A practical guide to the management of immune thrombocytopenia co-existing with acute coronary syndrome.

Introduction: Immune thrombocytopenia (ITP) management with co-existing acute coronary syndrome (ACS) remains challenging as it requires a clinically relevant balance between the risk and outcomes of thrombosis and the risk of bleeding. However, the literature evaluating the treatment approaches in this high-risk population is scarce. Methods and Results: In this review, we aimed to summarize the available literature on the safety of ITP first- and second-line therapies to provide a practical guide on the management of ITP co-existing with ACS. We recommend holding antithrombotic therapy, including antiplatelet agents and anticoagulation, in severe thrombocytopenia with a platelet count < 30 × 109/L and using a single antiplatelet agent when the platelet count falls between 30 and 50 × 109/L. We provide a stepwise approach according to platelet count and response to initial therapy, starting with corticosteroids, with or without intravenous immunoglobulin (IVIG) with a dose limit of 35 g, followed by thrombopoietin receptor agonists (TPO-RAs) to a target platelet count of 200 × 109/L and then rituximab. Conclusion: Our review may serve as a practical guide for clinicians in the management of ITP co-existing with ACS.

Switch to oral antibiotics in Gram-negative bacteraemia: a randomized, open-label, clinical trial.

OBJECTIVES: To evaluate the safety and efficacy of switching from intravenous (IV) to oral antimicrobial therapy in patients with Enterobacterales bacteraemia, after completion of 3-5 days of microbiologically active IV therapy. METHODS: A multicentre, open-label, randomized trial of adults with monomicrobial Enterobacterales bacteraemia caused by a strain susceptible to ≥1 oral beta-lactam, quinolone, or trimethoprim/sulfamethoxazole. Inclusion criteria included completion of 3-5 days of microbiologically active IV therapy, being afebrile and haemodynamically stable for ≥48 hours, and absence of an uncontrolled source of infection. Pregnancy, endocarditis, and neurological infections were exclusion criteria. Randomization, stratified by urinary source of bacteraemia, was to continue IV (IV Group) or to switch to oral therapy (Oral Group). Agents and duration of therapy were determined by the treating physicians. The primary endpoint was treatment failure, defined as death, need for additional antimicrobial therapy, microbiological relapse, or infection-related re-admission within 90 days. Non-inferiority threshold was set at 10% in the 95% CI for the difference in the proportion with treatment failure between the Oral and IV Groups in the modified intention-to-treat population. The protocol was registered at ClinicalTrials.gov (NCT04146922). RESULTS: In the modified intention-to-treat population, treatment failure occurred in 21 of 82 (25.6%) in the IV Group, and 18 of 83 (21.7%) in the Oral Group (risk difference -3.7%, 95% CI -16.6% to 9.2%). The proportions of subjects with any adverse events (AE), serious AE, or AE leading to treatment discontinuation were comparable. DISCUSSION: In patients with Enterobacterales bacteraemia, oral switch, after initial IV antimicrobial therapy, clinical stability, and source control, is non-inferior to continuing IV therapy.

Percutaneous coronary intervention can be safely performed with left ventricular thrombus without increasing stroke risk: A 5-year retrospective review using real-world data.

INTRODUCTION: Left ventricular thrombus (LVT) increases the risk of ischemic stroke. However, it remains uncertain if the percutaneous coronary intervention (PCI) in the confirmed LVT setting further augments the stroke risk. Therefore, in this study, we evaluated the risk of stroke among patients with LVT undergoing CAG +/- PCI. METHODS: This retrospective observational cohort study included all the patients encountered with LVT from 1st of April 2015, to 31st of March 2020. The study population was divided into two groups: Longobardo et al. (2018) [1] patients with LVT who underwent CAG +/- PCI; Solheim et al. (2010) [2] patients with LVT who did not undergo CAG +/- PCI. The primary outcome evaluated was stroke during the index admission, and the secondary outcomes included in-hospital mortality, all-cause mortality, and stroke at 12 months post-discharge. Logistic regression was used to determine the risk of stroke associated with PCI among patients with LVT, and a p-value<0.05 indicated statistical significance. RESULTS: Of the 210 patients included, 119 underwent CAG +/- PCI, while 91 patients did not undergo CAG +/- PCI. Most of the patients were Asian (67%), male (96%), with a mean age of 56 years. Ischemic cardiomyopathy was the primary etiology of LVT in both groups (96% in the CAG +/- PCI group and 80% in non CAG +/- PCI group). During the index admission, stroke among patients with LVT did not differ between the CAG +/- PCI and non CAG +/- PCI groups (5% versus 3.3%; odds ratio (OR) 1.6, 95% confidence interval (CI) 0.34-6.4, p = 0.539; adjusted OR 0.9, 95% CI 0.09-10.6, p = 0.968). Similarly, in-hospital mortality, all-cause mortality, and stroke at 12 months did not differ between the study groups. CONCLUSION: Performing CAG +/- PCI among patients with LVT was not associated with an increased risk of stroke during admission or within 12 months in comparison to patients who did not undergo CAG +/- PCI, which may reassure cardiologists to perform CAG +/- PCI among patients with LVT safely.

Concurrent coronary artery disease and immune thrombocytopenia: a systematic review.

Introduction: Coronary artery disease (CAD) management in the setting of immune thrombocytopenia (ITP) remains very challenging to clinicians as a reasonable balance between bleeding and thrombosis risks needs to be achieved, and the evidence guiding such management is scarce. Methods: We conducted a systematic review following the PRISMA guidelines to summarize the available literature on the management and outcomes of CAD coexisting with ITP. We searched PubMed and Embase for studies published in English exploring CAD and ITP management until 05 October 2022. Two independent reviewers screened and assessed the articles for inclusion. Patients' characteristics, CAD treatment modalities, ITP treatment, and complications were reported. Results: We identified 32 CAD cases, among which 18 cases were revascularized with percutaneous coronary intervention (PCI), 12 cases underwent coronary artery bypass graft surgery (CABG), and two cases were managed conservatively. More than 50% were men, with a mean age of 61 ± 13 years and a mean baseline platelet count of 52 ± 59 × 109/L. Irrespective of the revascularization modality, most patients were treated with either corticosteroids alone, intravenous immunoglobulins (IVIG) alone, or in combination. Among those who underwent PCI, two patients had bleeding events, and one patient died. Similarly, among those with CABG, one patient developed bleeding, and one patient died. Conclusion: We found that revascularization with either PCI or CABG with the concurrent use of corticosteroids and/or IVIG for ITP was feasible, with an existing non-negligible risk of bleeding and mortality.

Prevalence, Outcome, and Optimal Management of Free-Floating Right Heart Thrombi in the Context of Pulmonary Embolism, a Systematic Review and Meta-Analysis.

Free-floating right-heart thrombus (FFRHT) in the context of a pulmonary embolism (PE) is a rare but serious encounter with no guidelines addressing its management. We performed a systematic review and meta-analysis addressing prevalence, clinical behavior, and outcomes of FFRHT associated with PE. Among the included 397 patients with FFRHT and PE, dyspnea was the main presenting symptom (73.3%). Obstructive shock was documented in 48.9% of cases. Treatment with thrombolytic therapy, surgical thrombectomy, and percutaneous thrombectomy was documented in 43.8%, 32.7%, and 6.5% of patients, respectively. The overall mortality rate was 20.4%. Syncope (p: 0.027), chest pain (p: 0.006), and obstructive shock (p: 0.037) were significantly associated with mortality. Use of thrombolytic therapy was significantly associated with survival (p: 0.008). A multivariate logistic regression model to determine mortality predictors revealed that syncope (OR: 1.97, 95% CI: 1.06-3.65, p: 0.03), and obstructive shock (OR: 2.23, 95% CI: 1.20-4.14, p: 0.01) were associated with increased death odds. Treatment with thrombolytic therapy (OR: 0.22, 95% CI: 0.086-0.57, p: 0.002) or surgical thrombectomy (OR: 0.35, 95% CI: 0.137-0.9, p: 0.03) were associated with reduced death odds. Meta-analysis of observational studies revealed a pooled prevalence of FFRHT among all PE cases of 8.1%, and overall mortality of 23%. Although uncommon, the presence of FFRHT in the context of PE is associated with high obstructive shock and mortality rates. Favorable survival odds are observed with thrombolytic therapy and surgical thrombectomy. Data are derived from case reports and observational studies. Clinical trials elucidating these findings are needed.

Prevalence of Venous Thromboembolism in Critically Ill COVID-19 Patients: Systematic Review and Meta-Analysis.

Background: Recent studies revealed a high prevalence of venous thromboembolism (VTE) events in coronavirus disease 2019 (COVID-19) patients, especially in those who are critically ill. Available studies report varying prevalence rates. Hence, the exact prevalence remains uncertain. Moreover, there is an ongoing debate regarding the appropriate dosage of thromboprophylaxis. Methods: We performed a systematic review and proportion meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for studies exploring the prevalence of VTE in critically ill COVID-19 patients till 25/07/2020. We pooled the proportion of VTE. Additionally, in a subgroup analysis, we pooled VTE events detected by systematic screening. Finally, in an exploratory analysis, we compared the odds of VTE in patients on prophylactic compared with therapeutic anticoagulation. Results: The review comprised 24 studies and over 2,500 patients. The pooled proportion of VTE prevalence was 0.31 [95% confidence interval (CI) 0.24, 0.39; I 2 94%], of VTE utilizing systematic screening was 0.48 (95% CI 0.33, 0.63; I 2 91%), of deep venous thrombosis was 0.23 (95% CI 0.14, 0.32; I 2 96%), and of pulmonary embolism was 0.14 (95% CI 0.09, 0.20; I 2 90%). Exploratory analysis of few studies, utilizing systematic screening, VTE risk increased significantly with prophylactic, compared with therapeutic anticoagulation [odds ratio (OR) 5.45; 95% CI 1.90, 15.57; I 2 0%]. Discussion: Our review revealed a high prevalence of VTE in critically ill COVID-19 patients. Almost 50% of patients had VTE detected by systematic screening. Higher thromboprophylaxis dosages may reduce VTE burden in this patient's cohort compared with standard prophylactic anticoagulation; however, this is to be ascertained by ongoing randomized controlled trials.

Long-term mortality after massive, submassive, and low-risk pulmonary embolism.

Guidelines for management of normotensive patients with acute pulmonary embolism (PE) emphasize further risk stratification on the basis of right ventricular (RV) size and biomarkers of RV injury or strain; however, the prognostic importance of these factors on long-term mortality is not known. We performed a retrospective cohort study of subjects diagnosed with acute PE from 2010 to 2015 at a tertiary care academic medical center. The severity of initial PE presentation was categorized into three groups: massive, submassive, and low-risk PE. The primary endpoint of all-cause mortality was ascertained using the Centers for Disease Control National Death Index (CDC NDI). A total of 183 subjects were studied and their median follow-up was 4.1 years. The median age was 65 years. The 30-day mortality rate was 7.7% and the overall mortality rate through the end of follow-up was 40.4%. The overall mortality rates for massive, submassive, and low-risk PE were 71.4%, 44.5%, and 28.1%, respectively (p < 0.001). Landmark analysis using a 30-day cutpoint demonstrated that subjects presenting with submassive PE compared with low-risk PE had increased mortality during both the short- and the long-term periods. The most frequent causes of death were malignancy, cardiac disease, respiratory disease, and PE. Independent predictors of all-cause mortality were cancer at baseline, age, white blood cell count, diabetes mellitus, liver disease, female sex, and initial presentation with massive PE. In conclusion, the diagnosis of acute PE was associated with substantial long-term mortality. The severity of initial PE presentation was associated with both short- and long-term mortality.