Singlet oxygen inactivates fibrinogen, factor V, factor VIII, factor X, and platelet aggregation of human blood.
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.
Stief
T W
TW
Institute of Clinical Chemistry, Philipps-University, D-35033, Marburg, Germany. thstief@post.med.uni-marburg.de
Kurz
J
J
Doss
M O
MO
Fareed
J
J
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D005164:Factor IX / Q000378:metabolism; D005165:Factor V / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005174:Factor XII / Q000378:metabolism; D005176:Factor XIII / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000494:pharmacology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism / Q000502:physiology*; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011516:Prothrombin / Q000378:metabolism; D011517:Prothrombin Time; D026082:Singlet Oxygen; D013918:Thrombin Time
D001779:Blood Coagulation Factors; D026082:Singlet Oxygen; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D005169:Factor VIII; D005164:Factor IX; D005170:Factor X; D005174:Factor XII; D005340:Fibrinogen; D005176:Factor XIII; D008715:Methionine; D001205:Ascorbic Acid; D010100:Oxygen