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described T. kirtlandii venom as an activator of prothrombin and Factor X (see previ-
ous section). Thus, both Thelotornis and Dispholidus venoms have properties similar
to those of R. tigrinus and R. subminiatus (see Figure 4.1 ), and the resulting patho-
physiology from venoms of all of these species correlates closely with clinical mani-
festations in the envenomated patient.
Other studies have revealed different venom activities. For instance, Theakston et al.
(1979) reported that R. subminiatus venom functioned as a Ca 2 independent, potent
Factor X activator and a mild prothrombin-activator. In contrast, Zotz et al. (1991)
described a potent prothrombin-activator present in gland extract from R. subminiatus .
The thrombin thus generated was not inhibited by antithrombin III or by antithrombin
III-heparin complex. Unlike Theakston et al. (1979), Zotz et al. (1991) found no direct
Factor X activation. Several investigators have reported powerful Ca 2 independent
Factor X activation in R. subminiatus or R. tigrinus venom or Duvernoy's gland extract
(Nahas et al., 1976; Theakston et al., 1979), while others have emphasized prothrom-
bin activation (Sakai et al., 1983; Zotz et al., 1991). All of these studies have reported
potent defibrinating action of venoms from both species; none reported thrombin-like
activity (Weinstein and Kardong, 1994).
Several investigators have detected proteolytic activity in venoms of R. subminia-
tus and R. tigrinus (Ferlan et al., 1983; Komori et al., 2006). Phospholipases A activ-
ity in R. subminiatus venom was reported by Ferlan et al. (1983). A recent study of
hemorrhagic toxins in venom of R. t. tigrinus discovered and characterized a novel
metalloprotease that may be regulated by the cysteine-switch mechanism (Komori
et al., 2006). The authors considered that this protease was likely to be a matrix
metalloprotease, rather than a snake venom metalloprotease (Komori et al., 2006).
As previously discussed, proteases, related rhexic hemorrhagins, and, possibly, dis-
integrins, combined with the powerful defibrinating activity of potent procoagulant
toxins are likely to contribute to the severe hemorrhagic diathesis/DIC observed
in serious envenoming from these natricids, as well as the medically important
Dispholidini, Thelotornis spp., and D. typus ( Figure 4.1 ).
4.3.2.4 Summary of Experimental Pathophysiological Effects of Duvernoy's
Secretion from R. tigrinus tigrinus
Pathophysiological studies of R. tigrinus venom in rats and mice have offered a
glimpse into some of the potential pathology that might be induced by this venom
in a mammalian system. Injected mice exhibited systemic hemorrhage, including
subendocardial and pulmonary foci and alveolar as well as glomerular microthrombi
(Sakai et al., 1983). The magnitude of pathological effects were correlated with
dose as rats injected with either 300 μg or 1.5 mg of Duvernoy's gland extract devel-
oped consumption coagulopathy, while those injected with the lower dose recov-
ered fibrinogen, platelets, and erythrocyte levels more rapidly than those receiving
the higher dose. Animals injected with 1.5 mg developed marked pulmonary edema,
hemorrhage and hyaline droplet degeneration, and renal casts. Glomerular deposi-
tion of fibrin thrombi and renal tubular necrosis were observed. They were especially
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