Blood acting coagulation lecture (original) (raw)
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The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis also termed primary, secondary and tertiary hemostasis. From the platelet transcriptome 6000 mRNA species and represent receptors, ion channels, signalling molecules, kinases, phosphatases, and structural, metabolic and regulatory proteins. This abundance of regulatory proteins points towards the importance of signal transduction in platelet function. First platelets adhere to collagen, this induces activation signals such as TXA 2 that induces further Ca 2+ increase. Consecutively, fibrinogen binds to the integrin α IIb β 3 resulting in aggregation.This self-amplifying process is controlled by signals, from endothelial cells, to restrict the platelet plug to the site of vessel injury.
Management of bleeding disorders by prohemostatic therapy
International Journal of Hematology, 2002
Pro-hemostatic therapy aims at an improvement of hemostasis, which may be achieved by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis. These treatment strategies may be applied to specifically correct a defect in one of the pathways of coagulation, but have in some situations also been shown to be effective in reducing bleeding in patients without a primary defect in coagulation. Besides the transfusion of platelets in case of thrombocytopenia or severe platelet disorders, a pharmacological improvement of primary hemostasis may be achieved by the administration of desmopressin. The administration of DDAVP results in a marked increase in the plasma concentration of Von Willebrand factor (and associated coagulation factor VIII) and (also by yet unexplained additional mechanisms) a remarkable potentiation of primary hemostasis as a consequence. DDAVP is used for the prevention and treatment of bleeding in patients with von Willebrand disease or mild hemophilia A, and further in patients with an impaired function of primary hemostasis, such as in patients with uremia, liver cirrhosis or in patients with aspirin-associated bleeding. Based on the current insight that activation of coagulation in vivo predominantly proceeds by the tissue factor/factor VII(a) pathway, recombinant factor VIIa has been developed as a prohemostatic agent and has recently become available for clinical use. Indeed, in uncontrolled clinical studies this compound has been shown to exert a potent procoagulant activity and appeared to be highly effective in the prevention and treatment of bleeding, although most experience so far has been obtained in patients with severe and complicated coagulation defects. At present, a more general use of this agent for bleeding patients without an apparent coagulation defect is the subject of a number of ongoing clinical trials. Agents that exert anti-fibrinolytic activity are aprotinin and the group of lysine analogues. The pro-hemostatic effect of these agents proceeds not only by the inhibition of fibrinolysis (thereby shifting the procoagulant/anticoagulant balance towards a more procoagulant state), but also due to a protective effect on platelets, as has been demonstrated at least for aprotinin. The mechanism of this platelet-protective effect has, besides a potential prevention of plasmin-mediated loss of platelet receptors not been elucidated. Whether the pro-hemostatic effect of the anti-fibrinolytic agents will eventually result in a higher incidence of thromboembolic complications is still a matter of debate (see further), however, this has so far not been shown in straightforward clinical trials.
Introduction to haemostasis from a pharmacodynamic perspective
British Journal of Clinical Pharmacology, 2011
Biochemical characterization of the haemostatic system has advanced significantly in the past decades. Sub-systems, such as coagulation, fibrinolysis, blood cells and platelets and the vessel wall have been studied by specialists, mostly separately and independently. The time has come to integrate the approaches, and, in particular, to develop tests to document the state of the whole system and to have available adequate pharmacodynamic tests to evaluate treatments. Many examples are available to show that traditional general methods of clotting and lysis do not provide the information that is desired. The present tendency is to use specific methods for specific factors or effects which are very limited in pharmacological information. There is also increasing awareness of the occurrence of rather broad interindividual variability in the haemostatic system. This suggests that individually tailored treatments are required. This is the more relevant since haemostasis is a balance and treatment should be positioned between efficacy and safety. The conclusion is reached that there is a need for integrated or global methods or sets of methods that reflect the complexity and individual status appropriately and allow the practitioner to judge the effects of interventions and their individual aspects.
The hemostatic system. 1st Part
2019
The hemostatic system is a complex ancestral pathway physiologically dedicated to protect the individual from bleeding. It starts immediately after an endothelial injury. Platelets and blood coagulation act synergically to provide a strength clot able to stop bleeding. In healthy subjects, the hemostatic system is able to work to avoid an excess of fibrin formation and deposition within the blood vessels on the one hand but is ready to stop bleeding on the other. To reach this crucial objective, a fine regulation of its activity is required. In other words, all actions of the hemostatic system are under control to assure a perfect balance to maintain people distant from both Scylla (bleeding) and Charybdis (thrombosis). Fibrinolysis is a complementary defensive system essential to regulate fibrin deposition via its dissolution. It is, in turn, well controlled to avoid bleeding and thrombosis by a fine control of its inducers and inhibitors. The aim of this review is to provide a pic...