Related Experiment Video
Updated: Jun 29, 2025
09:42
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
2.7K
R-tPA Resistance Is Specific for Platelet-Rich Stroke Thrombi and Can Be Overcome by Targeting Nonfibrin Components.
Sarah Vandelanotte1, Olivier François2, Linda Desender1
1Laboratory for Thrombosis Research, KU Leuven Kulak, Kortrijk, Belgium (S.V., L.D., S.S., C.T., K.V., S.F.D.M.).
Stroke
|March 25, 2024
Summary
Stroke thrombus composition determines resistance to recombinant tissue-type plasminogen activator (r-tPA). Red blood cell-poor thrombi are resistant but can be lysed by combining r-tPA with DNase-1 or N,N'-diacetyl-l-cystine.
Area of Science:
- Biomedical research
- Thrombosis and hemostasis
- Ischemic stroke treatment
Background:
- Recombinant tissue-type plasminogen activator (r-tPA) resistance is a significant challenge in acute ischemic stroke treatment.
- Understanding thrombus composition is crucial for improving recanalization rates.
- Patient-derived thrombi offer a clinically relevant model for studying thrombolysis resistance.
Purpose of the Study:
- To investigate the impact of thrombus composition on r-tPA efficacy in acute ischemic stroke.
- To explore novel strategies for overcoming r-tPA resistance in stroke thrombi.
- To correlate histological thrombus characteristics with lysis susceptibility.
Main Methods:
- Analysis of patient-derived acute ischemic stroke thrombi.
- Histological examination of thrombus composition (red blood cells, DNA, von Willebrand Factor).
- In vitro thrombolysis assays using r-tPA alone or in combination with DNase-1 or N,N '-diacetyl-l-cystine.
Main Results:
- Thrombolysis efficacy strongly correlated with thrombus composition.
- Thrombi rich in red blood cells and low in DNA/von Willebrand Factor were efficiently lysed by r-tPA.
- Thrombi with low red blood cells and high DNA/von Willebrand Factor content exhibited resistance to r-tPA.
Conclusions:
- Stroke thrombus composition is a key determinant of r-tPA-mediated thrombolysis.
- Red blood cell-poor thrombi demonstrate specific resistance to r-tPA.
- Combination therapy with DNase-1 or N,N '-diacetyl-l-cystine effectively overcomes r-tPA resistance in these thrombi.
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