Bothrops lanceolatus Envenoming in Martinique: A Historical Perspective of the Clinical Effectiveness of Bothrofav Antivenom Treatment

Abstract

Bothrofav, a monospecific antivenom, was introduced in June 1991 and has shown excellent effectiveness against life-threatening and thrombotic complications of Bothrops lanceolatus envenoming. Because of the reoccurrence of cerebral stroke events despite the timely administration of antivenom, new batches of Bothrofav were produced and introduced into clinical use in January 2011. This study’s aim was to evaluate the effectiveness of Bothrofav generations at treating B. lanceolatus envenoming. During the first period of the study (2000–2010), 107 patients were treated with vials of antivenom produced in June 1991, while 282 envenomed patients were treated with vials of antivenom produced in January 2011 in the second study period (2011–2023). Despite timely antivenom administration, thrombotic complications reoccurred after an interval free of thrombotic events, and a timeframe analysis suggested that the clinical efficacy of Bothrofav declined after it reached its 10-year shelf-life. In of the case of an antivenom shortage due to the absence of regular batch production, no adverse effects were identified before the antivenom reached its 10-year shelf-life, which is beyond the accepted shelf-life for a liquid-formulation antivenom. While our study does not support the use of expired antivenom for potent, life-threatening B. lanceolatus envenoming, it can be a scientific message to public entities proving the necessity of new antivenom production for B. lanceolatus envenoming.

A murine experimental model of the unique pulmonary thrombotic effect induced by the venom of the snakeBothrops lanceolatus

“…In contrast, when the venom of B. asper, which induces a typical consumption coagulopathy, was tested in a similar mouse model, there were drastic alterations in these parameters [45]. This agrees with clinical observations of B. lanceolatus envenomings since, in most cases, a consumption coagulopathy is not observed [3,5,11].…”

“…However, in contrast to the typical hemostatic alterations induced by Bothrops sp venoms, characterized by a consumption coagulopathy and defibrinogenation [8,9], envenomings by B. lanceolatus, in the absence of antivenom treatment, involve a severe thrombotic effect which may result in cerebral, myocardial, and pulmonary infarctions [3,10,11], and a diffuse thrombotic microangiopathy [12]. Interestingly, clotting laboratory tests are altered to a much lower extent in these envenomings as compared to those inflicted by other Bothrops species, although thrombocytopenia is frequent [3,5,11]. This thrombotic effect has been also described in envenomings by the closely relates species B. caribbaeus, endemic to the neighboring island of Saint Lucia [13].…”

“…It inflicts between 20-30 cases of envenoming per year [2,3]. The clinical manifestations of these envenomings include local effects, i.e., pain, edema, and necrosis, and systemic alterations, i.e., hemodynamic disturbances and, in some cases, alterations in hemostasis [2][3][4][5], most of which are characteristic of envenomings by Bothrops sp [6][7][8]. However, in contrast to the typical hemostatic alterations induced by Bothrops sp venoms, characterized by a consumption coagulopathy and defibrinogenation [8,9], envenomings by B. lanceolatus, in the absence of antivenom treatment, involve a severe thrombotic effect which may result in cerebral, myocardial, and pulmonary infarctions [3,10,11], and a diffuse thrombotic microangiopathy [12].…”