Introduction to haemostasis from a pharmacodynamic perspective

Abstract

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. IntroductionMaintenance of blood fluidity within the vascular system is an important physiological theme. At the same time, the local formation of a clot serves to assist in preventing excessive blood leakages, and in aiding tissue repair. In addition clot formation is involved in host defence.A balance with, on the one hand, a deviation in excessive clot formation and, on the other hand, defective clot formation was proposed originally by Astrup in 1958 [1]. The system requires delicate biochemical regulation to maintain this balance and to serve the various functions adequately.Deviations in the haemostasis of excessive clot formation or thrombosis are involved in arterial diseases such as myocardial infarction and ischaemic stroke, in venous diseases such as deep vein thrombosis and pulmonary embolism, and in organ failure during trauma and infections.This is a major cause of death and disabilities. Another deviation concerns defects in clot formation and subsequent bleeding, known from congenital deficiencies in clotting factors such as factor VIII and IX, but also potentially life threatening during trauma and a major issue in critical care medicine.Many treatment options to reinforce the system or to inhibit parts of it have been developed and are still under active development. These treatments inevitably interfere with the balance mentioned earlier and besides the intended effect, the opposite effect (bleeding or thrombosis) is always associated with the treatments as a safety issue.The present introduction evaluates recent developments in concepts in haemostasis, the status of biomarker analysis and the desired development of pharmacodynamic tests. Development of concepts Biochemical conceptsHaemostasis is regulate...

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