Peroxynitrite decreases hemostasis in Human plasma in vitro

Vance G Nielsen, John P. Crow, Ashish Mogal, Fen Zhou, Dale A. Parks

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Coagulopathy has been associated with clinical scenarios that involve reactive nitrogen species such as peroxynitrite (OONO-). Further, OONO- decreases tissue factor and fibrinogen function in vitro. Thus, we hypothesized that exposure of plasma to the OONO- generated with 3-morpholinosydnonimine (SIN-1), a molecule that produces both nitric oxide and superoxide, would result in a decrease in hemostatic function via diminished coagulation protein activity. Hemostatic function of plasma exposed to SIN-1 (0, 1, 5, and 10 mM for 60 min at 37°C) was assessed with thrombelastography, activated partial thromboplastin time, and prothrombin time in the presence or absence of superoxide dismutase (SOD) or an OONO- scavenger. SIN-1 exposure resulted in a significant (P < 0.05), dose-dependent decrease in plasma hemostatic function and concurrent significant (P < 0.05) decreases in activities of factor VII, factor VIII complex, and factor X. Fibrinogen concentration was not affected by SIN-1. Antithrombin and protein C activity also decreased significantly (P < 0.05). Coincubation with SOD or an OONO- scavenger significantly (P < 0.05) attenuated SIN-1 mediated changes in hemostasis and procoagulant/anticoagulant activity. We conclude that OONO- may decrease hemostatic function in human plasma by nitration of key procoagulants and that OONO- may play a significant role in hemorrhagic states.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalAnesthesia and Analgesia
Volume99
Issue number1
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Hemostatics
Hemostasis
Fibrinogen
Superoxide Dismutase
Antithrombin Proteins
Thrombelastography
Reactive Nitrogen Species
Factor X
Factor VII
Partial Thromboplastin Time
Prothrombin Time
Factor VIII
Thromboplastin
Protein C
Superoxides
Anticoagulants
Nitric Oxide
In Vitro Techniques
Proteins

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Nielsen, V. G., Crow, J. P., Mogal, A., Zhou, F., & Parks, D. A. (2004). Peroxynitrite decreases hemostasis in Human plasma in vitro. Anesthesia and Analgesia, 99(1), 21-26.

Peroxynitrite decreases hemostasis in Human plasma in vitro. / Nielsen, Vance G; Crow, John P.; Mogal, Ashish; Zhou, Fen; Parks, Dale A.

In: Anesthesia and Analgesia, Vol. 99, No. 1, 07.2004, p. 21-26.

Research output: Contribution to journalArticle

Nielsen, VG, Crow, JP, Mogal, A, Zhou, F & Parks, DA 2004, 'Peroxynitrite decreases hemostasis in Human plasma in vitro', Anesthesia and Analgesia, vol. 99, no. 1, pp. 21-26.
Nielsen VG, Crow JP, Mogal A, Zhou F, Parks DA. Peroxynitrite decreases hemostasis in Human plasma in vitro. Anesthesia and Analgesia. 2004 Jul;99(1):21-26.
Nielsen, Vance G ; Crow, John P. ; Mogal, Ashish ; Zhou, Fen ; Parks, Dale A. / Peroxynitrite decreases hemostasis in Human plasma in vitro. In: Anesthesia and Analgesia. 2004 ; Vol. 99, No. 1. pp. 21-26.
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