Dataset Information

Effect of Clot Stiffness on Recombinant Tissue Plasminogen Activator Lytic Susceptibility in Vitro.

ABSTRACT: The lytic recombinant tissue plasminogen activator (rt-PA) is the only drug approved by the Food and Drug Administration for treating ischemic stroke. Less than 40% of patients with large vessel occlusions who are treated with rt-PA have improved blood flow. However, up to 6% of all patients receiving rt-PA develop intracerebral hemorrhage. Predicting the efficacy of rt-PA treatment a priori could help guide therapeutic decision making, such that rt-PA is administered only to those individuals who would benefit from this treatment. Clot composition and structure affect the lytic efficacy of rt-PA and have an impact on elasticity. However, the relationship between clot elasticity and rt-PA lytic susceptibility has not been adequately investigated. The goal of this study was to quantify the relationship between clot elasticity and rt-PA susceptibility in vitro. Human and porcine highly retracted and mildly retracted clots were fabricated in glass pipettes. The rt-PA lytic susceptibility was evaluated in vitro using the percent clot mass loss. The Young's moduli of the clots were estimated using ultrasound-based single-track-location shear wave elasticity imaging. The percent mass loss in mildly retracted porcine and human clots (28.9 ± 6.1% and 45.2 ± 7.1%, respectively) was significantly higher (p < 0.05) than in highly retracted porcine and human clots (10.9 ± 2.1% and 25.5 ± 10.0%, respectively). Furthermore, the Young's moduli of highly retracted porcine and human clots (5.33 ± 0.92 and 3.21 ± 1.97 kPa, respectively) were significantly higher (p < 0.05) than those of mildly retracted porcine and human clots (2.66 ± 0.55 and 0.79 ± 0.21 kPa, respectively). The results revealed an inverse relationship between the percent clot mass loss and Young's modulus. These findings motivate continued investigation of ultrasound-based methods to assess clot stiffness in order to predict rt-PA thrombolytic efficacy.

SUBMITTER: Mercado-Shekhar KP

PROVIDER: S-EPMC6551517 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Clot Stiffness on Recombinant Tissue Plasminogen Activator Lytic Susceptibility in Vitro.

Mercado-Shekhar Karla P KP Kleven Robert T RT Aponte Rivera Hermes H Lewis Ryden R Karani Kunal B KB Vos Hendrik J HJ Abruzzo Todd A TA Haworth Kevin J KJ Holland Christy K CK

Ultrasound in medicine & biology 20180926 12

The lytic recombinant tissue plasminogen activator (rt-PA) is the only drug approved by the Food and Drug Administration for treating ischemic stroke. Less than 40% of patients with large vessel occlusions who are treated with rt-PA have improved blood flow. However, up to 6% of all patients receiving rt-PA develop intracerebral hemorrhage. Predicting the efficacy of rt-PA treatment a priori could help guide therapeutic decision making, such that rt-PA is administered only to those individuals w ...[more]

PMID: 30268531

Similar Datasets

Project description:Background and objectivesEvidence to guide hemodialysis catheter locking solutions is limited. We aimed to assess effectiveness and cost of recombinant tissue plasminogen activator (rt-PA) once per week as a locking solution, compared with thrice weekly citrate or heparin, in patients at high risk of complications.Design, setting, participants, & measurementsWe used a prospective design and pre-post comparison in three sites across Canada. Pre-post comparisons were conducted using multilevel mixed effects regression models accounting for cluster with site and potential enrollment of patients more than once. In the pre period, catheter malfunction was managed as per site-specific standard of care. The intervention in the post period was once weekly rt-PA as a locking solution (with citrate or heparin used for other sessions). The primary outcome was rate of rt-PA use for treatment of catheter malfunction. Secondary outcomes included rates of bacteremia, management of catheter malfunction, and cost.ResultsThere were 374 patients (mean age 68 years; 52% men) corresponding to 506 enrollments. Mean length of enrollment was 200 days (SD 119) in the pre period and 187 days (SD 101) in the post period. There was a significant decline in rate of rt-PA use for treatment of catheter malfunction in the post compared with pre period (adjusted incidence rate ratio, 0.39; 95% confidence interval, 0.30 to 0.52); however, there was no difference in the rate of bacteremia, or catheter stripping or removal/replacement. The increase in mean total health care cost in the post period was CAD$962 per enrollment, largely related to costs of rt-PA as a locking solution.ConclusionsOnce weekly rt-PA as a catheter locking solution was associated with a reduction in rt-PA use for treatment of catheter malfunction. Our results showing a reduction in rescue rt-PA use are consistent with a prior randomized trial, although we did not observe a reduction in bacteremia or catheter stripping/removal and did observe an increased incremental cost of this strategy primarily accounted for by the cost of the rt-PA.

Dataset Information

Effect of Clot Stiffness on Recombinant Tissue Plasminogen Activator Lytic Susceptibility in Vitro.

Publications

Effect of Clot Stiffness on Recombinant Tissue Plasminogen Activator Lytic Susceptibility in Vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets