Premium
FXII a inhibitor rHA ‐Infestin‐4: Safe thromboprotection in experimental venous, arterial and foreign surface‐induced thrombosis
Author(s) -
May Frauke,
Krupka Jennifer,
Fries Marion,
Thielmann Ina,
Pragst Ingo,
Weimer Thomas,
Panousis Con,
Nieswandt Bernhard,
Stoll Guido,
Dickneite Gerhard,
Schulte Stefan,
Nolte Marc W.
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13990
Subject(s) - thrombosis , medicine , antithrombotic , venous thrombosis , coagulation , cardiology , heparin , platelet , vascular occlusion , pharmacology , anesthesia
Summary Haemostasis including blood coagulation is initiated upon vessel wall injury and indispensable to limit excessive blood loss. However, unregulated pathological coagulation may lead to vessel occlusion, causing thrombotic disorders, most notably myocardial infarction and stroke. Furthermore, blood exposure to foreign surfaces activates the intrinsic pathway of coagulation. Hence, various clinical scenarios, such as extracorporeal membrane oxygenation, require robust anticoagulation consequently leading to an increased bleeding risk. This study aimed to further assess the antithrombotic efficacy of the activated factor XII ( FXII a) inhibitor, rHA ‐Infestin‐4, in several thrombosis models. In mice, rHA ‐Infestin‐4 decreased occlusion rates in the mechanically‐induced arterial (Folt's) and the FeCl 3 ‐induced venous thrombosis model. rHA ‐Infestin‐4 also protected from FeCl 3 ‐induced arterial thrombosis and from stasis‐prompted venous thrombosis in rabbits. Furthermore, rHA ‐Infestin‐4 prevented occlusion in the arterio‐venous shunt model in mice and rabbits where thrombosis was induced via a foreign surface. In contrast to heparin, the haemostatic capacity in rabbits was unaffected by rHA ‐Infestin‐4. Using rodent and non‐rodent species, our data demonstrate that the FXII a inhibitor rHA ‐Infestin‐4 decreased arterial, venous and foreign surface‐induced thrombosis without affecting physiological haemostasis. Hence, we provide further evidence that targeting FXII a represents a potent yet safe antithrombotic treatment approach, especially in foreign surface‐triggered thrombosis.