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potential efficacy of LMWH in comparison to unfractionated heparin (UFH) was due
to their differing activities as “LMWH exerts its anticoagulant effect by inactivating
factor Xa, while UFH has effect on factors IIa, Ixa, xIa, XIIa, and XIIIa” (Paul et al.,
2007). These authors also stated that unlike UFH, LMWH has “no effect on plate-
lets,” and that due to these differences in action, speculated that there is “less chance
of severe bleeding when LMWH is used” (Paul et al., 2007).
A common property of many venoms that contain prothrombin-activators
or thrombin-like enzymes is the venom-induced generation of thrombin that is
uninhibited or only partially inhibited by antithrombin III or antithrombin-hepa-
rin complex (Marsh and Williams, 2005; Salazar et al., 2008; Schneemann et al.,
2004). Zotz et al. (1991) reported that an extract from Duvernoy's glands of R.
subminiatus contained a powerful prothrombin-activator that generated throm-
bin with antithrombin III and antithrombin-heparin complex resistant proper-
ties. Therefore, although a lack of antithrombin III consumption has been noted
in R. subminiatus envenoming (Zotz et al., 1991), UFH would not likely achieve
any therapeutic advantage in these cases. Similarly, although LMWH exhibits an
approximately 4:1 action in relation to binding to Factor X:thrombin, respectively,
it would probably still be ineffective in envenomings from hazard level 1 colubrids
that possess similar venom properties.
The main risk of heparin, even in low doses, is its exacerbation of bleeding. For
this reason its use for ancillary treatment of a number of diseases, such as severe falci-
parum malaria and dengue hemorrhagic syndrome, has been abandoned. An additional
consideration is the risk of heparin-induced thrombocytopenia (HIT). Heparin can bind
to platelet factor IV and this may induce an antibody response against those platelets.
This can result in aggregation and subsequent clearance of large numbers of platelets
resulting in thrombocytopenia (Napolitano et al., 2006). The antiplatelet IgG popula-
tions are usually transient, and last for approximately 3 months (Ahmed et al., 2007).
Although HIT is significantly less frequent with LMWH therapy compared to UFH
therapy, it still may occur and is a risk (Jang and Hursting, 2005; Shuster et al., 2003).
Therefore, the assertion of Paul et al. (2007) regarding the lack of effect of LMWH on
platelets is inaccurate. The risk of HIT must be considered an additional concern due
to the possibility of HIT compounding the venom-induced thrombocytopenia associ-
ated with some hazard level 1 colubrid envenomings. The paradoxically increased pro-
thrombotic tendency in some patients when treated with heparin for several days may
comprise additional risk (Warkentin, 1999).
The preponderance of current evidence suggests that heparin probably increases
the risk of hemorrhage in patients afflicted with viperid venom-induced coagulopa-
thy, and its use is therefore contraindicated in these cases (Mahasandana et al., 1980;
Schneemann et al., 2004). Also, UFH and, to a lesser extent, LMWH, carry signifi-
cant risk in a number of clinical presentations and have uncertain benefit in the man-
agement of coagulopathic envenoming. Therefore, current evidence indicates that the
risks of heparin therapy outweigh any marginal benefit demonstrated to date. Thus,
heparin therapy cannot be endorsed for use in hazard level 1 colubrid envenomation
and is positively contraindicated.
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