Background. Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. Methods. We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm3, fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. Results. 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. Conclusions. In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

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Testicular weights and concentrations of LH in plasma were measured in individually housed adult male ring doves given five daily intracerebroventricular injections of saline-NaHCO3 vehicle (2 microliter), ovine prolactin (0.1, 0.5, 1.0 or 2.0 micrograms/day), turkey prolactin (1.0 micrograms/day), turkey GH (1.0 micrograms/day) or ovine GH (1.0 micrograms/day). Administration of ovine prolactin resulted in a dose-dependent suppression of plasma LH concentration, with values in the two highest dose groups averaging three- to fivefold less than those of vehicle-injected controls. Reductions of similar magnitude were obtained following intracranial administration of turkey, ovine or human GH. Whilst effective in reducing plasma LH, turkey prolactin was less effective than an equivalent dose of ovine prolactin. Testicular regression was observed in all treatment groups which showed a significant decrease in plasma LH concentrations. Because crop sacs remained undeveloped in all treatment groups, it was concluded that these centrally administered hormones acted primarily at the level of the brain or pituitary to exert their suppressive effects. The possibility that prolactin and GH interact with different binding sites to inhibit LH secretion is discussed, together with evidence for a possible role of prolactin and GH in gonadotrophin regulation under normal physiological conditions.

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