporting patient engagement practices relative to all published trials. We found that very few trials report any patient engagement activities even though it is widely supported by many major funding organizations. The findings of our work will advance patient-oriented research by showing how patients can be engaged and by stressing that patient engagement practices need to be better reported. Background: Patient-Oriented Research (POR) is research informed by patients and is centred on what is of importance to them. A fundamental component of POR is that patients are included as an integral part of the research process from conception to dissemination and implementation, and by extension, across the research continuum from basic research to pragmatic trials [J Comp Eff Res 2012, 1:181-94, JAMA 2012, 307:1587-8]. Since POR's inception, questions have been raised as to how best to achieve this goal.We conducted a systematic review of randomized controlled trials and non-randomized comparative trials that report engaging patients in their research. Our main goal was to describe the characteristics of published trials engaging patients in research, and to identify the extent of patient engagement activities reported in these trials. Methods: The MEDLINE®, EMBASE®, Cinahl, PsycINFO, Cochrane Methodology Registry, and Pubmed were searched from May 2011 to June 16th, 2016. Title, abstract and full text screening of all reports were conducted independently by two reviewers. Data were extracted from included trials by one reviewer and verified by a second. All trials that report patient engagement for the purposes of research were included. Results: Of the 9490 citations retrieved, 2777 were reviewed at full text, of which 23 trials were included. Out of the 23 trials, 17 were randomized control trials, and six were non-randomized comparative trials. The majority of these trials (83%, 19/23) originated in the United States and United Kingdom. The trials engaged a range of 2-24 patients/ community representatives per study. Engagement of children and minorities occurred in 13% (3/23) and 26% (6/23) of trials; respectively. Engagement was identified in the development of the research question, the selection of study outcomes, and the dissemination and implementation of results. Conclusions: The prevalence of patient engagement in patient-oriented interventional research is very poor with 23 trials reporting activities engaging patients. Research dedicated to determining the best practice for meaningful engagement is still needed, but adequate reporting measures also need to be defined.

Patient engagement: What partnering with patient in research is all about.

The inclusion of patients on important decision related to healthcare has marked a significant 'patient revolution' during the last several decades. Patients now played active roles in personal health decisions, healthcare delivery and policy making, and the development of clinical practice guidelines. Such inclusion of patients' values has resulted in largely positive effects. The next wave of this 'patient revolution' is active and meaningful engagement with patients in health related research. Similar to other aspects of healthcare, it is increasingly recognized that experienced patients, their families, and caregivers, have a wealth of knowledge that comes from living and experiencing a medical condition. By understanding and valuing this experience-based knowledge, research priority setting, research study design, trial conduct, analysis of results and knowledge dissemination can be positively influenced. Patients can challenge our assumptions, align research with the needs of patients, increase transparency and trust in research, and lead to research that has a greater impact on the ultimate care of patients. This new approach to research is timed well with a larger movement towards simple, pragmatic clinical trials better reflecting realistic patient care. While there is still much to be learned about the best methods and exact impacts of patient engagement in research, preliminary results are promising and future venous thromboembolism research will likely benefit from the adoption of patient engagement in research.

LMWH to prevent placenta-mediated pregnancy complications: an update.

Placenta-mediated pregnancy complications, including preeclampsia, placental abruption, intrauterine growth restriction/small for gestational age and recurrent or late pregnancy loss, affect over 5% of pregnancies and can result in significant maternal and perinatal morbidity and mortality. These complications have been suggested to at least partly arise from placental insufficiency, possibly as a result of inappropriate coagulation activation. This association has led to the hypothesis that anticoagulant therapy, such as low molecular weight heparin, might reduce their occurrence. The following review will attempt to summarize the extensive research that has been performed to date exploring this hypothesis and provide guidance on the current and future role of low molecular weight heparin in women at risk for placenta-mediated pregnancy complications. A case will be made to question the widely adopted practice of prescribing low molecular weight heparin to women with prior placenta-mediated pregnancy complications and suggest possible areas for future research.