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End-to-side (ETS) microsurgical anastomosis is a powerful technique in microsurgery. It can overcome vessel's diameter discrepancy and preserve the distal blood flow. Optimal angle of the ETS anastomosis has been debated and studied, and is currently limited to animal models. Computational model using Finite Element Analysis (FEA) was used to simulate the models with 45 (model 45 ), 90 (model 90 ), and 135 (model 135 ) ETS anastomosis angles. Flow dynamics including flow velocity and wall shear rate were studied and compared. Maximum flow velocity ranged from the highest to the lowest in model 135 , model 90 , and model 45 , respectively. The velocity in model135 showed fluctuation flow. The maximum wall shear rate and distribution were highest in model 45 and lowest in model 90 . ETS anastomosis angle of 90 degrees provided the most favourable flow dynamics to prevent shear related thrombosis in comparison to ETS anastomosis at 45 and 135 degrees., (© 2024. The Author(s).)

BACKGROUND Incidental findings of renal infarct secondary to thrombosis in acutely ill patients present a unique challenge in diagnosis. We present a case of idiopathic renal infarct to highlight its workup and management and encourage further investigation of renal infarctions. CASE REPORT A 68-year-old woman with a past medical history of diet-controlled diabetes, hypertension, and hyperlipidemia presented to the Emergency Department (ED) for abdominal pain. She was found to be in diabetic ketoacidosis with pyelonephritis, so she was admitted to the Intensive Care Unit (ICU) for insulin and dextrose drip. Due to her abdominal pain, she underwent computed tomography (CT) of her abdomen and pelvis with contrast. This revealed multifocal infarcts of her right kidney with noncalcified thrombus at the proximal right renal artery. Subsequent CT angiography confirmed a right renal artery thrombus. She was started on subcutaneous enoxaparin and downgraded to basic level of care. Her history was negative for prior thrombosis, hypercoagulable state, and abdominal trauma. Echocardiogram and limited hypercoagulable workup were largely unremarkable. A multidisciplinary team evaluated the patient and recommended no surgical intervention. Following downgrade from the ICU, the patient was transitioned from enoxaparin to apixaban. She was discharged with plans for anticoagulation for 6 months, aspirin daily, and repeat CT angiogram abdomen/pelvis in 1 month. CONCLUSIONS This case illustrates the difficulties in elucidating the cause of incidental renal thrombosis in an acutely ill patient. Diagnostic workup is limited in the inpatient setting, but therapeutic anticoagulation remains the standard of treatment regardless of etiology.

This viewpoint summarizes findings from analyses of large personal patient databases of myeloproliferative neoplasms (MPNs) to assess the impact of thrombosis on mortality, disease progression, and second cancers (SC). Despite advances, the current incidence of arterial and venous thrombosis remains a challenge. These events appear to signal a more aggressive disease course, as evidenced by their association with myelofibrosis progression and mortality using multistate models and time-dependent multivariable analysis. Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), are associated with the aggressiveness of polycythemia vera (PV) and essential thrombocythemia (ET), linking thrombosis to SC risk. This suggests a common inflammatory pathway likely influencing cardiovascular disease and cancer incidence. Notably, this is observed more frequently in younger patients, likely due to prolonged exposure to MPN and environmental inflammatory triggers. These data underscore the need for new studies to validate these associations, delineate the sequence of events, and identify therapeutic targets to mitigate thrombotic events and potentially improve overall patient outcomes in MPN., (© 2024. The Author(s).)

Thrombosis is a common clinical feature associated with morbidity and mortality in coronavirus disease-2019 (COVID-19) patients. Cytokine storm in COVID-19 increases patients' systemic inflammation, which can cause multiple health consequences. In this work, we aimed to indicate the effect of Pfizer-BioNTech vaccination on the modulation of monocyte chemoattractant protein-3 (MCP-3), matrix metalloproteinase 1 (MMP-1), and tumor necrosis factor-alpha (TNF-α) levels, and other systemic inflammatory biomarkers that associates with COVID-19 severity in patients who suffers from thrombosis consequences. For this purpose, ninety people were collected from Ibn Al-Nafees Hospital and divided into three groups each of which contained 30 people, 15 of them were venous thromboembolism (VTE) positive and the other were VTE negative. The three groups were non-vaccinated COVID-19, vaccinated COVID-19, and control. The levels of MCP-3 and TNF-α were significantly (p < 0.05) increased in vaccinated and non-vaccinated COVID-19 patients regardless of their thrombosis condition, while MMP-1 level was non-significantly (p > 0.05) higher in vaccinated patients compared to control. MCP-3 and TNF-α were correlated positively with D-dimer (r = 0.544 and r = 0.513, respectively) in non-vaccinated patients, while MMP-1 and TNF-α were correlated positively with D-dimer (r = 0.624 and r = 0.575, respectively) in vaccinated patients. The odds ratio of MCP-3 (2.252), MMP-1 (1.062), and TNF-α (1.360) were reduced in vaccinated patients (2.093, 1.022, and 1.301 for MCP-3, MMP-1, and TNF-α respectively). Thus, MCP-3 plays a vital role in COVID-19 pathophysiology, and vaccination can reduce the risk of developing VTE in COVID-19 patients, and improve the inflammatory condition of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Case: A 44-year-old man sustained a thrombosed popliteal artery after a closed left knee dislocation after a high-energy motor vehicle collision. He underwent emergency open popliteal artery embolectomy, with insertion of endovascular stent. After arthroscopic multiligamentous knee injury reconstruction (MLKI-R) on day 18 after injury, he developed stent thrombosis, which resolved with urgent percutaneous thrombectomy., Conclusion: This is the first report of popliteal artery stent thrombosis after MLKI-R. Knee surgery in a revascularized limb has remained controversial, but studies are scarce in the literature. Frequent circulation monitoring and vascular specialist availability postoperatively are still key to detecting this complication and early revascularization., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C472)., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated.)

Importance: Postoperative thrombosis is a significant complication in pediatric cardiac surgery patients, contributing to morbidity and mortality. Identifying clinical factors associated with thrombosis can improve patient outcomes by guiding early detection and intervention., Objectives: This study aimed to assess factors associated with postoperative thrombosis or thromboembolism in pediatric patients under 12 months old who underwent surgery for congenital heart disease (CHD). Design, Setting, and Participants: This retrospective cohort study analyzed electronic medical records from pediatric patients admitted to the Pediatric Cardiovascular Intensive Care Unit (PCICU) at the German Paediatric Heart Center, Bonn, between March 1, 2020, and March 1, 2021. A total of 197 children under 12 months old who underwent cardiac surgery were included in the analysis., Main Outcomes and Measures: Thrombosis was diagnosed postoperatively using imaging modalities such as ultrasound, echocardiography, and computed tomography. The primary outcome was the incidence of thrombosis and its association with clinical factors such as age, central venous catheter (CVC) duration, CRP levels, and D-dimer levels., Results: Among 197 patients, the incidence of thrombosis was 8.63%, predominantly venous (70.6%). Initial associations were observed between thrombosis and younger age, lower body weight, higher hematocrit, cyanosis, longer central venous catheter (CVC) use, and elevated C-reactive protein (CRP) and d-dimer levels. Receiver operating characteristic analysis indicated a higher risk in patients with d-dimer levels above 5.47 mg/L. The stepwise multiregression analysis identified longer CVC duration in situ (β = 0.553; p < 0.001), higher CRP levels (β = 0.217; p = 0.022), and younger age at admission (β = -0.254; p = 0.006) as significant predictors of thrombosis. Decision tree analysis identified CVC use longer than 12.5 days and CRP levels above 118.01 mg/L as the most critical risk factors., Conclusions and Relevance: Postoperative thrombosis is a notable risk in pediatric CHD patients, particularly in neonates. Prolonged CVC use and elevated CRP levels are critical risk factors. Routine monitoring of D-dimer and CRP levels, along with timely sonographic screening, can aid early thrombosis detection and intervention. Further research is warranted to optimize thrombosis prevention strategies in this population., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed "immunothrombosis". In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms.

Background and Aims: There is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in "real life" in Spain., Methods: A prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy., Results: We included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents., Conclusions: Despite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the "real world" remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Abstract: A common feature in patients with abdominal aortic aneurysms (AAAs) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA-associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation affects the pathogenesis of AAA. Using RNA sequencing, we identified that the platelet-associated transcripts are significantly enriched in the ILT compared with the adjacent aneurysm wall and healthy control aortas. We found that the platelet-specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of patients with AAAs. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in 2 independent cohorts of patients with AAAs is highly predictive of an AAA diagnosis and associates more strongly with aneurysm growth rate than D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in 2 independent mouse models. In conclusion, we show that the levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, for which none currently exists., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred., Methods: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count < 50 × 10 9 /L were studied. Patients were categorized into bleeding/nonbleeding and thrombotic/nonthrombotic groups on the basis of hospital course. Relevant clinical data were collected, and univariate/multivariate logistic regression was used to analyse the influencing factors. The platelet count at admission was assessed via ROC curves for thrombosis prediction., Results: In the bleeding group, higher proportions of patients with leukaemia, myeloid tumours, lung infections, and a central venous catheter (CVC) with two lumens were observed, along with shorter catheter durations, lower initial and minimum platelet counts during hospitalization, and prolonged plasminogen times (all P < 0.05). The thrombotic group had a greater thrombosis history, initial platelet count, use of two venous catheter lumens, parenteral nutrition, sedation, and autologous haematopoietic stem cell transplantation (Auto-HSCT), with a lower leukaemia proportion (P < 0.05). Logistic regression identified lymphoma type and minimum platelet count as bleeding protective factors and the Charlson Comorbidity Index (CCI) score as an independent risk factor. Thrombosis history, two venous catheter lumens, and sedation were risk factors for thrombosis. The median platelet count was lower at bleeding and thrombosis than at admission (P = 0.007). The platelet count at admission had predictive value for thrombosis, especially severe thrombocytopenia, with an AUC of 0.735 (95% CI 0.613-0.858, P = 0.003) and a cut-off value of 42.5 × 10 9 /L., Conclusions: For haematological neoplasm patients with a high risk of venous thromboembolism (VTE), severe thrombocytopenia and high CCI scores, risk prevention and control of bleeding take precedence over thrombosis prophylaxis. Prophylactic anticoagulation is still recommended for patients with lymphoma assessed at high risk for VTE and with platelet counts of at least 42.5 × 10 9 /L., (© 2024. The Author(s).)

Competing Interests: Dr Libby is an unpaid consultant to or involved in clinical trials for Amgen, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Novo Nordisk, Novartis, and Sanofi-Regeneron. Dr Libby is a member of the scientific advisory board for Amgen, Caristo Diagnostics, CSL Behring, Elucid, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Novartis, PlaqueTec, Polygon Therapeutics, TenSixteen Bio, Soley Thereapeutics, and XBiotech, Inc. Dr Libby’s laboratory has received research funding in the last 2 years from Novartis, Novo Nordisk and Genentech. Dr Libby is on the Board of Directors of XBiotech, Inc. Dr Libby has a financial interest in Xbiotech, a company developing therapeutic human antibodies; in TenSixteen Bio, a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential to discover and develop novel therapeutics to treat age-related diseases; and in Soley Therapeutics, a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics. Dr Libby’s interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies.

Context: People with type 1 diabetes (T1D) are at increased risk of thrombosis compared to the general population; however, the underlying mechanisms remain unclear. Hypoglycemia induced at rest can induce coagulation activation, but little is known about the hemostatic effects of exercise-related hypoglycemia in people with T1D., Objective: We compared hemostatic profiles of individuals with T1D with healthy controls and explored hemostatic effects of hypoglycemia, induced with or without exercise, in participants with T1D., Methods: Thrombelastography was used for a baseline hemostatic comparison between fifteen men with T1D and matched healthy controls. In addition, the participants with T1D underwent two euglycemic-hypoglycemic clamp days in a randomized, crossover fashion. Hypoglycemia was induced with the participants at rest (Hypo-rest) or during exercise (Hypo-exercise). Thrombelastography provides data on the rate of coagulation activation (R-time), the rate of clot formation (K-time, α-Angle), the maximum clot amplitude (MA), the functional fibrinogen contribution to the clot strength (MA-FF) and the fibrinolysis (LY-30)., Results: The T1D group exhibited a faster rate of coagulation activation (shorter R-time) and a faster clot formation (greater α-Angle) compared with the controls. During the clamp experiments, Hypo-exercise induced an increased clot strength (MA) with a mean difference from baseline of 2.77 mm (95% CI, 2.04-3.51) accompanied with a decreased fibrinolysis (LY-30) of -0.45 percentage point (-0.60 to -0.29). Hypo-rest resulted in increased functional fibrinogen (MA-FF) of 0.74 mm (0.13-1.36) along with an increased fibrinolysis (LY-30) of 0.54 percentage point (0.11-0.98)., Conclusion: Individuals with T1D exhibit a hypercoagulable hemostatic profile compared with healthy controls and exercise-related hypoglycemia may increase the susceptibility to thrombosis via both procoagulant and antifibrinolytic effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

The coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 has posed a significant threat to global health since its outbreak in early 2020. Various thrombotic complications have been reported in COVID-19 cases. This study aims to investigate the incidence of various types of thromboses during the COVID-19 pandemic, and explore the potential correlation between the number of COVID-19 infections and occurrence of thrombosis. The present retrospective, single-center study recorded the number of new cases with various types of thromboembolism among all hospital admissions between 2019 and 2023 in a single center. The correlation between the number of total thromboembolism cases and number of inpatients who tested positive for COVID-19 was assessed using Spearman rank correlation coefficient. A total of 3926 thromboembolism cases were recorded in men, while 3657 cases were reported in women. The total number of new thromboembolism cases among all inpatients annually increased from 2019 to 2022, and reached a peak during the "full liberalization" period from December 2022 to January 2023. The most substantial increase was observed in microthrombosis cases, followed by venous and arterial thrombosis cases. In addition, thromboembolism primarily occurred in the lower extremities, followed by the abdomen. The fewest cases were observed in the upper extremities. Furthermore, the correlation coefficient between the total number of thromboembolism cases and number of COVID-19-positive patients between January 2020 and June 2023 was 0.501 (P = .001). The number of thromboembolism cases among all inpatients was correlated to the number of COVID-19-positive patients during the pandemic. Early thromboembolism prophylaxis and thrombotic complications monitoring should be considered for hospitalized patients, when necessary., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The aim of this study is to assess the risk factors associated with thrombotic events in obstetric antiphospholipid syndrome (OAPS) patients and to develop a predictive model specifically tailored to predict the risk of postpartum thrombosis in OAPS patients without prior thrombotic events. This research seeks to enhance clinician's awareness regarding the postpartum care and monitoring of OAPS patients., Methods: A retrospective study was conducted at the First Affiliated Hospital of the Fourth Military Medical University including 269 consecutive inpatients diagnosed with antiphospholipid syndrome (APS) from July 1, 2008 to July 31, 2022. All participants met the 2006 Sydney APS classification criteria or the "non-criteria OAPS classification". Out of 98 candidate clinical and laboratory parameters considered, 40 potential variables were selected for analysis based on expert opinion. The logistic regression mode with the Least Absolute Shrinkage and Selection Operator (LASSO) were used to identify optimal predictive characteristics. All samples were included in the model building and a nomogram was generated based on these characteristics. The differentiation, calibration, and clinical utility of the predictive model were evaluated using the area under the curve (AUC), calibration curve, and decision curve analysis. The model was also validated by a 1000 bootstrap tests., Results: 126 patients with OAPS were enrolled, and a total of 89 OAPS patients who had never experienced thrombosis were retrospectively analyzed. After 3 years follow-up, 32.58% of the patients (29/89) developed thrombosis. In order to create, LASSO logistic regression identified three optimal variables: the platelet count less than 125×109/L, more than one positive aPLs (antiphospholipid antibody), and the use of low molecular weight heparin (LMWH) or low dose aspirin (LDA) after delivery. A predictive model was conducted using these three predictive indicators for patients with OAPS who experience thrombosis for the first-time. This prediction model has good distinction, good calibration, and fair clinical practicality., Conclusion: Our model has good predictive ability in assessing the risk of thrombosis in patients with OAPS without prior thrombotic events. This model is easy to predict, has good discriminability and calibration, and can be utilized as a routine tool for thrombus screening in OAPS patients., 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., (Copyright © 2024 Gao, Zheng, Wang, Jia, Wan, Han, Zheng, Liu, Zheng, Wu and Zhu.)

Background: There is limited data on the association between inflammation and the formation of early left ventricular thrombus (LVT) following ST-elevation myocardial infarction (STEMI). This study aimed to explore the predictive value of several inflammatory biomarkers for LVT formation following STEMI., Methods and Results: Our cohort included 2534 consecutive patients admitted to the cardiac intensive care unit (CICU) with STEMI. The final analysis included 51 patients with LVT and 102 patients without LVT, matched for age, sex, anterior infarct and ejection fraction. Upon admission, patients with LVT had higher white blood cell counts (WBC) (12.8 ± 7 vs. 12.4 ± 4 ×10 3 /µL, p = 0.01), higher absolute neutrophil counts (10.5 ± 4 vs. 8.6 ± 4 ×10 3 /µL, p = 0.003), neutrophil-to-lymphocyte ratio (8.2 ± 6 vs. 4.8 ± 4, p = 0.04), and C-reactive protein (CRP) levels (35.9 ± 62 vs. 18.6 ± 40 mg/L, p = 0.04). Peak values for WBC and CRP were also higher in the LVT group (17.8 ± 8 vs. 14.6 ± 5 ×10 3 /µL, p = 0.003 and 95.8 ± 82 vs. 64.2 ± 76 mg/L, p = 0.02, respectively). In univariate regression analysis, WBC upon admission (OR: 1.12, 95% CI: 1.02-1.21, p = 0.02), peak WBC (OR: 1.09, 95% CI: 1.02-1.17, p = 0.009), neutrophil count upon admission (OR: 1.15, 95% CI: 1.04-1.26, p = 0.004), and peak CRP (OR: 1.01, 95% CI: 1-1.01, p = 0.03) predicted LVT formation, which was also evident in multivariate regression models., Conclusion: WBC and neutrophil counts upon admission, as well as peak WBC and CRP, have additional predictive value for LVT formation following STEMI, beyond classical risk factors., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism., Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves., Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year., Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009., Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Background: The optimal strategy in prosthetic heart valve thrombosis (PVT) remains controversial, with no randomized trials and conflicting observational data. We performed a systematic review and meta-analysis of evidence comparing systemic thrombolysis and cardiac surgery in PVT., Methods and Results: We searched PubMed, the Cochrane Library, and Embase for studies on treatment strategies in patients with left-sided PVT since 2000. The primary outcome was death, and the secondary outcomes were major bleeding and thromboembolism during follow-up (International Prospective Register of Systematic Reviews No. CRD42022384092). We identified 2298 studies, of which 16 were included, comprising 1389 patients with PVT (mean age, 50.4±9.3 years; 60.0% women). Among them, 67.2% were New York Heart Association stage III/IV at admission. Overall, 48.1% were treated with systemic thrombolysis and 51.9% with cardiac surgery. The mortality rate was 10.8% in the thrombolysis group and 15.3% in the surgery group. The pooled risk difference for death with systemic thrombolysis was 1.13 (exact CI, 0.74-1.79; ζ 2 =0.89; P <0.001) versus cardiac surgery. Rates of both transient ischemic attack and non-central nervous system embolism were higher in the thrombolysis group ( P =0.002 and P =0.02, respectively). Treatment success, major bleeding, and stroke were similar between groups. Sensitivity analysis including studies that used low-dose or slow-infusion thrombolysis showed that the mortality rate was lower, and treatment success was higher, in patients referred to systemic thrombolysis, with similar rates of other secondary outcomes., Conclusions: There is evidence to suggest that thrombolysis might be the preferred option for the management of PVT without cardiogenic shock, pending future randomized controlled trials or larger observational studies.

Percutaneous coronary and structural heart interventions are increasingly preferred over cardiac surgery due to reduced rates of periprocedural complications and faster recovery but often require postprocedural antithrombotic therapy for the prevention of local thrombotic events. Antithrombotic therapy is inevitably associated with increased bleeding, the extent of which is proportional to the number, duration, and potency of the antithrombotic agents used. Bleeding complications have important clinical implications, which may outweigh the expected benefit of reducing thrombotic events. Herein, we provide a comprehensive description of the classification and clinical relevance of high bleeding risk in patients undergoing coronary and structural heart interventions., Competing Interests: Disclosure M. Galli declares that he has received honoraria from Terumo, outside the present study. D. D’Amario reports no disclosures for the present study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Percutaneous left atrial appendage closure (LAAC) is a valid alternative to oral anticoagulation to prevent ischemic stroke in patients with atrial fibrillation.The devices approved in Europe and United States for percutaneous LAAC contain metal and temporary antithrombotic therapy is strongly recommended following implantation to prevent thrombus formation on the atrial device surface. There is still uncertainty regarding to the optimal antithrombotic drug regimen after device implantation for several reasons. Thus, this review aims at summarizing the available evidence and the remaining challenges related to the management of antithrombotic therapy in the context of LAAC procedure., Competing Interests: Disclosures R. Galea reports no relationships relevant to the contents of this paper to disclose. L. Raber reports research grants to institution by Abbott Vascular, United States, Boston-Scientific, Biotronik, Germany, InfraRedx, United States, HeartFlow, United States, Sanofi, United States, Regeneron and Swiss National Science Foundation. He reports speaker/consultation fees by Abbott-Vascular, Amgen, AstraZeneca, Canon, Novo Nordisk, Medtronic, Occlutech, Sanofi., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications., Methods: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications., Results: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported., Conclusions: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively., Levels of Evidence: Level II, retrospective study., Competing Interests: Conflicts of interest None of the authors have financial disclosures related to the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite the advancements in extracorporeal membrane oxygenation (ECMO) technology, balancing the prevention of thrombosis and the risk of bleeding in patients on ECMO is still a significant challenge for physicians. This systematic review and meta-analysis aimed to assess the efficacy and safety of viscoelastic point-of-care (POC)-guided coagulation management in adult patients on ECMO., Methods: PubMed Medline, Embase, Scopus, Web of Science, and Cochrane Library databases were searched. After quality assessment, meta-analysis was carried out using random effects model, heterogeneity using I 2 and publication bias using Doi and Funnel plots., Results: A total of 1718 records were retrieved from the searches. Fifteen studies that enrolled a total of 583 participants met the inclusion criteria. Of those, 3 studies enrolling 181 subjects were eligible for meta-analysis. In patients managed with POC-guided algorithms, the odds were coherently lower for bleeding (OR 0.71, 95%CI 0.36-1.42), thrombosis (OR 0.91, 95%CI 0.32-2.60), and in-hospital mortality (OR 0.54, 95%CI 0.29-1.03), but not for circuit change or failure (OR 1.50, 95%CI 0.59-3.83). However, the differences were not statistically significant due to wide 95%CIs., Conclusion: Viscoelastic POC monitoring demonstrates potential benefits for coagulation management in ECMO patients. Future research should focus on standardizing evidence to improve clinical decision-making., Registration: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with registration ID CRD42023486294., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2023. Published by Elsevier Inc.)

There has been an expansion in our understanding of the multifaceted roles of circulating blood cells in regulating haemostasis and contributing to thrombosis. Notably, there is greater recognition of the interplay between coagulation with inflammation and innate immune activation and the contribution of leucocytes. The full blood count (FBC) is a time-honoured test in medicine; however, its components are often viewed in isolation and without consideration of their haemostatic and thrombotic potential. Here, we review how the individual components of the FBC, that is, haemoglobin, platelets and leucocytes, engage with the haemostatic system and focus on both their quantitative and qualitative attributes. We also explore how this information can be harnessed into better management of people with multiple long-term conditions because of their higher risk of adverse clinical events., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: To assess the anatomical complexity of the left atrial appendage (LAA) using fractal dimension (FD) based on cardiac computed tomography angiography (CTA) and the association between LAA FD and LAA thrombosis., Materials and Methods: Patients with atrial fibrillation (AF) who underwent both cardiac CTA and transesophageal echocardiography (TEE) between December 2018 and December 2022 were retrospectively analyzed. Patients were categorized into normal (n = 925), circulatory stasis (n = 82), and thrombus groups (n = 76) based on TEE results and propensity score matching (PSM) was performed for subsequent analysis. FD was calculated to quantify the morphological heterogeneity of LAA. Independent risk factors for thrombus were screened using logistic regression. The diagnostic performance of FD and CHA 2 DS 2 -VaSc score for predicting thrombus was evaluated using the area under the receiver operating characteristics curve (AUC)., Results: LAA FD was higher in the thrombus group (1.61 [1.49, 1.70], P < 0.001) than in the circulatory stasis (1.33 [1.18, 1.47]) and normal groups (1.30 [1.18, 1.42]) both before and after PSM. LAA FD was also an independent risk factor in the thrombus (OR [odds ratio] = 570,861.15 compared to normal, 41,122.87 compared to circulatory stasis; all P < 0.001) and circulatory stasis group (OR = 98.87, P = 0.001) after PSM. The diagnostic performance of LAA FD was significantly better than the CHA 2 DS 2 -VaSc score in identifying thrombus., Conclusions: Patients with high LAA FD are more likely to develop LAA thrombus, and the use of FD provides an effective method for assessing the risk of thrombosis in AF patients, thereby guiding individualized clinical treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Evidence suggests that some COVID-19 survivors experience a wide range of post-COVID-19 sequelae; however, the majority of studies were conducted before the emergence of the milder Omicron variant. We examined the post-acute risk of new-incident cardiovascular complications after SARS-CoV-2 infection in a multi-ethnic Asian population, during Omicron predominance., Methods: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals with confirmed SARS-CoV-2 infection during Omicron BA.1/2 transmission and a contemporaneous test-negative group. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular complications using doubly robust competing-risks survival analysis. Risks were reported using two measures: hazard ratio and excess burden., Results: We included 375 903 test-positive, infected individuals (mean age 48 years) and 619 379 test-negative controls (mean age 47 years). The majority (97.5%, 366 593/375 903) of infected individuals had mild infection not requiring hospitalization. There was no overall increased risk of new-incident cardiovascular complications, (adjusted hazards ratio, aHR = 1.01 [0.97-1.07]) amongst COVID-19 survivors when compared against test-negatives. A modestly increased risk and excess burden of dysrhythmias amongst COVID-19 survivors (aHR = 1.09 [1.01-1.19]) was observed. Risk and burdens of new-incident cardiovascular complications predominantly accrued in hospitalized (aHR = 2.81 [2.26-3.50]) and severe COVID-19 cases (aHR = 5.52 [3.76-8.10])., Discussion: No significantly increased overall risk of any cardiovascular complication was observed in the 300 days following COVID-19 infection during the Omicron-dominant period when compared against test-negatives, with the exception of a small increased occurrence of dysrhythmias., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Study Objective: Catheter-related thrombosis (CRT) is a major complication of central venous catheters (CVCs). However, the incidence, onset, and dependence of CRT on CVC material and/or type in critically ill surgical patients is unknown. Therefore, we here investigated the incidence, onset, and dependence of CRT on a variety of risk factors, including CVC material and type, in critically ill surgical patients., Design: Prospective, investigator-initiated, observational study., Setting: A surgical intensive care unit at a university hospital., Patients: All critically ill patients with CVCs (surgical: 79.8%/medical: 20.2%) who were treated in our surgical intensive care unit during a six-month period., Interventions: None., Measurements: All CVCs were examined for CRT every other day using ultrasound, starting within 24 h of placement. The primary outcome was the time of onset of CRT, depending on the type of CVC (three to five lumens, three different manufacturers). The CRT risk factors were analyzed using multiple Cox proportional hazards regression models., Main Results: We included 94 first-time CVCs in the internal jugular vein. The median time to CRT varied from one to five days for different types of CVCs. Within one day, 37 to 64% of CVCs and within one week, 64 to 100% of CVCs developed a CRT. All but one of the CRT observed were asymptomatic and caused no complications. Multiple regression analyses of CRT risk factors showed that beside cancer and omitting prophylactic anticoagulation, some types of CVC were also associated with a higher risk of CRT., Conclusions: Almost all CVCs in the internal jugular vein in critically ill surgical patients developed an asymptomatic CRT in the first days after catheterization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The incidence of vascular injury associated with knee arthroplasty is scarce, but, when they occur, the consequences are serious., Objectives: Describe the incidence of vascular lesions in our center and evaluate time to diagnosis, resolution and follow-up., Materials and Methods: Retrospective cohort during the 2010-2019 period of primary arthroplasties and knee revision. The incidence of vascular lesions and their demographic characteristics were analyzed. Type of lesion, diagnostic method and treatment were recorded. It was evaluated in distant follow-up of pain and functionality., Results: 7.940 primary total knee arthroplasty and revision surgeries were recorded, and a report of 7 emergency cases for vascular lesions was also recorded, with an incidence of 0.088%. 3 vascular lesions were caused by direct laceration of the popliteal artery, 1 case of thrombosis of the popliteal artery and 3 cases of pseudoaneurysmal lesion of the superior genicular artery. Three vascular lesions that occurred in primary arthroplasty were immediately repaired by a vascular surgeon. Pseudoaneurysm lesions and thrombosis were resolved by angiographic procedure., Discussion: Vascular complications around the knee are rare. Time to diagnosis and treatment is essential. Digital angiography is a diagnostic and therapeutic tool. There are various repair techniques, whether it's embolization, cauterization, stenting or endoprosthesis; therefore, digital angiography is a safe method with a low complication rate., Conclusion: The incidence of vascular lesions in knee arthroplasty in our center is very low. The cases were diagnosed and resolved early, without registering subsequent complications with good functional results in distant follow-up., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Competing Interests: D.J.A. received funding from Bayer PLC to setup the multicenter database of CA-COVID-19 study as an investigator-initiated funding (P87339) and received research grant from Leo Pharma. M.L. received consultation and speaker fees from AstraZeneca, Sobi, LEO Pharma, Takeda, and Pfizer. Others have no conflict of interest to declare.

Purpose of Review: Although lung transplantation stands as the gold standard curative therapy option for end-stage lung disease, the scarcity of available organs poses a significant challenge in meeting the escalating demand. This review provides an overview of recent advancements in ambulatory respiratory assist systems, selective anticoagulation therapies that target the intrinsic pathway, and innovative surface coatings to enable permanent respiratory support as a viable alternative to lung transplantation., Recent Findings: Several emerging ambulatory respiratory assist systems have shown promise in both preclinical and clinical trials. These systems aim to create more biocompatible, compact, and portable forms of extracorporeal membrane oxygenation that can provide long-term respiratory support. Additionally, innovative selective anticoagulation strategies, currently in various stages of preclinical or clinical development, present a promising alternative to currently utilized nonselective anticoagulants. Moreover, novel surface coatings hold the potential to locally prevent artificial surface-induced thrombosis and minimize bleeding risks., Summary: This review of recent advancements toward permanent respiratory support summarizes the development of ambulatory respiratory assist systems, selective anticoagulation therapies, and novel surface coatings. The integration of these evolving device technologies with targeted anticoagulation strategies may allow a safe and effective mode of permanent respiratory support for patients with chronic lung disease., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This prospective study investigated the relationship between inflammation, damage-associated molecular patterns (DAMPs), and thrombus formation on dialyzer membranes in critically ill patients undergoing renal replacement therapy (RRT) from July 2020 to August 2022, identifying mechanisms and interventions to prevent clotting. The patients were divided into two groups: inflammatory (n = 56, serum C-reactive protein >10 mg/dl) and noninflammatory control (n = 45, serum C-reactive protein <5 mg/dl). Cell-free deoxyribonucleic acid (DNA) levels, high mobility group box 1 protein (HMGB1), histone H3, and myeloperoxidase (MPO) in the lumen of the hollow fiber membrane of the dialyzer were quantified. Immunostaining assessed leukocytes, fibrin fibers, and platelet thrombi on the luminal surface of the hollow fiber membrane. The inflammatory group, compared to controls, exhibited elevated cell-free DNA, HMGB1, and MPO levels, although histone H3 remained unchanged. Damage-associated molecular patterns increased with disseminated intravascular coagulation (DIC) severity. Immunostaining in the inflammatory group revealed leukocytes, amorphous nuclei, neutrophil extracellular trap-like structures, fibrin fibers, and platelet thrombi on the hollow fiber membrane's luminal surface. Elevated DAMP levels in severely inflamed patients' dialyzer membranes, correlating with DIC severity, indicate a link between inflammation, coagulation activation, and dialyzer clotting. Research into thrombus prevention in RRT for DIC-affected critically ill patients is warranted., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Ovarian cancer, an aggressive malignancy of the female reproductive tract, is frequently linked to an elevated risk of thrombotic events. This association is manifested by a pronounced rise in platelet counts and activation levels. Current research firmly supports the pivotal role of platelets in the oncogenic processes of ovarian cancer, influencing tumor cell proliferation and metastasis. Platelets influence these processes through direct interactions with tumor cells or by secreting cytokines and growth factors that enhance tumor growth, angiogenesis, and metastasis. This review aims to thoroughly dissect the interactions between platelets and ovarian cancer cells, emphasizing their combined role in tumor progression and associated thrombotic events. Additionally, it summarizes therapeutic strategies targeting platelet-cancer interface which show significant promise. Such approaches could not only be effective in managing the primary ovarian tumor but also play a pivotal role in preventing metastasis and attenuating thrombotic complications associated with ovarian cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This case report documents the management of a 66-year old man with atrial fibrillation with recent placement of a WATCHMAN ® Flex atrial appendage occlusion device. The patient presented with renal failure, abdominal pain, and difficulty walking 2 months after placement. The WATCHMAN ® Flex device was found to have embolized to his abdominal aorta at the level of the renal arteries with associated thrombus. Extensive workup revealed reduced left ventricular cardiac function and decreased renal function, both of which were felt to be potentially reversible with device removal. The patient then underwent retrieval of the device and all associated thrombus via an open retroperitoneal approach. This case demonstrates a potential consequence of implanting devices such as an atrial appendage occlusion device and describes a technique for removal., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Retransplantation has been the primary treatment for hepatic artery thrombosis (HAT) in patients with orthotopic liver transplant (OLT); however, because of scarcity of grafts, endovascular revascularization via mechanical thrombectomy offers an alternative to retransplantation should it provide similar long-term benefits. Data regarding a series of 8 patients with hepatic artery thrombectomies across 10 procedures (1 early HAT and 9 late HAT) utilizing stent retriever and/or suction catheter were collected. All had technically successful restoration of flow with stent placement of the anastomotic stenosis in 8 cases. Two patients required reintervention for HAT at 18 and 701 days after primary intervention, with the first dying from liver failure but with a patent hepatic artery on explant. One case had a procedure-related adverse event, hepatic artery dissection, Society of Interventional Radiology (SIR) adverse event classification of 2. Technical success was achieved in all procedures, demonstrating promise in effectively treating HAT in patients with OLT., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Multidisciplinary collaboration to create formal education/training programmes in women's thrombosis and haemostasis will ideally lead to improved knowledge and health equity and potentially improve patient outcomes., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: The continuity of arteriovenous fistula (AVF) patency is essential for effective hemodialysis. In the present study, we aimed to investigate the relationship between AVF patency and atherogenic index of plasma (AIP) in patients with native proximal upper-extremity AVF., Methods: A total of 143 patients with native proximal upper-extremity AVF created in our clinic between January 2014 and April 2022 were analyzed retrospectively. Those with at least 24 months of follow-up and intact AVF were defined as "Group 1" ( n  = 97), and those with AVF thrombosis were defined as "Group 2" ( n  = 46)., Results: The primary patency rates of the patient groups included in the study were found to be 88.1% at 6th month, 79% at 12th month, and 67.8% at 24th month. The mean AIP values that were calculated in Group 2 were found to be statistically significantly higher than the mean value calculated in Group 1 (0.30 ± 0.12 vs 0.20 ± 0.10, p  < 0.001). In a multivariate logistic regression analysis made to identify the predictors of proximal upper-extremity AVF thrombosis development, total cholesterol (OR [odds ratio] = 2.259, 95% CI [confidence interval] = 1.468-3.475, p  < 0.001), and triglyceride (OR = 13.777, 95% CI = 3.740-50.750, p  < 0.001) were identified as independent predictors., Conclusion: A significant relationship was detected in the analyses between the easily calculated AIP values and the development of AVF thrombosis. The AIP is a remarkable preoperative parameter regarding proximal upper-extremity AVF patency., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cardiomyopathies cause most intracardiac thrombosis (ICT), and Behçet's syndrome (BS) is a rare inflammatory disease that can be responsible for a proportion of ICT. Other inflammatory disorders involved in the aetiology of ICT include antiphospholipid syndrome, Henoch-Schonlein purpura, COVID-19, and Loeffler endocarditis. ICT usually occur during the active phase of BS, and they have a close relationship with vascular involvement. Atrial myxomas are benign cardiac tumours arising from the interatrial septum. They can lead to a substantial acute phase response, making them difficult to distinguish from inflammatory diseases. In this case study, we present a 46-year-old female BS patient who presented with constitutional symptoms mimicking BS flare in a routine follow-up visit and was diagnosed with left atrial myxoma after administration of several lines of immunosuppressives. Then, she underwent surgical tumour excision, and a histopathological examination confirmed the diagnosis.In conclusion, atrial myxoma should be kept in mind first of all when suspecting ICT, and advanced imaging methods such as cardiac magnetic resonance imaging (MRI) should be used if necessary.

Anti-platelet factor 4 immunothrombotic syndromes comprise a group of disorders that include heparin-induced thrombocytopenia and vaccine-induced immune thrombocytopenia and thrombosis. These are highly prothrombotic, immunological disorders characterised by specific clinical and pathological criteria which include thrombocytopenia and thrombosis. While they are predominantly triggered by heparin and the adenoviral vector vaccines, respectively, other provoking factors have been described, as well as spontaneous forms. The unexplained co-occurrence of thrombocytopenia with thrombosis should raise suspicion and prompt testing. This nutshell review discusses the pathophysiology, presenting features and diagnostic criteria for these conditions., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices-such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass-require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices., Competing Interests: J.J.S reports receiving consulting fees from Aronora Inc. The remaining authors have nothing to disclose., (Thieme. All rights reserved.)

Background: Device-related thrombus (DRT) after left atrial appendage occlusion (LAAO) is potentially linked to adverse events. Although clinical reports suggest an effect of the device type and position on the DRT risk, in-depth studies of its mechanistic basis are needed. This in silico study aimed to assess the impact of the position of non-pacifier (Watchman) and pacifier (Amulet) LAAO devices on surrogate markers of DRT risk., Methods: The LAAO devices were modeled with precise geometry and virtually implanted in different positions into a patient-specific left atrium. Using computational fluid dynamics, the following values were quantified: residual blood, wall shear stress (WSS) and endothelial cell activation potential (ECAP)., Results: In comparison to an ostium-fitted device position, deep implantation led to more residual blood, lower average WSS and higher ECAP surrounding the device, especially on the device's atrial surface and the surrounding tissue, suggesting increased risk for potential thrombus. For the non-pacifier device, an off-axis device orientation resulted in even more residual blood, higher ECAP and similar average WSS as compared to an ostium-fitted device position. Overall, the pacifier device showed less residual blood, higher average WSS and lower ECAP, compared to the non-pacifier device., Conclusions: In this in silico study, both LAAO device type and implant position showed an impact on potential markers of DRT in terms of blood stasis, platelet adhesion and endothelial dysfunction. Our results present a mechanistic basis for clinically observed risk factors of DRT and the proposed in silico model may aid in the optimization of device development and procedural aspects., (© 2023. The Author(s).)

Objective: The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine-induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination., Methods: This study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine-induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine-induced TTS across 156 countries., Results: We identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine-induced TTS among 404 388 reports of all-cause TTS. There has been a significant increase in reports of vaccine-induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID-19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75-3.00]; IC [IC 0.25 ], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07-2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78-2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50-2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50-1.86]; 0.73 [0.55]), adenovirus Type 5 vector-based (Ad5-vectored) COVID-19 (1.64 [1.59-1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49-1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12-1.78]; 0.49 [0.11]). Concerning age and sex-specific risks, reports of vaccine-induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%)., Conclusion: A rise in vaccine-induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5-vectored COVID-19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine-induced TTS for preventive interventions and early diagnosis., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Patients with Antiphospholipid Syndrome (APS) undergoing cardiopulmonary bypass (CPB) surgery are at increased risk for thrombotic and hemorrhagic complications. Anticoagulation during CPB is typically monitored with activated clotting time (ACT) which may be falsely prolonged in patients with APS. The Hepcon Hemostasis Management System quantitatively determines the whole blood heparin concentration through heparin/protamine titration., Methods: This was a retrospective study of APS patients who underwent cardiac surgery requiring CPB at the Cleveland Clinic between April 2013, and July 2020. The primary endpoint was the composite rate of hemorrhagic or thromboembolic complications per surgical case in patients monitored by Hepcon versus patients monitored by ACT. Secondary endpoints were median volume of chest tube output and packed red blood cell (PRBC) transfusion within the first three post-operative days., Results: 43 patients were included. 20 (47%) patients were monitored using Hepcon while 23 (53%) were monitored using ACT. For the primary endpoint of rate of thromboembolic or hemorrhagic complications per surgical case, there was no statistically significant difference between the Hepcon and ACT groups (HMS, 6/20 [30%]; ACT, 7/23 [30%]; p = >0.99). For the secondary endpoints, there was no statistically significant difference in median post-operative chest tube output (780 mL vs. 850 mL; p = 0.88) and median post-operative PRBC transfusion (1 unit vs. 0 unit; p = 0.28) between the Hepcon and ACT groups, respectively., Conclusion: There was no difference in the composite outcome of thrombotic or hemorrhagic complications in patients monitored by Hepcon versus those monitored by ACT., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Patrick Grady: Consultancy for Medtronic.

Competing Interests: Dr Weber reports advisory panel/consultant fees from Novo Nordisk, Horizon Therapeutics (now Amgen), and Kiniksa Pharmaceuticals. Dr Abbate reports advisory panel/consultant fees from CardiolRx, Kiniksa, and Novo Nordisk.

Abstract: Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. Although studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in PE remains controversial. LMWH may convey beneficial effects in PE independent of their anticoagulant activity, possibly by inhibiting inflammation. Here, we evaluated whether LMWH inhibit placental thromboinflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle-induced and platelet-dependent PE-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation, and improves trophoblast proliferation in vivo and in vitro. Moreover, LMWH inhibits platelet-independent trophoblast NLRP3 (NLR family pyrin domain containing 3) inflammasome activation. Mechanistically, LMWH activates via heparin-binding epidermal growth factor (HBEGF) signaling the PI3-kinase-AKT pathway in trophoblasts, thus preventing inflammasome activation. In human PE placental explants, inflammasome activation and PI3-kinase-AKT signaling events were reduced with LMWH treatment compared with those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates PE-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in PE and identify a signaling mechanism through which LMWH ameliorates PE, thus providing a rationale for the use of LMWH in PE., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Patients with thrombotic antiphospholipid syndrome (APS) are at high risk for recurrent thrombosis, and indefinite anticoagulation is recommended. Patients with APS merit indefinite anticoagulation, and vitamin K antagonists (VKAs) have historically been the standard treatment. Direct oral anticoagulants (DOACs) present an appealing alternative to VKAs. Due to their pharmacokinetic and pharmacodynamic characteristics, DOACs offer advantages over VKAs, namely the lack of need for laboratory monitoring, the usage of a fixed dosage, and the absence of significant interaction with dietary components and drugs. The efficacy and safety of DOACs in patients with APS have been studied in four phase II/III clinical trials (three with rivaroxaban and one with apixaban). These studies showed DOACs' inferiority compared to VKAs in preventing recurrent thrombosis. Recurrence was significantly greater in patients with arterial thrombotic events and a triple positivity for antiphospholipid antibodies. No differences were observed in the incidence of venous thromboembolism between both groups. Major bleeding was similar in patients treated with DOACs or VKAs. Several observational studies have reported similar results. This review aims to analyse the existing evidence on the efficacy and safety of DOACs for secondary prevention in patients with APS.

Platelets are small cell fragments that play a crucial role in hemostasis, requiring fast response times and fine signaling pathway regulation. For this regulation, platelets require a balance between two pathway types: the activatory and negative signaling pathways. Activatory signaling mediators are positive responses that enhance stimuli initiated by a receptor in the platelet membrane. Negative signaling regulates and controls the responses downstream of the same receptors to roll back or even avoid spontaneous thrombotic events. Several blood-related pathologies can be observed when these processes are unregulated, such as massive bleeding in activatory signaling inhibition or thrombotic events for negative signaling inhibition. The study of each protein and metabolite in isolation does not help to understand the role of the protein or how it can be contrasted; however, understanding the balance between active and negative signaling could help develop effective therapies to prevent thrombotic events and bleeding disorders.