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Patients with thrombophilia show a higher incidence of VTE due to a disturbance in the hemostatic system. Hereditary thrombophilia can be identified by laboratory diagnostics, however most guidelines advise against thrombophilia testing in the majority of the patients with VTE, since the outcome rarely affects clinical decisions for the treatment. In this article we describe two cases in which hereditary thrombophilia testing could be considered. Thrombophilia testing should only be performed in specific patients, where it is already decided beforehand how the outcome will guide future decision making.

The coagulation and thrombotic systems of an infant are fundamentally different from those of adults and older children. Hemostatic factors have inherently lower circulation levels in infants and are also affected prenatally by conditions of pregnancy. The unique physiology of neonates can contribute to a procoagulant state, which can result in a high level of morbidity and mortality. This review outlines the epidemiology, clinical characteristics, diagnosis and management, and etiologies of congenital and acquired forms of thrombotic disorders, with a discussion of the evaluation for hypercoagulation., (Copyright © 2024 by the American Academy of Pediatrics.)

Transesophageal echocardiography (TEE) is the standard method for diagnosing left atrial appendage (LAA) hypercoagulability in patients with atrial fibrillation (AF), which means LAA thrombus/sludge, dense spontaneous echo contrast and slow LAA blood flow velocity (< 0.25 m/s). Based on machine learning algorithms, cardiac computed tomography angiography (CCTA) radiomics features were adopted to construct prediction models and explore a suitable approach for diagnosing LAA hypercoagulability and adjusting anticoagulation. This study included 652 patients with non-valvular AF. The univariate analysis were used to select meaningful clinical characteristics to predict LAA hypercoagulability. Then 3D Slicer software was adopted to extract radiomics features from CCTA imaging. The radiomics score was calculated using the least absolute shrinkage and selection operator logistic regression analysis to predict LAA hypercoagulability. We then combined clinical characteristics and radiomics scores to construct a nomogram model. Finally, we got prediction models based on machine learning algorithms and logistic regression separately. The area under the receiver operating characteristic curve of radiomics score was 0.8449 in the training set and 0.7998 in the validation set. The nomogram model had a concordance index of 0.838. The final machine-learning based prediction models had good performances (best f1 score = 0.85). Radiomics features of long maximum diameter and high uniformity of Hounsfield unit in left atrial were significant predictors of the hypercoagulable state in LAA, with better predictive efficacy than clinical characteristics. Our combined models based on machine learning were reliable for hypercoagulable state screening and anticoagulation adjustment., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The radiological pattern of stroke patients with thrombophilia is unknown. Our aim is to compare the MRI radiological pattern of silent and acute lesions in cryptogenic stroke/TIA patients under 60 years of age with and without thrombophilia., Methods: Cryptogenic stroke/TIA patients under 60 years of age hospitalized at our Stroke Unit during four years were consecutively included. Thrombophilia screening was performed at 3 months after stroke and verified 12 weeks later. The follow-up was performed at 3, 12 and 24 months. Radiological pattern was assessed with the Fazekas and van Swieten scales., Results: During four years, 185 cryptogenic stroke/TIA patients under 60 years of age were included; mean age was 51 years, 61% were female, with a follow-up of 22±3.2 months. Thrombophilia was detected in 20% of patients. We detected a significant increase of previous vascular events (29.7% vs 7.5%, p=.01) as well as lower hypercholesterolemia (27% vs 62.5% p=.003) in the thrombophilia group, without significant differences in other vascular risk factors or vascular recurrence during follow-up. Regarding the acute lesion, we did not detect significant differences between groups. The radiological pattern of silent lesions showed that the thrombophilia group presented more large confluent lesions (39.1% vs 19.2%, p=.02) with greater sparing of the anterior territory (0% vs 30%, p=.01)., Conclusions: Our data suggest a characteristic radiological pattern of silent lesions in cryptogenic stroke/TIA patients with thrombophilia, with more confluent lesions and less involvement of the anterior territory., 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.)

Although inherited thrombophilias are lifelong risk factors for a first thrombotic episode, progression to thrombosis is multifactorial and not all individuals with inherited thrombophilia develop thrombosis in their lifetimes. Consequently, indiscriminate screening in patients with idiopathic thrombosis is not recommended, since presence of a thrombophilia does not necessarily predict recurrence or influence management, and testing should be selective. It follows that a decision to undertake laboratory detection of thrombophilia should be aligned with a concerted effort to identify any significant abnormalities, because it will inform patient management. Deficiencies of antithrombin and protein C are rare and usually determined using phenotypic assays assessing biological activities, whereas protein S deficiency (also rare) is commonly detected with antigenic assays for the free form of protein S since available activity assays are considered to lack specificity. In each case, no single phenotypic assay is capable of detecting every deficiency, because the various mutations express different molecular characteristics, rendering thrombophilia screening repertoires employing one assay per potential deficiency, of limited effectiveness. Activated protein C resistance (APCR) is more common than discrete deficiencies of antithrombin, protein C, and protein S and also often detected initially with phenotypic assays; however, some centres perform only genetic analysis for factor V Leiden, as this is responsible for most cases of hereditary APCR, accepting that acquired APCR and rare F5 mutations conferring APCR will go undetected if only factor V Leiden is evaluated. All phenotypic assays have interferences and limitations, which must be factored into decisions about if, and when, to test, and be given consideration in the laboratory during assay performance and interpretation. This review looks in detail at performance and limitations of routine phenotypic thrombophilia assays., Competing Interests: G.W.M. reports consultancy fees from Technoclone., (Thieme. All rights reserved.)

Objectives: To compare standard tests of haemostasis in hypercoagulable and normocoagulable sick dogs as identified by thromboelastography., Materials and Methods: We compared prothrombin time, activated partial thromboplastin time, D-dimers, packed red blood cell volume and platelet counts in client-owned sick dogs with hypercoagulable (n = 36) and normocoagulable (n = 35) states as identified by thromboelastography maximum amplitude above or within the established reference interval, respectively., Results: Seventy-one dogs were included. Thirty-six dogs were hypercoagulable and 35 were normocoagulable on thromboelastography. Using multivariable linear models, prothrombin time, activated partial thromboplastin time and D-dimers were not associated with hypercoagulability. Platelet counts and packed red blood cell volume were significantly associated with hypercoagulability., Clinical Significance: Prothrombin time, activated partial thromboplastin time and D-dimers were not useful in the identification of hypercoagulability in dogs as defined by thromboelastography., (© 2024 The Author(s). Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Background: Epidemiologic studies have shown that patients with acute exacerbation of COPD (AECOPD) suffer from morbidity and mortality from venous thromboembolism (VTE) and poor diagnosis. Von Willebrand factor (vWF) and plasminogen activator inhibitor type-1 (PAI-1) are frequently investigated in COPD as crucial parameters for coagulation and fibrinolysis. Nevertheless, the role of vWF and PAI-1 in AECOPD needs further exploration., Objective: We sought to evaluate the hypercoagulability in AECOPD and investigate the association of plasma vWF and PAI-1 with occurrence and exacerbation risk of AECOPD patients., Methods: Fifty-seven AECOPD patients and 34 control subjects were enrolled in our study. The concentrations of plasma vWF and PAI-1 antigens were measured by ELISA kit. Independent samples t -test or Wilcoxon rank sum test was applied for group comparison. Spearman correlation analysis, subject work curve (ROC) analysis, and Logistic regression were used to evaluate the role of the plasma vWF and PAI-1 in AECOPD., Results: We observed increased vWF (770.15 ± 325.52 vs 327.62 ± 210.97 ng/mL, P < 0.001) and PAI-1 (0.47 vs 0.17 ng/mL, P < 0.001) levels in AECOPD patients compared with control subjects. Both vWF and PAI-1 are closely related to COPD (vWF: AUC = 0.8741, P < 0.001; PAI-1: AUC = 0.8222, P < 0.001). Moreover, elevated vWF could be an independent risk factor for COPD (OR = 1.01, 95% CI: 1.00-1.01, P = 0.01). We also discovered higher plasma levels of vWF and PAI-1 in the COPD "E" group in contract to "AB" group (vWF: 966.29 ± 251.18 vs 552.21 ± 253.28, P < 0.0001; PAI-1: 1.02 vs 0.38, P = 0.003). And vWF levels increased with increasing COPD exacerbation risk, moreover, plasma vWF positively related with patients' CAT scores and SGRQ scores. In addition, plasma vWF and PAI-1 correlated with each other in total participants and AECOPD subgroup analysis., Conclusion: This study demonstrated that AECOPD patients have a prothrombotic state, as demonstrated by vWF and PAI-1 levels in plasma compared with those in control subjects, and the prothrombotic state increases with increasing COPD exacerbation risk., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Jin et al.)

Inadequate treatment of venous thromboembolism can have fatal consequences that are often irreversible. If the indication is given, long-term therapeutic anticoagulation may be necessary to reduce the risk of recurrence for those affected. On the other hand, there is an increased risk of bleeding due to continued anticoagulation, so an individual risk/benefit assessment is necessary. A careful assessment of possible contributing factors is therefore essential. If uncertainty persists, comprehensive environmental diagnostics with regard to thrombophilia or cancer can be helpful., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Abstract: Inherited thrombophilia (IT) workup is commonly pursued in patients with venous thromboembolism (VTE). Recent American Society of Hematology guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large, prospective Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were analyzed to compare VTE risk factors, management, and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and after its discontinuation. Among 103 818 patients enrolled in RIETE, 21 089 (20.3%) were tested for IT, 8422 (8.1%) tested positive, and 82 729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors and less common in those with major risk factors such as surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However, IT-negative patients with pregnancy or postpartum-related VTE had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates after treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities. The trial was registered at www.clinicaltrials.gov as #NCT02832245., (© 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.)

Importance: Antiphospholipid syndrome in neonates and children is a rare, but in some cases life-threatening condition with arterial and/or venous thrombosis and/or non-thrombotic neurological, skin, ophthalmological and other manifestations., Observations: This review highlights the available information about the features of pediatric APS, including the rare catastrophic form, the differences between pediatric and adult APS, and the role of genetic thrombophilia in APS manifestation., Conclusions and Relevance: The clinical manifestations and treatment options for APS in children may differ from those in adults, and prescribing therapy can be challenging due to the unique clinical and morphological characteristics of the pediatric patient. Pediatric APS may be a predictor of the development of certain autoimmune diseases and classic manifestations of APS in adulthood, therefore, a revision of the existing criteria for the diagnosis and treatment of APS in children is necessary.

Patients diagnosed with lymphoma or multiple myeloma are at elevated risk of venous thromboembolism (VTE). Optimum risk stratification and effective thromboprophylaxis can only be achieved through the development of a multiple-specific risk score that successfully captures all aspects of the heterogeneous prothrombotic environment existing in these patients. Our aim was to identify risk factors for thrombosis and suggest an improved tool combining clinical data, thrombo-inflammatory biomarkers and genetic (Thrombo inCode® test) variables for predicting thrombotic risk in patients with lymphoma and multiple myeloma. A prospective longitudinal study was conducted on newly-diagnosed lymphoma and multiple myeloma patients who presented at our institution between February 2020 and January 2021. The study included 47 patients with lymphoma and 16 patients with multiple myeloma. We performed a follow-up of 1 year or until September 2021. The incidence of venous thrombosis and associated risk factors were analysed, including the genetic Thrombo inCode® test. Khorana and ThroLy scores for lymphoma patients and IMPEDE VTE score for myeloma patients were calculated. At a median follow-up of 9.1 months, VTE incidence was 9.5% (6/63), with 4 and 2 patients with lymphoma and myeloma who developed the events, respectively. Univariate analysis showed that the incidence of thrombosis was significantly higher in patients with ECOG ≥ 2 and prior immobility. Median factor VIII levels were significantly higher in patients with thrombosis (with increased values in all of them). Moreover, there was a trend in genetic variant rs5985 (factor XIII) as a protective factor, and a trend to higher thrombotic risk in patients with factor V Leiden, rs2232698 variant (serpinA10), low total protein S activity, elevated D-dimer, aggressive lymphoma and treatment with dexamethasone. The results of our study demonstrate promise for the potential use of widely accessible markers to increase precision in risk prediction for VTE in patients with lymphoma and multiple myeloma, particularly ECOG ≥ 2, immobility and higher factor VIII levels, as well as lymphoma aggressiveness, treatment with dexamethasone and the haemostatic biomarkers D-dimer and total protein S activity. Additionally, genetic variants factor V Leiden, serpinA10 rs2232698 and factor XIII-A Val34Leu warrant further investigation for use in the research setting., (© 2024. The Author(s).)

β-Thalassemia especially transfusion-dependent thalassemia (TDT) associates with a hypercoagulable state, which is the main cause of thromboembolic events (TEE). Plasma viscosity and rheological parameters could be essential markers for determining hypercoagulable state in β-thalassemia patients. The traditional methods for measuring viscosity are often limited by large sample volumes and are impractical for routine clinical monitoring. The compact differential dynamic microscopy-based device (cDDM), an optical microscopy for quantitative rheological assessment, was developed and applied for prognosis of the hypercoagulable state in β-TDT with and without splenectomy. The device was performed plasma viscosity measurement using low plasma volume (8 μL) and revealed a value as modulus of complex viscosity |η(ω)| in 7 min. We also parallelly demonstrated the correlation of the viscosity and related-coagulable parameters: complete blood count, prothrombin time (PT), activated partial thromboplastin time (APTT), protein C (PC), protein S (PS), CD62P and CD63 expression, and platelet aggregation test. The thalassemia plasma exhibited a higher value of |η(ω)| than healthy plasma, which can represent a different viscoelastic property among the groups. Even all related-coagulable parameters indicated hypercoagulable state in both nonsplenectomies and splenectomies β-TDT patients when compared to control, only high platelet numbers significantly correlated to high plasma viscosity in the splenectomy group. However, the other coagulable parameters have shown a trend of positive relationship with high plasma viscosity in all β-1thalassemia TDT patients. The relative results suggested that our device would be an approach tool for early detection of hypercoagulable state in transfusion-dependent-β-thalassemia patients, which can help to prevent TEE and the critical consequent-complications.

Abstract: Decision analysis can play an essential role in informing practice guidelines. The American Society of Hematology (ASH) thrombophilia guidelines have made a significant step forward in demonstrating how decision modeling integrated within Grading of Recommendations Assessment, Developing, and Evaluation (GRADE) methodology can advance the field of guideline development. Although the ASH model was transparent and understandable, it does, however, suffer from certain limitations that may have generated potentially wrong recommendations. That is, the panel considered 2 models separately: after 3 to 6 months of index venous thromboembolism (VTE), the panel compared thrombophilia testing (A) vs discontinuing anticoagulants (B) and testing (A) vs recommending indefinite anticoagulation to all patients (C), instead of considering all relevant options simultaneously (A vs B vs C). Our study aimed to avoid what we refer to as the omitted choice bias by integrating 2 ASH models into a single unifying threshold decision model. We analyzed 6 ASH panel's recommendations related to the testing for thrombophilia in settings of "provoked" vs "unprovoked" VTE and low vs high bleeding risk (total 12 recommendations). Our model disagreed with the ASH guideline panels' recommendations in 4 of the 12 recommendations we considered. Considering all 3 options simultaneously, our model provided results that would have produced sounder recommendations for patient care. By revisiting the ASH guidelines methodology, we have not only improved the recommendations for thrombophilia but also provided a method that can be easily applied to other clinical problems and promises to improve the current guidelines' methodology., (© 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.)

Background: Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients., Aim: To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN)., Materials and Methods: The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed., Results: Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS ( p <0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS ( p <0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained., Conclusion: In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.

Introduction: There is good evidence that specific autoimmune rheumatic diseases (RDs), for example, rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with a state of hypercoagulability and an increased risk of venous thromboembolism (VTE). However, limited information regarding this association is available for other autoimmune or autoinflammatory RDs. We sought to address this issue by conducting a systematic review and meta-analysis of the association between the d-dimer, an established marker of hypercoagulability and VTE, and RDs and the possible clinical and demographic factors mediating this association., Methods: We searched the electronic databases PubMed, Web of Science, and Scopus from inception to January 31, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively., Results: In 31 studies selected for analysis (2724 RD patients and 3437 healthy controls), RD patients had overall significantly higher d-dimer concentrations when compared to controls (standard mean difference = 0.93, 95% CI 0.76-1.10, p < .001; I 2  = 86.1%, p < .001; moderate certainty of evidence). The results were stable in a sensitivity analysis. Significant associations were observed between the effect size of the between-group differences in d-dimer concentration and age, specific RD and RD category, RD duration, fibrinogen, plasminogen activator inhibitor, C-reactive protein, and erythrocyte sedimentation rate., Conclusions: Overall, patients with RDs have significantly higher d-dimer concentrations when compared with healthy controls, indicating a state of hypercoagulability. The alterations in d-dimer concentrations are mediated by age, specific RD and RD category, RD duration, and markers of anticoagulation and inflammation. Further research is warranted to investigate d-dimer concentrations across the spectrum of RDs and their utility in predicting and managing VTE in these patients (PROSPERO registration number: CRD42024517712)., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Thrombophilia, a predisposition to thrombosis, poses significant diagnostic challenges due to its multi-factorial nature, encompassing genetic and acquired factors. Current diagnostic paradigms, primarily relying on a combination of clinical assessment and targeted laboratory tests, often fail to capture the complex interplay of factors contributing to thrombophilia risk. This paper proposes an innovative artificial intelligence (AI)-based methodology aimed to enhance the prediction of thrombophilia risk. The designed multidimensional risk assessment model integrates and elaborates through AI a comprehensive collection of patient data types, including genetic markers, clinical parameters, patient history, and lifestyle factors, in order to obtain advanced and personalized explainable diagnoses.

Objective: Thromboelastography (TEG) is a whole blood assay that yields global assessment of hemostasis, as it evaluates clot time, strength, and kinematics of clot formation and lysis. The main objective was to describe preoperative TEG findings in dogs that had an adrenalectomy performed and, secondarily, to describe TEG findings in the dogs with or without hyperadrenocorticism (HAC)., Animals: 30 dogs that had preoperative TEG and adrenalectomy performed., Methods: Medical records between 2018 and 2022 were reviewed. Signalment, diagnostic data, and perioperative treatment were abstracted., Results: 53% (16/30) of the dogs were hypercoagulable, and none were hypocoagulable. Based on histopathology, 6 of 9 dogs with adenocarcinoma were hypercoagulable, 4 of 8 with pheochromocytoma were hypercoagulable, and 6 of 10 with adenoma were hypercoagulable. None of the 3 dogs with other histopathologic diagnoses or combinations of diagnoses (adrenocortical hyperplasia, poorly differentiated sarcoma, and both adrenocortical adenocarcinoma and pheochromocytoma) were hypercoagulable. Of the 14 dogs tested preoperatively for HAC, 4 of 8 HAC dogs were hypercoagulable and 2 of 6 non-HAC dogs were hypercoagulable., Clinical Relevance: The present report describes for the first time TEG findings for dogs undergoing adrenalectomy and suggests that the majority of dogs with adrenal neoplasia are hypercoagulable based on TEG results.

Viscoelastic testing is a clinically available method to assess hypercoagulability. This systematic review aims to provide a comprehensive overview of the existing literature and the potential use of such testing in patients with breast cancer. A systematic literature search for studies investigating the application of viscoelastic testing for patients with breast cancer was conducted. Studies were included as long as they were original, peer-reviewed, and in the English language. Studies were excluded if they were review articles, did not include breast cancer patients, or if the full text was unavailable. This review identified 10 articles that met the inclusion criteria. Two of the studies utilized rotational thromboelastometry, and an additional four studies used thromboelastography, to assess hypercoagulability in patients with breast cancer. Three of the identified articles discussed the use of thromboelastometry in free flap breast reconstruction for patients with breast cancer. One study was a retrospective chart review looking at thromboelastography and microsurgical breast reconstruction. Current literature regarding the application of viscoelastic testing in breast cancer and free flap breast reconstruction is limited, with no randomized trials thus far. However, some studies suggest that there may be potential utility in viscoelastic testing to assess risk for thromboembolism in breast cancer patients, and future research in this area is warranted., Competing Interests: J.H. is an employee of Haemonetics. S.P. is related to a senior executive for Haemonetics., (Thieme. All rights reserved.)

Aim: Hereditary thrombophilia (HT) testing is frequently conducted during the evaluation of patients with pulmonary embolism (PE). However, the utility of routine HT testing in this setting is unclear. We sought to assess the association of HT with risk of recurrent venous thromboembolism (VTE) following first-time PE., Methods: We conducted a multi-hospital retrospective study. Two hundred and ninety (290) patients with a first-time PE, who had been tested for HT, completed at least 3 months of therapeutic anticoagulation (AC), subsequently discontinued AC, and were followed for at least 36 months thereafter, were included., Results: HT was present in 48 of the 290 included patients (17%). Median follow-up after discontinuing AC was 61 months (interquartile range, 43-79 months). The overall recurrence rate of VTE during follow-up was 58 per 290 (20%). A total of 47 of 242 patients (19%) in the HT-absent group had a recurrent VTE, compared with 11 of 48 (22%) in the HT-present group. There was no significant difference in VTE-free survival between groups on Kaplan-Meier analysis; the hazard ratio (HR) for VTE recurrence for those with HT compared to those without (HR HT-present: HT-absent) was 1.240 (95% confidence interval [CI] 0.614-2.502; p=0.548). On multivariable analysis, HT was not associated with risk of recurrent VTE (HR 1.262; 95% CI 0.640-2.488), and the only variable associated with VTE recurrence was unprovoked PE (HR 2.954; 95% CI 1.64-5.314)., Conclusions: These findings demonstrate that the presence of HT is not associated with the risk of recurrent VTE following first PE, and support limiting the use of HT testing among patients with first PE., Competing Interests: Conflicts of Interests There are no conflicts of interest to disclose., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Hypercoagulable disorders are best described as a group of acquired and hereditary conditions that increase the risk for the development of thrombi within veins or arteries. In the setting of an unprovoked venous thromboembolism, common practice in the inpatient setting has been further investigation via a thrombophilia workup to establish an underlying cause. Current Hematology-Oncology guidelines argue against inpatient workup as the results rarely influence inpatient management. Following American Society of Hematology guidelines (Middledorp), the current study found that only 15% (11/72) of patients met appropriate criteria for thrombophilia testing. There was no relationship between appropriate thrombophilia testing and diagnosis of thrombophilia or initiation of anticoagulation. There was a relationship between appropriate thrombophilia testing and Hematology-Oncology consultation. This demonstrates the need for expert consultation if thrombophilia testing is being considered. The current study provides more evidence that a strong recommendation against inpatient testing should be made as testing does not aid in diagnosis or change management and is an overutilization of healthcare resources., 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.

Early since the onset of the COVID-19 pandemic, the medical and scientific community were aware of extra respiratory actions of SARS-CoV-2 infection. Endothelitis, hypercoagulation, and hypofibrinolysis were identified in COVID-19 patients as subsequent responses of endothelial dysfunction. Activation of the endothelial barrier may increase the severity of the disease and contribute to long-COVID syndrome and post-COVID sequelae. Besides, it may cause alterations in primary, secondary, and tertiary hemostasis. Importantly, these responses have been highly decisive in the evolution of infected patients also diagnosed with diabetes mellitus (DM), who showed previous endothelial dysfunction. In this review, we provide an overview of the potential triggers of endothelial activation related to COVID-19 and COVID-19 under diabetic milieu. Several mechanisms are induced by both the viral particle itself and by the subsequent immune-defensive response (i.e., NF-κB/NLRP3 inflammasome pathway, vasoactive peptides, cytokine storm, NETosis, activation of the complement system). Alterations in coagulation mediators such as factor VIII, fibrin, tissue factor, the von Willebrand factor: ADAMST-13 ratio, and the kallikrein-kinin or plasminogen-plasmin systems have been reported. Moreover, an imbalance of thrombotic and thrombolytic (tPA, PAI-I, fibrinogen) factors favors hypercoagulation and hypofibrinolysis. In the context of DM, these mechanisms can be exacerbated leading to higher loss of hemostasis. However, a series of therapeutic strategies targeting the activated endothelium such as specific antibodies or inhibitors against thrombin, key cytokines, factor X, complement system, the kallikrein-kinin system or NETosis, might represent new opportunities to address this hypercoagulable state present in COVID-19 and DM. Antidiabetics may also ameliorate endothelial dysfunction, inflammation, and platelet aggregation. By improving the microvascular pathology in COVID-19 and post-COVID subjects, the associated comorbidities and the risk of mortality could be reduced., (© 2024. The Author(s).)

We report the case of a middle-aged hypertensive woman presenting to the neurology department with short-lasting episodic headaches for 4 years. She was initially diagnosed and treated with cluster headaches for one year. Following this, she presented with right lower limb arterial claudication. Arterial Doppler of lower limbs showed thrombosis of the bilateral common femoral arteries. Further computed tomography (CT) angiogram of the lower limbs confirmed extensive arterial thrombosis in bilateral lower limbs. The CT angiogram incidentally detected a left adrenal lesion. She had elevated urinary vanillylmandelic Acid and 24-hour metanephrines suggesting the presence of a pheochromocytoma. She was initially medically managed and later underwent left open adrenalectomy. Histopathology examination of the sections proved pheochromocytoma. Postsurgery, the patient's symptoms improved remarkably. This case highlights the importance of diagnosing pheochromocytoma when you encounter a patient with refractory short-lasting headaches, hypertension and hypercoagulability., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Thrombophilia testing (TT) is a laboratory procedure designed to detect the risk factors involved in the pathogenesis of vascular occlusions. The role of TT is also controversial because it has a limited impact on the choice and duration of antithrombotic treatments., Areas Covered: We reviewed, by examining MEDLINE up to October 2023. Accepted and not accepted thrombophilia markers are discussed along with the appropriateness or not of prescribing TT in several conditions such as: provoked and unprovoked venous thromboembolism (VTE), women who are planning a pregnancy whose relatives had VTE or have a hereditary thrombophilia, before assumption of estro-progestins, after multiple pregnant loss, arterial thrombosis, retinal vein occlusion, and splanchnic vein thrombosis., Expert Opinion: TT is not essential in the management of VTE, but it may be useful for limiting adverse events in case of thrombophilia. We expose our criticism of items afforded by other guidelines by presenting our opinion based on both the scientific evidence and clinical practice. We also deal with common mistakes in prescribing and interpretations of TT hoping to purpose an educational approach on this topic. Finally, we emphasize the creation of the expert in hemostasis and thrombosis who should be present in every hospital.

This study aimed to investigate the influence of prothrombotic risk factors on long-term outcomes of patients with perinatal arterial ischemic stroke. The study was conducted through an analysis of monitoring results that were regularly maintained for approximately 20 years at a tertiary stroke-monitoring center. The study assessed prothrombotic risk factors, radiological area of involvement, clinical presentation, treatments, clinical outcomes, and long-term outcomes of the 48 patients included in the study, with a mean monitoring time of 77.6 ± 45.7 months (range: 6-204). Our results showed that the presence of prothrombotic risk factors did not affect long-term outcomes. However, patients with middle cerebral artery infarction had the highest risk of developing cerebral palsy, whereas those with presumed stroke had the highest risk of developing epilepsy. This study suggests that prothrombotic risk factors should not be evaluated during the acute stage unless there is a strong suspicion of the patient's history, and prevention or early diagnosis of presumed stroke patients will positively impact their long-term prognosis., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: In patients with cancer-associated hypercoagulability (CAH)-related stroke, D-dimer trends after anticoagulant therapy may offer a biomarker of treatment efficacy. The purpose of this study was to clarify the association between D-dimer trends and recurrent stroke after anticoagulant therapy in patients with CAH-related stroke., Methods: We performed retrospective cohort study of consecutive patients with CAH-related stroke at two stroke centers from 2011 to 2020. The ratio of posttreatment to pretreatment D-dimer levels (post/pre ratio) was used as an indicator of D-dimer trends after anticoagulant therapy. Fine-Gray models were used to evaluate the association between post/pre ratio and recurrent stroke., Results: Among 360 acute ischemic stroke patients with active cancer, 73 patients with CAH-related stroke were included in this study. Recurrent stroke occurred in 13 patients (18%) during a median follow-up time of 28 days (interquartile range, 11-65 days). Multivariate analysis revealed that high post/pre ratio was independently associated with recurrent stroke (per 0.1 increase: hazard ratio 2.20, 95% confidence interval 1.61-3.01, p = 0.012)., Conclusion: D-dimer levels after anticoagulant therapy were associated with recurrent stroke in CAH-related stroke patients. Patients with neutral trends in high D-dimer levels after anticoagulant therapy were at high risk of recurrent stroke., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Considerable progress has been made in elucidating genetic and biologic risk factors for venous thromboembolism (VTE). Despite being able to identify heritable defects in a substantial proportion of patients with VTE, testing has not, in general, proven useful in management. Despite efforts to reduce inappropriate testing, it often falls to the hematologist to consult on patients having undergone thrombophilia testing. Through a series of cases, we discuss how D-dimer testing can be helpful in VTE recurrence risk stratification in younger women as well as how to approach patients with persistently elevated D-dimer levels in the absence of thrombosis. While elevated factor VIII coagulant activity levels are a significant risk factor for a first episode of VTE, its biologic basis is not fully understood, and studies have not shown it to be a useful predictor of recurrence. Abnormal results of genetic tests for methylene tetrahydrofolate reductase or plasminogen activator 1 promoter polymorphisms may be encountered, which carry little if any thrombotic risk and should never be ordered. We also discuss protein S deficiency, the most difficult of the hereditary thrombophilias to diagnose due to a wider "normal" range in the general population as compared with protein C, the presence of both free and bound forms in plasma, and the characteristics of the various assays in use. We also present a rare type of protein C deficiency that can be missed by functional assays using an amidolytic rather than a clotting end point., (Copyright © 2023 by The American Society of Hematology.)

Background: The coagulopathy of traumatic brain injury (TBI) remains poorly understood. Contradictory descriptions highlight the distinction between systemic and local coagulation, with descriptions of systemic hypercoagulability despite intracranial hypocoagulopathy. This perplexing coagulation profile has been hypothesized to be due to tissue factor release. The objective of this study was to assess the coagulation profile of TBI patients undergoing neurosurgical procedures. We hypothesize that dura violation is associated with higher tissue factor and conversion to a hypercoagulable profile and unique metabolomic and proteomic phenotype., Methods: This is a prospective, observational cohort study of all adult TBI patients at an urban, Level I trauma center who underwent a neurosurgical procedure from 2019 to 2021. Whole blood samples were collected before and then 1 hour following dura violation. Citrated rapid and tissue plasminogen activator (tPA) thrombelastography (TEG) were performed, in addition to measurement of tissue factory activity, metabolomics, and proteomics., Results: Overall, 57 patients were included. The majority (61%) were male, the median age was 52 years, 70% presented after blunt trauma, and the median Glasgow Coma Score was 7. Compared with pre-dura violation, post-dura violation blood demonstrated systemic hypercoagulability, with a significant increase in clot strength (maximum amplitude of 74.4 mm vs. 63.5 mm; p < 0.0001) and a significant decrease in fibrinolysis (LY30 on tPAchallenged TEG of 1.4% vs. 2.6%; p = 0.04). There were no statistically significant differences in tissue factor. Metabolomics revealed notable increases in metabolites involved in late glycolysis, cysteine, and one-carbon metabolites, and metabolites involved in endothelial dysfunction/arginine metabolism/responses to hypoxia. Proteomics revealed notable increase in proteins related to platelet activation and fibrinolysis inhibition., Conclusion: A systemic hypercoagulability is observed in TBI patients, characterized by increased clot strength and decreased fibrinolysis and a unique metabolomic and proteomics phenotype independent of tissue factor levels., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps guide management decisions is controversial. These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing. ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) was used. Recommendations were subject to public comment. The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions. The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COCs) and conditional recommendations for thrombophilia testing in the following scenarios: (a) patients with VTE associated with nonsurgical major transient or hormonal risk factors; (b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; (c) individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance to avoid COCs/hormone replacement therapy; (d) pregnant women with a family history of high-risk thrombophilia types; and (e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia., (© 2023 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.)

Background: Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear., Objectives: Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy., Methods: We conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated., Results: Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding., Conclusion: Our results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy., Competing Interests: Declaration of competing interests T.-F.W. reports advisory board honoraria from Servier and Valeo and research funding from Leo Pharma. M.C. reports grants from BMS, Leo Pharma, and Pfizer and honoraria from BMS, Leo Pharma, Bayer, Pfizer, Servier, and Sanofi. D.R., R.M., D.B., S.H., and P.S.W. have no conflicts of interest to declare., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Livedoid vasculopathy (LV) is a rare, disabling disease characterized by painful ulcers, livedo reticularis and atrophy blanche. Hypercoagulation, endothelial, and microcirculatory dysfunction are believed to be responsible for the pathogenesis of this difficult-to-treat disease., Objectives: This study sought to investigate the frequency of endothelial dysfunction, hypercoagulability, and nailfold capillaroscopic features in LV patients to shed light on its etiology., Methods: This case-control study included 16 patients with LV, 24 with systemic sclerosis (SSc), and 23 control subjects. Serum markers of endothelial dysfunction soluble endoglin, endocan, endothelin-1, lipoprotein a, plasminogen activator inhibitor-1 (PAI-1), soluble thrombomodulin, and von Willebrand factor were measured using enzyme-linked immunosorbent assays. Flow-mediated dilation and carotid intima-media thickness were examined as markers of endothelial dysfunction, and microcirculation was assessed with nailfold capillaroscopy. Thrombophilia-related parameters, including gene polymorphisms of factor V Leiden, prothrombin, PAI-1 genes, methylenetetrahydrofolate reductase (MTHFR) and factor XIII mutation and serum levels of protein C, protein S, antithrombin, homocysteine, D-dimer and antiphospholipid antibodies were investigated in LV patients., Results: Plasminogen activator inhibitor-1 and soluble thrombomodulin levels were significantly higher in LV patients compared to control subjects (2.3 [2.05-2.79] ng/ml vs. 1.89 [1.43-2.33] ng/ml, p = 0.007; 1.15 [0.88-1.4] ng/ml vs. 0.76 [0.56-0.9] ng/ml, p = 0.004, respectively). Flow-mediated dilation was 25.4 % lower in the LV patients compared to the control group (14.77 % [11.26-18.26] vs. 19.80 % [16.47-24.88], p = 0.034). Capillaroscopic features, including ramifications (75 % vs. 8.7 %, p < 0.001), avascular areas (25 % vs. 0 %, p = 0.011) and dilatations (33.2 % vs. 0 %, p = 0.016), were significantly higher in LV patients than in controls. LV patients had multiple biochemical or genetic abnormalities related to thrombophilia, including heterozygous factor V Leiden mutations (6.3 %), MTHFR (C677T) mutations (heterozygous 43.8 %, homozygous 18.8 %), MTHFR (A1298C) mutations (heterozygous 37.5 %, homozygous 12.5 %), factor XIII heterozygous mutation (12.5 %), antithrombin deficiency (31.3 %), protein S deficiency (12.5 %), hyperhomocysteinemia (31.3 %), D-dimer elevation (25 %), anti-β2-glycoprotein I (12.5 %), lupus anticoagulant antibodies (6.3 %), and anticardiolipin antibodies (6.3 %)., Conclusions: In conclusion, LV patients were characterized by an increased presence of thrombophilia-related parameters, and also exhibited vascular endothelial and microcirculatory dysfunction, resembling SSc. These findings support the complex interaction of thrombophilia, endothelial dysfunction, and microcirculation dysregulation in the pathogenesis of LV. Thus, the treatment of LV patients should be individualized, based on the identification of the predominant pathological pathways., 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 © 2023 Elsevier Inc. All rights reserved.)

Background/purpose: Inherited thrombophilia testing in the acute inpatient setting is controversial and expensive, and rarely changes clinical management. We evaluated ordering patterns and results of inpatient inherited thrombophilia testing for patients who presented with an isolated acute ischemic stroke or transient ischemic attack (TIA) without concurrent venous thromboembolism., Methods: We retrospectively analyzed patients admitted for acute ischemic stroke or TIA between January 1 st , 2019 and December 31 st , 2021 at Thomas Jefferson University Hospitals in Philadelphia, PA and who underwent inherited thrombophilia testing during the hospital admission. Charts were reviewed to determine stroke risk factors, test results, and clinical management., Results: Among 2108 patients admitted for acute ischemic stroke or TIA (including branch and central retinal artery occlusions) during the study period, the study included 249 patients (median age 49.0 years, 50.2% female) who underwent inpatient testing for factor V Leiden, prothrombin G20210A variant, hyperhomocysteinemia, PAI-1 elevation, and deficiencies of protein C and S and antithrombin. 42.2% of patients had at least one abnormal test, and among the 1035 tests ordered, 14.3% resulted abnormal. However, 28% of abnormal tests were borderline positive antigen or activity assays that likely represented false positives. There was no significant difference in the likelihood of a positive test among patients without stroke risk factors vs those with risk factors (47.1% vs 40.9%, P = .428), nor any significant difference between those under vs over age 50 years (45.7% vs 38.3%, P = .237). No patients with an abnormal result had their clinical management changed as a result. Charges for the tests totaled $468,588 USD., Conclusions: Inherited thrombophilia testing in the hospital immediately following isolated acute arterial ischemic stroke or TIA was associated with high rates of likely false positive results and was expensive. Positive results did not change clinical management in a single case., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest or competing interests. No funding or research grants were received in the course of study, research, or assembly of the manuscript to support this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend thrombophilia evaluation in childhood arterial ischemic stroke, but the impact of screening on management is unknown. The objective of the current study is to report the incidence of thrombophilia identified as part of routine clinical care in the context of available literature reports, and to describe the impact of a diagnosis of thrombophilia on patient management., Methods: We conducted a single-institution retrospective chart review for all children with arterial ischemic stroke occurring between January 1, 2009 and January 1, 2021. We collected thrombophilia screening results, stroke etiology, and management. We also reviewed the literature of thrombophilia testing in childhood arterial ischemic stroke published prior to June 30, 2022. Meta-analysis methods were used to assess prevalence rates., Results: Among children with thrombophilia testing performed, 5% (six of 122 patients) were factor V Leiden heterozygous, 1% (one of 102 patients) were prothrombin gene mutation heterozygous, 1% (one of 122) had protein S deficiency, 20% (23/116 patients) had elevated lipoprotein(a), 3% (three of 110 patients) had elevated homocysteine levels, and 9% (10/112) had elevated antiphospholipid antibodies, only two of whom had persistently elevated levels. There was no change in stroke therapy due to these results. Literature review revealed a wide range of prevalence for most thrombophilia traits, with high cross-study heterogeneity in most cases., Conclusions: The rates of thrombophilia in our cohort were consistent with that expected in the general population. The identification of thrombophilia did not alter stroke care. However, some of the results were actionable, prompting evaluation for lipid disorders and patient-specific counseling on cardiovascular risk and risk for venous thrombosis., (© 2023 Wiley Periodicals LLC.)

Venous thromboembolism is one of the most common vascular diseases. Increased thrombin formation together with reduced blood flow create a hypercoagulable environment that induces thrombus formation. Anticoagulants play a pivotal role in the treatment and secondary prophylaxis of venous thromboembolism because they effectively interrupt this hypercoagulability. A personalized assessment of the thrombotic risk is essential for planning the duration and intensity of secondary prophylaxis. The occurrence of thrombosis outside a typical risk situation, an atypical localization and a family history of thrombosis indicate a thrombophilic state. In these cases, thrombophilia diagnostics are useful for extended risk assessment. If anti-phospholipid antibodies are detected, the risk of recurrence is particularly increased., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Patients with thrombophilia are underrepresented in studies evaluating outcomes after closure of patent foramen ovale (PFO). Real-world data on long term outcomes in this population are very limited., Objectives: This study compared outcomes in patients with and without thrombophilia undergoing PFO closure, using data from a large, clinical database linked to population-based databases., Methods: This retrospective cohort study included consecutive patients who had a transcatheter PFO closure and had preprocedural thrombophilia screening. Data from a retrospective, clinical registry were linked to population-based administrative databases in Ontario Canada to evaluate outcomes. Outcomes were reported as rates per 100 person-years and compared using Poisson regression., Results: We included 669 patients, with a mean age of 56.4 years, 97.9% of whom underwent PFO closure for a cryptogenic stroke. Thrombophilia was diagnosed among 174 (26.0%), of which 86% had inherited mutations. In-hospital, procedural complications were observed in 3.1% of patients with no difference by thrombophilia status. Similarly, no differences were observed in 30-day emergency department visits and readmissions. Over the median follow-up of 11.6 years, the most common adverse outcome was new-onset atrial fibrillation (1.0 per 100 person-years; 95% CI: 0.8-1.2), followed by recurrent cerebrovascular events (0.8 per 100 person-years; 95% CI: 0.6-1.1) with no differences between the groups (P > 0.05)., Conclusions: After PFO closure, no differences were observed in long-term adverse outcomes between patients with and without thrombophilia. Though these patients have been excluded from randomized clinical trials of PFO closure in the past, real-world evidence supports their eligibility for the procedure., Competing Interests: Funding Support and Author Disclosures This work is supported by the Peter Munk chair in Structural Heart Disease Intervention. ICES is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). Parts of this material are based on data and information compiled and provided by Canadian Institute for Health Information (CIHI). The analyses, conclusions, opinions and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. Dr Lee is the Ted Rogers Chair in Heart Function Outcomes, a joint Hospital-University Chair of the University Health Network and the University of Toronto. Dr Horlick is supported by the Peter Munk Chair in Structural Heart Disease Intervention. The Structural Heart Disease program at University Health Network receives educational support from Abbott, Edwards Lifesciences, and Medtronic; these companies were not involved in planning or execution of this study. Dr Horlick is a consultant for Abbott, Edwards Lifesciences, and Medtronic; and has received research grants from Abbott and Occlutech. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)