Effects of purified human fibrinogen modified with carbon monoxide and iron on coagulation in rabbits injected with Crotalus atrox venom
While snake venom derived enzymes, such as the thrombin-like activity possessing ancrod, have been used to treat thrombotic disease by defibrinogenating patients, the therapeutic potential of fibrinogenolytic snake venom enzymes, such as those derived from Crotalus atrox, have not been fully explored. However, one of the potential risks of administering fibrinogenolytic enzymes to effect defibrinogenation is hemorrhage secondary to hypofibrinogenemia. The present investigation sought to determine if human fibrinogen modified with carbon monoxide (CO) and iron (Fe) could resist degradation by C. atrox venom as has been seen in vitro in a recently developed rabbit model of envenomation. Compared with unmodified human fibrinogen, CO/Fe modified fibrinogen administered prior to envenomation had significantly shorter onset of coagulation and greater strength; however, when administered after envenomation, there was no differences between the two types of fibrinogen. Of interest, when administered after envenomation, both types of fibrinogen delayed the onset of coagulation while increasing plasma clot strength, a mixed effect likely secondary to formation of fibrinogen degradation products. Further preclinical investigations are needed to further define the benefits and risks of the use of fibrinogenolytic enzymes as defibrinogenating agents, as well as the risks of the “biochemical brakes” used to modulate the activity or substrate of the fibrinogenolytic enzyme.
KeywordsSnake venom metalloproteinase Fibrinogenolysis Fibrinogen Iron Carbon monoxide Thrombelastography
- 11.Olver CS, Nielsen VG (2017) Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom. Biometals. doi:10.1007/s10534-017-0035-9
- 12.Kim CH, McBride DW, Raval R, Sherchan P, Hay KL, Gren EC, Kelln W, Lekic T, Hayes WK, Bull BS, Applegate R, Tang J, Zhang JH (2017) Crotalus atrox venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury. Sci Rep 7:40821CrossRefPubMedPubMedCentralGoogle Scholar