The coagulation cascade leads to formation
of fibrin polymers which consolidate the platelet plug formed during primary hemostasis.20 Abnormalities in tests measuring the function of primary hemostasis and clotting cascade (coagulation) have been reported in case reports and cohort studies in patients treated with antidepressants. During primary hemostasis, the platelets form a plug at a site of injury in order to stop bleeding. This phase, which is the functional response of activated platelets, comprises four different Proteasome purification processes: adhesion, aggregation, secretion, and procoagulant activity.21 During the vascular phase, vasoconstriction occurs Inhibitors,research,lifescience,medical and procoagulant (von Willebrand factor [vWF], tissue factor) as well as anticoagulant substances prostaglandin I2 [PGI2], thrombomodulin, urokinase, tissue plasminogen activator [tPA], antithrombin, nitric oxide [NO], and endotheliumderived relaxing factor [EDRF]) are secreted by the endothelium. The most potent platelet activators Inhibitors,research,lifescience,medical are collagen and thrombin, whereas ADP and epinephrine are weak activators. 5-HT itself is a weak platelet agonist, but it amplifies the effect of other platelet agonists.22 The process comprises successive steps, illustrating the central role of platelets (Figure 1): Figure 1. Diagrammatic representation of primary hemostasis. 5-HT, serotonin; vWF, von Willebrand factor; ADP, adenosine diphosphate;
Inhibitors,research,lifescience,medical βTG, β-thromboglobulin; PF4, platelet factor 4; MLC, myosine light chain; MLCK, myosine light chain kinase; PGG … Adhesion: Platelets change shape in response to activation, allowing adhesion to subendothelial matrix. This process is mediated by the binding of platelet surface receptor GPIb/IX/V complex to vWF. Binding Inhibitors,research,lifescience,medical of collagen to platelet collagen receptor GPIa/IIa also plays a role in platelet adhesion. Aggregation: Both conformational and exposure changes in the GPIIb/IIIa Inhibitors,research,lifescience,medical on the platelet surface due to activation, result in binding of vWF and
fibrinogen. Secretion: Substances are secreted from platelet granules upon stimulation. ADP and 5-HT stimulate and recruit other platelets. Fibronectin stabilizes Oxymatrine platelet aggregates. Secreted fibrinogen provides a source of fibrinogen at sites of endothelial injury in that present in the plasma. Thromboxane A2 (TXA2, from arachidonic acid [AA] release) stimulates platelet aggregation and causes vasoconstriction. Platelet-derived growth factor (PDGF) mediates tissue reparation. Procoagulant activity: Exposure of procoagulant phospholipids and the subsequent assembly of the enzyme complexes on the platelet surface represent procoagulant activity. Among others, the following laboratory tests explore primary hemostasis: platelet count, bleeding time, platelet function analyzer (PFA), platelet functional assessment, medullogram, and vWF (Table I). Normal values are not mentioned, since they are provided by the laboratory when these examinations are requested. Table I.