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Singlet oxygen inactivates fibrinogen, factor V, factor VIII, factor X, and platelet aggregation of human blood.
- Source :
-
Thrombosis research [Thromb Res] 2000 Mar 15; Vol. 97 (6), pp. 473-80. - Publication Year :
- 2000
-
Abstract
- Activated polymorphonuclear leukocytes participate in hemostasis. These phagocytes generate up to 5 mmol/l of oxidants of the HOCl- and chloramine-type. The present study shows, for the first time, that physiological concentrations of NaOCl or chloramines act as anticoagulants in human plasma. Prothrombin time, activated partial thromboplastin time, and thrombin time at chloramine concentrations greater than 1 mmol/l are prolonged proportional to the oxidant concentration. Plasmatic coagulation factors sensible to oxidation are fibrinogen, factor V, factor VIII, and factor X with a 50% effective dose of 2-3 mmol/l NaOCl or taurine-chloramine. Chloramines or chloramine-like agents (e.g., chloramine T(R) or vancomycin) also inactivate platelet aggregation (in whole blood or platelet-rich plasma) at an 50% effective dose of about 1.0 mmol. This irreversible oxidation of the hemostasis components is inhibited by addition of methionine, cysteine, ascorbic acid, or azide in 10-fold molar excess prior to oxidation. The oxy-radical inhibitors mannitol, superoxide dismutase, or catalase do not antagonize the action of NaOCl or chloramines. Therefore, the oxidant here involved has reaction characteristics of singlet oxygen (1O(2)), a nonradical, excited (i.e., light-emitting) oxidant. The hemostasis factors sensible to oxidation might dispose of oxidizable, for their function critical, methionine or cysteine residues. In conclusion, blood coagulation factors I, V, VIII, X and thrombocytes are sensible to nonradical oxidants of activated phagocytes. Via 1O(2) generation, polymorphonuclear leukocytes can generate a local pericellular zone of anticoagulation. The data suggest that the cell signal 1O(2) in physiological amounts is an antithrombotic agent.
- Subjects :
- Animals
Ascorbic Acid pharmacology
Blood Platelets drug effects
Blood Platelets physiology
Cattle
Factor IX metabolism
Factor V metabolism
Factor VII metabolism
Factor VIII metabolism
Factor X metabolism
Factor XII metabolism
Factor XIII metabolism
Fibrinogen metabolism
Humans
Methionine pharmacology
Oxidation-Reduction
Oxygen metabolism
Partial Thromboplastin Time
Platelet Aggregation drug effects
Prothrombin metabolism
Prothrombin Time
Singlet Oxygen
Thrombin Time
Blood Coagulation Factors metabolism
Oxygen physiology
Platelet Aggregation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0049-3848
- Volume :
- 97
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Thrombosis research
- Publication Type :
- Academic Journal
- Accession number :
- 10704657
- Full Text :
- https://doi.org/10.1016/s0049-3848(99)00211-x