The inhibition of platelet aggregation and blood coagulation by Micropechis ikaheka venom

Uncoagulable blood and life-threatening bleeding can result from the action of some snake venom toxins on haemostatic components of blood and vessel w alls. Although envenoming by Micropechis ikaheka primarily affects neurones and muscle cells causing post-synaptic neuromuscular blockade and rhabdomy olysis, disturbances of haemostasis also occur. Therefore, the present stud y explored the effects of M. ikaheka venom on platelets and endothelium, wh ich are important components of the haemostatic mechanism. The venom inhibi ted 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 A(2) (PLA(2)) inhibitor and could be reproduced by a 1 7 kDa venom fraction containing a PLA(2). In addition, an 11 kDa fraction c ontaining a long-chain neurotoxin. reduced ADP-induced aggregation. The ven om was also found to reduce endothelial cell adherence to vitronectin-, fib ronectin- and collagen-coated surfaces. These results suggest that, by inhi biting procoagulant activities of platelets and endothelial cells, a 17 kDa PLA(2) plays an important role in the anticoagulant action of M. ikaheka v enom.