Evaluation of the Clinical Impact of Thromboprophylaxis in Patients With COVID-19 Following Hospital Discharge

Background: Data are limited regarding the incidence of thromboembolism post-hospital discharge among COVID-19 patients. Guidelines addressing the role of extended thromboprophylaxis for COVID-19 patients are limited and conflicting. Objective: The purpose of this study was to evaluate the incidence of post-discharge thromboembolic and bleeding events and the role of thromboprophylaxis among COVID-19 patients. Methods: A retrospective analysis was conducted of hospitalized patients with symptomatic COVID-19 infection who were discharged from a University of Colorado Health (UCHealth) hospital between March 1, 2020, and October 31, 2020. The primary outcome was objectively confirmed thromboembolism within 35 days post-discharge. The main secondary outcome was the incidence of bleeding events within 35 days post-discharge. Outcomes were compared between those who received extended prophylaxis and those who did not. Results: A total of 1171 patients met the study criteria. A total of 13 (1.1%) of patients had a documented thromboembolic event and 10 (0.9%) patients had a documented bleeding event within 35 days post-discharge. None of the 132 patients who received extended prophylaxis had a thromboembolic event compared to 13 of 1039 who did not receive extended prophylaxis (0 and 1.3%, respectively; P = .383). The incidence of bleeding was higher among patients who received extended prophylaxis compared to those who did not (3.0% vs 0.6%, P = .019). Conclusions and Relevance: These results suggest that post-discharge extended prophylaxis may be beneficial for select COVID-19 patients, while carefully weighing the risk of bleeding. Application of our findings may assist institutions in development of thromboprophylaxis protocols for discharged COVID-19 patients.

Splenic Infarction in a COVID-19 Patient without Respiratory Symptoms

High rates of thromboembolic events have been seen in cases of COVID-19. Here, we report a case of 23-year-old previously healthy female presented with left-sided abdominal pain associated with vomiting. The computed tomography scan showed multiple ill-defined wedge-shaped low attenuating areas of the spleen, suggesting splenic infarction. In the absence of other thromboembolic contributing factors, we believe this was a thromboembolic event in splenic circulation in relation to COVID-19 infection. Our case adds to the evidence of an arterial thrombotic event in a noncritical COVID-19 patient, emphasizing the importance of addressing thromboembolism diagnosis and management measures to avoid potentially deadly consequences.

Relapse of Nephrotic Syndrome with Unusual Thromboembolic Event: A Case Report

The thromboembolism (TE) as a complication of nephrotic syndrome (NS) is rare and serious and may involve renal, cerebral, pulmonary, or peripheral venous and/or arterial thrombosis. Here, we describe a 4.5-year-old male with a history of nephrotic syndrome, who developed a hemorrhagic stroke in the territory of middle cerebral artery.

Apixaban Discontinuation for Invasive Or major Surgical procedures (ADIOS): A prospective cohort study

Background: Apixaban pharmacokinetic properties and some clinical reports suggest cessation 48 hours prior to surgery is safe, but this has not been demonstrated in a naturalistic setting. We sought to measure the residual apixaban exposure in patients who had apixaban held as part of standard of care perioperative management. Methods: This was a prospective, observational study of patients in whom apixaban plasma concentration and anti-Xa activity were measured while at steady state apixaban dosing and again immediately prior to surgery. Clinical management of cessation and resumption of apixaban was at the discretion of the treating physician. Results: Paired blood samples were provided by 111 patients. Ninety-four percent (104/111) of patients had measured apixaban concentrations of ⩽ 30 ng/mL. Only one patient had a value > 50 ng/mL. The median time between the self-reported last dose and presurgery blood sampling was 76 hours (range 32–158) for those who achieved concentrations ⩽ 30 ng/mL and 59 hours (range 49–86) for those > 30 ng/mL. Measured anti-Xa activity correlated well with apixaban exposure. Clinically significant nonmajor bleeding was reported in one patient at 1 week postsurgery. There was one venous thromboembolic event and one stroke in the perioperative period. Conclusion: In a naturalistic setting with a heterogeneous patient population, apixaban discontinuation for at least 48 hours before a procedure resulted in a clinically insignificant degree of anticoagulation prior to a surgical procedure. ClinicalTrials.gov Identifier: NCT02935751

Immunomodulation and Reduction of Thromboembolic Risk in Hospitalized COVID-19 Patients: Systematic Review and Meta-Analysis of Randomized Trials

Background: We aimed to investigate the potential beneficial effect of immunomodulation therapy on the thromboembolic risk in hospitalized COVID-19 patients. Methods: We searched PubMed and Scopus for randomized trials reporting the outcomes of venous thromboembolism (VTE), ischemic stroke or systemic embolism, myocardial infarction, any thromboembolic event, and all-cause mortality in COVID-19 patients treated with immunomodulatory agents. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using the Mantel–Haenszel random effects method. Results: Among 8499 patients hospitalized with COVID-19, 4638 were treated with an immunomodulatory agent, 3861—with usual care only. Among the patients prescribed immunomodulatory agents, there were 1.77 VTEs per 100 patient-months compared to 2.30 among those treated with usual care (OR: 0.84, 95% CI: 0.61–1.16; I2: 0%). Among the patients who received an interleukin 6 (IL-6) antagonist, VTEs were reported in 12 among the 1075 patients compared to 20 among the 848 receiving the usual care (OR: 0.52, 95% CI: 0.22–1.20; I2: 6%). Immunomodulators as an add-on to usual care did not reduce the risk of stroke or systemic embolism (OR: 1.10, 95% CI: 0.50–2.40; I2: 0%) or of myocardial infarction (OR: 1.06, 95% CI: 0.47–2.39; I2: 0%) and there was a nonsignificant reduction in any thromboembolic event (OR: 0.86, 95% CI: 0.65–1.14; I2: 0%). Conclusions: We did not identify a statistically significant effect of immunomodulation on prevention of thromboembolic events in COVID-19. However, given the large effect estimate for VTE prevention, especially in the patients treated with IL-6 antagonists, we cannot exclude a potential effect of immunomodulation.

Left atrial thrombosis in patients with atrial fibrillation during uninterrupted oral anticoagulation

Atrial fi brillation (AF) is the most common arrhythmia in adults and requires permanent anticoagulation in the presence of risk factors. Left atrial (LA) thrombus is found in a signifi cant minority of patients despite anticoagulant treatment. We aimed to estimate the prevalence of LA thrombosis on uninterrupted oral anticoagulation (OAC) in AF patients and to determine associated demographic, clinical, echocardiographic and tomographic parameters. Material and methods: We present retrospective study of 702 hospitalizations in 582 patients (397 males, 68.2%) with AF and/or atrial fl utter on uninterrupted OAC for at least 3 weeks, assessed for LA thrombosis with transoesophageal echocardiography and/or cardiac computed tomography. Probability value of p < 0.05 was considered signifi cant for all statistical analyses. Results: The prevalence of LA thrombosis was 6.2%, without signifi cant difference between patients on direct OAC (DOAC) or acenocoumarol (VKA). Non-paroxysmal arrhythmia was signifi cantly associated with LA thrombus, OR 0.369, 95% CI 0.159-0.857, p = 0.02. The proportion of patients on VKA with subtherapeutic INR was signifi cantly higher (30.7%), than the proportion of patients receiving too low dose of DOAC (9.7%), OR 4.1, 95%, CI 2 CI 2.7-6.23, р < 0.001. No association was found between the LA appendage morphology type and the presence of LA thrombus. During a median follow-up of 30 days new stroke/transitory ischemic attack (TIA)/systemic embolism (SE) was registered in seven patients (1.34%), none of them with LA thrombus. Conclusion: The prevalence of LA thrombosis in the studied cohort is comparable to the published data and seemingly had no association with the OAC type. The incidence of stroke/TIA/SE was low on uninterrupted oral anticoagulation during short-term follow-up and there was no association between the presence of LA thrombus and thromboembolic event on follow-up.

Clinical application of the novel 4S-AF scheme for the characterisation of patients with atrial fibrillation: a report from the ESC-EHRA EORP Atrial Fibrillation General Long-Term (AFGen LT) registry

Background Current classification systems recommended by major international guidelines are based on a single domain of atrial fibrillation (AF): temporal pattern, symptom severity or underlying comorbidity. Lack of integration between these various elements limits our approach to patients with AF and acts as a barrier against the delivery of better holistic care. The 4S-AF classification scheme was recently introduced as a means for the characterisation of patients with AF. It comprises of 4 domains: stroke risk (St), symptoms (Sy), severity of AF burden (Sb) and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and effects of individual domains on outcomes in AF. Methods Patients with AF from 250 centres across 27 participating European countries were included. All patients were over 18 years old and had electrocardiographic confirmation of AF within 12 months prior to enrolment. Data on demographics and comorbidities were collected at baseline. Individual domains of the 4S-AF scheme were assessed using the CHA2DS2-VASc score (St), European Heart Rhythm Association classification (Sy), temporal classification of AF (Sb), and cardiovascular risk factors and the degree of left atrial enlargement (Su). Each of these domains were used during multivariable cox regression analysis. Results A total of 6321 patients were included in the present analysis, corresponding to 57.0% of the original cohort of 11096 patients. The median age of patients was 70 (interquartile range [IQR] 62–77) years with 2615 (41.4%) females. Among these patients, 528 (8.4%) had low stroke risk (St=0), 3002 (47.5%) no or mild symptoms (Sy=0), 2558 (40.5%) newly diagnosed or paroxysmal AF (Sb=0), and 322 (5.1%) no cardiovascular risk factors or left atrial enlargement (Su=0). Median follow-up was 24 months. Using multivariable cox regression analysis, independent predictors of all-cause mortality were (St) (adjusted hazard ratio [aHR] 8.21 [95% CI, 2.60–25.9]), (Sb) (aHR 1.21 [95% CI, 1.08–1.35]) and (Su) (aHR 1.27 [95% CI, 1.14–1.41]). For cardiovascular mortality and any thromboembolic event, only (Su) (aHR 1.73 [95% CI, 1.45–2.06]) and (Sy) (aHR 1.29 [95% CI, 1.00–1.66]) were statistically important, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Conclusion Overall, we demonstrated that the 4S-AF scheme may be used to provide clinical characterisation of patients with AF using routinely collected data, and each of the domains within the 4S-AF scheme were independently associated with adverse long-term outcomes of all-cause mortality, cardiovascular mortality and/or any thromboembolic event. FUNDunding Acknowledgement Type of funding sources: None.

Thromboembolic risk of movable type left atrial appendage thrombi in patients with atrial fibrillation under widespread use of anticoagulants

Background Left atrial appendage thrombi (LAAT), especially movable type LAAT, have been reported to be high-risk for thromboembolic events in patients with atrial fibrillation (AF). However, thromboembolic risk of the movable-type LAAT under widespread use of anticoagulant therapy remains unclear. Methods We retrospectively studied 65 LAAT patients taking anticoagulants out of 1381 consecutive patients who underwent transthoracic echocardiography prior to cardioversion or catheter ablation for AF. Patients with significant valvular disease and coagulation disorder were excluded. Clinical data were evaluated at the time of TEE. The LAAT were classified into movable and fixed type LAAT by three independent observers. Results Sixteen of 65 LAAT patients showed movable type LAAT. During follow-up (42±34 months), one patient underwent emergency thrombectomy, 5 patients developed thromboembolic event, and 12 patients died. There were no differences in clinical data, parameters, thrombectomy/thromboembolic event, and survival rate between patients with movable and fixed type LAAT. Conclusion Thromboembolic risk of the movable-type LAAT is the same as fixed type LAAT, under widespread use of anticoagulant therapy. FUNDunding Acknowledgement Type of funding sources: None.