TY - JOUR
T1 - Effects of purified human fibrinogen modified with carbon monoxide and iron on coagulation in rabbits injected with Crotalus atrox venom
AU - Nielsen, Vance G.
N1 - Funding Information:
Funding This investigation was supported by the University of Arizona (Tech Launch Arizona Asset Development Award 15–160) and the Department of Anesthesiology.
Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - Carbon monoxide
KW - Fibrinogen
KW - Fibrinogenolysis
KW - Iron
KW - Snake venom metalloproteinase
KW - Thrombelastography
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U2 - 10.1007/s11239-017-1549-2
DO - 10.1007/s11239-017-1549-2
M3 - Article
C2 - 28889321
AN - SCOPUS:85028978436
SN - 0929-5305
VL - 44
SP - 481
EP - 488
JO - Journal of Thrombosis and Thrombolysis
JF - Journal of Thrombosis and Thrombolysis
IS - 4
ER -