Thrombocytopenia with and without thrombosis following COVID-19 vaccination: long-term management.

Background: Since administration of COVID-19 vaccines, there has been growing evidence of thrombotic and thrombocytopenic events following vaccination. However, there remains limited data on long-term management of these adverse hematologic events. Key Clinical Question: We report on 9 patients presenting with thrombocytopenia following COVID-19 vaccination, with 4 subsequently diagnosed with vaccine-induced thrombocytopenia and thrombosis (VITT) and 5 with immune thrombocytopenia. Clinical Approach: A retrospective chart review was completed for adults >18 years of age presenting to a tertiary care center with new-onset thrombocytopenia occurring 4 to 42 days following COVID-19 vaccination. Presenting symptoms, laboratory investigations, and response to treatment are described. Conclusion: Two of 4 patients with VITT developed refractory thrombocytopenia successfully treated with intravenous immunoglobulin, corticosteroids, and plasma exchange therapy. Patients with VITT remained on anticoagulation for at least 9 months due to persistently positive diagnostic tests. Four of 5 patients with immune thrombocytopenia received intravenous immunoglobulin and corticosteroids with good recovery. Patients who received a subsequent COVID-19 mRNA vaccine had no adverse hematologic effects.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

A 4He vector zero-field optically pumped magnetometer operated in the Earth-field.

Low intrinsic noise, high bandwidth, and high accuracy vector magnetometers are key components for many ground or space geophysical applications. Here, we report the design and the test of a 4He vector optically pumped magnetometer specifically dedicated to these needs. It is based on a parametric resonance magnetometer architecture operated in the Earth magnetic field with closed-loop compensation of the three components of the magnetic field. It provides offset-free vector measurements in a ±70 µT range with a DC to 1 kHz bandwidth. We demonstrate a vector sensitivity up to 130 fT/√Hz, which is about ten times better than the best available fluxgate magnetometers currently available for the same targeted applications.

Ohmic contact engineering in few-layer black phosphorus: approaching the quantum limit.

Achieving good quality Ohmic contacts to van der Waals materials is a challenge, since at the interface between metal and van der Waals material different conditions can occur, ranging from the presence of a large energy barrier between the two materials to the metallization of the layered material below the contacts. In black phosphorus (bP), a further challenge is its high reactivity to oxygen and moisture, since the presence of uncontrolled oxidation can substantially change the behavior of the contacts. Here we study three of the most commonly used metals as contacts to bP, chromium, titanium, and nickel, and investigate their influence on contact resistance against the variability between different flakes and different samples. We investigate the gate dependence of the current-voltage characteristics of field-effect transistors fabricated with these metals on bP, observing good linearity in the accumulation regime for all metals investigated. Using the transfer length method, from an analysis of ten devices, both at room temperature and at low temperature, Ni results to provide the lowest contact resistance to bP and minimum scattering between different devices. Moreover, we observe that our best devices approach the quantum limit for contact resistance both for Ni and for Ti contacts.

Functional, neuroplastic and biomechanical changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with unilateral cerebral palsy: study protocol of a randomized control trial.

BACKGROUND: Cerebral palsy (CP) causes motor, cognitive and sensory impairment at different extents. Many recent rehabilitation developments (therapies) have focused solely on the upper extremities (UE), although the lower extremities (LE) are commonly affected. Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) applies the concepts of motor skill learning and intensive training to both the UE and LE. It involves constant stimulation of the UE and LE, for several hours each day over a 2-week period. The effects of HABIT-ILE have never been evaluated in a large sample of young children. Furthermore, understanding of functional, neuroplastic and biomechanical changes in infants with CP is lacking. The aim of this study is to carry out a multi-center randomized controlled trial (RCT) to evaluate the effects of HABIT-ILE in pre-school children with unilateral CP on functional, neuroplastic and biomechanical parameters. METHODS: This multi-center, 3-country study will include 50 pre-school children with CP aged 1-4 years. The RCT will compare the effect of 50 h (two weeks) of HABIT-ILE versus usual motor activity, including regular rehabilitation. HABIT-ILE will be delivered in a day-camp setting, with structured activities and functional tasks that will be continuously progressed in terms of difficulty. Assessments will be performed at 3 intervals: baseline (T0), two weeks later and 3 months later. Primary outcomes will be the Assisting Hand Assessment; secondary outcomes include the Melbourne Assessment-2, executive function assessments, questionnaires ACTIVLIM-CP, Pediatric Evaluation of Disability Inventory, Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, as well as neuroimaging and kinematics measures. DISCUSSION: We expect that HABIT-ILE will induce functional, neuroplastic and biomechanical changes as a result of the intense, activity-based rehabilitation process and these changes will impact the whole developmental curve of each child, improving functional ability, activity and participation in the short-, mid- and long-term. Name of the registry: Changes Induced by Early HABIT-ILE in Pre-school Children With Uni- and Bilateral Cerebral Palsy (EarlyHABIT-ILE). TRIAL REGISTRATION: Trial registration number: NCT04020354-Registration date on the International Clinical Trials Registry Platform (ICTRP): November 20th, 2018; Registration date on NIH Clinical Trials Registry: July 16th, 2019.

Diagnosis and management of congenital thrombophilia in the era of direct oral anticoagulants.

Direct oral anticoagulants (DOAC)s are often preferred to other anticoagulants as they are more practical and do not require routine laboratory monitoring. Less is known about their use in congenital thrombophilia. Efficacy of DOACs in congenital thrombophilia, effect of DOACs and other anticoagulants on diagnostic tests as well as efficacy and safety of anticoagulant use in this population is still a matter of debate. In this review we intended to analyze the potential pitfalls of testing for thrombophilia in patients using DOACs and vitamin K antagonists (VKA)s as well as to suggest strategies to improve diagnostic accuracy in this setting. We also reviewed the literature for evidence regarding the safety and efficacy of DOACs in patients with congenital thrombophilia. Some evidence was found supporting the use of DOACs in low risk thrombophilia, although evidence for their use in high risk thrombophilia is limited to small series and case reports. Our findings support the generation of better evidence to support DOAC use for congenital thrombophilia, especially in the high risk subgroups.

Venous thromboembolism risk stratification for patients with lower limb trauma and cast or brace immobilization.

BACKGROUND: Thromboprophylaxis for patients with non-surgical isolated lower-limb trauma requiring immobilization is a matter of debate. Our aim was to develop and validate a clinical risk- stratification model based on Trauma, Immobilization and Patients' characteristics (the TIP score). METHODS: The TIP score criteria and the cut-off were selected by a consensus of international experts (n = 27) using the Delphi method. Retrospective validation was performed in a population-based case-control study (MEGA study). The potential score's impact in anticoagulant treatment was assessed in a prospective single-center observational cohort study. FINDINGS: After four successive rounds, 30 items constituting the TIP score were selected: thirteen items for trauma, three for immobilization and 14 for patient characteristics were selected, each rated on a scale of 1 to 3. In the validation database, the TIP score had an AUC of 0·77 (95% CI 0.70 to 0.85). Using the cut-off proposed by the experts (≥5) and assuming a prevalence of 1·8%, the TIP scores had a sensitivity, specificity and negative predictive values of 89·9%, 30·7% and 99·4% respectively. In the prospective cohort, 84·2% (165/196) of all the patients concerned who presented at the emergency department had a low VTE risk not requiring thromboprophylaxis according to their TIP scores. The 3-month rate of symptomatic VTE was 1/196 [95% CI 0.1-2.8] this patient was in the sub-group TIP score ≥5. CONCLUSION: For patients with non-surgical lower-limb trauma and orthopedic immobilization, the TIP score allows an individual VTE risk-assessment and shows promising results in guiding thromboprophylaxis.

Relationship between type of unprovoked venous thromboembolism and cancer location: An individual patient data meta-analysis.

BACKGROUND: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE. METHODS: Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations. RESULTS: A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79). CONCLUSION: The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.

[Diagnosis of pulmonary embolism]. / Diagnostic de l'embolie pulmonaire.

The diagnosis of pulmonary embolism (PE) is nowadays based on the sequential use of several diagnostic tests rather than on a single test. These diagnostic strategies are safe and have been prospectively validated. The first step after identifying patients with suspicion of PE is to establish the pre-test clinical probability. Several scores are available in order to make a standardised and reproducible assessment of the clinical probability, and therefore represent precious diagnostic tools. Indeed, clinical probability guides further investigations. Indeed, in patients with a low or an intermediate clinical probability or an "unlikely" probability, PE can be safely ruled out by negative D-dimers in approximately one third of outpatients without additional imaging. In case of positive D-dimers and a high clinical probability or a "likely" clinical probability, CT pulmonary angiography is now the recommended imaging technique. However, lower limb venous compression ultrasound and ventilation/perfusion scans remain useful in patients with contra-indications to CT, mainly those with renal insufficiency. Finally, some novel diagnostic tests seem promising. For example, V/Q SPECT has arisen as a highly accurate test and a potential alternative to CTPA. However, prospective management outcome studies are still lacking and are warranted before its implementation in routine clinical practice.

Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus.

Management of anticoagulant therapy for the treatment of venous thromboembolism (vte) in cancer patients is complex because of an increased risk of recurrent vte and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent vte and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental vte, to prevent recurrent vte, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug-drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient's cancer status and management change over time.

Ruling out pulmonary embolism across different subgroups of patients and healthcare settings: protocol for a systematic review and individual patient data meta-analysis (IPDMA).

BACKGROUND: Diagnosing pulmonary embolism in suspected patients is notoriously difficult as signs and symptoms are non-specific. Different diagnostic strategies have been developed, usually combining clinical probability assessment with D-dimer testing. However, their predictive performance differs across different healthcare settings, patient subgroups, and clinical presentation, which are currently not accounted for in the available diagnostic approaches. METHODS: This is a protocol for a large diagnostic individual patient data meta-analysis (IPDMA) of currently available diagnostic studies in the field of pulmonary embolism. We searched MEDLINE (search date January 1, 1995, till August 25, 2016) to retrieve all primary diagnostic studies that had evaluated diagnostic strategies for pulmonary embolism. Two authors independently screened titles, abstracts, and subsequently full-text articles for eligibility from 3145 individual studies. A total of 40 studies were deemed eligible for inclusion into our IPDMA set, and principal investigators from these studies were invited to participate in a meeting at the 2017 conference from the International Society on Thrombosis and Haemostasis. All authors agreed on data sharing and participation into this project. The process of data collection of available datasets as well as potential identification of additional new datasets based upon personal contacts and an updated search will be finalized early 2018. The aim is to evaluate diagnostic strategies across three research domains: (i) the optimal diagnostic approach for different healthcare settings, (ii) influence of comorbidity on the predictive performance of each diagnostic strategy, and (iii) optimize and tailor the efficiency and safety of ruling out PE across a broad spectrum of patients with a new, patient-tailored clinical decision model that combines clinical items with quantitative D-dimer testing. DISCUSSION: This pre-planned individual patient data meta-analysis aims to contribute in resolving remaining diagnostic challenges of time-efficient diagnosis of pulmonary embolism by tailoring available diagnostic strategies for different healthcare settings and comorbidity. SYSTEMATIC REVIEW REGISTRATION: Prospero trial registration: ID 89366.

Predicting the risk of cancer after unprovoked venous thromboembolism: external validation of the RIETE score.

Essentials Patients at high-risk of occult cancer may benefit from extensive screening. We validated the RIETE cancer score in the MVTEP study. One in three patients were classified as high-risk, 10% of whom had cancer diagnosed. The RIETE score identifies a subgroup at high risk for cancer. SUMMARY: Background Most recent trials evaluating extensive screening strategies for occult cancer in patients with unprovoked venous thromboembolism have failed, because, among other reasons, of an overall low rate of occult cancer. The RIETE investigators recently proposed a score aimed at identifying a subgroup at higher risk. Methods We retrospectively computed the RIETE score for all patients included in the MVTEP study, which evaluated the accuracy of [¹8F]fluorodeoxyglucose-positron emission tomography in the screening of occult cancer in patients with unprovoked venous thromboembolism. Performance of the RIETE score was assessed according to the proportion of patients classified in each risk group, and the corresponding rates of cancer diagnosis. Results Among the 386 patients included in the analysis, 136 patients (35.3%) were classified as high risk by the RIETE score. Cancer was diagnosed in 16 (11.8%) of them, whereas it was diagnosed in nine (3.6%) of the 250 patients with a low RIETE cancer score: odds ratio of 3.6 (95% confidence interval [CI] 1.53-8.32). The area under the receiver operating characteristic curve was 0.63 (95% CI 0.51-0.74). Conclusion The RIETE score seems to be able to identify a subgroup at high risk for cancer (10%) in our specific dataset of patients with unprovoked venous thromboembolism.

Association between remote major venous thromboembolism risk factors and the risk of recurrence after a first unprovoked episode.

Essentials Is remote exposure to major venous thromboembolism (VTE) risk factor related to lower recurrence? We analyzed data from the REVERSE study, a cohort of patients with no recent major risk factor. We found no association between remote risk factors and the risk of recurrence. Patients with remote VTE risk factor should be managed as having had an unprovoked VTE. SUMMARY: Background It has been shown that the risk of recurrence of venous thromboembolism (VTE) is significantly lower when provoked by a major risk factor such as surgery or trauma compared with an event that was unprovoked. Objectives In this study we aimed to assess the association between remote exposure (3-12 months prior to VTE) to major VTE risk factors and the risk of recurrent VTE. Methods This was a post-hoc analysis of the REVERSE study, a prospective cohort of 646 patients with a first VTE, not provoked by a recent (< 3 months) major risk factor. Results We found no difference in the recurrence rate in patients with or without remote exposure to major VTE risk factors, including immobilization (hazard-ratio [HR], 1.4; 95% confidence interval, 0.7-2.6), surgery (HR, 0.8; 0.3-1.9) and trauma (HR, 1.3; 0.5-3.6). Conclusion None of the tested risk factors were associated with a lower risk of recurrence during follow-up. Patients with remote exposure to major risk factors at the time of a first VTE should not be managed differently from patients with no VTE risk factors.

Diagnosis of acute pulmonary embolism.

Advances in the management of patients with suspected pulmonary embolism (PE) have improved diagnostic accuracy and made management algorithms safer, easier to use, and well standardized. These diagnostic algorithms are mainly based on the assessment of clinical pretest probability, D-dimer measurement, and imaging tests-predominantly computed tomography pulmonary angiography. These diagnostic algorithms allow safe and cost-effective diagnosis for most patients with suspected PE. In this review, we summarize signs and symptoms of PE, current existing evidence for PE diagnosis, and focus on the challenge of diagnosing PE in special patient populations, such as pregnant women, or patients with a prior VTE. We also discuss novel imaging tests for PE diagnosis and highlight some of the additional challenges that might require adjustments to current diagnostic strategies, such as the reduced clinical suspicion threshold, resulting in a lower proportion of PE among suspected patients as well as the overdiagnosis of subsegmental PE.

Assessing clinical probability of pulmonary embolism: prospective validation of the simplified Geneva score.

Essentials The simplified Geneva score allows easier pretest probability assessment of pulmonary embolism (PE). We prospectively validated this score in the ADJUST-PE management outcome study. The study shows that it is safe to manage patients with suspected PE according to this score. The simplified Geneva score is now ready for use in routine clinical practice. SUMMARY: Background Pretest probability assessment by a clinical prediction rule (CPR) is an important step in the management of patients with suspected pulmonary embolism (PE). A limitation to the use of CPRs is that their constitutive variables and corresponding number of points are difficult to memorize. A simplified version of the Geneva score (i.e. attributing one point to each variable) has been proposed but never been prospectively validated. Aims Prospective validation of the simplified Geneva score (SGS) and comparison with the previous version of the Geneva score (GS). Methods In the ADJUST-PE study, which had the primary aim of validating the age-adjusted D-dimer cut-off, the SGS was prospectively used to determine the pretest probability in a subsample of 1621 study patients. Results Overall, PE was confirmed in 294 (18.1%) patients. Using the SGS, 608 (37.5%), 980 (60.5%) and 33 (2%) were classified as having a low, intermediate and high clinical probability. Corresponding prevalences of PE were 9.7%, 22.4% and 45.5%; 490 (30.1%) patients with low or intermediate probability had a D-dimer level below 500 µg L-1 and 653 (41.1%) had a negative D-dimer test according to the age-adjusted cut-off. Using the GS, the figures were 491(30.9%) and 650 (40.9%). None of the patients considered as not having PE based on a low or intermediate SGS and negative D-dimer had a recurrent thromboembolic event during the 3-month follow-up. Conclusions The use of SGS has similar efficiency and safety to the GS in excluding PE in association with the D-dimer test.

Safety of multidetector computed tomography pulmonary angiography to exclude pulmonary embolism in patients with a likely pretest clinical probability.

Essentials Safety of computed tomography (CTPA) to exclude pulmonary embolism (PE) in all patients is debated. We analysed the outcome of PE-likely outpatients left untreated after negative CTPA alone. The 3-month venous thromboembolic risk in these patients was very low (0.6%; 95% CI 0.2-2.3). Multidetector CTPA alone safely excludes PE in patients with likely clinical probability. SUMMARY: Background In patients with suspected pulmonary embolism (PE) classified as having a likely or high pretest clinical probability, the need to perform additional testing after a negative multidetector computed tomography pulmonary angiography (CTPA) finding remains a matter of debate. Objectives To assess the safety of excluding PE by CTPA without additional imaging in patients with a likely pretest probability of PE. Patients/Methods We retrospectively analyzed patients included in two multicenter management outcome studies that assessed diagnostic algorithms for PE diagnosis. Results Two thousand five hundred and twenty-two outpatients with suspected PE were available for analysis. Of these 2522 patients, 845 had a likely clinical probability as assessed by use of the simplified revised Geneva score. Of all of these patients, 314 had the diagnosis of PE excluded by a negative CTPA finding alone without additional testing, and were left without anticoagulant treatment and followed up for 3 months. Two patients presented with a venous thromboembolism (VTE) during follow-up. Therefore, the 3-month VTE risk in likely-probability patients after a negative CTPA finding alone was 2/314 (0.6%; 95% confidence interval [CI] 0.2-2.3%). Conclusions In outpatients with suspected PE and a likely clinical probability as assessed by use of the simplified revised Geneva score, CTPA alone seems to be able to safely exclude PE, with a low 3-month VTE rate, which is similar to the VTE rate following the gold standard, i.e. pulmonary angiography.

Thrombotic and bleeding outcomes following perioperative interruption of direct oral anticoagulants in patients with venous thromboembolic disease.

Essentials Studies evaluating the procedural interruption of direct oral anticoagulants (DOACs) are lacking. We conducted a study of the interruption of DOACs for prior venous thromboembolic disease (VTE). The post-operative risks of recurrent VTE and major bleeding are low in this patient population. A scheme based on half-life and procedure-related bleeding appears safe and efficacious. SUMMARY: Background Direct oral anticoagulants (DOACs) are increasingly being used in the setting of venous thromboembolic disease (VTE). There is little evidence to guide the peri-procedural interruption of DOACs in this patient population. A number of studies have evaluated the perioperative interruption of DOACs based on half-life of the anticoagulant and the underlying procedural bleeding risk in patient with atrial fibrillation, but it remains unclear whether these findings can be extended to patients with VTE. Objective Evaluate thrombotic and bleeding outcomes following the perioperative interruption of direct oral anticoagulation in patients with prior VTE. Methods We conducted a retrospective analysis of consecutive patients on a DOAC for prior VTE requiring temporary interruption of anticoagulation for an invasive procedure. The primary efficacy outcome was the 30-day symptomatic VTE rate, and the primary safety outcome was the 30-day major bleeding rate. Secondary outcomes included overall mortality and the rate of clinically relevant non-major bleeding. Results A total of 190 patients were included in the analysis. The 30-day VTE rate was 1.05% (95% CI, 0.29-3.8%) and the 30-day major bleeding rate was 0.53% (95% CI, 0.09-2.93%). There were no deaths during the 30-day follow-up period. The rate of clinically relevant non-major bleeding was 3.16% (95%CI , 1.46-6.72%). Conclusions The perioperative interruption of DOACs in the setting of VTE, using a strategy that considers the half-life of the DOAC and the underlying procedural bleeding risk, appears to be both safe and effective.

Performance of the age-adjusted cut-off for D-dimer in patients with cancer and suspected pulmonary embolism.

BACKGROUND: Cancer patients frequently present with suspected pulmonary embolism (PE). The D-dimer (DD) test is less useful in excluding PE in cancer patients due to the lower specificity. In the general population, the age-adjusted cutoff for DD combined with a clinical decision rule (CDR) improved specificity in the diagnosis of PE. OBJECTIVES: To evaluate the safety and efficacy of the age-adjusted cutoff (defined as age∗10µg/L in patients >50years) combined with a CDR for the exclusion of PE in cancer patients. METHODS: We conducted a prospective study to evaluate the age-adjusted cutoff in patients with suspected PE. Here we report a post-hoc analysis on the performance of the age-adjusted cutoff in patients with and without cancer. The primary outcome was the rate of venous thromboembolic events (VTE) during three-month follow-up. RESULTS: Of 3324 patients with suspected PE, 429 (12.9%) patients had cancer. The prevalence of PE was 25.2% in cancer patients and 18% in patients without cancer (p<0.001). Among cancer patients with an unlikely CDR, 9.9% had a DD <500µg/L as compared with 19.7% using the age-adjusted cutoff. In patients without cancer, these rates were 30.1% and 41.9%. The proportion of cancer patients in whom PE could be excluded by CDR and DD doubled from 6.3% to 12.6%. No VTE occurred during three-month follow-up (failure rate 0.0% (95% CI 0.0-6.9%)). CONCLUSION: Compared with the conventional cutoff, the age-adjusted D-dimer cutoff doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and DD without imaging.

Net clinical benefit of hospitalization versus outpatient management of patients with acute pulmonary embolism.

Essentials Clinical benefit of hospitalization vs. outpatient treatment in pulmonary embolism (PE) is unknown. We performed a propensity matched cohort study of hemodynamically stable PE patients. Regardless of the risk assessment, hospitalized patients had the highest rate of adverse event. If confirmed, ambulatory care of normotensive PE patients may be preferred whenever possible. SUMMARY: Background The decision to hospitalize or not patients with acute pulmonary embolism (PE) is controversial. Despite the advantages of close monitoring, hospitalization by itself may lead to in-hospital complications and potentially worsen the prognosis of PE patients. Objectives To determine the net clinical benefit of hospitalization vs. outpatient management of normotensive patients with acute pulmonary embolism (PE). Methods Retrospective cohort propensity score analysis (radius marching with replacement). Hemodynamically stable PE patients treated as outpatients or inpatients were matched to balance out differences for 28 patient characteristics and known risk factors for adverse events. The primary outcome was the rate of adverse events at 14 days, including recurrent venous thromboembolism, major bleeding or death. Results Among 1127 eligible patients, 1081 were included in the matched cohort, 576 treated as inpatients and 505 as outpatients. The 14-day rate of adverse events was 13.0% for inpatients and 3.3% for outpatients (adjusted OR, 5.07; 95% CI, 1.68-15.28). The 3-month rate was 21.7% for inpatients and 6.9% for outpatients (OR, 4.90; 95% CI, 2.62-9.17). In the high-risk subgroup (Pulmonary Embolism Severity Index class III-V; n = 597), the 14-day rate of adverse events was 16.5% for hospitalized patients vs. 4.5% for outpatients (OR, 4.16; 95% CI, 1.2-14.35). Conclusion Outpatient treatment of hemodynamically stable PE patients seems to be associated with a lower rate of adverse events than hospitalization and, if confirmed, may be considered as first-line management in patients not requiring specific in-hospital care, regardless of their initial risk stratification, if proper outpatient care can be provided.