In accordance with the recommendations of the report of a WHO Coordination Meeting on Venoms and Antivenoms, methods have been developed for the assessment of lethal, defibrinogenating, procoagulant, haemorrhagic, and necrotizing properties of venoms, and used to study 53 venoms from 30 different species of snakes of medical importance throughout the world The venoms studied included Echis carinatus (Iran), Naja naja kaouthia (Thailand), Notechis scutatus (Australia), Trimeresurus flavoviridis (Japan), Vipera russelli (Thailand), and Crotalus atrox (USA), which comprise six of the eight venoms designated by WHO as international reference venoms (IRVs) (C atrox venom replaced C adamanteus venom, as an adequate supply of the latter was not available) The tests used were simple and should be reproducible in other laboratories throughout the world Procedures for assaying neuromuscular paralytic activity and systemic myotoxic activity have yet to be developedThe tests will be used to assay the neutralizing potency of both international standard antivenoms (raised using the IRVs) and new and currently available commercial antivenoms Such studies should result in the production of more potent antivenoms for use in both developing and developed countries, and improve the understanding and management of snake bite throughout the world

Development of simple standard assay procedures for the characterization of snake venom.

Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils or macrophages, whereas uncoated or plasma-coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation.

/pdf/fibrin-ogen-mediates-acute-inflammatory-responses-to-1s3t75ljv4.pdf

Fibrin(ogen) mediates acute inflammatory responses to biomaterials.

Snake venoms and coagulopathy.

ContextApproved treatment options for acute ischemic stroke in the United States
and Canada are limited at present to intravenous tissue-type plasminogen activator,
but bleeding complications, including intracranial hemorrhage, are a recognized
complication.ObjectiveTo evaluate the efficacy and safety of the defibrinogenating agent ancrod
in patients with acute ischemic stroke.DesignThe Stroke Treatment with Ancrod Trial (STAT), a randomized, parallel-group,
double-blind, placebo-controlled trial conducted between August 1993 and January
1998.SettingForty-eight centers, primarily community hospitals, in the United States
and Canada.PatientsA total of 500 patients with an acute or progressing ischemic neurological
deficit were enrolled and included in the intent-to-treat analysis.InterventionsPatients were randomly assigned to receive ancrod (n=248) or placebo
(n=252) as a continuous 72-hour intravenous infusion beginning within 3 hours
of stroke onset, followed by infusions lasting approximately 1 hour at 96
and 120 hours. The ancrod regimen was designed to decrease plasma fibrinogen
levels to 1.18 to 2.03 µmol/L.Main Outcome MeasuresThe primary efficacy end point was functional status, with favorable
functional status defined as survival to day 90 with a Barthel Index of 95
or more or at least the prestroke value, compared by treatment group. Primary
safety variables included symptomatic intracranial hemorrhage and mortality.ResultsFavorable functional status was achieved by more patients in the ancrod
group (42.2%) than in the placebo group (34.4%; P=.04)
by the prespecified covariate-adjusted analysis. Mortality was not different
between treatment groups (at 90 days, 25.4% for the ancrod group and 23% for
the placebo group; P=.62), and the proportion of
severely disabled patients was less in the ancrod group than in the placebo
group (11.8% vs 19.8%; P=.01). The favorable functional
status observed with ancrod vs placebo was consistent in all subgroups defined
for age, stroke severity, sex, prestroke disability, and time to treatment
(≤3 or >3 hours after stroke onset). There was a trend toward more symptomatic
intracranial hemorrhages in the ancrod group vs placebo (5.2% vs 2.0%; P=.06), as well as a significant increase in asymptomatic
intracranial hemorrhages (19.0% vs 10.7%; P=.01).ConclusionIn this study, ancrod had a favorable benefit-risk profile for patients
with acute ischemic stroke.

/pdf/intravenous-ancrod-for-treatment-of-acute-ischemic-stroke-3loc62tvil.pdf

Intravenous Ancrod for Treatment of Acute Ischemic Stroke: The STAT Study: A Randomized Controlled Trial

REID, Thean, Chan and Baharon (1963) and Reid, Chan and Thean (1963) have described a defibrination syndrome following envenoming by the Malayan Pit-Viper (Ancistrodon rhodostoma). It was found that the patient’s blood was rendered incoagulable for periods as long as 14 days after a snake bite, and that during this time there were no episodes of severe bleeding. The anticoagulant effect of the venom appears to be the result of the progressive conversion of circuIating fibrinogen to fibrin (Regoeczi, Gergely and McFarlane, 1966) ; the fibrinogen being converted into microclots which were found in various organs. Recently Marsten, Chan, Ankeney and Botti (1966). have found that dogs injected with partially purified preparations of the venom would be protected from artificially induced thrombosis of the vena cava. Because of these findings and the apparently low toxicity of the crudevenom it might be possible to use this venom clinically as an anticoagulant. This paper describes the isolation and characterization of the thrombin-like activity from the whole venom.

H.A. Reid

Papers

Prolonged coagulation defect (defibrination syndrome) in Malayan viper bite.