The Hemostatic System

Abstract

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 alpha(IIb)beta(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. Secondary hemostasis (coagulation) consists of an extrinsic and intrinsic pathway. Thrombin is generated via Factor Xa resulting from the extrinsic tenase reaction that is turned of by tissue factor pathway inhibitor. While thrombin generation is maintained via positive feedback mechanisms activating factors V, VIII and XI. Excess thrombin is inhibited by antithrombin or by autodownregulation via activation of protein C. Since minor injuries are common, platelets and plasma clotting factors constantly produce clots to stop bleeding. If clots remained after the tissue healing, the vascular bed would become obstructed with clots therefore this is regulated by fibrinolysis, tertiary hemostasis. Tissue-type plasminogen activator synthesised by the endothelium, converts plasminogen to plasmin, the clot lysis enzyme. Plasmin clears the blood vessels by degrading fibrin. Fibrinolysis is controlled by plasminogen activators inhibitor (PAI-1), alpha2-antiplasmin and alpha2-macroglobulin, and thrombin-activatable fibrinolysis inhibitor (TAFI).

Anti-Helicobacter pyloriand Thrombin Inhibitory Components from Chinese Dragon’s Blood,Dracaena cochinchinensis

“…Thrombin also activates upstream zymogen factors V, VIII, and XI, which further accelerate the clotting cascade by thrombin synthesis. 46 At present, clinical treatment of thrombosis involves the administration of heparin and its low molecular weight derivatives or oral anticoagulants of the dicumarol type, which all indirectly inhibit thrombin. These drugs have limitations with regard to their efficacy and low therapeutic index, leading to the need for extensive monitoring.…”

Alboserpin, a Factor Xa Inhibitor from the Mosquito Vector of Yellow Fever, Binds Heparin and Membrane Phospholipids and Exhibits Antithrombotic Activity

“…As a result, wounded tissues and injured blood vessels trigger the host hemostatic process, which is a complex and redundant, interlinked biological system consisting of platelet aggregation, blood clotting, and vasoconstriction (3)(4)(5). The clotting cascade can be activated by the intrinsic or extrinsic pathways, both converging to the activation of factor X (FX) 2 to FXa, which converts prothrombin to thrombin; the latter cleaves fibrinogen to produce fibrin (6).…”

A mechanobiological investigation of platelets

“…The fusion of platelet organelles facilitates the translocation of the intracellular metabolites to the extracellular plasma medium, leading to exponential 8 activation of neighboring platelets. These chemicals stimulate the increased expression of cell membrane adhesion receptors such as GP Ilb-IIIa, which also encourages the recruitment of platelets to the site of injury (29). During this time, a transient chemical change occurs with a notable change in cytoplasmic calcium (Ca 2+ ), whose increased intracellular concentration induces contraction of the platelet via the activation of the actino-myosin motor complexes responsible for platelet cell shape (5).…”

“…During aggregation, platelet-platelet interaction is reinforced by the contributions of vWF, a large plasma protein that also bridges the gap between the damaged tissue and platelets by means of its shear-induced connection to the platelet membrane glycoprotein receptors (GP Iba) (26,29,32). Collagen and vWF engage the GP VI and GP Ib-IX-V complexes to induce events such as platelet shape change, aggregation and secretion (14), with notable activation of the GP Ilb-IIIa receptor to increase its adhesive properties via shear stress-induced vWF binding to the GP Ib-IX-V complex (26,33).…”