Maintenance therapy was administered to two patients (17%), not administered to 9 patients (75%), and not documented for one patient (8%). With one exception (recurrent limb pain and swelling),

all cases of recurrence or delayed onset of severe venom effects involved defibrination (with or without prothrombin time elevation) and/or thrombocytopenia, and were clinically occult. Although these events were judged a priori to represent “a severe threat of bleeding,” Inhibitors,research,lifescience,medical none of the 11 patients (0%) with recurrent or delayed-onset hematologic venom effects developed bleeding. Table 6 Recurrence or delayed onset of severe venom effects Permanent sequelae of envenomation Few publications assessed and reported long-term outcomes. Therefore, the available Inhibitors,research,lifescience,medical data are inadequate to describe the long term outcomes after crotaline snakebite treated with FabAV. No published manuscripts described death following FabAV administration were identified in the literature search. Reports to the US National Inhibitors,research,lifescience,medical Poison Data System The TESS/NPDS data include 21 deaths due to snakebite reported to participating US poison control centers from 2000 – 2006[1,14-19]. Of these, five patients received FabAV prior to death; two additional patients received unspecified antivenom. These cases

are summarized in Table ​Table7.7. Five patients presented in extremis and died of cerebral anoxia and/or multisystem organ failure; the other two patients died from complications of substance abuse. Table 7 Reports of death after FabAV administration reported to the US National Inhibitors,research,lifescience,medical Poison Data System, 2000–2006 Discussion Physicians in the United States treating victims bitten by rattlesnakes, cottonmouth and copperhead snakes,

and pygmy rattlesnakes no longer have access to an antivenom that is licensed and approved to treat severely Inhibitors,research,lifescience,medical envenomated victims. The previous standard therapy, whole IgG antivenom, is no longer available; the currently-available antivenom, FabAV, was tested and approved only for use in mildly and moderately envenomated MRIP patients. Those patients with severe envenomation – hypotension, severe hematologic effects, and/or severe limb findings – are clinical “orphans.” Data from the American Association of Poison Control Centers suggest that, when faced with the choice of off-label administration of FabAV or supportive care only, treating physicians most often choose to administer FabAV to severely envenomated patients[39]. It is difficult to conceive of a placebo-controlled trial of FabAV in severe snakebite; to our knowledge, no such study has been MGCD0103 conducted.