Sometimes size does matter: Anticoagulant pathophysiological effects of Southwestern Speckled Rattlesnake (Crotalus pyrrhus) venoms are dichotomous by body size.

The Southwestern Speckled Rattlesnake (Crotalus pyrrhus) is a medically significant pit viper with envenomation effects that include depletion of fibrinogen levels. Despite this the venom has been poorly studied. To fill this knowledge gap, we 57 venom samples obtained from 19 geographic localities, including both juvenile and adult venoms, for their effect upon human plasma and purified fibrinogen. For most localities, we were able to include both female and male specimens of varying sizes to test possible sexual venom variation and size-related shifts. We found that instead of a geographical variation in coagulotoxicity, C. pyrrhus venoms exhibit a consistent size-related trend, whereby small snakes and adult snakes were both anticoagulant, but differed sharply in the underly biochemistry. Smaller snakes deplete fibrinogen levels through a pseudo-procoagulant (thrombin-like) mechanism whereby fibrinogen is cleaved by kallikrein-scaffold serine proteases to produce weak, transient clots that rapidly break down. In contrast, larger snakes are classically anticoagulant through the inhibition of the blood clotting factors VIIa, FIXa, FXIa and thrombin, while also depleting fibrinogen levels through destructive (non-clotting) cleavage. Antivenom testing on pseudo-procoagulant venoms for three regionally available antivenoms showed an efficacy pattern of Antivipmyn® > BIRMEX® > CroFab®. As such, this study revealed a dramatic ontogenetic change in the venom biochemistry that was conserved across the vast range of this medically important rattlesnake species. In turn, this variation in venom biochemistry may produce differential pathophysiological effects during a human envenomation.