Uric acid enhances alteplase-mediated thrombolysis as an antioxidant

Sci Rep. 2018 Oct 26;8(1):15844. doi: 10.1038/s41598-018-34220-1.


Uric acid (UA) therapy may prevent early ischemic worsening after acute stroke in thrombolysis patients. The aim of this study was to examine the influence of UA on the thrombolytic efficacy of alteplase in human blood samples by measuring thrombolysis under flow conditions using a newly developed microchip-based flow-chamber assay. Human blood samples from healthy volunteers were exposed to UA, alteplase, or a combination of UA and alteplase. Whole blood and platelet-rich plasma were perfused over a collagen- and thromboplastin-coated microchip, and capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 92% lower in the UA-alteplase-treated group compared with the alteplase-treated group. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, UA significantly inhibited the effect of hydrogen peroxide. Meanwhile, rat models of thromboembolic cerebral ischemia were treated with either alteplase or UA-alteplase combination therapy. Compared with alteplase alone, the combination therapy reduced the infarct volume and inhibited haemorrhagic transformation. UA enhances alteplase-mediated thrombolysis, potentially by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Area Under Curve
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis
  • Fibrinolysis / drug effects*
  • Humans
  • Ischemia / drug therapy
  • Ischemia / pathology
  • Male
  • Microscopy, Video
  • Oxidative Stress / drug effects
  • ROC Curve
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Plasminogen Activator / pharmacology*
  • Tissue Plasminogen Activator / therapeutic use
  • Uric Acid / pharmacology*
  • Uric Acid / therapeutic use
  • Young Adult


  • Antioxidants
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Uric Acid
  • Tissue Plasminogen Activator