Implementation of a transition of care pathway for low-risk patients presenting to the emergency department with venous thromboembolism.

Inpatient management of low-risk patients with venous thromboembolism (VTE) places a large resource burden on the healthcare system. Adult patients diagnosed with deep vein thrombosis (DVT) or pulmonary embolism (PE) in the emergency department (ED) have historically been hospitalized and treated with therapeutic anticoagulation. However, over the last two decades, outpatient treatment of patients with acute DVT and low risk PE has become increasingly accepted as an effective and safe option for patients given the low risk of short-term clinical deterioration. The purpose of this project was to establish a transition of care (TCM) program for patients with acute VTE presenting to the ED. The primary goals for the project included better quality patient follow-up in the Vascular Medicine Nurse Practitioner (NP) within one week and medication adherence. The second goal was increasing appropriate ED discharges for patients with low-risk VTE. Outcome metrics include the rate of early discharge of low-risk patients with VTE, follow-up in the Vascular Medicine NP clinic, and anticoagulant adherence.

Letter to the editor regarding the paper by A. Boileve et al.: Safety of direct oral anticoagulants in patients with advanced solid tumors receiving anti­VEGF agents: a retrospective study.

Concomitant direct oral anticoagulants (DOACs) and tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (anti-VEGF TKI) have been associated with a higher risk of bleeding. Nevertheless, concomitant administration seems frequent in clinical practice in patients with cancer-associated thrombosis and appears to be safe according to the retrospective study by Boileve A. et al. But the risk of an additional pharmacokinetic interaction between anti-VEGF TKI and DOACs must be considered, in case of P-glycoprotein (P-gp) inhibition by the TKI. We describe a case report with a major bleeding event in a renal metastatic cancer patient treated with cabozantinib and rivaroxaban. This case highlights the difficult therapeutic decision in a complex patient with cancer-associated thrombosis, who refused the anticoagulant subcutaneous route. Accumulation of bleeding risk factors (genito-urinary tumor localization) was additive to several pharmacodynamic interactions (acetylsalicylic acid, venlafaxine) and a potential pharmacokinetic interaction between cabozantinib and rivaroxaban. Indeed, cabozantinib-related P-glycoprotein inhibition could have led to a supratherapeutic level of rivaroxaban, contributing partly to the bleeding event. Before combining an anti-VEGF TKI and DOACs, a multidisciplinary pretherapeutic assessment seems crucial to evaluate the patient's bleeding risk factors, pharmacodynamic interactions, and the risk of pharmacokinetic interactions mediated by P-gp.

Regulation of Platelet Activation and Coagulation: Current Concepts, Novel Targets, and Therapies.

Antiplatelet and anticoagulant therapies are cornerstones of secondary prevention in high-risk cardiovascular patients. Whereas in former days the focus was set on effective antithrombotic effects, more recent trials and guidelines placed emphasis on a more balanced approach, thus including the bleeding risk for an individualized therapy. Type, strength, combination, and duration are important components to modify the individual bleeding risk. Novel antiplatelet and anticoagulant agents have shown promising results that might offer safer options in the future for high-risk cardiovascular patients. This review aims to give an overview about established drug target and pharmacologic approaches that are currently in the pipeline.

Antithrombotic Therapy in Patients with Complex Percutaneous Coronary Intervention and Cardiogenic Shock.

Managing antithrombotic therapy in patients undergoing complex and high-risk in indicated patients, including those treated with complex percutaneous coronary intervention (PCI) or presenting with cardiogenic shock (CS), is challenging. This review highlights the critical role of antithrombotic therapy, during and after PCI, to optimize the efficacy while minimizing risks. Unfractionated heparin remains the mainstay anticoagulant for complex PCI and CS, with bivalirudin as a potential safer alternative. Cangrelor offers consistent antiplatelet effects, especially when timely absorption of oral agents is uncertain.

Antiplatelet Therapy in Patients Requiring Oral Anticoagulation and Undergoing Percutaneous Coronary Intervention.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs.

Antithrombotic Therapy in Patients Undergoing Percutaneous Left Atrial Appendage Occlusion.

Percutaneous left atrial appendage closure (LAAC) is a valid alternative to oral anticoagulation to prevent ischemic stroke in patients with atrial fibrillation.The devices approved in Europe and United States for percutaneous LAAC contain metal and temporary antithrombotic therapy is strongly recommended following implantation to prevent thrombus formation on the atrial device surface. There is still uncertainty regarding to the optimal antithrombotic drug regimen after device implantation for several reasons. Thus, this review aims at summarizing the available evidence and the remaining challenges related to the management of antithrombotic therapy in the context of LAAC procedure.

Antithrombotic Therapy in Patients with Chronic Coronary Syndromes.

The antithrombotic management of chronic coronary syndrome (CCS) involves a 6-month course of dual antiplatelet therapy (DAPT), followed by chronic aspirin therapy. In patients with a baseline indication for anticoagulation, a variable duration of triple antithrombotic therapy is administered, followed by dual antithrombotic therapy until the sixth month post-percutaneous coronary intervention (PCI), and ultimately a transition to chronic anticoagulation. However, advancements in stent technology reducing the risk of stent thrombosis and a growing focus on the impact of bleeding on prognosis have prompted the development of new therapeutic strategies. These strategies aim to enhance protection against ischemic events in the initial stages after PCI while mitigating the risk of bleeding in the long term. This article delineates the therapeutic strategies outlined in European and American guidelines for CCS management, with special attention to investigational strategies.

Antithrombotic Therapy in Acute Coronary Syndrome.

Early mechanical reperfusion, primarily via percutaneous coronary intervention, combined with timely antithrombotic drug administration, constitutes the main approach for managing acute coronary syndrome (ACS). Clinicians have access to a variety of antithrombotic agents, necessitating careful selection to balance reducing thrombotic events against increased bleeding risks. This review offers a comprehensive update on current antithrombotic therapy in ACS, emphasizing the need for individualized treatment strategies.

Anticoagulant Therapy in Patients Undergoing Acute Pulmonary Embolism Interventions.

Catheter-based interventions and surgical embolectomy represent alternatives to systemic fibrinolysis for patients with high-risk pulmonary embolism (PE) or those with intermediate-high-risk PE who deteriorate hemodynamically. They are indicated when systemic fibrinolysis is contraindicated or ineffective, or if obstructive shock is imminent. Extracorporeal membrane oxygenation can be added to reperfusion therapies or used alone for severe right ventricular dysfunction and cardiogenic shock. These advanced therapies complement but do not replace anticoagulation, which remains the cornerstone in PE management. This review summarizes the evidence and shares practical recommendations for the use of anticoagulant therapy before, during, and after acute PE interventions.

Prophylaxis of venous thromboembolism in hospitalized patients admitted from Spanish emergency departments: the PROTESU II study. / Profilaxis de la enfermedad tromboembólica venosa en pacientes hospitalizados por patología médica desde los servicios de urgencias españoles: estudio PROTESU II.

OBJECTIVE: To estimate the prevalence of inappropriate use of prophylaxis to prevent venous thromboembolism (VTE) in patients with medical diseases admitted to hospital from the emergency department. To explore variables associated with inappropriate thromboprophylaxis. METHODS: Prospective multicenter cohort study in 15 hospital emergency departments. We included patients admitted for a medical condition during 7 days in the first quarter of 2022. We assessed risk for VTE with the Padua Prediction Score (PPS). Inappropriate thromboprophylaxis was defined by failure to prescribe prophylaxis in patients with a high-risk PPS assessment unless there were absolute contraindications (active bleeding or severe thrombopenia) or, alternatively, the prescription of prophylaxis in patients with a low-risk PPS assessment or absolute contraindications. A logistic regression model was adjusted for risk level to identify variables associated with inappropriate use of thromboprophylaxis. RESULTS: Of a total of 630 patients included, 450 (71.4%) had PPS scores indicating high risk for VTE; 180 patients were at low risk. Thromboprophylaxis was inappropriate in 248 patients (39.4%): 165 high-risk patients who received no prophylaxis, 82 low-risk patients who were nonetheless treated, and 1 patient who was treated in spite of severe thrombopenia. Odds ratios (ORs) revealed that the variables associated with inappropriate use of thromboprophylaxis were trauma or recent surgery (OR, 5.53; 95% CI, 1.58-19.34), presence of factors indicating risk for bleeding (OR, 2.61; 95% CI, 1.44-4.73), and hospital admission for either urinary tract infection (OR, 2.29; 95% CI, 1.07-4.87) or gastrointestinal disease (OR, 4.30; 95% CI, 1.71-10.85). CONCLUSIONS: The inappropriate use of thromboprophylaxis in Spanish emergency departments is high and associated with certain clinical characteristics.

OBJETIVO: Evaluar la inadecuación de la tromboprofilaxis farmacológica, según la escala Padua (PPS), para prevenir la enfermedad tromboembólica venosa (ETV) entre los pacientes que ingresan desde el servicio de urgencias hospitalario (SUH) por patología médica, así como las variables asociadas a su uso inadecuado. METODO: Estudio de cohortes, prospectivo, multicéntrico donde participaron 15 SUH. Se incluyeron los pacientes atendidos que requirieron ingreso por enfermedad médica durante 7 días del primer trimestre de 2022. La inadecuación de la tromboprofilaxis farmacológica se definió como la no utilización en pacientes clasificados por PPS de alto riesgo sin contraindicaciones absolutas para su uso (hemorragia activa o trombopenia grave) o su utilización en pacientes de riesgo bajo o con contraindicaciones absolutas. Se ajustó, para cada grupo de riesgo, un modelo de regresión logística para identificar las variables asociadas a la inadecuación. RESULTADOS: Se incluyeron 630 pacientes, 450 (71,4%) tenían riesgo alto y 180 (28,6%) riesgo bajo para ETV según la PPS. De ellos, la tromboprofilaxis fue inadecuada en 248 pacientes (39,4%) (165 tenían riesgo alto pero no recibieron tromboprofilaxis, 1 la recibió teniendo trombopenia grave y 82 tenían riesgo bajo pero recibieron tromboprofilaxis). Las variables asociadas con la inadecuación en pacientes de alto riesgo fueron trauma o cirugía recientes con odds ratio (OR) de OR 5,53 (IC 95%: 1,58-19,34), presencia de factores de riesgo hemorrágico con OR de 2,61 (IC 95%: 1,44-4,73), e infección del tracto urinario con OR de 2,29 (IC 95%: 1,07-4,87) y enfermedad gastrointestinal con OR de 4,30 (IC 95%: 1,71-10,85) como motivos de ingreso. CONCLUSIONES: En los SUH españoles, el uso inadecuado de la tromboprofilaxis farmacológica es elevado. Algunas características clínicas se asocian al uso inadecuado de dicha tromboprofilaxis.

Thromboprophylaxis in oesophageal cancer patients-a study protocol for a randomised, controlled trial (TOP-RCT).

BACKGROUND: The purpose of the study is to examine if prolonged thromboprophylaxis decreases the risk of thrombosis after intended curative surgery for oesophageal cancer. Study results are expected to inform a guideline for thromboprophylaxis after oesophageal cancer surgery. The perspective is to reduce morbidity and mortality in this critically ill patient group. Thrombosis is the second-most common cause of cancer death after the cancer itself. The risk of thrombosis depends on the cancer type, and upper gastrointestinal cancers are considered high risk. This risk is further increased when patients undergo surgery. However, only few studies have investigated the peri- and postoperative coagulation profile in oesophageal cancer patients. Due to this lack of knowledge, prophylaxis is currently restricted to 5000 IU (international units) low-molecular weight heparin daily from surgery until discharge from hospital (approximately 10 days), whereas patients with gastric cancer receive 30 days of treatment. The present study examines whether a 30-day treatment is superior and safe, compared with the current standard treatment. METHODS: The study is a randomised controlled trial. Inclusion is ongoing, and we aim to include 100 patients. Blood samples are drawn before and after surgery, and the coagulation is extensively examined. The primary endpoint is the difference in plasma levels of prothrombin fragment 1 + 2 (F1 + 2) 30 days after surgery between the intervention and the standard group. Furthermore, patients are examined with ultrasound to screen for asymptomatic venous thrombotic events (VTE). Secondary endpoints are incidence of bleeding, symptomatic and asymptomatic VTE and mortality 30 days 1 one year after surgery. DISCUSSION: The study will provide valuable information on the perioperative coagulation profile and VTE risk of oesophageal cancer patients. The study seeks to aid in optimising the postoperative thromboprophylaxis, and the perspective is to reduce morbidity and mortality in this at-risk patient population. TRIALS REGISTRATION: The trial was prospectively registered at the EU Clinical Trials Register with ID 2021-001335-24 on 30 June 2021 and at ClinicalTrials.gov with study identifier NCT05067153.

Rescue therapy of early neurological deterioration in lacunar stroke.

BACKGROUND: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. METHODS: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. RESULTS: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. CONCLUSIONS: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Catheter and Non-Catheter-Related Venous Thromboembolism in Cancer Patients: Survival, Anticoagulation Efficacy, and Safety.

PURPOSE: To investigate the differences in survival after venous thromboembolism (VTE) and anticoagulation efficacy and safety between catheter (CRVTE) and non-catheter-related VTE (NCRVTE) in cancer patients. METHODS: A retrospective research was conducted, and consecutive cancer (digestive, respiratory, genitourinary, blood and lymphatic, and the other cancers) patients with VTE were enrolled. The anticoagulation therapies included low-molecular-weight heparin (LMWH), warfarin, new type of direct oral anticoagulants (NDOACs), LMWH combined with warfarin, and LMWH combined with NDOACs. Data were collected from the electronic medical record database of our hospital and were analyzed accordingly by Kruskal-Wallis H Test, Chi-square test, Fisher's exact test, Logistic regressions, Kaplan-Meier analysis, and Cox regressions. RESULTS: 263 patients were included, median age in years (interquartile range) was 64(56-71) and 60.5% were male. VTE recurrence rate was 16.7% in CRVTE group which was significantly lower than 34.8% in NCRVTE group (P = .032). Heart diseases were independently associated with VTE recurrence (P = .025). Kaplan-Meier survival estimates at 1, 2, and 3 years for CRVTE group were 62.5%, 60.0%, and 47.5%, respectively, compared with 47.9% (P = .130), 38.7% (P = .028), and 30.1% (P = .046), respectively, for NCRVTE group. Cox regression showed surgery (P = .003), anticoagulation therapy types (P = .009), VTE types (P = .006) and cancer types (P = .039) were independent prognostic factors for 3-year survival after VTE. Nonmajor and major bleeding were not significantly different (P = .417). Anticoagulation therapy types were independently associated with the bleeding events (P = .030). CONCLUSIONS: Cancer patients with CRVTE potentially have a better anticoagulation efficacy and survival compared to NCRVTE, and the anticoagulation safety seems no significant difference.

Coronary thrombosis and myocardial ischemia in Kawasaki disease: a case report.

BACKGROUND: Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. CASE PRESENTATION: In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child's thrombus has dissolved, and the myocardial ischemia has resolved. CONCLUSIONS: This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

Anticoagulant Impact on Clinical Outcomes of Pulmonary Embolism Compared With Thrombolytic Therapy; Meta-Analysis.

BACKGROUND: Pulmonary embolism (PE) is a critical condition requiring effective management strategies. Several options are available, including thrombolytic therapy and anticoagulants. OBJECTIVES: To assess the impact of thrombolytic therapy either combined with anticoagulant (AC) or alone versus AC alone on mortality, recurrence, clinical deterioration, bleeding, and hospital stay. METHOD: This study included 25 previously published studies from 1990 to 2023, with a total of 12 836 participants. Dichotomous and continuous analysis models were used to evaluate outcomes, with heterogeneity and publication bias tests applied. A random model was used for data analysis. Several databases were searched for the identification and inclusion of studies, such as Ovid, PubMed, Cochrane Library, Google Scholar, and Embase. RESULTS: For sub-massive PE, CDT plus AC significantly reduced in-hospital, 30-day, and 12-month mortality compared to AC alone, odds ratio (OR) of -0.99 (95% CI [-1.32 to -0.66]), with increased major bleeding risk but no difference in minor bleeding or hospital stay, OR = 0.46, 95% CI [-0.03 to 0.96]). For acute intermediate PE, systemic thrombolytic therapy did not affect all-cause or in-hospital mortality but increased minor bleeding, reduced recurrent PE, and prevented clinical deterioration. The heterogeneity of different models in the current study varied from 0% to 37.9%. CONCLUSION: The addition of CDT to AC improves mortality outcomes for sub-massive PE but raises the risk of major bleeding. Systemic thrombolytic therapy reduces recurrence and clinical decline in acute intermediate PE despite increasing minor bleeding. Individualized patient assessment is essential for optimizing PE management strategies.

Knowledge, attitude and practices of surgeons regarding venous thromboembolism prophylaxis in tertiary healthcare hospitals of the Rawalpindi Districts.

Objective: To assess doctors' knowledge, attitudes and practices regarding venous thromboembolism prophylaxis. METHODS: The cross-sectional study was conducted from April to September 2021 in three public-sector hospitals affiliated with the Rawalpindi Medical University: Holy Family Hospital, Benazir Bhutto Hospital and Rawalpindi District Headquarters Hospital, Rawalpindi, Pakistan, and comprised physicians of either gender who were actively involved in patient care. Data was collected using a predesigned questionnaire regarding venous thromboembolism. Data was analysed using SPSS 25. RESULTS: All the 220(100%) subjects approached responded positively to the study questionnaire. There were 144(65.45%) general surgeons, 50(22.72%) gynaecologists and 26(11.81%) orthopaedic surgeons. Overall, there were 26(11.81%) senior consultants, 65(29.54%) postgraduate residents and 129(58.63%) house officers. There were 150(68.2%) doctors who reported having witnessed deep-vein thrombosis in their patients, and 113(51.4%) had witnessed deaths related to pulmonary embolism. Among the methods employed for DVT diagnosis, the use of clinical criteria was the most common 136(36.1%), while venography was the least common technique used by 8(2.2%). While 210(95.5%) subjects expressed the desire for adopting an institute-wide regimen for venous thromboembolism prophylaxis, only 66(30%) were currently following such a regimen.