Modern imaging of acute pulmonary embolism.

The first-choice imaging test for visualization of thromboemboli in the pulmonary vasculature in patients with suspected acute pulmonary embolism (PE) is multidetector computed tomography pulmonary angiography (CTPA) - a readily available and widely used imaging technique. Through technological advancements over the past years, alternative imaging techniques for the diagnosis of PE have become available, whilst others are still under investigation. In particular, the evolution of artificial intelligence (AI) is expected to enable further innovation in diagnostic management of PE. In this narrative review, current CTPA techniques and the emerging technology photon-counting CT (PCCT), as well as other modern imaging techniques of acute PE are discussed, including CTPA with iodine maps based on subtraction or dual-energy acquisition, single-photon emission CT (SPECT), magnetic resonance angiography (MRA), and magnetic resonance direct thrombus imaging (MRDTI). Furthermore, potential applications of AI are discussed.

Discharge from the emergency department and outpatient clinic in cancer patients with acute symptomatic and incidental pulmonary embolism: A multicenter retrospective cohort study.

BACKGROUND: It is unclear how often cancer patients with acute pulmonary embolism (PE) are discharged from the emergency department (ED) or outpatient clinic and whether direct discharge is safe. We assessed treatment setting and early safety outcomes in cancer patients with acute symptomatic and incidental PE. METHODS: Cancer patients diagnosed with PE at the ED or outpatient clinic between August 2017 and May 2021 were included in Four Cities VTE Cancer, a Dutch multicenter retrospective cohort study. The main outcome was direct discharge versus hospitalization. Safety outcomes were cumulative 14-day mortality and PE-related readmission incidences. RESULTS: We included 602 patients (median age 71 years; 49.5 % female) of whom 285 (47.3 %) were discharged directly and 317 (52.7 %) were hospitalized. The cumulative 14-day mortality incidence was 0.7 % (95 % CI, 0.1-2.4 %) in patients discharged directly and 9.0 % (95 % CI, 6.2-12.5 %) in those hospitalized. The cumulative 14-day PE-related readmission incidence was 1.8 % (95 % CI, 0.7-3.9 %) and 1.4 % (95 % CI, 0.5-3.3 %) in directly discharged and hospitalized patients, respectively. Of the 220 patients with incidental PE, 180 (81.8 %) were discharged directly compared to 105 of 382 (27.5 %) patients with symptomatic PE (P < 0.001). Mortality and readmission incidences in symptomatic and incidental PE were consistent with the main analysis. CONCLUSIONS: About 28 % and 82 % of cancer patients with symptomatic or incidental PE, respectively, were discharged directly, with low 14-day mortality and PE-related readmission incidences. These data underline the need for PE risk stratification in oncological populations and suggest that clinicians successfully identify a proportion of patients in whom direct discharge is safe.

External validation of AF-BLEED for predicting major bleeding and for tailoring NOAC dose in AF patients: A post hoc analysis in the ENGAGE AF-TIMI 48.

OBJECTIVE: AF-BLEED, a simple bleeding risk classifier, was found to predict major bleeding (MB) in patients with atrial fibrillation (AF) and identify AF patients at high risk of MB who might potentially benefit from a lower direct oral anticoagulant dose. This post hoc study aimed to externally validate these findings in the ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor Xa next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction study 48) trial. METHODS: The ENGAGE AF-TIMI 48 trial randomized AF patients to higher-dose edoxaban regimen (HDER 60/30 mg) versus lower-dose edoxaban regimen (LDER 30/15 mg), with prespecified dose reduction criteria. AF-BLEED was calculated in the modified intention-to-treat cohort (n = 21,026 patients) used for primary outcome analysis. Annualized event rates and hazard ratios (HRs) were obtained for the primary composite outcome (PCO) and its single components (MB, ischemic stroke/systemic embolism and death) to compare LDER 30 mg with HDER 60 mg in both AF-BLEED classes. RESULTS: AF-BLEED classified 2882 patients (13.7 %) as high-risk, characterized by a two- to three-fold higher MB risk than AF-BLEED classified low-risk patients. AF-BLEED classified high-risk patients randomized to LDER 30 mg demonstrated a 3.3 % reduction in MB at the cost of a 0.5 % increase in ischemic stroke/systemic embolism. LDER 30 mg resulted in a 3.1 % reduction of PCO compared to HDER 60 mg (HR of 0.81; 95%CI 0.65-1.01). Additional to existing dose reduction criteria, another 6 % of patients could potentially benefit of this dose adjustment strategy. CONCLUSION: AF-BLEED could identify AF patients to be at high risk of major bleeding. Our findings support the hypothesis that LDER 30 mg might provide a reasonable option in AF patients with legitimate bleeding concerns.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Idarucizumab for dabigatran reversal: A systematic review and meta-analysis of indications and outcomes.

BACKGROUND: Idarucizumab has been approved to reverse the anticoagulant effect of dabigatran. However, there is little knowledge of the effectiveness and safety of idarucizumab in daily practice. AIMS: This systematic review and meta-analysis aims to evaluate the use, effectiveness and outcomes of idarucizumab. METHODS: A systematic literature search was performed up to September 8th 2022. Original studies including patients prescribed idarucizumab, evaluating prescription indications, prescription appropriateness, haemostatic efficacy and/or the occurrence of adverse events were eligible. Case-reports and studies performed in patients ≤18 years or in healthy volunteers were excluded. Study selection and data extraction were performed by two independent reviewers. Pooled estimates were calculated using the random-effects model, after Freeman-Tukey double-arcsine transformation. RESULTS: Thirty studies comprising 3602 patients were included. Idarucizumab was prescribed for bleeding (63.1 %, 95%CI 57.0 %-69.0 %), invasive procedures (30.5 %, 95%CI: 24.1 %-37.2 %), to enable thrombolysis (range: 2.0 %-27.3 %), dabigatran intoxication without bleeding (range: 3.6 %-7.0 %) or unspecified reasons (range: 0.4 %-18.8 %). Overall, 2.8 % (95%CI 0.5 %-6.2 %) of prescription indications were reported to be inappropriate upon post-hoc evaluation. Hemostatic effectiveness was achieved in 77.7 % (95%CI 66.7 %-87.2 %) and peri-procedural haemostasis was normal in 98.5 % (95%CI 86.6 %-100 %) of patients. The pooled incidences of all-cause mortality and thromboembolic events at any follow-up duration were 13.6 % (95%CI 9.6 %-17.9 %) and 2.0 % (95%CI 0.8 %-3.4 %), respectively. CONCLUSION: Idarucizumab was mainly prescribed in the setting of bleeding. The reported hemostatic effectiveness was good, especially perioperatively, and the incidence of thromboembolic events was low. Patients with dabigatran-associated bleeding or requiring an urgent procedure nonetheless face a high mortality risk.

Inappropriate prescriptions of direct oral anticoagulants (DOACs) in hospitalized patients: A narrative review.

Direct oral anticoagulants (DOACs) have become the cornerstone for prevention of thromboembolic events in patients with atrial fibrillation and patients with a history of venous thromboembolism. However, studies show that DOAC prescriptions are commonly inconsistent with guideline recommendations. DOAC dosing in the acutely ill patient could impose an even greater challenge. In this review, we describe the prevalence of inappropriate inpatient prescribing of DOACs and the associated rationales, predictors and clinical consequences. With the aim of promoting appropriate prescriptions of DOACs to hospitalized patients, we further outline DOAC dose reduction criteria justified by various guidelines, illustrating the complexities of appropriate dosing, especially in acutely ill patients. Moreover, we will discuss the impact of anticoagulant stewardship programs and the vital role that pharmacists may play in optimizing inpatient DOAC treatment.

Impact of pulmonary infarction in pulmonary embolism on presentation and outcomes.

BACKGROUND: Pulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown. AIM: To evaluate the predictive value of radiological PI signs at acute PE diagnosis on 3-month outcomes. METHODS: We studied a convenience cohort with computed tomography pulmonary angiography (CTPA)-confirmed PE for whom extensive 3-month follow-up data were available. The CTPAs were re-evaluated for signs of suspected PI. Associations with presenting symptoms, adverse events (recurrent thrombosis, PE-related readmission and mortality) and self-reported persistent symptoms (dyspnea, pain and post-PE functional impairment) at 3-month follow-up were investigated using univariate Cox regression analysis. RESULTS: At re-evaluation of the CTPAs, 57 of 99 patients (58 %) had suspected PI, comprising a median of 1 % (IQR 1-3) of total lung parenchyma. Patients with suspected PI more often presented with hemoptysis (11 % vs. 0 %) and pleural pain (OR 2.7, 95%CI 1.2-6.2), and with more proximal PE on CTPA (OR 1.6, 95%CI 1.1-2.4) than patients without suspected PI. There was no association with adverse events, persistent dyspnea or pain at 3-month follow-up, but signs of PI predicted more functional impairment (OR 3.03, 95%CI 1.01-9.13). Sensitivity analysis with the largest infarctions (upper tertile of infarction volume) yielded similar results. CONCLUSIONS: PE patients radiologically suspected of PI had a different clinical presentation than patients without those signs and reported more functional limitations after 3 months of follow-up, a finding that could guide patient counselling.

Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation.

Aims: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. Methods and results: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96-1.00). Conclusion: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

Current clinical practice for thromboprophylaxis management in patients with Cushing's syndrome across reference centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN).

BACKGROUND: Cushing's syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. RESULTS: The majority of the RCs provided thromboprophylaxis to patients with CS (n = 23/25), although only one center had a standardized thromboprophylaxis protocol (n = 1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n = 11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n = 15/23). Factors influencing the initiation of thromboprophylaxis were 'medical history of VTE' (n = 15/23) and 'severity of hypercortisolism' (n = 15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n = 23/23). Postoperatively, the majority of RCs reported 'severe immobilization' as an indication to start thromboprophylaxis in patients with CS (n = 15/25). Most RCs (n = 19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n = 23/25). About half of these RCs (n = 12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n = 15/23) included 'reduction of VTE risk' as a goal of treatment. CONCLUSIONS: There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis.

Challenges in the diagnostic approach of suspected pulmonary embolism in COVID-19 patients.

Accumulating studies on COVID-19 patients report high incidences of thrombotic complications, but guidance on the best diagnostic approach for suspected pulmonary embolism (PE) in COVID-19 patients is lacking. Diagnosing PE in these patients is challenging as signs and symptoms of PE and COVID-19 show wide overlap, D-dimer levels are often elevated in the absence of thrombosis and computed tomography pulmonary angiography (CTPA) may be unfeasible in the case of severe renal impairment and/or hemodynamic instability.This narrative review discusses available literature and guidelines on current diagnostic algorithms for suspected PE in special patient populations, in particular COVID-19. A special focus is on reviewing the literature aimed at identifying symptoms with a high suspicion for PE and on the diagnostic performance of diagnostic algorithms for suspected PE in the setting of COVID-19.Based on available literature, the index of suspicion for PE should be high in the case of unexplained abrupt worsening of respiratory status, typical symptoms of deep-vein thrombosis and/or acute unexplained right ventricular dysfunction. Despite the lack of prospective diagnostic management studies, we propose to adhere to current diagnostic algorithms applying assessment of pretest probability and D-dimer testing as available evidence suggests that these might be considered safe. Preferably, algorithms using adjusted D-dimer thresholds are recommended as it likely improves the yield of the clinical decision rule/D-dimer combination.

Pulmonary infarction in acute pulmonary embolism.

Pulmonary infarction results from occlusion of the distal pulmonary arteries leading to ischemia, hemorrhage and ultimately necrosis of the lung parenchyma. It is most commonly caused by acute pulmonary embolism (PE), with a reported incidence of around 30%. Following an occlusion of the pulmonary artery, the bronchial arteries are recruited as primary source of perfusion of the pulmonary capillaries. The relatively higher blood pressure in the bronchial circulation causes an increase in the capillary blood flow, leading to extravasation of erythrocytes (i.e. alveolar hemorrhage). If this hemorrhage cannot be resorbed, it results in tissue necrosis and infarction. Different definitions of pulmonary infarction are used in literature (clinical, radiological and histological), although the diagnosis is nowadays mostly based on radiological characteristics. Notably, the infarcted area is only replaced by a fibrotic scar over a period of months. Hence and formally, the diagnosis of pulmonary infarction cannot be confirmed upon diagnosis of acute PE. Little is known of the impact and relevance of pulmonary infarction in acute PE, and whether specific management strategies should be applied to prevent and/or treat complications such as pain, pneumonia or post-PE syndrome. In this review we will summarize current knowledge on the pathophysiology, epidemiology, diagnosis and prognosis of pulmonary infarction in the setting of acute PE. We highlight the need for dedicated studies to overcome the current knowledge gaps.

Prophylaxis and treatment of COVID-19 related venous thromboembolism.

COVID-19 pneumonia has been associated with high rates of thrombo-embolic complications, mostly venous thromboembolism (VTE), which is thought to be a combination of conventional VTE and in situ immunothrombosis in the pulmonary vascular tree. The incidence of thrombotic complications is dependent on setting (intensive care unit (ICU) versus general ward) and the threshold for performing diagnostic tests (screening versus diagnostic algorithms triggered by symptoms). Since these thrombotic complications are associated with in-hospital mortality, all current guidelines and consensus papers propose pharmacological thromboprophylaxis in all hospitalized patients with COVID-19. Several trials are ongoing to study the optimal intensity of anticoagulation for this purpose. As for the management of thrombotic complications, treatment regimens from non-COVID-19 guidelines can be adapted, with choice of anticoagulant drug class dependent on the situation. Parenteral anticoagulation is preferred for patients on ICUs or with impending clinical deterioration, while oral treatment can be started in stable patients. This review describes current knowledge on incidence and pathophysiology of COVID-19 associated VTE and provides an overview of guideline recommendations on thromboprophylaxis and treatment of established VTE in COVID-19 patients.

Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave.

INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.

Antithrombotic management of patients with atrial fibrillation-Dutch anticoagulant initiatives anno 2020.

In recent years, as more and more experience has been gained with prescribing direct oral anticoagulants (DOACs), new research initiatives have emerged in the Netherlands to improve the safety and appropriateness of DOAC treatment for stroke prevention in patients with atrial fibrillation (AF). These initiatives address several contemporary unresolved issues, such as inappropriate dosing, non-adherence and the long-term management of DOAC treatment. Dutch initiatives have also contributed to the development and improvement of risk prediction models. Although fewer bleeding complications (notably intracranial bleeding) are in general seen with DOACs in comparison with vitamin K antagonists, to successfully identify patients with high bleeding risk and to tailor anticoagulant treatment accordingly to mitigate this increased bleeding risk, is one of the research aims of recent and future years. This review highlights contributions from the Netherlands that aim to address these unresolved issues regarding the anticoagulant management in AF in daily practice, and provides a narrative overview of contemporary stroke and bleeding risk assessment strategies.

Lack of diagnostic utility of the ECG-derived ventricular gradient in patients with suspected acute pulmonary embolism.

INTRODUCTION: The YEARS algorithm was successfully developed to reduce the number of computed tomography pulmonary angiography (CTPA) investigations in the diagnostic management of patients with suspected pulmonary embolism (PE), although half of patients still needed to be referred for CTPA. We hypothesized that ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO), an easy to use tool for detecting PE-induced pulmonary hypertension (PH), may further improve the efficiency of the YEARS algorithm. METHODS: In this post-hoc analysis of the Years study, ECGs of 479 patients with suspected PE managed according to the YEARS algorithm were available for analysis. The diagnostic performance of VG-RVPO was assessed and likelihood ratios were calculated. RESULTS: PE was diagnosed in 88 patients (18%). In patients with confirmed PE, 34% had an abnormal VG-RVPO versus 24% of those without PE (odds ratio 1.6; 95%CI 0.94-2.6). The mean VG-RVPO was -22 ± 13 and did not differ between the two patient groups (-22 versus -20; mean difference - 2, 95% CI -4.8 to 1.3). The sensitivity of VG-RVPO for PE was 24% (95%CI 34-45), the specificity 76% (95%CI 71-80) and the c-statistic 0.45 (95% CI 0.38-0.51). When combined with the YEARS algorithm, the likelihood ratios of VG-RVPO remained close to 1.0. Ruling out PE in patients with an indication for CTPA based on a normal VG-RVPO would have resulted in 58 missed cases. CONCLUSIONS: The VG-RVPO has no diagnostic value for suspected acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. CONDENSED ABSTRACT: This post-hoc analysis of the YEARS study failed to demonstrate incremental diagnostic value of VG-RVPO for acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. Nevertheless, the role of VG-RVPO recorded on admission could potentially be valuable in the risk stratification of PE during hospitalization, although this remains to be studied.

Clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism: A different phenotype of thrombotic disease?

INTRODUCTION: COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in situ immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown. METHODS: In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak. Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli score) were measured and compared. RESULTS: We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19. Also, the thrombus load was lower in COVID-19 patients (Qanadli score -8%, 95% confidence interval [95%CI] -16 to -0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; -30%, 95%CI -44% to -8.2). Moreover, the mean RV/LV ratio (mean difference -0.23, 95%CI -0.39 to -0.07) and the prevalence of RV/LV ratio >1.0 (prevalence difference -23%, 95%CI -41 to -0.86%) were lower in the COVID-19 patients. CONCLUSION: Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology.

Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis.

INTRODUCTION: We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses. METHODS: We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first. RESULTS: We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8). CONCLUSION: In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

Measuring functional limitations after venous thromboembolism: Optimization of the Post-VTE Functional Status (PVFS) Scale.

INTRODUCTION: We recently proposed a scale for assessment of patient-relevant functional limitations following an episode of venous thromboembolism (VTE). Further development of this post-VTE functional status (PVFS) scale is still needed. METHODS: Guided by the input of VTE experts and patients, we refined the PVFS scale and its accompanying manual, and attempted to acquire broad consensus on its use. RESULTS: A Delphi analysis was performed involving 53 international VTE experts with diverse scientific and clinical backgrounds. In this process, the number of scale grades of the originally proposed PVFS scale was reduced and descriptions of the grades were improved. After these changes, a consensus was reached on the number/definitions of the grades, and method/timing of the scale assessment. The relevance and potential impact of the scale was confirmed in three focus groups totaling 18 VTE patients, who suggested additional changes to the manual, but not to the scale itself. Using the improved manual, the κ-statistics between PVFS scale self-reporting and its assessment via the structured interview was 0.75 (95%CI 0.58-1.0), and 1.0 (95%CI 0.83-1.0) between independent raters of the recorded interview of 16 focus groups members. CONCLUSION: We improved the PVFS scale and demonstrated broad consensus on its relevance, optimal grades, and methods of assessing among international VTE experts and patients. The interobserver agreement of scale grade assignment was shown to be good-to-excellent. The PVFS scale may become an important outcome measure of functional impairment for quality of patient care and in future VTE trials.