title: The inhibition of platelet aggregation and blood coagulation by Micropechis ikaheka venom.
abstract: Uncoagulable blood and life-threatening bleeding can result from the action of some snake venom toxins on haemostatic components of blood and vessel walls. Although envenoming by Micropechis ikaheka primarily affects neurones and muscle cells causing post-synaptic neuromuscular blockade and rhabdomyolysis, disturbances of haemostasis also occur. Therefore, the present study explored the effects of M. ikaheka venom on platelets and endothelium, which are important components of the haemostatic mechanism. The venom inhibited platelet aggregation in response to ADP and collagen, and also delayed clotting dependent on platelet activation or endothelial cell tissue factor expression. Some of these effects were reduced by the incubation of venom with a phospholipase A2 (PLA2) inhibitor and could be reproduced by a 17 kDa venom fraction containing a PLA2. In addition, an 11 kDa fraction containing a long-chain neurotoxin reduced ADP-induced aggregation. The venom was also found to reduce endothelial cell adherence to vitronectin-, fibronectin- and collagen-coated surfaces. These results suggest that, by inhibiting procoagulant activities of platelets and endothelial cells, a 17 kDa PLA2 plays an important role in the anticoagulant action of M. ikaheka venom.
authors.affiliation: Department of Haematology, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. bsundell@liverpool.ac.uk
authors.forename: I B
authors.initials: IB
authors.lastname: Sundell
authors.forename: R D
authors.initials: RD
authors.lastname: Theakston
authors.forename: A S
authors.initials: AS
authors.lastname: Kamiguti
authors.forename: R J
authors.initials: RJ
authors.lastname: Harris
authors.forename: A T
authors.initials: AT
authors.lastname: Treweeke
authors.forename: G D
authors.initials: GD
authors.lastname: Laing
authors.forename: J W
authors.initials: JW
authors.lastname: Fox
authors.forename: D A
authors.initials: DA
authors.lastname: Warrell
authors.forename: M
authors.initials: M
authors.lastname: Zuzel
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D034341:Aristolochic Acids; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000737:chemistry / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D010616:Phenanthrenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010974:Platelet Aggregation / Q000187:drug effects*; D011506:Proteins / Q000032:analysis; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D034341:Aristolochic Acids; D004546:Elapid Venoms; D005353:Fibronectins; D010616:Phenanthrenes; D011506:Proteins; D019096:Vitronectin; D003094:Collagen; D013925:Thromboplastin; C000228:aristolochic acid I; D010741:Phospholipases A; D054467:Phospholipases A2