Treatment of Portal, Mesenteric, and Splenic Vein Thrombosis with Rivaroxaban: A Pilot, Prospective Cohort Study

Introduction: Anticoagulation plays a crucial role in the treatment of splanchnic vein thrombosis (SVT), including thrombosis of the portal (PVT), mesenteric (MVT) and splenic (SpVT) veins. Rivaroxaban is a potential alternative to heparins and vitamin K antagonists (VKA) in these patients, but data to support its use are scant. Several recent guidelines highlighted the limited evidence available for the use of the direct oral anticoagulants in these patients. In addition, despite anticoagulation, SVT patients carry high risk of recurrent venous thromboembolic events. The aim of this study was to evaluate the safety and efficacy of rivaroxaban for the acute-phase treatment of SVT (first 3 months of treatment). Methods: RIVASVT-100 (NCT02627053) was a prospective cohort study of adult patients with a first episode of symptomatic, objectively diagnosed PVT, MVT or SpVT. Exclusion criteria were known liver cirrhosis, Budd-Chiari syndrome, previous or ongoing variceal bleeding, portal cavernoma, thrombocytopenia, severe renal failure, life expectancy <3 months, concomitant interfering medications, treatment with therapeutic dose of heparins for >7 days, ongoing VKA treatment. Patients received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg once daily for a total of 3 months. Afterwards, the decision to continue any available anticoagulant drug was left to the discretion of the attending physicians. Follow-up was performed at 3 weeks, 2 months, 3 months and 6 months. Primary outcome was the occurrence of ISTH-defined major bleeding events during the 3 months of active treatment and up to 2 days after the end of study treatment. Secondary outcomes included death, clinically relevant non-major bleeding (CRNMB), recurrent SVT or symptomatic venous thromboembolism in other sites. We here report the results of the 3-month follow-up. Results: Between June 2015 and March 2021, 103 patients were enrolled from 18 participating centres. After excluding 3 patients who did not meet the criteria for eligibility, 100 patients were included in the analysis. Mean (SD) age was 54.4 (± 15.5) years; 64% were males. Overall, 74% of patients had PVT, 61% MVT and 48% SpVT; 53% of SVT occurred in multiple sites. The most common risk factors were abdominal inflammation/infection (26%), followed by solid cancer (9%), overt myeloproliferative neoplasms (9%) and oestrogen hormonal therapy (9%), while 43% of cases were unprovoked. The JAK2 V617F mutation was detected in 13 out of 50 tested patients (26%). Rivaroxaban was the sole anticoagulant agent used in 21% of patients, whereas the remaining received a combination of anticoagulants, which included low molecular weight heparin, unfractionated heparin or fondaparinux for a median of 5.0 days before transitioning to rivaroxaban. Three patients were lost to follow-up but known to be alive at the end of the study. At 3-month follow-up, 1 (1.0%) patient died due to a non-SVT related cause. Two patients (2.06%; 95% CI, 0.57-7.21) had major bleeding events (both gastrointestinal), while 3 patients (3.09%) had CRNMB. There were 2 recurrent SVT (2.06%) during rivaroxaban treatment, one of these occurred in a patient with metastatic solid cancer. The 6-month follow-up for the last enrolled patient is ongoing. Conclusions: Rivaroxaban appears to be safe and effective for the acute-phase treatment of SVT in non-cirrhotic patients. Disclosures Beyer-Westendorf: Bayer: Other: Personal fees; Daiichi Sankyo: Other: Personal fees; Pfizer: Other: Personal fees; Portola-Alexion: Other: Personal fees. Carrier: BMS: Honoraria, Research Funding; Leo Pharma: Honoraria, Research Funding; Bayer: Honoraria; Pfizer: Honoraria, Research Funding; Servier: Honoraria; Sanofi: Honoraria. Bertoletti: BMS: Honoraria, Other: Personal Fees; Pfizer: Honoraria, Other: Personal fees; Aspen: Other: Personal Fees; Bayer: Other: Personal Fees; Leo Pharma: Other: Personal Fee. Di Nisio: Bayer, Daiichi Sankyo, BMS-Pfizer, Leo Pharma, and Sanofi: Other: Personal fees. Ageno: Bayer: Research Funding; Bayer, Portola, Janssen, Aspen, Norgine, Sanofi.: Other: Advisory Board. OffLabel Disclosure: The use of rivaroxaban in splanchnic vein thrombosis is off label in most countries.

The Role of Biomarkers in Atherothrombotic Stroke—A Systematic Review

Stroke represents the primary debilitating disease in adults and is the second-highest cause of death worldwide. Atherosclerosis, the most prevalent etiology for vascular conditions, is a continuous process that gradually creates and develops endothelial lesions known as atherosclerotic plaques. These lesions lead to the appearance of atherothrombotic stroke. In the last decades, the role of biological biomarkers has emerged as either diagnostic, prognostic, or therapeutic targets. This article aims to create a list of potential biomarkers related to atherothrombotic stroke by reviewing the currently available literature. We identified 23 biomarkers and assessed their roles as risk factors, detection markers, prognostic predictors, and therapeutic targets. The central aspect of these biomarkers is related to risk stratification, especially for patients who have not yet suffered a stroke. Other valuable data are focused on the predictive capabilities for stroke patients regarding short-term and long-term prognosis, including their influence over the acute phase treatment, such as rt-PA thrombolysis. Although the role of biomarkers is anticipated to be of extreme value in the future, they cannot yet compete with traditional stroke neuroimaging markers but could be used as additional tools for etiological diagnosis.

Useful predictors of Kawasaki disease without complications before initial acute-phase treatment

Kawasaki disease (KD) is an acute febrile systemic vasculitis that primarily affects children younger than 5 years, with coronary artery lesions (CALs) as its severe complications. Intravenous immunoglobulin (IVIG) therapy resistance has been implicated in CAL development, and its known predictors are as follows: Egami score, Kobayashi score, C-reactive protein (CRP), albumin, CRP-to-albumin ratio, and neutrophil-to-lymphocyte ratio (NLR). However, the most useful predictor for IVIG resistance in patients with KD without complications before initial acute-phase treatment remains unclear. Therefore, this study aimed to determine the most useful predictor for IVIG resistance in such patients. This retrospective study included data from 202 patients with KD who underwent acute-phase treatment from January 2009 to March 2021. Among 46 IVIG-resistant patients, 22 patients required rescue therapy (rescued patients), while the remaining 24 received no rescue therapy for resistance and had no CALs. Among the 6 indices, NLR had the highest sensitivity and specificity for the detection of all IVIG-resistant patients and rescued patients (0.724 and 0.728, respectively), and logistic regression analysis showed that the NLR was the sole independent predictor both for the IVIG-resistant patients and for the rescued patients (P < 0.001 and = 0.002, Odds ratio = 5.797 and 5.814, 95% confidence interval = 2.687–12.504 and 1.954–17.299, respectively). NLR was the useful predictor for all IVIG-resistant patients and rescued patients among those with KD without complications before initial acute-phase treatment.

Clinical Features of Kawasaki Disease during SARS-CoV-2 Epidemic: A Single-Center Retrospective Study

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, causing coronavirus disease 2019 (COVID-19), has rapidly spread worldwide. Recently, cases of Kawasaki-like syndrome associated with COVID-19 (MIS‐C/PIMS) have been reported in the USA and Europe. However, the clinical features of Kawasaki disease (KD) in Japan during the SARS-CoV-2 epidemic remain unclear. Therefore, this retrospective study aimed to evaluate the clinical features of KD in our department during the year of the COVID-19 pandemic (2020). Data were obtained from 45 KD patients who underwent acute-phase treatment from January 2018 to December 2020. The patients were divided into three groups: (1) 2018 group, in which 18 patients receiving acute-phase treatment during 2018; (2) 2019 group, in which 17 patients receiving acute-phase treatment during 2019; and (3) 2020 group, in which 10 patients receiving acute-phase treatment during 2020. The comparison of the clinical findings, treatments, and outcomes among the three groups (2018 vs. 2019 vs. 2020 group) revealed a significant difference in the rate of the male gender (72.2% vs. 41.2% vs. 10.0%, P < 0.010), recurrence (0.0% vs. 0.0% vs. 25.0%, P = 0.015), and coronary artery lesions (16.7% vs. 0.0% vs. 0.0%, P = 0.044). No patients required ventilation assistance or inotropic agents and met the diagnostic criteria of MIS‐C/PIMS. Further studies are warranted to elucidate the clinical features of KD during the SARS-CoV-2 epidemic.

Clinical Approach for Patients with Hypertriglyceridemia-Induced Acute Pancreatitis

Hypertriglyceridemia is an important cause of acute pancreatitis, and its symptoms are similar to those of pancreatitis of other causes. Moreover, the possibility of recurrence renders accurate diagnosis critical, and treatment, lifestyle modifications, and education should be performed simultaneously. For treatment during the acute phase of the disease, insulin or plasmapheresis can be combined with modalities used for acute pancreatitis of other causes; fibrate administration is recommended. In addition, hypertriglyceridemia-induced acute pancreatitis requires daily management, such as continuous administration of lipid-lowering agents, and lifestyle modifications are needed even after completion of acute-phase treatment.

Current Real-World Outcomes of Recurrent Kawasaki Disease

Studies have shown that recurrent Kawasaki disease (KD) is a risk factor for resistance to initial intravenous immunoglobulin (IVIG) therapy and development of coronary artery lesions (CALs). However, current real-world outcomes of recurrent KD patients remain unclear. The objective of this retrospective study was to elucidate the outcomes of recurrent KD patients in the era of 2 g/kg IVIG therapy. Data were included from 201 KD patients who underwent acute-phase treatment from January 2009 to September 2020, with 184 (91.5%) receiving 2 g/kg IVIG therapy. The patients were divided into 7 with (recurrent group) and 194 without (nonrecurrent group) recurrent KD. At the first onset, the rates of initial IVIG therapy resistance (28.6% vs. 21.5%, P = 1.000), rescue therapy (14.3% vs. 14.4%, P = 1.000), and CALs (0.0% vs. 2.6%, P = 1.000) were similar between the recurrent and nonrecurrent groups. The rates of initial IVIG therapy resistance (14.3% vs. 21.5%, P = 1.000), rescue therapy (14.3% vs. 14.4%, P = 1.000), and CALs (0.0% vs. 2.6%, P = 1.000) were also similar between the recurrent group at the second onset and the nonrecurrent group at the first onset. KD recurrence may no longer be a risk factor for developing CALs in the era of 2 g/kg IVIG therapy, unless CALs appear at the initial episode.

Outcomes of Kawasaki Disease in Families

An epidemiological study showed that a positive family history of Kawasaki disease (KD) was a risk factor for intravenous immunoglobulin (IVIG) therapy resistance, coronary artery lesions (CALs), and KD recurrence. However, real-world outcomes of KD patients with a family history remain unclear. The objective of this study was to elucidate the outcomes of KD patients with a family history in the era of 2 g/kg IVIG therapy. This retrospective study included data from 201 KD patients who underwent acute-phase treatment from January 2009 to June 2020, with 184 (91.5%) receiving 2 g/kg IVIG therapy. The patients were divided into 13 (family group) with and 188 (nonfamily group) without a family history of KD. The rates of IVIG resistance (8.3% vs. 22.1%, P = 0.315), rescue therapy (8.3% vs. 12.8%, P = 1.000), CALs (0.0% vs. 2.7%, P = 1.000), and KD recurrence (0.0% vs. 3.2%, P = 1.000) were similar between the family and nonfamily groups.

Acute Phase Treatment and Medium-Term Outcomes in Kawasaki Disease

An acute phase treatment for prevention of coronary artery stenosis caused by Kawasaki disease (KD) has not been established. The objective of this study was to clarify the medium-term outcomes of patients who received acute phase treatment in our department. This retrospective study included data from 214 patients with KD who received acute phase treatment from January 2009 to May 2020. A total of 196 (92.1%) received an initial single dose of intravenous immunoglobulin (IVIG) therapy. One patient with status epilepticus at presentation received initial IVIG plus steroid therapy. A total of 17 patients did not receive IVIG. The rate of coronary artery lesions (CALs) 1 month and 1 year after KD onset were 1.9% and 0.9%, respectively. Two patients had CAL 1 year after KD onset. However, no patients had coronary artery stenosis. One patient with a right giant CAL had a medium CAL before initial therapy. During a median follow-up period of 3 years and 4 months, no patients had cardiac events that required therapy.