[Activation of the blood coagulation system during gram-negative infections and endotoxemias].
Blood coagulation may be activated by the extrinsic or intrinsic pathways. The extrinsic clotting system is put into action by tissue thromboplastin, originating from injured tissue cells, but also from damaged leukocytes and erythrocytes. Tissue thromboplastin is a phospholipoprotein with an enzymatic component, capable of converting the clotting factor VII to its activated form, factor VIIa, which in turn activates factor X. The factor Xa-complex (containing also factor Va, phospholipid, and calcium) is the prothrombinconverting principle. The intrinsic clotting system is based on factors which are contained in the circulating blood. Its activation requires the availability of phospholipid and of activated factor XII (factor XIIa), or factor XIa. Factor XII is activated by collagen, i.e., whenever the vascular endothelium is injured, and to a lesser extent also by "activated" blood platelets. Platelets in turn are activated primarily by thrombin, collagen, and, in a self-perpetuating process, since all these materials are released from activated platelets, also by adenosine-5-diphosphate, adrenaline, and serotonin. The activation of platelets leads to a variety of morphological and biochemical alterations, culminating in their aggregation and in the selective release from storage organelles of different substances, among them those mentioned above. Of particular importance is the fact that in the course of platelet alterations, procoagulant phospholipid also becomes available on the platelet surface. The significance of the activation of the intrinsic system is seen in the possibility of the initiation of a self-sustained process which, after a primary event, e.g. vascular or cellular injury, will continue to convert prothrombin into thrombin. The effects of endotoxin on the blood clotting system show striking species differences. In the rabbit, endotoxin, with the involvement of factors of the complement system, will directly act upon blood platelets and thus initiate intravascular, intrinsic coagulation. In man, endotoxin remains without a direct effect on platelets and alternative possibilities of initiating thrombin formation must be considered. One possibility is extrinsic activation via tissue thromboplastin from injured leukocytes. Another pathway, which is supported by several experimental findings, starts out with endotoxin-mediated endothelial damage. Endothelial cells are in fact severely affected by endotoxin and may even be removed from the vascular wall, thus making accessible the subendothelial activator of factor XII. Thrombin in turn affects the vascular endothelium: therefore, one initiated, the process of intravascular activation of coagulation will perpetuate, this the more as platelets in turn will be stimulated into activity. The possible intervention of other vasoactive factors must also be considered...
D000818:Animals; D001424:Bacterial Infections / Q000097:blood / Q000503:physiopathology*; D001679:Biogenic Amines / Q000378:metabolism; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology; D003165:Complement System Proteins; D004731:Endotoxins / Q000494:pharmacology; D005167:Factor VII / Q000032:analysis; D005174:Factor XII / Q000502:physiology; D005342:Fibrinolysis / Q000187:drug effects; D006088:Gram-Negative Aerobic Bacteria; D006801:Humans; D011817:Rabbits; D013917:Thrombin / Q000502:physiology
D001679:Biogenic Amines; D004731:Endotoxins; D005167:Factor VII; D005174:Factor XII; D003165:Complement System Proteins; D013917:Thrombin
Die Aktivierung des Gerinnungssystems im Verlauf gramnegativer Infektionen und Endotoxämien