Browsing by Subject "Thrombosis"

Now showing 1 - 10 of 20
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    Acetylation of albumin by low doses of aspirin
    (1981-08) Burch, John W.; Blazer-Yost, Bonnie
    Aspirin has a variety of pharmacologic actions, which are expressed at different doses of the drug. An effect on platelet function occurs at very low doses of aspirin (1,2). Indeed, a large number of clinical trials have been carried out to assess whether low to moderate doses of aspirin (180 to 1500 mg per day) taken prophylactically will affect the natural history of a variety of diseases in which thrombosis is thought to play a role (3).
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    Circulating trimethylamine N-oxide levels following fish or seafood consumption
    (Springer, 2022) Wang, Zeneng; Tang, W. H. Wilson; O’Connell, Thomas; Garcia, Erwin; Jeyarajah, Elias J.; Li, Xinmin S.; Jia, Xun; Weeks, Taylor L.; Hazen, Stanley L.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Purpose: Some species of fish and seafood are high in trimethylamine N-oxide (TMAO), which accumulates in muscle where it protects against pressure and cold. Trimethylamine (TMA), the metabolic precursor to TMAO, is formed in fish during bacterial spoilage. Fish intake is promoted for its potential cardioprotective effects. However, numerous studies show TMAO has pro-atherothrombotic properties. Here, we determined the effects of fish or seafood consumption on circulating TMAO levels in participants with normal renal function. Methods: TMAO and omega-3 fatty acid content were quantified across multiple different fish or seafood species by mass spectrometry. Healthy volunteers (n = 50) were recruited for three studies. Participants in the first study consented to 5 consecutive weekly blood draws and provided dietary recall for the 24 h preceding each draw. In the second study, TMAO levels were determined following defined low and high TMAO diets. Finally, participants consumed test meals containing shrimp, tuna, fish sticks, salmon or cod. TMAO levels were quantified by mass spectrometry in blood collected before and after dietary challenge. Results: TMAO + TMA content varied widely across fish and seafood species. Consumption of fish sticks, cod, and to a lesser extent salmon led to significant increases in circulating TMAO levels. Within 1 day, circulating TMAO concentrations in all participants returned to baseline levels. Conclusions: We conclude that some fish and seafood contain high levels of TMAO, and may induce a transient elevation in TMAO levels in some individuals. Selection of low TMAO content fish is prudent for subjects with elevated TMAO, cardiovascular disease or impaired renal function.
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    Cisplatin, environmental metals, and cardiovascular disease: an urgent need to understand underlying mechanisms
    (BMC, 2021-10-10) Clasen, Suparna C.; Dinh, Paul C., Jr.; Hou, Lifang; Fung, Chunkit; Sesso, Howard D.; Travis, Lois B.; Medicine, School of Medicine
    Significantly increased risks of cardiovascular disease occur in testicular cancer survivors given cisplatin-based chemotherapy. The postulated mechanism of platinum-based chemotherapy's vascular toxicity has been thought secondary to its different early- and late- effects on vascular injury, endothelial dysfunction, and induction of a hypercoagulable state. We highlight for the first time the similarities between platinum-associated vascular adverse events and the vascular toxicity associated with other xenobiotic-metal contaminants. The vascular toxicity seen in large epidemiologic studies of testicular cancer survivors may in part be similar and mechanistically linked to the risk seen in environmental heavy metal contaminants linked to cardiovascular disease. Future research should be directed to better understand the magnitude of the adverse cardiovascular effects of platinum and to elucidate the underlying mechanisms of action.
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    Clinical applications of thrombopoietin silencing: A possible therapeutic role in COVID-19?
    (Elsevier, 2021-10) Alentado, Vincent J.; Moliterno, Alison R.; Srour, Edward F.; Kacena, Melissa A.; Medicine, School of Medicine
    Thrombopoietin (TPO) is most recognized for its function as the primary regulator of megakaryocyte (MK) expansion and differentiation. MKs, in turn, are best known for their role in platelet production. Research indicates that MKs and platelets play an extensive role in the pathologic thrombosis at sites of high inflammation. TPO, therefore, is a key mediator of thromboinflammation. Silencing of TPO has been shown to decrease platelets levels and rates of pathologic thrombosis in patients with various inflammatory disorders (Barrett et al, 2020; Bunting et al, 1997; Desai et al, 2018; Kaser et al, 2001; Shirai et al, 2019). Given the high rates of thromboinflammmation in the novel coronavirus 2019 (COVID-19), as well as the well-documented aberrant MK activity in affected patients, TPO silencing offers a potential therapeutic modality in the treatment of COVID-19 and other pathologies associated with thromboinflammation. The current review explores the current clinical applications of TPO silencing and offers insight into a potential role in the treatment of COVID-19.
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    COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease
    (Elsevier, 2023-11-21) Fusco, Flavia; Krasuski, Richard A.; Sadeghi, Soraya; Rosenbaum, Marlon S.; Lewis, Matthew J.; Carazo, Matthew R.; Rodriguez, Fred H.; Halpern, Dan G.; Feinberg, Jodi L.; Galilea, Francisca A.; Baraona, Fernando; Cedars, Ari M.; Ko, Jong M.; Porayette, Prashob; Maldonado, Jennifer R.; Frogoudaki, Alexandra A.; Nir, Amiram; Chaudhry, Anisa; John, Anitha S.; Karbassi, Arsha; Ganame, Javier; Hoskoppal, Arvind; Frischhertz, Benjamin P.; Hendrickson, Benjamin; Rodriguez-Monserrate, Carla P.; Broda, Christopher R.; Tobler, Daniel; Gregg, David; Martinez-Quintana, Efrén; Yeung, Elizabeth; Krieger, Eric V.; Ruperti-Repilado, Francisco J.; Giannakoulas, George; Lui, George K.; Ephrem, Georges; Singh, Harsimran S.; Hasan, Almeneisi; Bartlett, Heather L.; Lindsay, Ian; Grewal, Jasmine; Nicolarsen, Jeremy; Araujo, John J.; Cramer, Jonathan W.; Bouchardy, Judith; Al Najashi, Khalid; Ryan, Kristi; Alshawabkeh, Laith; Andrade, Lauren; Ladouceur, Magalie; Schwerzmann, Markus; Greutmann, Matthias; Merás, Pablo; Ferrero, Paolo; Dehghani, Payam; Tung, Poyee P.; Garcia-Orta, Rocio; Tompkins, Rose; Gendi, Salwa M.; Cohen, Scott; Klewer, Scott E.; Hascoet, Sebastien; Upadhyay, Shailendra; Fisher, Stacy D.; Cook, Stephen; Cotts, Timothy B.; Kovacs, Adrienne H.; Aboulhosn, Jamil A.; Scognamiglio, Giancarlo; Broberg, Craig S.; Sarubbi, Berardo; Medicine, School of Medicine
    Background: Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. Objectives: The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. Methods: COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. Results: Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. Conclusions: ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.
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    Dueling with the dual artery blood supply in pancreas transplantation: why replace the Y?
    (AME, 2024) Fridell, Jonathan A.; Stratta, Robert J.; Surgery, School of Medicine
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    Effect of Chandler loop shear and tubing size on thrombus architecture
    (Springer, 2023-05-12) Zeng, Ziqian; Chakravarthula, Tanmaye Nallan; Christodoulides, Alexei; Hall, Abigail; Alves, Nathan J.; Emergency Medicine, School of Medicine
    Thrombosis can lead to a wide variety of life-threatening circumstances. As current thrombolytic drug screening models often poorly predict drug profiles, leading to failure of thrombolytic therapy or clinical translation, more representative clot substrates are necessary for drug evaluation. Utilizing a Chandler loop device to form clot analogs at high shear has gained popularity in stroke societies. However, shear-dependent clot microstructure has not been fully addressed and low shear conditions are often overlooked. We herein characterized the impact of wall shear rate (126 to 951 s-1) on clot properties in the Chandler loop. Different revolutions (20-60) per minute and tubing sizes (3.2 to 7.9 mm) were employed to create different sized clots to mimic various thrombosis applications. Increased shear resulted in decreased RBC counts (76.9 ± 4.3% to 17.6 ± 0.9%) and increased fibrin (10 to 60%) based on clot histology. Increased fibrin sheet morphology and platelet aggregates were observed at higher shear under scanning electron microscope. These results show the significant impact of shear and tubing size on resulting clot properties and demonstrate the capability of forming a variety of reproducible in-vivo-like clot analogs in the Chandler loop device controlling for simple parameters to tune clot characteristics.
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    Exploring microplastic impact on whole blood clotting dynamics utilizing thromboelastography
    (Frontiers Media, 2023-07-13) Christodoulides, Alexei; Hall, Abigail; Alves, Nathan J.; Emergency Medicine, School of Medicine
    This study investigates the influence of microplastics on blood clotting. It addresses the lack of comprehensive research on the effects of microplastic size and surface modification on clotting dynamics in human whole blood. Thromboelastography was used to examine aminated (aPS), carboxylated (cPS), and non-functionalized (nPS) polystyrene particles with sizes of 50, 100, and 500  nm. Results show that cPS consistently activated the clotting cascade, demonstrating increased fibrin polymerization rates, and enhanced clot strength in a size and concentration-dependent manner. nPS had minimal effects on clotting dynamics except for 50  nm particles at the lowest concentration. The clotting effects of aPS (100  nm particles) resembled those of cPS but were diminished in the 500  nm aPS group. These findings emphasize the importance of microplastic surface modification, size, concentration, and surface area on in-vitro whole blood clotting dynamics.
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    Fluorescently conjugated annular fibrin clot for multiplexed real-time digestion analysis
    (Royal Society of Chemistry, 2021-12) Zeng, Ziqian; Nallan Chakravarthula, Tanmaye; Muralidharan, Charanya; Hall, Abigail; Linnemann, Amelia K.; Alves, Nathan J.; Emergency Medicine, School of Medicine
    Impaired fibrinolysis has long been considered as a risk factor for venous thromboembolism. Fibrin clots formed at physiological concentrations are promising substrates for monitoring fibrinolytic performance as they offer clot microstructures resembling in vivo. Here we introduce a fluorescently labeled fibrin clot lysis assay which leverages a unique annular clot geometry assayed using a microplate reader. A physiologically relevant fibrin clotting formulation was explored to achieve high assay sensitivity while minimizing labeling impact as fluorescence isothiocyanate (FITC)-fibrin(ogen) conjugations significantly affect both fibrin polymerization and fibrinolysis. Clot characteristics were examined using thromboelastography (TEG), turbidity, scanning electron microscopy, and confocal microscopy. Sample fibrinolytic activities at varying plasmin, plasminogen, and tissue plasminogen activator (tPA) concentrations were assessed in the present study and results were compared to an S2251 chromogenic assay. The optimized physiologically relevant clot substrate showed minimal reporter-conjugation impact with nearly physiological clot properties. The assay demonstrated good reproducibility, wide working range, kinetic read ability, low limit of detection, and the capability to distinguish fibrin binding-related lytic performance. In combination with its ease for multiplexing, it also has applications as a convenient platform for assessing patient fibrinolytic potential and screening thrombolytic drug activities in personalized medical applications.