The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro.
Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain.
Laboratory for Neurological Research, Sheba Medical Center, Tel HaShomer, Israel.
Valery
V
Golderman
Department of Neurology, the Chaim Sheba Medical Center, Tel HaShomer, Israel.
Efrat
E
Shavit-Stein
Department of Hematology, Coagulation Laboratory, Sheba Medical Center, Tel HaShomer, Israel.
Ilia
I
Tamarin
Surgeon General Headquarters, Israel Defense Force Medical Corps, Tel Hashomer, Ramat Gan, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Yossi
Y
Rosman
Surgeon General Headquarters, Israel Defense Force Medical Corps, Tel Hashomer, Ramat Gan, Israel.|Department of radiology, MedStar Georgetown University Hospital, Washington DC, United States of America.
Shai
S
Shrot
Department of Hematology, Coagulation Laboratory, Sheba Medical Center, Tel HaShomer, Israel.
Nurit
N
Rosenberg
Department of Neurology, the Chaim Sheba Medical Center, Tel HaShomer, Israel.|Department of Neurology, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Nicola
N
Maggio
Department of Neurology, the Chaim Sheba Medical Center, Tel HaShomer, Israel.|Department of Neurology, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.|Robert and Martha Harden Chair in Mental and Neurological Diseases Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Joab
J
Chapman
Surgeon General Headquarters, Israel Defense Force Medical Corps, Tel Hashomer, Ramat Gan, Israel.|NBC Protection Division, IMoD, Hakyria, Tel Aviv, Israel.|Institute for Research in Military Medicine, the Hebrew University of Jerusalem, Jerusalem, Israel.
Arik
A
Eisenkraft
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