Browsing by Subject "Blood platelets"

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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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    Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism
    (Elsevier, 2020-03-01) Kline, Jeffrey A.; Puskarich, Michael A.; Pike, Jonathan; Zagorski, John; Alves, Nathan J.; Emergency Medicine, School of Medicine
    Background: We test if inhaled nitric oxide (NO) attenuates platelet functional and metabolic hyper-reactivity in subjects with submassive pulmonary embolism (PE). Methods: Participants with PE were randomized to either 50 ppm NO + O2 or O2 only for 24 h with blood sampling at enrollment and after treatment; results were compared with healthy controls. Platelet metabolic activity was assessed by oxygen consumption (basal and uncoupled) and reactivity was assessed with agonist-stimulated thromboelastography (TEG) and fluorometric measurement of agonist-stimulated cytosolic [Ca++] without and with pharmacological soluble guanylate (sGC) modulation. Results: Participants (N = 38 per group) were well-matched at enrollment for PE severity, comorbidities as well as TEG parameters and platelet O2 consumption. NO treatment doubled the mean plasma [NO3-] (P < 0.001) indicating successful delivery, but placebo treatment produced no change. After 24 h, neither TEG nor O2 consumption parameters differed significantly between treatment groups. Platelet cytosolic [Ca++] was elevated with PE versus controls, and was decreased by treatment with cinaciguat (an sGC activator), but not riociguat (an sGC stimulator). Stimulated platelet lysate sGC activity was increased with PE compared with controls. Conclusions: In patients with acute submassive PE, despite evidence of adequate drug delivery, inhaled NO had no major effect on platelet O2 consumption or agonist-stimulated parameters on TEG. Pharmacological activation, but not stimulation, of sGC effectively decreased platelet cytosolic [Ca++], and platelet sGC activity was increased with PE, confirming the viability of sGC as a therapeutic target.
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    Viscoelastic Testing and Coagulopathy of Traumatic Brain Injury
    (MDPI, 2021-10-28) Bradbury, Jamie L.; Thomas, Scott G.; Sorg, Nikki R.; Mjaess, Nicolas; Berquist, Margaret R.; Brenner, Toby J.; Langford, Jack H.; Marsee, Mathew K.; Moody, Ashton N.; Bunch, Connor M.; Sing, Sandeep R.; Al-Fadhl, Mahmoud D.; Salamah, Qussai; Saleh, Tarek; Patel, Neal B.; Shaikh, Kashif A.; Smith, Stephen M.; Langheinrich, Walter S.; Fulkerson, Daniel H.; Sixta, Sherry; Neurological Surgery, School of Medicine
    A unique coagulopathy often manifests following traumatic brain injury, leading the clinician down a difficult decision path on appropriate prophylaxis and therapy. Conventional coagulation assays—such as prothrombin time, partial thromboplastin time, and international normalized ratio—have historically been utilized to assess hemostasis and guide treatment following traumatic brain injury. However, these plasma-based assays alone often lack the sensitivity to diagnose and adequately treat coagulopathy associated with traumatic brain injury. Here, we review the whole blood coagulation assays termed viscoelastic tests and their use in traumatic brain injury. Modified viscoelastic tests with platelet function assays have helped elucidate the underlying pathophysiology and guide clinical decisions in a goal-directed fashion. Platelet dysfunction appears to underlie most coagulopathies in this patient population, particularly at the adenosine diphosphate and/or arachidonic acid receptors. Future research will focus not only on the utility of viscoelastic tests in diagnosing coagulopathy in traumatic brain injury, but also on better defining the use of these tests as evidence-based and/or precision-based tools to improve patient outcomes.