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.

OBJECTIVE: Tibetan patients undergoing total knee arthroplasty (TKA) have greater fluctuations in perioperative haemoglobin levels and blood hypercoagulability. This study was to investigate whether ethnicity and altitude affect perioperative blood loss and the risk of complications after TKA.
METHODS: We retrospectively enrolled 1,116 patients undergoing TKA for knee osteoarthritis at our hospital between January 2016 and September 2021. We divided patients into four groups according to whether they were of Tibetan or Han ethnicity and whether they lived above or below 2500 m above sea level. Primary outcomes were total, intraoperative, and hidden blood losses, while secondary outcomes were complications and homologous transfusion. Factors associated with increased blood loss were analyzed by multivariate regression.
RESULTS: Total blood loss was higher among patients residing at high altitude compared with lower altitude, whether they were of Han (794.6 mL vs. 667.2 mL, P = 0.020) or Tibetan (904.4 mL vs. 663.8 mL, P < 0.001). Total blood loss was similar between the two ethnic groups at the same altitude. Altitude, but not Tibetan ethnicity, remained associated with increased blood loss after being analyzed by multivariate regression. Complications among the four groups were generally similar, although the frequency of calf muscular venous thrombosis was higher among Tibetan patients, while the frequency of blood transfusion was higher among Han subjects.
CONCLUSIONS: Our findings indicate that residence at high altitude, but not ethnicity, may contribute to increased total blood loss during TKA. Thrombotic complications were more frequent among Tibetan than Han patients.

UNASSIGNED: Type 2 diabetes mellitus (T2DM) presents a thrombotic environment, contributing to diabetic macroangiopathy and microangiopathy. In this study, the regulation of microthrombosis in T2DM was assessed.
UNASSIGNED: Platelets from T2DM patients and healthy controls were analyzed using 4D label-free proteomics and bioinformatics. The role of autophagy in T2DM platelet activation and conversion of platelet-derived angiotensinogen (AGT) was investigated.
UNASSIGNED: The results showed that complement and coagulation cascades, platelet activation, metabolic pathways, endocytosis, autophagy, and other protein digestion-related pathways were enriched. The levels of the key protein AGT were increased in T2DM platelets. Chloroquine (CQ) inhibited ADP- or arachidonic acid (AA)-stimulated platelet aggregation and granule release in a dose-dependent manner, while the effects were less pronounced or even reversed for the proteasome inhibitor PYR-41 and the endocytosis inhibitor Pitstop 2. This indicated the dependence of platelet activation and the accompanying protein digestion on the autophagy-lysosome pathway. Mitophagy occurred in fresh T2DM platelets and ADP- or storage-stimulated platelets; mitophagy was inhibited by CQ. However, the mitophagy inhibitor Mdivi-1 failed to show effects similar to those of CQ. AGT, which could be transformed into ANGII in vitro by ADP-stimulated platelets, was upregulated in T2DM platelets and in MEG-01 cell-derived platelets cultured in a high-glucose medium. Finally, microthrombosis was alleviated as indicated by a reduction in the levels of red blood cells in the liver, spleen, heart, and kidney tissues of db/db mice treated with CQ or valsartan.
UNASSIGNED: In platelets, macroautophagy promotes protein digestion, subsequently facilitating platelet activation, ANGII-mediated vasoconstriction, and microthrombosis. Our results suggested that lysosome is a promising therapeutic target for antithrombotic treatment in T2DM.

UNASSIGNED: Early thromboprophylaxis does not prevent hospital admissions and death among outpatients with symptomatic COVID-19. Its impact on long-term outcomes, including long COVID symptoms and performance status, is unknown.
UNASSIGNED: To assess the long-term effects of thromboprophylaxis given at the time of acute COVID-19 in outpatients.
UNASSIGNED: The OVID (enoxaparin for outpatients with COVID-19) trial randomized outpatients older than 50 years with acute COVID-19 to receive either subcutaneous enoxaparin 40 mg once daily for 14 days or standard of care (no thromboprophylaxis). In this follow-up study, we assessed the 2-year outcomes, including all-cause hospitalization and death, cardiovascular events, long COVID symptoms, and functional limitations based on the Post-COVID-19 Functional Status (PCFS) scale and EuroQol-5 Dimensions-5 Levels scale.
UNASSIGNED: Of 469 potentially eligible patients, 468 survived, of whom 439 (mean age 59 years; 54% men) participated in the Post-OVID study. There was no difference in terms of hospitalization and death (8.3% in the treatment group vs 10% in controls; relative risk, 0.83; 95% CI, 0.5-1.5) and of cardiovascular events between groups. The risk of presenting with long COVID symptoms was similar in the 2 groups (44% in the treatment group vs 47% in the standard of care group), with no difference between groups also concerning individual symptoms. A PCFS grade of 1 to 3, indicating light-to-moderate functional limitation, was recorded in 15% of patients in each group (odds ratio, 0.98; 95% CI, 0.6-1.7). No patients reported severe limitations (PCFS grade 4). Median EuroQol visual analog scale score was 85 on 100 points (IQR, 80-90 for the standard of care group and 75-90 for the enoxaparin group).
UNASSIGNED: Early thromboprophylaxis does not improve long-term, 2-year clinical and functional outcomes among symptomatic ambulatory patients with acute COVID-19.

UNASSIGNED: Platelet function is driven by the expression of specialized surface markers. The concept of distinct circulating subpopulations of platelets has emerged in recent years, but their exact nature remains debatable.
UNASSIGNED: To design a spectral flow cytometry-based phenotyping workflow to provide a more comprehensive characterization, at a global and individual level, of surface markers in resting and activated healthy platelets, and to apply this workflow to investigate how responses differ according to platelet age.
UNASSIGNED: A 14-marker flow cytometry panel was developed and applied to vehicle- or agonist-stimulated platelet-rich plasma and whole blood samples obtained from healthy volunteers, or to platelets sorted according to SYTO-13 (Thermo Fisher Scientific) staining intensity as an indicator of platelet age. Data were analyzed using both user-led and independent approaches incorporating novel machine learning-based algorithms.
UNASSIGNED: The assay detected differences in marker expression in healthy platelets, at rest and on agonist activation, in both platelet-rich plasma and whole blood samples, that are consistent with the literature. Machine learning identified stimulated populations of platelets with high accuracy (>80%). Similarly, machine learning differentiation between young and old platelet populations achieved 76% accuracy, primarily weighted by forward scatter, cluster of differentiation (CD) 41, side scatter, glycoprotein VI, CD61, and CD42b expression patterns.
UNASSIGNED: Our approach provides a powerful phenotypic assay coupled with robust bioinformatic and machine learning workflows for deep analysis of platelet subpopulations. Cleavable receptors, glycoprotein VI and CD42b, contribute to defining shared and unique subpopulations. This adoptable, low-volume approach will be valuable in deep characterization of platelets in disease.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) that predispose individuals to thrombotic events and pregnancy-related complications. APS can occur as a primary condition or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). Catastrophic APS (CAPS) is a rare, severe variant of APS, marked by rapid-onset, widespread thrombosis leading to multi-organ failure, often triggered by infections, surgical procedures, or cessation of anticoagulation therapy. Both APS and CAPS present significant clinical challenges due to their potential for severe morbidity and mortality. This comprehensive review aims to provide a detailed overview of the pathogenesis, clinical features, diagnostic criteria, and management strategies for APS and CAPS. The review highlights the immunological mechanisms underlying APS, including the role of aPLs, complement system activation, and endothelial cell dysfunction in developing thrombosis. It also outlines the clinical manifestations of APS, such as venous and arterial thrombosis, pregnancy morbidity, and neurological symptoms, along with the diagnostic criteria based on clinical and laboratory findings. The review delves into its pathogenesis, clinical presentation, and diagnostic challenges in the context of CAPS, emphasizing the need for immediate and intensive therapy to manage this life-threatening condition. Current management strategies for APS, including anticoagulant therapy, immunomodulatory treatments, and specific interventions for pregnancy-related complications, are discussed. The review highlights the importance of a multidisciplinary approach for CAPS, combining anticoagulation, high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin. The review also addresses the prognosis and long-term outcomes for patients with APS and CAPS, underlining the necessity for ongoing monitoring and follow-up to prevent recurrent thrombotic events and manage chronic complications. Finally, future directions in research are explored, focusing on emerging therapies, biomarkers for early diagnosis, and the need for clinical trials to advance the understanding and treatment of these complex syndromes. By enhancing the understanding of APS and CAPS, this review aims to improve diagnosis, treatment, and patient care, ultimately leading to better health outcomes for those affected by these conditions.

Skull base osteomyelitis (SBO) is a severe and uncommon infection that typically affects the skull base and may arise from undiagnosed otogenic or sinonasal infection. This case describes a rare presentation of SBO, accompanied by thrombosis of the bilateral internal carotid artery with neurological deficits in a resource-limited environment, illustrating diagnostic and management dilemmas. A male patient aged 40 years with poorly controlled type 2 diabetes presented with sudden onset loss of consciousness and worsening right-sided weakness. MRI studies revealed SBO with cerebral involvement with thrombosis in major cerebral arteries and multiple brain infarcts. After receiving broad-spectrum antibiotics and supportive care shortly after admission, the patient developed septic shock and died two days after admission. The fast course of the disease in this case shows how severe SBO and its complications may be, calling for early diagnosis and intensive management of SBO, especially in diabetic patients. The fact that Staphylococcus epidermidis was established as a causative agent of disease in the absence of artificial heart valves or joints, it is becoming clear that there is a need to increase awareness of such rare pathogens, and probably new strategies for handling such infections should be developed. Additional research is required to elucidate the precise role of the pathogen and refine treatment approaches, especially for low-resource healthcare systems.

UNASSIGNED: Various degrees of thrombosis have been reported in patients with giant aneurysms. However, small, unruptured aneurysms rarely resolve spontaneously. Herein, we report a case of a small unruptured aneurysm in the clinoid segment (C3) of the left internal carotid artery (ICA) that showed almost complete occlusion at the 1-year follow-up.
UNASSIGNED: A 66-year-old woman developed a subarachnoid hemorrhage on the left side of the perimesencephalic cistern. Cerebral angiography performed on admission revealed no evidence of hemorrhage. Subsequent cerebral angiography on day 12 revealed a dissecting aneurysm on a branch of the superior cerebellar artery (SCA), and the patient underwent parental artery occlusion with 25% n-butyl-2-cyanoacrylate. The postoperative course was uneventful, and the patient was discharged on day 22 with a modified Rankin Scale score of 1. The 1 year follow-up cerebral angiogram demonstrated that the dissecting aneurysm in the SCA branch remained occluded. Notably, a small 2-mm unruptured aneurysm in the clinoid segment (C3) of the left ICA, which was present at the onset of subarachnoid hemorrhage, was almost completely occluded without intervention. Magnetic resonance angiography 1 year after spontaneous resolution of the aneurysm showed no apparent recurrence.
UNASSIGNED: This case highlights that even small, unruptured aneurysms can develop spontaneous occlusions.

Evaluation of treatment outcomes in patients supported by temporary mechanical circulatory support (tMCS) currently relies mainly on mortality, which may not sufficiently address other patient benefits or harms. Bleeding and thrombosis are major contributors to mortality. Still, current bleeding scores are not designed for critically ill patients undergoing tMCS, only consider selected populations, and do not account for the high heterogeneity among bleeding and thrombotic adverse events. To improve clinical management, a group of European experts has proposed a revised scoring system based on the MOMENTUM 3 Hemocompatibility Score and the Society of Cardiac Angiography and Interventions (SCAI)classification of cardiogenic shock. The new system termed the Scoring Haemostasis Events and Assessment for Risk (SHEAR) score, is divided into a baseline characterization stage and four escalating scoring stages encompassing all aspects of clinical relevance. This report summarizes the literature on hemocompatibility-related adverse events associated with tMCS, including bleeding, stroke, vascular access complications, hemolysis, thrombosis, and device failure. The SHEAR score provides a simple and rapid bedside scoring system aiming to provide a univocal tool to increase physician awareness of hemocompatibility complications at baseline and beyond, improve clinical research, and enable the capture of device-related complications that will inform relevant outcomes beyond mortality.

Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.