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Background: Variations in light exposure are associated with changes in inflammation and coagulation. The impact of light spectra on venous thrombosis (VT) and arterial thrombosis is largely unexplored., Objectives: To investigate the impact of altering light spectrum on platelet function in thrombosis., Methods: Wild-type C57BL/6J mice were exposed to ambient (mice white , 400 lux), blue (mice blue , 442 nm, 1400 lux), or red light (mice red , 617 nm, 1400 lux) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, platelet aggregation, activation, transcriptomic, and metabolomic changes were measured. The ability of released products of platelet activation to induce thrombosis-generating neutrophil extracellular trap formation was quantified. Subsequent thrombosis was measured using murine models of VT and stroke. To translate our findings to human patients, light-filtering cataract patients were evaluated over an 8-year period for rate of venous thromboembolism with multivariable logistic regression clustered by hospital., Results: Exposure to long-wavelength red light resulted in reduced platelet aggregation and activation. RNA-seq analysis demonstrated no significant transcriptomic changes between mice red and mice white . However, there were global metabolomic changes in platelets from mice red compared with mice white . Releasate from activated platelets resulted in reduced neutrophil extracellular trap formation. Mice red also had reduced VT weight and brain infarct size following stroke. On subgroup analysis of cataract patients, patients with a history of cancer had a lower lifetime risk of venous thromboembolism after implantation with lenses that filter low-wavelength light., Conclusion: Light therapy may be a promising approach to thrombus prophylaxis by specifically targeting the intersection between innate immune function and coagulation., Competing Interests: Declaration of competing interests E.A.A.: nothing to disclose; F.D.: nothing to disclose; C.K.: nothing to disclose; A.A.: nothing to disclose; E.P.M.: nothing to disclose; M.D.: nothing to disclose; G.K.A.: nothing to disclose; M.Z.: nothing to disclose; P.L.: nothing to disclose; M.O.: nothing to disclose; K.W.: nothing to disclose; R.I.M.-A.: nothing to disclose; K.T.: nothing to disclose; S.S.: nothing to disclose; S.M.S.: nothing to disclose; R.A.S.: nothing to disclose; R.A.C.: nothing to disclose; M.R.R.: nothing to disclose; M.D.N.: Chief Medical Officer, Haima Therapeutics. Research funding: NIGMS, NHLBI, DoD. Honoraria for consulting: Haemonetics, Takeda, CSL Behring. Research funding: Janssen, Haemonetics, Instrumentation Laboratories, Alexion Pharmaceuticals., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the clinical, diagnostic, and therapeutic profile of patients with left intraventricular thrombus (LVT) in three high-complexity centers in Medellín, Colombia, between January 2000 and January 2022., Materials and Methods: This was an observational and cross-sectional study that included 307 patients with LVT. Hospital records were analyzed to identify the clinical and therapeutic profile, and thrombus resolution and systemic embolism were evaluated. Univariate and bivariate analyses were performed using Fisher's exact test and a logistic regression model., Results: The prevalence of LVT was 9.75%. In 85% of cases, LVT was diagnosed using transthoracic echocardiography; 75.9% of patients were male, and the median age was 62 years. The most frequent comorbidities were heart failure (95.77%) and hypertension (69.7%).LVT occurred in 27% of cases in the context of acute coronary syndrome (ACS). Low molecular weight heparin (LMWH) was administered in 78.5% of cases, and warfarin was the most commonly used anticoagulant (82.7%). Hemorrhagic complications occurred in 19.2%, mainly gastrointestinal, and 35% of patients achieved thrombus resolution. Systemic embolism developed in 30% of cases, primarily affecting the central nervous system. Overall mortality was 15%., Conclusions: The prevalence of LVT was 9.75%. Warfarin remains the standard treatment, although alternative therapies are used in special cases. Apical dysfunction was associated with systemic embolism., Competing Interests: Conflictos de interés: Ninguno por declarar

Cardiovascular disease (CVD) remains a major health burden despite significant therapeutic advances accomplished over the last decades. It is widely and increasingly recognized that systemic inflammation not only represents a major cardiovascular risk and prognostic factor but also plays key pathogenic roles in CVD development and progression. Despite compelling preclinical evidence suggesting large potential of anti-inflammatory pharmacological interventions across numerous CVDs, clinical translation remains incomplete, mainly due to (1) yet undefined molecular signaling; (2) challenges of safety and efficacy profile of anti-inflammatory drugs; and (3) difficulties in identifying optimal patient candidates and responders to anti-inflammatory therapeutics, as well as optimal therapeutic windows. Randomized controlled trials demonstrated the safety/efficacy of canakinumab and colchicine in secondary cardiovascular prevention, providing confirmation for the involvement of a specific inflammatory pathway (NLRP3 [NACHT, LRR, and PYD domain-containing protein 3] inflammasome/IL [interleukin]-1β) in atherosclerotic CVD. Colchicine was recently approved by the US Food and Drug Administration for this indication. Diverse anti-inflammatory drugs targeting distinct inflammatory pathways are widely used for the management of other CVDs including myocarditis and pericarditis. Ongoing research efforts are directed to implementing anti-inflammatory therapeutic strategies across a growing number of CVDs, through repurposing of available anti-inflammatory drugs and development of novel anti-inflammatory compounds, which are herein concisely discussed. This review also summarizes the main characteristics and findings of completed and upcoming randomized controlled trials directly targeting inflammation in CVDs, and discusses major challenges and future perspectives in the exciting and constantly expanding landscape of cardioimmunology., Competing Interests: N. Potere received training fellowships and travel grants from the International Society on Thrombosis and Società Italiana per lo Studio dell’Emostasi e della Trombosi, and research grants, paid to his institution, from the International Society on Thrombosis and Haemostasis and the International Network of Venous Thromboembolism Clinical Research Networks. A. Abbate received consulting fees from Cardiol Therapeutics, Kiniksa Pharmaceuticals, Monte Rosa Therapeutics, and Novo Nordisk.

Background: Patients requiring lower limb immobilization after injury have an increased venous thromboembolism (VTE) risk. The extent of this risk in published studies varies. The Thrombosis Risk Prediction for Patients with Cast Immobilization (TRiP[cast]) model quantifies VTE risk using clinical parameters. Delineating low-risk from high-risk patients remains challenging., Objectives: Determine the 90-day incidence of symptomatic VTE following temporary lower limb immobilization after injury in an unselected cohort. Prospectively collect data on risk factors, including those incorporated in the TRiP(cast) model, to calculate TRiP(cast) scores., Methods: TILLIRI is a multicenter, pragmatic, observational cohort study including 10 sites within the Irish Network for VTE Research. Patients aged ≥18 years with an immobilized injured lower limb were included. Twenty-one clinical variables were collected at presentation. Thromboprophylaxis was prescribed according to clinical gestalt. Patients were followed up at 90 days to determine if VTE occurred., Results: Between November 2018 and February 2023, 1242 patients were recruited. Follow-up was complete for 1199 patients (96.5%). Forty-three patients (3.5%) were lost to follow-up. Forty-four (3.6%) patients and 125 (10%) patients were prescribed anticoagulation and aspirin, respectively. Twenty-one patients receiving regular anticoagulation were removed from the final analysis. VTE incidence at 90-day follow-up was 6/1179 (0.51%; 95% CI, 0.1%-0.92%). TRiP(cast) scores were calculated for 1176/1221 patients. A total of 846 patients (71.9%) had a TRiP(cast) score < 7, received no prophylaxis, and had no VTE., Conclusion: TILLIRI indicates a low VTE incidence in an unselected cohort following lower limb immobilization with low rates of prophylaxis use. The proportion of patients with low TRiP(cast) scores and no symptomatic VTE suggests that thromboprophylaxis may be avoided in patients with TRiP(cast) scores < 7 with a low 90-day VTE risk., Competing Interests: Declaration of Competing Interests T.P.O.H., B.A.B., B.N., S.C., T.B., A.W., J.O'D., S.O'R., N.O'C., M.W., and D.O.K. declare no conflicts of interest. F.N.Á. reports a relationship with Bayer, Daiichi-Sankyo, and Sanofi that includes research funding (investigator-initiated studies [IIS]: paid to the university)., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain., Methods: We included all cases of venous or arterial thrombosis with thrombocytopenia following administration of adenoviral vector vaccines (AstraZeneca or Janssen) against COVID-19 disease between 1 February and 26 September 2021. We describe the crude rate and the standardised morbidity ratio. We assessed the predictors of mortality., Results: Sixty-one cases were reported and 45 fulfilled eligibility criteria; 82% of patients were women. The crude TTS rate was 4 cases/1 000 000 doses, and 14-15 cases/1 000 000 doses among patients aged 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 times higher than that expected in patients younger than 49 years. Symptoms started a median (quartiles 1 and 3 [Q 1 -Q 3 ]) of 10 (7-14) days after vaccination. Eighty percent (95% confidence interval [CI]: 65%-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (49%-78%) had D-dimer levels > 2000 ng/mL. Patients had thromboses affecting multiple locations in 36% of cases and fatal outcomea in 24%. Platelet nadir < 50 000/μL (odds ratio [OR]: 7.4; 95% CI: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; 95% CI: 1.3-47.0) were associated with fatal outcomes., Conclusion: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or elevated D-dimer levels., (Copyright © 2022 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Factor XI/XIa (FXI/XIa) has emerged as a potential target for antithrombotic therapy, driven by preclinical evidence showing the role of FXI/XIa inhibition for preventing thrombosis without impeding hemostasis. This is particularly promising for patients at high risk of both thromboembolic events and bleeding, such as patients with end-stage kidney disease (ESKD) on hemodialysis (HD)., Methods: We systematically searched Embase, MEDLINE, and ClinicalTrials.gov for randomized controlled trials evaluating FXI/XIa inhibitors in patients with ESKD on HD, without restricting inclusion to specific comparators or indications. Interventional treatment arms were pooled, and study results were synthesized by fitting random-effects models, calculating odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Five phases 2 studies encompassing 1270 participants were identified, investigating gruticibart, IONIS-FXI Rx, osocimab, or fesomersen in the general HD population and using placebo as a comparator. Four studies were fully published and included in the meta-analysis. Use of FXI/XIa inhibitors was associated with an OR of 0.80 (95% CI = 0.47-1.35) for clinically relevant bleeding, 0.51 (95% CI = 0.21-1.28) for major bleeding, and 0.90 (95% CI = 0.49-1.68) for clinically relevant nonmajor bleeding. The ORs for thromboembolic events and all-cause mortality were 0.66 (95% CI = 0.28-1.56) and 0.46 (95% CI = 0.15-1.40), respectively., Conclusion: Currently available evidence does not indicate a significantly increased bleeding risk of FXI/XIa inhibitors in patients with ESKD on HD compared to placebo. Their efficacy and their association with all-cause mortality need to be investigated in sufficiently powered, randomized controlled phase 3 trials., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

We report an elderly male patient with frequent episodes of dizziness due to a complete atrioventricular block who underwent temporary pacemaker insertion in a local hospital. After the implantation of a permanent pacemaker and removal of the temporary pacemaker lead, the patient developed sudden neurological symptoms, upon which an acute cerebellar infarction was diagnosed via head CT. We will discuss the adequacy of the periprocedural administration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Chen, Zhu, Liu, Li, Chang and Li.)

Background: New-onset postoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG) surgery, increasing the risk of embolism and stroke. There is a lack of information on the use of anticoagulants in this context. The choice between Warfarin and Direct oral anticoagulants (DOACs) also is not well-established. This randomized study aimed to compare the feasibility and safety of Warfarin and Rivaroxaban in preventing thrombotic events in POAF patients after isolated CABG., Methods: A total of 66 patients were randomized parallelly with 1:1 allocation to receive either Rivaroxaban (n = 34) or Warfarin (n = 32). Major bleeding events within 30 days after discharge were the primary outcome. Secondary outcomes included minor bleeding events and thrombotic episodes. Clinical characteristics, medication regimens, and left atrial diameter were assessed. Statistical analyses were performed using appropriate tests., Results: No thrombotic episodes were observed in either treatment arm. No major bleeding events occurred in either group. Four minor bleeding events were reported, with no significant difference between the treatment groups (P = 0.6). Patients with atrial fibrillation had significantly larger left atrial diameters compared to those with normal sinus rhythm (40.5 vs. 37.8 mm, P = 0.01)., Conclusions: This pilot study suggests that Warfarin and Rivaroxaban are both safe and effective for preventing thrombotic episodes in POAF patients after isolated CABG. No significant differences in major bleeding events were observed between the two anticoagulants. These findings may support the preference for DOACs like Rivaroxaban due to their convenience and easier maintenance., Trial Registration: Number IRCT20200304046696N1, Date 18/03/2020 https//irct.behdasht.gov.ir/ ., (© 2024. The Author(s).)

Background: The interrelation between COVID-19 and various cardiovascular and metabolic disorders has been a critical area of study. There is a growing need to understand how comorbidities such as cardiovascular diseases (CVDs) and metabolic disorders affect the risk and severity of COVID-19., Objective: The objective of this study is to systematically analyze the association between COVID-19 and cardiovascular and metabolic disorders. The focus is on comorbidity, examining the roles of CVDs such as embolism, thrombosis, hypertension, and heart failure, as well as metabolic disorders such as disorders of glucose and iron metabolism., Methods: Our study involved a systematic search in PubMed for literature published from 2000 to 2022. We established 2 databases: one for COVID-19-related articles and another for CVD-related articles, ensuring all were peer-reviewed. In terms of data analysis, statistical methods were applied to compare the frequency and relevance of MeSH (Medical Subject Headings) terms between the 2 databases. This involved analyzing the differences and ratios in the usage of these terms and employing statistical tests to determine their significance in relation to key CVDs within the COVID-19 research context., Results: The study revealed that "Cardiovascular Diseases" and "Nutritional and Metabolic Diseases" were highly relevant as level 1 Medical Subject Headings descriptors in COVID-19 comorbidity research. Detailed analysis at level 2 and level 3 showed "Vascular Disease" and "Heart Disease" as prominent descriptors under CVDs. Significantly, "Glucose Metabolism Disorders" were frequently associated with COVID-19 comorbidities such as embolism, thrombosis, and heart failure. Furthermore, iron deficiency (ID) was notably different in its occurrence between COVID-19 and CVD articles, underlining its significance in the context of COVID-19 comorbidities. Statistical analysis underscored these differences, highlighting the importance of both glucose and iron metabolism disorders in COVID-19 research., Conclusions: This work lays the foundation for future research that utilizes a knowledge-based approach to elucidate the intricate relationships between these conditions, aiming to develop more effective health care strategies and interventions in the face of ongoing pandemic challenges., (©Rene Markovič, Luka Ternar, Tim Trstenjak, Marko Marhl, Vladimir Grubelnik. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 24.07.2024.)

Patients with cancer are at increased risk of arterial thromboembolic disease due to the presence of risk factors common to both the development of cancer and arterial thrombosis, the cancer itself, and the treatments provided to treat cancer. We review here the epidemiology and pathophysiology of arterial thromboembolic disease in cancer, along with its prevention and treatment strategies. We also propose a generalized approach for the management of arterial thromboembolic disease in this patient population.

Background: We conducted a single-center, retrospective comparison of adult patients who received warfarin and ASA or warfarin alone after HeartMate 3 (HM3) LVAD placement., Methods: The primary outcome was a composite of bleeding and thrombotic events., Results: Of 81 patients, 53 patients received warfarin and ASA, and 28 patients received warfarin alone. A primary outcome event occurred in 22 of 53 patients (41.4%) in the warfarin and ASA group and in 2 of 28 patients (7.1%) in the warfarin alone group (p = 0.0533). The odds of a bleeding event occurring were higher in the warfarin and ASA group (32.1% vs. 7.1%, p = 0.01309). The odds of a thrombotic event occurring were not significantly different between the warfarin and ASA group and the warfarin alone group (9.4% vs. 0%, respectively, p = 0.1582)., Conclusion: The complete omission of ASA from the antithrombotic regimen of patients with a HM3 LVAD was associated with less bleeding events without an increase in thrombotic events., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

The foramen ovale serves as an opening between the right and left atria at the site of the fossa ovalis in the fetus during uterine life. During fetal life, it makes it possible for venous blood from the maternal placenta with oxygen and nutrients to bypass the immature fetal lung and get transported to the left side of the heart and onto the systemic circulation. This hole from the right to the left atrium is usually occluded at the time of birth or shortly after birth, due to increased pressures in the left-sided cardiac cavities associated with normal breathing during delivery or shortly afterwards. If the foramen ovale remains open and fails to fuse beyond the first year of life, it is known as a patent foramen ovale (PFO). PFO occurs when, during fetal life, the septum primum and secundum, which develop and overlap normally, fail to fuse at birth. This results in the persistence of communication between the right and left atria. Paradoxical embolism from the right to the left side of the heart can occur through a PFO, causing a cryptogenic stroke or embolic stroke of an undetermined source in an otherwise healthy adult. There was a debate on the long-term benefits of closure. However, data from the randomized evaluation of the recurrent stroke comparing PFO closure to established current standard of care treatment (RESPECT) trial and two randomized trials (patent foramen ovale closure or anticoagulants versus antiplatelet therapy to prevent stroke recurrence (CLOSE) and reduction by dutasteride of prostate cancer events (REDUCE)) have clarified that there is a benefit to closure. In this case report, we describe a patient who presented with cryptogenic stroke, the investigations, imaging modalities for diagnosis of PFO, and procedure for closure. We also describe long-term outcomes and management following closure., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ukponmwan et al.)

Background: Heparin-induced thrombocytopenia (HIT) is a major concern for all individuals that undergo cardiac bypass surgeries or require prolonged heparin exposure. HIT is a life- and limb-threatening adverse drug reaction with an immune response following the formation of ultra-large immune complexes that drive platelet activation through the receptor FcγRIIA. Thrombotic events remain high following the standard of care treatment with anticoagulants, while increasing risk of bleeding complications. This study sought to investigate a novel approach to treatment of HIT. Recent reports demonstrate increased procoagulant activity in HIT; however, these reports required analysis ex vivo, and relevance in vivo remains unclear., Methods: Using human and mouse model systems, we investigated the cooperativity of PARs (protease-activated receptors) and FcγRIIA in HIT. We challenged humanized FcγRIIA transgenic mice with or without endogenous mouse Par4 (denoted as IIA-Par4 +/+ or IIA-Par4 - /- , respectively) with a well-established model IgG immune complex (anti [α]-CD9). Furthermore, we assessed the procoagulant phenotype and efficacy to treat HIT utilizing inhibitor of 12-LOX (12[S]-lipoxygenase), VLX-1005, previously reported to decrease platelet activation downstream of FcγRIIA and PAR4, using the triple allele HIT mouse model., Results: IIA-Par4 +/+ mice given αCD9 were severely thrombocytopenic, with extensive platelet-fibrin deposition in the lung. In contrast, IIA-Par4 -/- mice had negligible thrombocytopenia or pulmonary platelet-fibrin thrombi. We observed that pharmacological inhibition of 12-LOX resulted in a significant reduction in both platelet procoagulant phenotype ex vivo, and thrombocytopenia and thrombosis in our humanized mouse model of HIT in vivo., Conclusions: These data demonstrate for the first time the need for dual platelet receptor (PAR and FcγRIIA) stimulation for fibrin formation in HIT in vivo. These results extend our understanding of HIT pathophysiology and provide a scientific rationale for targeting the procoagulant phenotype as a possible therapeutic strategy in HIT., Competing Interests: Disclosures S.E. McKenzie and M. Holinstat are on the scientific advisory board for Veralox Therapeutics. M.B. Boxer and D.J. Maloney are employees of Veralox Therapeutics. The other authors report no conflicts.

The perioperative management of patients medicated with antithrombotic agents who require elective spinal surgery is extremely challenging because of the increased risk of surgical bleeding and the concurrent need to minimize the thromboembolic risk. The aims of the present systematic review are to: (1) identify clinical practice guidelines (CPGs) and recommendations (CPRs) on this topic and (2) assess their methodological quality and reporting clarity. An electronic systematic search of the English Medical Literature up to January 31, 2021 was conducted using PubMed, Google Scholar, and Scopus. Two raters assessed the methodological quality and reporting clarity of the gathered CPGs and CPRs using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. The agreement between the two raters was assessed using Cohen's kappa. Of the initially gathered 38 CPGs and CPRs, 16 fulfilled our eligibility criteria and were evaluated using the AGREE II instrument. The reports published by "Narouze 2018" and "Fleisher 2014" were scored as being of "high-quality" and having an adequate interrater agreement (Cohen's kappa ≥0.60). Overall, the AGREE II domains of "clarity of presentation" and "scope and purpose" yielded the highest scores (100%), whereas the domain "stakeholder involvement" scored the lowest score (48.5%). The perioperative management of antiplatelet and anticoagulant agents in elective spine surgery may be challenging. Because of the lack of high-quality data in this field, uncertainty remains regarding the optimal practices to balance the risk of thromboembolism against that of bleeding.

Venous thromboembolism (VTE) remains a major health burden despite anticoagulation advances, suggesting incomplete management of pathogenic mechanisms. The NLRP3 (NACHT-, LRR- and pyrin domain-containing protein 3) inflammasome, interleukin (IL)-1, and pyroptosis are emerging contributors to the inflammatory pathogenesis of VTE. Inflammasome pathway activation occurs in patients with VTE. In preclinical models, inflammasome signaling blockade reduces venous thrombogenesis and vascular injury, suggesting that this therapeutic approach may potentially maximize anticoagulation benefits, protecting from VTE occurrence, recurrence, and ensuing post-thrombotic syndrome. The nonselective NLRP3 inhibitor colchicine and the anti-IL-1β agent canakinumab reduce atherothrombosis without increasing bleeding. Rosuvastatin reduces primary venous thrombotic events at least in part through lipid-lowering independent mechanisms, paving the way to targeted anti-inflammatory strategies in VTE. This review outlines recent preclinical and clinical evidence supporting a role for inflammasome pathway activation in venous thrombosis, and discusses the, yet unexplored, therapeutic potential of modulating inflammasome signaling to prevent and manage VTE., Competing Interests: Dr Potere has received a training fellowship from the International Society on Thrombosis and Haemostasis, and research grant funding from the International Network of VENous Thromboembolism Clinical Research Networks (INVENT). Dr Abbate has received research grant funding and has served as a paid scientific advisor to Implicit Biosciences, Kiniksa, Lilly, Merck, Novartis, Novo Nordisk, Olatec, R-Pharm, Serpin Pharma, and Swedish Orphan Biovitrum. Dr Kanthi has received research grant funding from the Intramural Research Program of the National Heart, Lung and Blood Institute, National Institutes of Health, and the Lasker Foundation, and is an inventor on a patent application by the University of Michigan on the use of biogases in vascular disease (US20180369278A1). Dr Carrier has received research funding from Leo Pharma, Bristol Myers Squibb, and Pfizer, and honoraria from Bayer, Bristol Myers Squibb, Sanofi, Servier, Pfizer, and Leo Pharma. Dr Toldo and Dr Abbate are supported by a National Institutes of Health grant (R01HL150115). Dr Toldo has served as a paid scientific advisor to Cardiol Therapeutics and Novo Nordisk, and received research grant funding from Kiniksa, Olatec, Serpin Pharma, and Cardiol Therapeutics. Dr Di Nisio has received personal fees from Bayer, Daiichi Sankyo, Sanofi, Bristol Myers Squibb, Pfizer, Leo Pharma, and Viatris. Dr Porreca has reported that he has no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Persistent sciatic artery (PSA) is a rare congenital anomaly considered an embryologic remnant of the internal iliac artery. Traditionally, the classification systems categorized PSA based on the completeness of PSA and superficial femoral artery (SFA) alongside the origin of PSA. The most common class has been known as type 2a in Pillet-Gauffre classification, meaning complete PSA with incomplete SFA. The mainstay of these patients with limb ischemia has been surgical bypass alongside excision or ligation of PSA aneurysm if present. However, the current PSA classification system does not account for collateral blood flow. Herein, we described two cases of type 2a PSA with distal embolization and explored therapeutic choices for PSA based on collateral presence. The first patient was treated with thromboembolectomy and patch angioplasty, and the second with conservative management. Despite distal embolization in both patients, bypass surgery was avoided, and distal circulation was maintained via collaterals from deep and superficial femoral arteries without increased risk of recurrent embolization. Thus, carefully examining collateral circulation and customized strategy is essential for managing PSA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yun, Kim, Hwang and Kim.)

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). The optimal heparin regimen remains unknown and should balance thromboembolic and bleeding risks. The aim of this study was to evaluate the efficacy and safety of standard or higher heparin regimens for the prevention of VTE in patients hospitalized due to COVID-19. We performed a systematic literature search; studies reporting on hospitalized patients with COVID-19 who received standard heparin prophylaxis vs. high (intermediate or therapeutic) heparin regimens were included if outcome events were reported by treatment group and more than 10 patients were included. Primary study outcome was in-hospital VTE. Secondary study outcomes were major bleeding (MB), all-cause death, fatal bleeding and fatal pulmonary embolism. Overall, 33 studies (11,387 patients) were included. Venous thromboembolic events occurred in 5.2% and in 8.2% of patients who received heparin prophylaxis with at high-dose or standard-dose, respectively (RR 0.71, 95% CI 0.55-0.90, I2 48.8%). MB was significantly higher in patients who received high- compared to the standard-dose (4.2% vs 2.2%, RR 1.94, 95% CI 1.47-2.56, I2 18.1%). Sub-analyses showed a slight benefit associated with high-dose heparin in patients admitted to non-intensive care unit (ICU) but not in those to ICU. No significant differences were observed for mortality outcomes. Heparin prophylaxis at high-dose reduces the risk of VTE, but increased the risk of MB compared to the standard-dose. No clinical benefit for heparin high-dose was observed for ICU setting, but its role in the non-ICU deserves further evaluation. PROSPERO registration number: CRD42021252550., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Purpose: JAK-inhibitors (JAK-i) might be associated with venous (VTE) and arterial thromboembolic events (ATE). To evaluate the association between JAK-i and the risk of VTE and ATE., Methods: A self-controlled case series was performed using data from the nationwide French healthcare insurance system database SNDS. We included all patients treated with JAK-i (baricitinib or tofacitinib), and having presented at least one VTE or ATE between November 1, 2017 and June 30, 2019. Associations were estimated using the incident rate ratio (IRR). Two post-exposure periods (until day 30 and until day 60) were individualized., Results: Among 5870 patients with JAK-i dispensing, 92 had an incident VTE or ATE within the study period. Their median age at JAK-i initiation was 65.7 years [IQR: 56.1-75.8] and 65.2% were female (n = 60). Before event incidence, 65.2% (n = 60) received baricitinib, 32.6% (n = 30) tofacitinib and 2.2% (n = 2) had both medications. Moreover, 41.3% (n = 38) presented a VTE and 58.7% (n = 54) an ATE. The median time-to-onset after JAK-i initiation was 4.6 months [IQR: 2.5-9.2] for VTE and 6.1 months [IQR: 3.0-8.5] for ATE. An IRR of 8.27 (95% CI 3.41-20.04) for VTE was detected during JAK-i treatment and remained increased over the 30-day period of post-exposure (6.52 [2.02-21.11]). An IRR of 9.27 (3.68-23.34) was also found for ATE, which remained increased over the 30-day period of post-exposure (10.12 [3.27-31.37]). No increased risk was detected during long-term post-exposure for either VTE or ATE., Conclusions: This study shows evidence of an increased risk of VTE and ATE associated with the use of baricitinib and tofacitinib., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pharmacological and mechanical thromboprophylaxis are frequently used together after total knee arthroplasty (TKA). Most studies in this context compare anticoagulants versus a combination of these drugs with an intermittent pneumatic compression device (IPCD). However, there is uncertainty about the need for the combination of both and whether a unilateral IPCD would alone affect other important clinical outcomes: edema and blood loss. We compared the effects of enoxaparin versus unilateral portable IPCD after TKA on edema and blood loss. We hypothesised that unilateral IPCD would cause the same level of edema and the same blood loss as enoxaparin., Methods: In this open, randomized trial (1:1), adults with no history of coagulation disorders, anticoagulant use, venous thromboembolism, liver or malignant diseases underwent TKA. For 10 days, participants received the IPCD, used 24 h/day on the operated leg from the end of surgery, or 40 mg of enoxaparin, starting 12 h after surgery. All underwent the same rehabilitation and were encouraged to walk on the same day of surgery. We measured edema (thigh, leg and ankle circumference) before and on the third postoperative day. Blood loss (volume accumulated in the suction drain and drop of hemoglobin and hematocrit in 48 h) was a secondary outcome., Results: We randomized 150 patients and lost 3 to follow-up with enoxaparin and 2 with IPCD. There was no case of symptomatic venous thromboembolism. Four patients needed transfusions (three receiving enoxaparin), one had infection and one hemarthrosis (both in the enoxaparin group). Leg circumference increased by approximately 2 cm for enoxaparin group and 1.5 cm in IPCD (p <  0.001). The increase in ankle circumference was about 1.5 cm in the enoxaparin group (p <  0.001), and almost zero in IPCD (p = 0.447). Enoxaparin group lost 566.1 ml (standard deviation, SD, 174.5) of blood in the first 48 h, versus 420.8 ml (SD 142.5) in the IPCD., Conclusions: Exclusively mechanical prophylaxis after TKA with portable IPCD only on the operated leg reduces leg and ankle swelling and post-operative blood loss compared to exclusively pharmacological prophylaxis with enoxaparin. Portable devices that can prevent deep vein thrombosis and pulmonary embolism without increasing blood loss or other risks should be further investigated., Trial Registration: REBEC RBR-8k2vpx. Registration date: 06/04/2019., (© 2022. The Author(s).)

Background: Measuring the venous diameter and choosing a compatible vena cava filter are essential to reduce the risk of complications resulting from implantation of these devices. However, there is little information on how the diameter of the inferior vena cava varies with sex and age., Objectives: To determine the influence of patients' gender and age on their inferior vena cava diameter and the suitability of the different models of available filters., Methods: Retrospective analytical study based on computed tomography images. The diameter of the inferior vena cava was measured at 3 points: above the confluence of the common iliac veins, below the renal veins, and midway between these two points (cranial point, caudal point, and midpoint) using Arya® and Carestream PACS® software. The results were classified by sex and age groups., Results: CT scans of 417 patients were analyzed: 245 women and 172 men. The diameters at the midpoint and caudal point were, respectively, 19.1 mm and 20.6 mm in women from 81 to 92 years old and were statistically smaller (p< 0.05) when compared to women aged 19 to 40 years (midpoint: 22.7 mm; caudal point: 23 mm). Similar results were seen in men. Venous diameters at the cranial and caudal points in patients aged from 51 to 70 years were statistically larger in men (cranial point: 24.4 mm; caudal point:22.3 mm) than in women (cranial point: 22.6 mm; caudal point:20.8 mm) (p< 0.05)., Conclusions: A smaller diameter was found for the inferior vena cava in older patients of both sexes and the rate of diameter change was similar among men and women., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2022 The authors.)

Background: Delayed-onset of headache seems a specific feature of cerebrovascular events after COVID-19 vaccines., Methods: All consecutive events reported to the United States Vaccine Adverse Reporting System following COVID-19 vaccines (1 January to 24 June 2021), were assessed. The timing of headache onset post-vaccination in subjects with and without concomitant cerebrovascular events, including cerebral venous thrombosis, ischemic stroke, and intracranial haemorrhage was analysed. The diagnostic accuracy in predicting concurrent cerebrovascular events of the guideline- proposed threshold of three-days from vaccination to headache onset was evaluated., Results: There were 314,610 events following 306,907,697 COVID-19 vaccine doses, including 41,700 headaches, and 178/41,700 (0.4%) cerebrovascular events. The median time between the vaccination and the headache onset was shorter in isolated headache (1 day vs. 4 (in cerebral venous thrombosis), 3 (in ischemic stroke), or 10 (in intracranial hemorrhage) days, all P < 0.001). Delayed onset of headache had an area under the curve of 0.83 (95% CI: 0.75-0.97) for cerebral venous thrombosis, 0.70 (95% CI: 0.63-76) for ischemic stroke and 0.76 (95% CI: 0.67-84) for intracranial hemorrhage, and >99% negative predictive value., Conclusion: Headache following COVID-19 vaccination occurs within 1 day and is rarely associated with cerebrovascular events. Delayed onset of headache 3 days post-vaccination was an accurate diagnostic biomarker for the occurrence of a concomitant cerebrovascular events.

Purpose: To evaluate the usefulness of compressive ultrasound (CUS) for the diagnosis of deep vein thrombosis (DVT) in patients with SARS-CoV-2-related infection., Methods: 112 hospitalized patients with confirmed SARS-CoV-2 infection were retrospectively enrolled. CUS was performed within 2 days of admission and consisted in the assessment of the proximal and distal deep venous systems. Lack of compressibility, or direct identification of an endoluminal thrombus, were the criteria used for the diagnosis of DVT. Pulmonary embolism (PE) events were investigated at computed tomography pulmonary angiography (CTPA) within 5 days of follow-up. Logistic binary regression was computed to determine which clinical and radiological parameters were independently associated with PE onset., Results: Overall, the incidence of DVT in our cohort was about 43%. The most common district involved was the left lower limb (68.7%) in comparison with the right one (58.3%) while the upper limbs were less frequently involved (4.2% the right one and 2.1% the left one, respectively). On both sides, the distal tract of the popliteal vein was the most common involved (50% right side and 45.8% left side). The presence of DVT in the distal tract of the right popliteal vein (OR = 2.444 95%CIs 1.084-16.624, p = 0.038), in the distal tract of the left popliteal vein (OR = 4.201 95%CIs 1.484-11.885, p = 0.007), and D-dimer values (OR = 2.122 95%CIs 1.030-5.495, p = 0.003) were independently associated with the onset on PE within 5 days., Conclusions: CUS should be considered a useful tool to discriminate which category of patients can develop PE within 5 days from admission., (© 2021. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Objective  The present study describes the preferences and current practices of a sample of knee surgeons in Brazil regarding thromboprophylaxis in total knee arthroplasty (TKA). Method  In the present internet survey, surgeons from the Brazilian Knee Surgery Society (SBCJ, in the Portuguese acronym) voluntarily answered an anonymous questionnaire including time of personal surgical experience, perceptions about the best thromboprophylaxis options, and actual practices in their work environment. Results  From December 2020 to January 2021, 243 participants answered the questionnaire. All, except for 3 (1.2%), reported using thromboprophylaxis, and most (76%) combined pharmacological and mechanical techniques. The most prescribed drug was enoxaparin (87%), which changed to rivaroxaban (65%) after discharge. The time of thromboprophylaxis initiation varied according to the length of training of the knee surgeon ( p ≤ 0.03), and their preferences and practices differed according to the Brazilian region ( p  < 0.05) and the health system in which the surgeons work (public or private sector; p  = 0.024). The option for mechanical thromboprophylaxis also depended on the training time of the surgeon. Conclusion  Thromboprophylaxis preferences and practices in TKA are diverse across Brazilian regions and health systems (public or private sectors). Given the lack of a national clinical guideline, most orthopedists follow either their hospital guidelines or none. The mechanical prophylaxis method and the little use of aspirin are the points that most diverge from international guidelines and practices., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The main burden of SARS-CoV-2 falls on the lungs but neurological manifestations, the most disabling of which are strokes and which correlate with disease severity, are common. We proffer a novel mechanism for acute COVID-19 stroke whereby pulmonary vein clots developing within the characteristic pulmonary intravascular thrombotic lesions can embolize to the brain. Appreciation of this mechanism requires an understanding of the tricompartmental model of lung parenchyma oxygenation (the alveolus, the bronchial artery, and the pulmonary artery), all of which are compromised in COVID-19. Of these 3 sources, the bronchial artery plays a crucial role in COVID-19 stroke because the unique collaterals from bronchial artery to pulmonary vein which exist under normal physiological conditions (and which maintain venous patency when the pulmonary artery is blocked by embolus) are occluded, thus leading to venular thrombosis in the presence of hypercoagulability. Dislodgement of clots from this source translocates the pathology to the brain and is a disease mechanism, formerly rare, which may account for many cases of large vessel occlusion stroke in COVID-19. This mechanism extends the concept of cardioembolic stroke from endocardium retrogradely into the pulmonary circulation with which the left cardiac chambers lie in direct continuity, and which is an accepted stroke mechanism under other circumstances such as lung lobectomy, where surgical ligation of the pulmonary vein creates a blind sac from which thrombi can embolize. The proposed model is supported by postmortem studies which have demonstrated venular thrombosis and by case reports of pulmonary vein thrombosis in COVID-19. This concept provides a more plausible cause for COVID-19 associated large vessel occlusion stroke than other putative mechanisms, such as cerebral endotheliitis, cytokine storm, and hypercoagulopathy, although it is acknowledged that the latter mechanism contributes to the genesis of pulmonary vein clots. Recognizing that extrapulmonary manifestations including stroke arise within thrombosed pulmonary veins is key to understanding of neurological manifestations of SARS-CoV-2 infection.

Objective: Peri-operative antiplatelet therapy (APT) aims to prevent thrombotic events such as stroke. High platelet reactivity ,despite the use use of APT, increases the risk of thrombotic events. Transcranial Doppler imaging (TCD) is used to detect peri-operative microembolic signals (MES) during carotid endarterectomy (CEA). Peri-operative MES are associated with an increased risk of procedural stroke and new silent lesions on diffusion weighted magnetic resonance imaging following surgery. The main components of TCD detected MES are platelet aggregates, and therefore patients displaying multiple MES during surgery could have benefited from more stringent APT. This study investigated whether the use of flow cytometry based platelet reactivity measurements were correlated with the incidence of pre-operative MES and thereby in the future suitable to predict patients at increased risk of peri-operative thrombotic events., Methods: Bilateral TCD with MES detection was performed in 197 patients undergoing CEA. Platelet reactivity was assessed with a flow cytometry based platelet reactivity assay measuring platelet response in whole blood. High on treatment platelet reactivity status was assessed for all patients. The secondary outcome was major adverse cardiovascular events (MACE) within one year., Results: In total, 197 patients were included, 49 had peri-operative MES. The platelet response to adenosine diphosphate (ADP) correlated with MES (p = .021), and high on treatment platelet reactivity after adenosine diphosphate stimulation was associated with MACE (OR 2.34, 95% confidence interval 1.126 - 4.890, p = .023)., Conclusion: Pre-operative platelet reactivity determined by flow cytometry after ADP stimulation correlated with the occurrence of intra-operative MES and post-operative MACE. Clopidogrel treatment showed the most substantial effect on reducing MES frequency and platelet reactivity measured by flow cytometry., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain., Methods: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1 st and September 26 th , 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality., Results: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range (IQR): 7-14) days after vaccination. Eighty percent (95% confidence interval (CI): 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir <50,000 /μL (odds ratio (OR): 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC95%: 1.3-47.0) were associated with fatal outcome., Conclusion: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase., (© 2022 Sociedad Española de Neurología. Published by Elsevier España, S.L.U.)

Aside from typical pneumonia, the coronavirus disease 2019 (COVID-19) has shown several extra-pulmonary manifestations. This study was done on a 66-year-old male patient who concomitantly had endogenous endophthalmitis and left ventricular thrombosis one month after being hospitalized due to COVID-19., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Portal vein thrombosis (PVT) is a disease in which thrombosis occurs from the intrahepatic branches of the portal vein, and may extend to the splenic vein and/or superior mesenteric vein. It is most often associated with liver cirrhosis. PVT not associated with cirrhosis is rare. The aim of this article is to report two cases of PVT in which it was not associated with cirrhosis. Both were treated with anticoagulation and clinical progress afterwards was good., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2021 The authors.)

Purpose: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with peritoneal metastases from colorectal cancer. Previous studies report conflicting rates of postoperative bleeding and venous thromboembolism (VTE) after CRS + HIPEC. The aim of the present study was to systematically review the literature and to estimate the overall 30-day incidence of postoperative bleeding and the overall 90-day incidence of VTE after CRS + HIPEC., Methods: Studies were identified in PubMed, Embase, and Web of Science on 29 April 2021. Data were extracted for a qualitative synthesis and to estimate an overall mean incidence in the meta-analysis., Results: Fourteen studies with a total of 3268 patients were included in the systematic review. Postoperative bleeding incidence rates within 30 days ranged from 1.7 to 8.3% with an overall 30-day postoperative bleeding incidence with [95% CI] at 4.2 [2.6;6.2]%. VTE incidence rates within 90 days ranged from 0.2 to 13.6% with an overall 90-day VTE incidence with [95% CI] at 2.7 [1;5.2]% after CRS + HIPEC., Conclusion: This systematic review and meta-analysis indicate a low risk for postoperative bleeding within 30 days and VTE within 90 days after CRS + HIPEC for peritoneal metastases from colorectal cancer., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A 55-year-old woman who had received an implantable left ventricular assist device 3 months earlier presented with dyspnea and a low-flow alarm of the device. Computed tomography and log-file analysis of the device system suggested inflow cannula obstruction. Since the patient had cardiogenic shock due to pump failure, venoarterial extracorporeal membrane oxygenation (ECMO) was initiated. With ECMO, surgical exchange of the pump was considered. However, the obstruction spontaneously resolved without surgical intervention. It turned out that an obstructive thrombus was washed out by rebooting the pump. Moreover, the thrombus was embolized in the patient's left subclavian artery. The patient underwent heart transplantation 4 months after the pump obstruction accident and continued to do well.

Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have a two- to threefold greater risk of developing venous as well as arterial thrombotic events. Although such thrombotic events are more commonly seen during phases of active AAV, they are also recognized to occur during AAV in remission. Endothelial injury is a key pathogenic event in AAV. Endothelial injury can be caused by neutrophil activation and release of thrombogenic tissue factor into the circulation. Neutrophil activation further results in the formation of neutrophil extracellular traps (NETs). NETs contribute to thrombosis by expressing tissue factor. NETs have also been detected in cutaneous thrombi from patients with AAV induced by hydralazine. Activated neutrophils in AAV patients release thrombogenic microparticles loaded with tissue factor which further enhances clotting of blood. Antiphospholipid antibodies (APLs) have been detected in up to a third of AAV and might also be induced by drugs such as cocaine adulterated with levamisole and propylthiouracil, which are known to trigger AAV. Such APLs further drive the thrombosis in AAV. Once thrombogenesis occurs, the homeostatic mechanisms resulting in clot dissolution are further impaired in AAV due to anti-plasminogen antibodies. The ongoing pandemic of coronavirus disease 2019 (COVID-19) is associated with endothelial injury and NETosis, mechanisms which are in common with AAV. Reports of new-onset AAV following COVID-19 have been described in the literature, and there could be shared mechanisms driving these processes that require further evaluation., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: COVID-19 is still a global challenge in regard for management and therapy. Pulmonary embolism (PE) seems to have a higher prevalence in COVID-19 instead of non-COVID patients. Clinical and laboratory parameters related with PE are still unknown., Methods: We conducted a retrospective unicentre study in Alto Vicentino Hospital between March 1st, 2020, and January 31st, 2021 in patients admitted for COVID-19 tested with a RT-PCR nasal swab. Data about patients studied with computed tomography pulmonary angiogram (CTPA) because of PE suspicion were collected, as their clinical and laboratory parameters too., Results: 2621 patients were admitted for COVID-19 in Alto Vicentino Hospital between March 1st, 2020, and January 31st, 2021 and in 267 of them a CTPA was performed finding 50 PE (18.7%). Only non-Caucasian race (OR = 5.44; 95% CI 1.22-24.35; p = 0.027) and previous VTE (OR = 5.3; 95% CI 1.09-26.17; p = 0.039) were found to be independently associated with PE., Conclusion: PE is a frequent complication of COVID-19 and clinician need high degree of suspicion because clinical and laboratoristic parameters cannot drive diagnosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing., Objectives: To develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients., Methods: This was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration., Results: A total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight. Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment., Conclusion: In ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To improve the quality and accuracy of the patient-reported outcome measures that assess health-related quality of life (HRQoL), guidelines have been developed to standardize the development and validation process. Considering the increasing importance of HRQoL questionnaires in research, we set out to review the literature and evaluate whether existing questionnaires developed for deep vein thrombosis (DVT) and pulmonary embolism (PE) fulfill state-of-the-art requirements. The literature search was conducted in March 2019 and updated in September 2020. Seven databases were searched. No time limit was set for the search to include all available questionnaires. The inclusion criteria were original publications describing the development of disease-specific HRQoL questionnaires specific to DVT or PE in adults and available in English. The questionnaires were assessed to determine whether they fulfill the requirements in the latest guidelines. A total of 3826 references were identified. After the exclusion process, 15 papers were reviewed in full, of which 7 were included. Four questionnaires were developed for chronic venous disease, two were specific to DVT, and one was specific to PE. Most questionnaires we found in this review, fulfilled some but none fulfilled all recommendations in existing guidelines. Because the development of current available HRQoL questionnaires specific to DVT or PE do not fulfil all recommendations of existing guidelines, there is room for improvements within this field. Such improvements could likely enhance the quality associated with the use of these end points in clinical trials and practice., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

The incidence of asymptomatic pulmonary embolism (PE) exceeds 70% in patients with deep venous thrombosis (DVT), even in cases of distal deep vein thrombosis. We report the case of a patient with a diagnosis of DVT in the lower left limb associated with asymptomatic PE who presented late symptoms due to this same PE. The absence of acute symptoms and the late onset of symptoms could have provoked doubts about the most appropriate treatment, resulting in unnecessary interventions, if pulmonary embolism had not already been diagnosed with tomography. In the present case, we demonstrate that computed tomography angiography conducted at the time of DVT diagnosis accurately diagnosed PE and prevented any misinterpretation of recurrent DVT in a patient already being medicated, which could have been mistakenly interpreted as demonstrating failure of anticoagulant therapy. Such a situation could lead to unnecessary intervention to fit an inferior vena cava filter. We cannot suggest that a classic medical conduct should be reformulated simply on the basis of a case report. However, we would be remiss not to suggest that well-designed studies should be carried out in the future to assess the need for this examination in the acute phase., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2021 The authors.)

Background: COVID-19 patients are considered at high risk of venous thromboembolism (VTE). The real nature of pulmonary artery occlusions (PAO) in COVID-19 has been questioned, suggesting that it is caused also by in situ thrombi, rather than only by emboli (PE) from peripheral thrombi., Methods: We searched MEDLINE for studies published until 6 June 2020 that included COVID-19 patients or non-COVID-19 medical patients at VTE risk, treated with heparins, in whom VTE (PE and deep vein thrombosis, DVT) had been reported. Systematic review and results reporting were conducted in accordance with PRISMA guidelines. Data were independently extracted by two observers, and estimates were pooled using random-effects meta-analysis., Results: We identified 17 studies including 3224 COVID-19 patients and 7 including 11 985 non-COVID-19 patients. Two analyses were performed: in all COVID-19 patients and only in those (n = 515) who, like non-COVID-19 patients, were screened systematically for DVT. The latter analysis revealed that the prevalence of DVT was 15.43% (95%CI, 4.08-31.77) in COVID-19 and 4.21% (2.27-6.68) in non-COVID-19 patients (P = .0482). The prevalence of PE was 4.85% (40.33-13.01) in COVID-19 patients and 0.22% (0.03-0.55) in non-COVID-19 patients (P = .0128). The percentage of PE among VTE events was 22.15% (5.31-44.60) in COVID-19 and 6.39% (3.17-10.41) in non-COVID-19 patients (P = .0482). Differences were even more marked when all COVID-19 patients were analysed., Conclusions: The results of our meta-analysis highlight a disproportion in the prevalence of PE among all VTE events in COVID 19 patients, likely reflecting PAO by pulmonary thrombi, rather than emboli from peripheral vein thrombi., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Recurrent venous thromboembolism (RVTE) is a multifactorial disease with occurrence rates which vary from 13 % to 25 % in 5 years after the initial event. Once a patient the first thrombotic event, the probability of recurrence should be determined, as well as the most adequate anticoagulant therapy. To our knowledge based on the published literature, three statistical models have been proposed to calculate RVTE probability. However, these models present several limitations, such as: limited input variables, lack of external validation and applicability only for patients with a first unprovoked thrombosis. Additionally, some of the models have been recognized to fail in determining RVTE when patients have a low risk of recurrence., Objective: An alternative procedure in which three Artificial Neural Network (ANN) models were developed to classify which patients will present RVTE based solely on clinical data., Methods: Data of 39 clinical factors from 235 patients were used to train several ANN structures. The difference among the three models was its inputs. In ANN 1, the inputs were all 39 factors. In ANN 2, 18 factors determined previously as the main predictors of RTVE using Principal Component Analysis (PCA). Finally, in ANN 3, 15 factors combining PCA results with practical aspects. Different number of hidden layers and neurons, and three optimization algorithms were considered. 5-fold cross validation was also performed., Results: The results showed that all models were capable of performing this task. Different optimization algorithms lead to different results. The best models presented high accuracy. The best structures were 39-10-10-1, 18-10-5-1, and 15-15-10-1 for ANN 1, ANN 2, and ANN 3 models, respectively. The cross-validation showed that the results are consistent., Conclusions: This work showed that the association of multivariate techniques and ANNs is a powerful tool that can be used to model a complex phenomenon such as RVTE without the restrictions of existing approaches., Application: After proper validation, these ANN models can be used to help clinicians with decisions regarding VTE treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The exact risk of developing a thromboembolic event (TEE) while using complement 1 esterase inhibitors (C1-INHs) is currently undetermined for patients with hereditary angioedema (HAE). This systematic review aimed to define the potential risk of TEEs from these agents., Areas Covered: This evaluation covers publications examining or mentioning the risk of TEEs in association with C1-INHs. A systematic literature search was conducted utilizing PubMed, Scopus, and ProQuest. This review utilized search results through January 2020 and followed the PRISMA recommendations for a systematic review. Articles not available in English and animal or in-vitro studies were excluded. For inclusion, studies had to be open-label, randomized-controlled, cross-sectional, or clinical observational studies. A total of 13 studies met inclusion criteria and yielded 1716 patients receiving at least one dose of C1-INH, though only 41 incidences of thrombosis were documented., Expert Opinion: Significant heterogeneity exists in the available literature concerning both study design and the reporting of data; therefore, interpretation of thrombotic risk is difficult. TEEs are rarely reported in the literature, and they seem unlikely to occur in patients without underlying risk factors. Important risk factors include those found in the prescribing information of C1-INHs.

Introduction: Considerably large numbers of bariatric surgery (BS) procedures are undertaken globally, and are projected to increase with the obesity epidemic. Venous thromboembolic events (VTE) comprise an important cause of postoperative morbidity and mortality after BS and an important issue with wide clinical and financial repercussions. Yet, a precise extent of the prevalence of VTE after BS for obesity and its mortality remains uncertain., Methods and Analysis: In order to respond to this knowledge gap, we will conduct a systematic review and meta-analysis of the prevalence of and mortality associated with VTE after BS. This protocol outlines the methodology that will be used and the search strategies and eligibility criteria that will be utilized to identify and select studies, as well as the method by which data from the selected studies will be extracted for analysis. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, Cochrane Library, MEDLINE, Scopus, clinicaltrials.gov and Google scholar will be searched from 01 January 1990 through 10th April 2020, for original studies written in English that provided prevalence estimates of VTE after BS. Articles will also be searched for mortality estimates of VTE after BS. STROCSS (Strengthening the Reporting of Cohort Studies in Surgery) criteria will evaluate the methodological quality of the selected studies. The use of fixed effect or random effects model will be subject to the findings of the statistical tests for heterogeneity. Publication bias will be visually estimated by inspecting the funnel plots. Pooled estimates will be computed. Th current protocol conforms to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines and has been submitted to the PROSPERO International Prospective Register of systematic reviews. No ethical clearance is required for this study. This systematic review and meta-analysis will be published in a peer-reviewed journal and presented at national and international conferences., (© 2020 The Author(s).)

Although the findings of some studies have been indicative of the direct relationship between the severity of clinical findings and imaging, reports have been published regarding inconsistency of clinical findings with imaging and laboratory evidence. Physicians treating these patients frequently report cases in which patients, sometimes in the recovery phase and despite improvements in imaging indices, suddenly deteriorate and in some instances suddenly expire. This letter aimed to draw attention to the role of pulmonary thromboembolism as a potential and possible cause of clinical deterioration in covid-19 patients.

Background: Left ventricular thrombus (LVT), a common complication of acute ST-segment elevation myocardial infarction (STEMI), is associated with increased risk of systemic embolism and high mortality. Current STEMI guidelines recommend adding anticoagulant therapy to dual antiplatelet therapy (DAPT) if early-formulated LVT were detected, for which vitamin K antagonist (VKA) is the standard anticoagulant agent. The role of non-VKA oral anticoagulants (NOACs) in this scenario is uncertain., Methods: The EARLY-MYO-LVT study will be a prospective, multi-center and randomized trial designed to investigate the efficacy and safety of rivaroxaban versus warfarin in the treatment of post-STEMI LVT. It will enroll 280 patients with STEMI who have developed LVT within the first month of symptom onset. They will be randomized at 1:1 ratio into the group of rivaroxaban 15 mg daily or VKA treatment (with targeted INR 2-2.5) on the basis of standard DAPT (100 mg daily aspirin plus 75 mg daily clopidogrel) for 3-6 months. The primary efficacy endpoint will be the probability of LVT resolution after 3-month triple therapy, and the principal safety outcome will be the incidence of major bleeding events during the treatment., Discussion: The described study will systemically assess the efficacy and safety of NOACs-based anticoagulant therapy in the treatment of LVT subsequent to STEMI., Trial Registration: The EARLY-MYO-LVT trial (Clinical trial number: NCT03764241)., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Background: Pregnancy in women with a Fontan circulation is understood to have a significantly increased risk of maternal morbidity and mortality. Potential longer-term effects on health outcomes remain unknown., Aim: Ascertainment of adverse events, post-delivery, in women from the Australia and New Zealand (ANZ) Fontan Registry. Comparator data from women without pregnancy and men was utilised., Methodology/results: Living adults were identified (n = 263 women, 280 men) with Registry analysis ascertaining cardiac morphology, type of Fontan procedure, pregnancy and significant cardiac adverse events. Data are described descriptively for morphology and as median (inter quartile range) for other variables. Thirty women reported 45 pregnancies beyond 20 weeks' gestation. Despite being older, these women, pre-delivery, had the lowest cardiac morbidity burden, compared to both male and female controls (OR = 3.25 (95% CI 1.44-8.35, p = 0.008 and OR = 2.59 (95% CI 1.14-6.70), p = 0.03). These differences were not present post-delivery. Median follow-up time post-delivery was 3.6 (1.2-7.5) years. Thrombus documentation and thromboembolic events were more common post-delivery, although differences were not significant in a propensity analysis model (adjusting for post-Fontan follow-up time, age and type of Fontan). There were no differences in arrhythmia, cardioversion, heart transplant, Fontan conversion or mortality between women post-delivery and either male or female controls., Conclusion: The apparent increase in thromboembolic events post pregnancy requires further investigation in a larger group of women over a longer period of follow-up time. This may have potential implications for post-partum anticoagulation, and for future health outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A 24-year-old woman who was 11 weeks pregnant and had a mechanical mitral valve presented at the emergency department with ischemic stroke. Although treatment with aspirin and unfractionated heparin was initially successful, subsequent management was almost impossible, as she eventually suffered a right hemispheric stroke, requiring percutaneous intervention and an emergency cesarian; prosthetic valve thrombosis with hemodynamic instability; and multiple bleeding complications. This case demonstrates how difficult it can be to select the appropriate treatment strategy for prosthetic valve thrombosis., (Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: Critical and chronic illness in youth such as diabetes can lead to impaired mental health. Despite the potentially traumatic and life-threatening nature of venous thromboembolism (VTE), the long-term mental health of adolescents and young adults with VTE is unclear. We compared the long-term mental health of adolescents and young adults with VTE versus adolescents and young adults with insulin-dependent diabetes mellitus (IDDM) using psychotropic drug purchase as proxy for mental health., Design: Nationwide registry-based cohort study., Setting: Denmark 1997-2015., Participants: All patients aged 13-33 years with an incident diagnosis of VTE (n=5065) or IDDM (n=6609)., Exposure: First time primary hospital diagnosis of VTE or IDDM., Primary and Secondary Outcome Measures: Adjusted absolute risk and risk difference at 1 and 5 years follow-up for first psychotropic drug purchase comparing patients with VTE and patients with IDDM., Results: The absolute 1 year risk of psychotropic drug use was 6.2% among VTE patients versus 3.6% among patients with IDDM, at 5 years this was 19.3%-14.7%, respectively. After adjusting for the effect of sex, age and risk factors for VTE this corresponded to a 1 year risk differences of 1.9% (95 % CI 0.1% to 3.3%). At 5 years follow-up the risk difference was 1.9% (95% CI 0.5% to 3.3%)., Conclusion: One-fifth of adolescents and young adults with incident VTE had claimed a prescription for a psychotropic drug within 5 years, a risk comparable to that of young patients with IDDM., Competing Interests: Competing interests: DHL has received investigator-initiated educational grants from Boehringer-Ingelheim and Bristol-Myers Squibb, served on speaker bureaus for Boehringer-Ingelheim, Bayer, Bristol-Myers Squibb/Pfizer and has consulted for Bristol-Myers Squibb, Bayer, Boehringer-Ingelheim and Daiichi-Sankyo. SG has received research support from BiO2 Medical, Boehringer-Ingelheim, BMS, BTG EKOS, Daiichi, National Heart Lung and Blood Institute of the National Institutes of Health, Janssen, Thrombosis Research Institute and served as a consultant for Bayer, Boehringer-Ingelheim, BMS, Daiichi, Janssen, Novartis, Portola, Zafgen. TBL has been an investigator for Janssen Scientific Affairs and Boehringer-Ingelheim, and served on speaker bureaus for AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, Roche Diagnostics, Siemens Diagnostics and Takeda. Other authors: none declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute limb ischemia (ALI) represents one of the most common emergent scenarios encountered by a vascular specialist. Despite expedient revascularization, high rates of limb loss are reported along with high mortality rates which are second only to ruptured abdominal aortic aneurysms. Surgical revascularization is standard of care. Endovascular techniques as an alternative have emerged to be appropriate first line therapy when addressing the threatened limb. We review the etiology and classification of ALI and current endovascular techniques and evidence to date in the management of patients acutely presenting with extremity ischemia., Competing Interests: CONFLICTS OF INTEREST The authors have nothing to disclose.

The rates of recurrent venous thromboembolism (RVTE) vary widely, and its causes still need to be elucidated. Statistical multivariate methods can be used to determine disease predictors and improve current methods for risk calculation. The objective of this study was to apply principal component analysis to a set of data containing clinical records of patients with previous venous thromboembolism and extract the main factors that predict recurrent thrombosis. Records of 39 factors including blood and lipid parameters, hereditary thrombophilia, antiphospholipid syndrome, clinical data regarding previous thrombosis and treatment, and Doppler ultrasound results were collected from 235 patients. The results showed that 13 principal components were associated with RVTE and that 18 of 39 factors are the important for the analysis. These factors include red blood cell, white blood cell, hematocrit, red cell distribution width, glucose, lipids, natural anticoagulant, creatinine, age, as well as first deep vein thrombosis data (distal/proximal, d-dimer, and time of anticoagulation). The results demonstrated that simple clinical parameters easy to be collected can be used to predict rates of recurrence and to develop new clinical decision support systems to predict the rates of RVTE.