The Haemostatic Balance – Astrup Revisited

Abstract

Prof. Tage Astrup first elaborated the notion that blood fluidity involved a balance between the tendency of blood to clot and for such clots to lyse. It would seem that, at that time, this haemostatic balance involved the notion that forming fibrin orchestrated its own destruction by stimulating fibrinolytic activity. In this review, we have clarified the detail of this balance and developed the thesis that Astrup’s far-sighted balance notions involve a variety of control mechanisms. These involve the notion that thrombin, being at first sight a procoagulant, can also, in conjunction with thrombomodulin, act as a stimulus of anticoagulant activity by the generation of activated protein C. The thrombin-activatable fibrinolytic inhibitor (TAFI) is also involved in this balance since the generation of thrombin provokes the neutralisation of fibrinolysis by the TAFI pathway. The kallikrein/factor XII/urokinase pathway is discussed indicating yet another aspect of balance between the generation of coagulation and fibrinolysis. The overall theme of this review, apart from an insight into various aspects of the haemostatic balance, is that blood has a strong tendency to clot when tissue is damaged, and the intact vasculature requires major anticoagulant systems to prevent clots adhering to and stabilising in the vasculature.

The Prothrombotic Paradox of Hypertension

“…[12][13][14] Fibrin degradation products themselves inhibit further fibrin formation. 15 Although the endothelium is the main production site for t-PA and PAI-1, the latter may also be released from hepatocytes, platelet ␣-granules, smooth muscle cells, and adipocytes. 13,16,17 …”

“…8 Furthermore, the ACEI ramipril has been found to reduce thrombinantithrombin complex formation, an indicator of coagulation activation. 15,57 Regarding hyperaggregability of platelets, ACE inhibition lowers platelet activation markers because of platelet-inhibiting PGI2 and NO, resulting in diminished adhesion and aggregation. 56 More related to atherosclerosis, ACEIs downregulate TF synthesis in monocytes, a mechanism possibly reflected in the preventive effect on thrombotic complications.…”

Analysis of Coagulation Cascade and Endothelial Cell Activation During Inhibition of Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor Pathway in Cancer Patients

“…TM is expressed on ECs as a membranebound protein that, when complexed with thrombin, increases the activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI) by Ͼ1000-fold. 11,12 Activated protein C (APC) is an inhibitor of the coagulation cascade, inasmuch as it neutralizes activated factor V and activated factor VIII. TAFI is involved in the inhibition of clot lysis.…”

St�rungen der H�mostase bei Patienten in der HNO-Heilkunde

“…Hierbei ist der "Adhäsionsstimulus" von Seiten der Thrombozyten offenbar umso stärker, je ausgedehnter die Endothelzerstörung ist. Wichtige Adhäsivproteine sind der ᭤ von-Willebrand-Faktor (vWF), sowie Fibrinogen, die an bereits beschriebene Glykoprotein-Rezeptoren auf der Thrombozytenoberfläche binden können [1,3,6,9]. Die erfolgte Adhäsion der Thrombozyten leitet die Thrombozytenaktivierung mit nachfolgender Aggregation ein, die darüber hinaus von ᭤ Sekretionsphänome-nen begleitet wird.…”

“…In Analogie zur Rolle der Thrombozyten und Endothelzellen in der Regulation der Hämostase sind eine Anzahl von prokoagulatorisch und antikoagulatorisch wirkende Faktoren im Plasma für eine ᭤ regulierte Aktivierung und Hemmung der Gerinnung verantwortlich [3,9].…”