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Golderman V, Shavit-Stein E, Tamarin I, et al. The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro. PLoS One. 2016;11(9):e0163787doi: 10.1371/journal.pone.0163787.
Golderman, V., Shavit-Stein, E., Tamarin, I., Rosman, Y., Shrot, S., Rosenberg, N., Maggio, N., Chapman, J., & Eisenkraft, A. (2016). The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro. PloS one, 11(9), e0163787. https://doi.org/10.1371/journal.pone.0163787
Golderman, Valery, et al. "The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro." PloS one vol. 11,9 (2016): e0163787. doi: https://doi.org/10.1371/journal.pone.0163787
Golderman V, Shavit-Stein E, Tamarin I, Rosman Y, Shrot S, Rosenberg N, Maggio N, Chapman J, Eisenkraft A. The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro. PLoS One. 2016 Sep 30;11(9):e0163787. doi: 10.1371/journal.pone.0163787. eCollection 2016. PMID: 27689805; PMCID: PMC5045196.
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PLoS One. 2016 Sep 30;11(9):e0163787. doi: 10.1371/journal.pone.0163787. eCollection 2016.

The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro.

PloS one

Valery Golderman, Efrat Shavit-Stein, Ilia Tamarin, Yossi Rosman, Shai Shrot, Nurit Rosenberg, Nicola Maggio, Joab Chapman, Arik Eisenkraft

Affiliations

  1. Laboratory for Neurological Research, Sheba Medical Center, Tel HaShomer, Israel.
  2. Department of Neurology, the Chaim Sheba Medical Center, Tel HaShomer, Israel.
  3. Department of Hematology, Coagulation Laboratory, Sheba Medical Center, Tel HaShomer, Israel.
  4. Surgeon General Headquarters, Israel Defense Force Medical Corps, Tel Hashomer, Ramat Gan, Israel.
  5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  6. Department of radiology, MedStar Georgetown University Hospital, Washington DC, United States of America.
  7. Department of Neurology, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
  8. Robert and Martha Harden Chair in Mental and Neurological Diseases Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  9. NBC Protection Division, IMoD, Hakyria, Tel Aviv, Israel.
  10. Institute for Research in Military Medicine, the Hebrew University of Jerusalem, Jerusalem, Israel.

PMID: 27689805 PMCID: PMC5045196 DOI: 10.1371/journal.pone.0163787

Abstract

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.

Conflict of interest statement

The authors have declared that no competing interests exist. This study was financed by a scientific grant of the Israel Defense Forces. The funders had no role in study design, data collection and an

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