Enoxaparin for symptomatic COVID-19 managed in the ambulatory setting: An individual patient level analysis of the OVID and ETHIC trials.

BACKGROUND: Antithrombotic treatment may improve the disease course in non-critically ill, symptomatic COVID-19 outpatients. METHODS: We performed an individual patient-level analysis of the OVID and ETHIC randomized controlled trials, which compared enoxaparin thromboprophylaxis for either 14 (OVID) or 21 days (ETHIC) vs. no thromboprophylaxis for outpatients with symptomatic COVID-19 and at least one additional risk factor. The primary efficacy outcome included all-cause hospitalization and all-cause death within 30 days from randomization. Both studies were prematurely stopped for futility. Secondary efficacy outcomes were major symptomatic venous thromboembolic events, arterial cardiovascular events, or their composite occurring within 30 days from randomization. The same outcomes were assessed over a 90-day follow-up. The primary safety outcome was major bleeding (ISTH criteria). RESULTS: A total of 691 patients were randomized: 339 to receive enoxaparin and 352 to the control group. Over 30-day follow-up, the primary efficacy outcome occurred in 6.0 % of patients in the enoxaparin group vs. 5.8 % of controls for a risk ratio (RR) of 1.05 (95%CI 0.57-1.92). The incidence of major symptomatic venous thromboembolic events and arterial cardiovascular events was 0.9 % vs. 1.8 %, respectively (RR 0.52; 95%CI 0.13-2.06). Most cardiovascular thromboembolic events were represented by symptomatic venous thromboembolic events, occurring in 0.6 % vs. 1.5 % of patients, respectively. A similar distribution of outcomes between the treatment groups was observed over 90 days. No major bleeding occurred in the enoxaparin group vs. one (0.3 %) in the control group. CONCLUSIONS: We found no evidence for the clinical benefit of early administration of enoxaparin thromboprophylaxis in outpatients with symptomatic COVID-19. These results should be interpreted taking into consideration the relatively low occurrence of events.

Percutaneous large-bore aspiration embolectomy with veno-arterial extracorporal membrane oxygenation support or standby in patients with high-risk pulmonary embolism and contraindications to thrombolysis: a preliminary single centre experience.

AIMS: Large-bore catheter aspiration embolectomy reduces thrombus burden and right ventricle strain and improves haemodynamics after pulmonary embolism (PE). Sparse data are available for patients with high-risk PE and contraindications to thrombolysis or thrombolysis failure, particularly if veno-arterial extracorporal membrane oxygenation (VA-ECMO) is required. METHODS AND RESULTS: All patients with acute high-risk PE and contraindications to thrombolysis undergoing FlowTriever® percutaneous embolectomy and VA-ECMO circulatory support (or standby) at the University Hospital Zurich between April 2021 and August 2022 were retrospectively analysed. The primary outcome was the combination of recurrent PE, heart failure hospitalization, and all-cause death at 30 days. The analysis included 15 patients: mean age was 63.1 years and 14 (93%) were men. Overall, four (27%) patients presented with cardiac arrest, eight (53%) with ongoing obstructive shock, and three (20%) with persistent arterial hypotension. Veno-arterial extracorporal membrane oxygenation was implanted prior to aspiration embolectomy in eight (53%) patients. Three of seven patients without initial VA-ECMO support experienced periprocedural cardiac arrest, of whom two received ECMO support before completion of embolectomy. Veno-arterial extracorporal membrane oxygenation weaning was successful in all patients after a mean of 5.4 days. There was one periprocedural death in a patient who did not receive VA-ECMO support following a periprocedural cardiac arrest. The primary outcome at 30 days occurred in five (33.3%; 95% confidence interval 13.0-61.3%) patients. CONCLUSION: This study provides preliminary evidence for the feasibility of percutaneous large-bore aspiration embolectomy in combination with VA-ECMO support (or standby) in patients with high-risk PE and contraindications to thrombolysis.

Fixed-Dose Ultrasound-Assisted Catheter-Directed Thrombolysis for Acute Pulmonary Embolism Associated with COVID-19.

Background. Fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT) rapidly improves hemodynamic parameters and reverses right ventricular dysfunction caused by acute pulmonary embolism (PE). The effectiveness of USAT for acute PE associated with coronavirus disease 2019 (COVID-19) is unknown. Methods and results. The study population of this cohort study consisted of 36 patients with an intermediate-high- or high-risk acute PE treated with a fixed low-dose USAT protocol (r-tPA 10-20 mg/15 h). Of these, 9 patients tested positive for COVID-19 and were age-sex-matched to 27 patients without COVID-19. The USAT protocol included, beyond the infusion of recombinant tissue plasminogen activator, anti-Xa-activity-adjusted unfractionated heparin therapy (target 0.3-0.7 U/mL). The study outcomes were the invasively measured mean pulmonary arterial pressure (mPAP) before and at completion of USAT, and the National Early Warning Score (NEWS), according to which more points indicate more severe hemodynamic impairment. Twenty-four (66.7%) patients were men; the mean age was 67 ± 14 years. Mean  ±  standard deviation mPAP decreased from 32.3 ± 8.3 to 22.4 ± 7.0 mmHg among COVID-19 patients and from 35.4 ± 9.7 to 24.6 ± 7.0 mmHg among unexposed, with no difference in the relative improvement between groups (p = 0.84). Within 12 h of USAT start, the median NEWS decreased from six (Q1-Q3: 4-8) to three (Q1-Q3: 2-4) points among COVID-19 patients and from four (Q1-Q3: 2-6) to two (Q1-Q3: 2-3) points among unexposed (p = 0.29). One COVID-19 patient died due to COVID-19-related complications 14 days after acute PE. No major bleeding events occurred. Conclusions. Among patients with COVID-19-associated acute PE, mPAP rapidly decreased during USAT with a concomitant progressive improvement of the NEWS. The magnitude of mPAP reduction was similar in patients with and without COVID-19.

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome.

Background: The Transient Perivascular Inflammation of the Carotid artery (TIPIC) syndrome is presumably a very rare disease characterized by a local transient inflammation of the tissue around the carotid artery. Its pathophysiology remains unknown. We performed an updated study of TIPIC syndrome cases in the setting of a multinational collaborative study. Methods: This study was conducted as an observational multinational retrospective individual patient level cohort study. Information from all known cases diagnosed with TIPIC syndrome in the literature (2005-2020) was collected after a semi-structured literature search of PubMed and Web of Science. We also collected unpublished information of patients from French, Swiss, and Italian vascular medicine or radiology departments. Results: A total of 72 patients were included and served for data analysis: 42 (58.3%) were women; the mean age was 47.9 (SD=11.4) years. Symptoms were unilateral in 92% of patients and 81.4% required pain killers. At baseline, irrespective of the imaging method used, the median thickness of the carotid lesions was 5 (Q1-Q3: 4-7; range: 2-11) mm and the median length of the lesion was 20 (Q1-Q3: 10-30; range: 3-50) mm. We found a positive linear correlation between thickness and length. At follow-up, the thickness of the carotid lesions decreased to a median of 2 (Q1-Q3: 1-3; range: 0-6) mm; the length decreased to a median 10 (Q1-Q3: 5-15; range: 0-41) mm. A linear correlation between baseline and follow-up values was observed for both thickness and length measurements. Symptoms disappeared after a median of 14 (Q1-Q3: 10-15) days. Thirteen patients experienced a recurrence after a median follow-up of 6 (Q1-Q3: 2-12) months. Conclusions: The present analysis elucidates clinical and sonographic characteristics of TIPIC syndrome, indicating the benign nature of this condition. A future international registry will study the long-term course of the disease.

Thrombosis and Dissection of the Abdominal Arteries Associated with Infarcts of Solid Organs in a Patient with COVID-19: A Novel Clinical Entity.

The clinical spectrum of patients with coronavirus disease 2019 (COVID-19) ranges from asymptomatic cases to severe pneumonia with acute respiratory distress syndrome. COVID-19 is associated with an increased risk of thromboembolic complications, notably pulmonary embolism and deep vein thrombosis. Arterial cardiovascular complications and myocarditis have also been described in association with COVID-19, but appear to be less prevalent. In this report of a 57-year-old man with multiple splanchnic infarctions, arterial dissections and COVID-19 as the sole potential trigger, we describe a novel type of complications and put it in the context of a growing literature on this topic.

An update on the global use of risk assessment models and thromboprophylaxis in hospitalized patients with medical illnesses from the World Thrombosis Day steering committee: Systematic review and meta-analysis.

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. The majority of VTE events are hospital-associated. In 2008, the Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) multinational cross-sectional study reported that only approximately 40% of medical patients at risk of VTE received adequate thromboprophylaxis. METHODS: In our systematic review and meta-analysis, we aimed at providing updated figures concerning the use of thromboprophylaxis globally. We focused on: (a) the frequency of patients with an indication to thromboprophylaxis according with individual models; (b) the use of adequate thromboprophylaxis; and (c) reported contraindications to thromboprophylaxis. Observational nonrandomized studies or surveys focusing on medically ill patients were considered eligible. RESULTS: After screening, we included 27 studies from 20 countries for a total of 137 288 patients. Overall, 50.5% (95% confidence interval [CI]: 41.9-59.1, I2 99%) of patients had an indication to thromboprophylaxis: of these, 54.5% (95% CI: 46.2-62.6, I2 99%) received adequate thromboprophylaxis. The use of adequate thromboprophylaxis was 66.8% in Europe (95% CI: 50.7-81.1, I2 98%), 44.9% in Africa (95% CI: 31.8-58.4, I2 96%), 37.6% in Asia (95% CI: 25.7-50.3, I2 97%), 58.3% in South America (95% CI: 31.1-83.1, I2 99%), and 68.6% in North America (95% CI: 64.9-72.6, I2 96%). No major differences in adequate thromboprophylaxis use were found across risk assessment models. Bleeding, thrombocytopenia, and renal/hepatic failure were the most frequently reported contraindications to thromboprophylaxis. CONCLUSIONS: The use of anticoagulants for VTE prevention has been proven effective and safe, but thromboprophylaxis prescriptions are still unsatisfactory among hospitalized medically ill patients around the globe with marked geographical differences.

Diagnosis and management of venous thromboembolism: Results of a survey on current clinical practice.

BACKGROUND: The implementation of evidence from clinical studies into daily clinical practice is not a straightforward process. We developed a standardized questionnaire to explore clinical practice patterns in the management of VTE, in particular about the use of pre-clinical probability and D-dimer testing and on the home treatment of pulmonary embolism (PE). METHODS: The standardized questionnaire was sent to all 394 physician members of the Italian Society of Thrombosis and Haemostasis (SISET) by e-mail. The questionnaire contained three groups of questions: about general information, about the diagnostic process for both deep venous thrombosis (DVT) and PE, and about home-therapy of PE. RESULTS: One hundred and twenty-eight (32.5%) physicians responded the questionnaire. For DVT diagnosis 69 (54.3%) physicians answered that they always use the D-dimer test; 4 (3.1%) do never use it; whereas only 11 (8.7%) take notice of the D-dimer result before visiting the patients; 38 (29.9%) use only clinical judgment to assess pre-clinical probability of disease. For the diagnosis of PE 80 (66.1%) physicians always use the D-dimer test, whereas 3 (2.5%) do never use it; whereas 14 (11.7%) take notice of the D-dimer result before visiting the patients; 50 (41.3%) use only clinical judgment to assess pre-clinical probability. Sixty-six (59.5%) clinicians declared to treat patients with PE at home, when feasible. CONCLUSION: The diagnostic approach to VTE among expert physicians appears to be heterogeneous; in particular there is no widespread use of clinical prediction rules. The majority of expert physicians appear to consider the possibility of treating at home patients with PE.

Oral anticoagulant therapy in patients with mechanical heart valve and intracranial haemorrhage. A systematic review.

Optimal timing for restarting anticoagulant therapy after intracranial bleeding is a critical issue. The purpose of this systematic review is to summarize published studies on the management of oral anticoagulant therapy after intracranial bleeding secondary to the use of vitamin K antagonists in patients with a mechanical heart valve. A computer-assisted search of the MEDLINE and EMBASE electronic databases till January 2008 was performed. Two investigators independently performed study selection and completed a predefined quality assessment and data extraction form. Main inclusion criterion was the enrolment of patients with a mechanical heart valve and intracranial haemorrhage during oral anticoagulant treatment. Any randomised controlled trial, observational cohort study, case series and reports was included. No randomised controlled trials were identified. Six observational cohort studies were included in the final analysis. All studies were of low quality. A total of 120 patients were enrolled. Anticoagulation was restarted within a broad time range (2 days to 3 months). Four ischaemic strokes and two recurrent cerebral haemorrhages occurred after anticoagulation was restarted after a mean follow-up of 7.9 months. Eighteen patients were described in the selected case reports. Anticoagulant therapy was restarted within four days to eight weeks. Two patients had a recurrent haemorrhagic event, and no ischaemic events were reported. In conclusion, restarting oral anticoagulant therapy few days and, indirectly, stopping anticoagulant therapy for a few days (even for 7-14 days) after the occurrence of cerebral haemorrhage are both safe. However, well-designed studies are strongly recommended to provide better evidence.

Venous and arterial thrombosis in patients with HIV infection.

Thromboembolic complications in HIV-infected patients have been reported. To our knowledge, no case-control studies have compared the prevalence of thromboembolic events between HIV-positive and HIV-negative individuals. One hundred and sixty-nine HIV-infected patients and 180 randomly selected blood donors were enrolled. Selected patients completed a specific questionnaire and were subsequently interviewed. Information was collected on family and personal history of cardiovascular disorders and the presence of personal risk factors for venous and arterial thrombosis. All reported events were adjudicated only if adequate documentation of objective tests was available. Mean age and sex were similar in the two groups. A vascular event was documented in six HIV-infected patients (3.55%) and in none of the controls (P=0.0108). Family history of cardiovascular disorders, cigarette smoking and hypertriglyceridemia were more prevalent in HIV patients than in controls. In multivariate analysis, neither family traditional cardiovascular risk factors nor HIV infection were independently associated with the presence of thromboembolic events. The results confirm the hypothesis that HIV-positive patients have an increased risk of thromboembolic disorders. Whether this increased risk has been provoked by HIV infection itself or by other associated risk factors for cardiovascular events, such as cigarette smoking and hypertriglyceridemia, remain to be clarified.