Thromb Haemost 2018; 118(01): 042-053
DOI: 10.1160/TH17-02-0132
Coagulation and Fibrinolysis
Schattauer GmbH Stuttgart

Amino-Fucoidan as a Vector for rtPA-Induced Fibrinolysis in Experimental Thrombotic Events

Radouane Ghebouli*
,
Stephane Loyau*
,
Murielle Maire
,
Pierre Saboural
,
Jean-Philippe Collet
,
Martine Jandrot-Perrus
,
Didier Letourneur
,
Frédéric Chaubet
,
Jean-Baptiste Michel
Further Information

Publication History

24 February 2017

22 August 2017

Publication Date:
05 January 2018 (online)

Abstract

Acute ischaemic stroke, myocardial infarction and pulmonary embolism are the main causes of mortality and morbidity worldwide. Thrombolysis by intravenous injection of recombinant tissue plasminogen activator (rtPA) remains the most common non-interventional treatment to recanalize occluded vessels. However, this procedure is limited by significant drawbacks, including high doses and bleeding complications. Recent studies showed that fucoidan targets the intraluminal thrombus in vivo. We have developed a chimaera covalently linking fucoidan, able to target platelets within the thrombus, to dilysine, able to non-covalently bind rtPA. We hypothesize that this construct should vectorize rtPA to the thrombus, thus increasing its fibrinolytic efficacy and avoiding its deleterious effects. In vitro, rtPA mixed to dilysine fucoidan (DLF) shows a greater fibrinolytic effect than rtPA alone, both on platelet-rich thrombus and in whole blood. In vivo, occluded mesenteric vessels, carotid artery and vena cava were more efficiently recanalized by DLF complexed to rtPA than by rtPA alone. This study thus provides evidence that DLF may be a promising therapeutic tool to fight against acute thrombosis by enhancing rtPA fibrinolytic efficiency.

* Radouane Ghebouli and Stephane Loyau contributed equally to this study.


Supplementary Material

 
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