{"id":4474,"date":"2021-02-11T18:38:31","date_gmt":"2021-02-11T17:38:31","guid":{"rendered":"https:\/\/meddists.com\/learn\/clinical\/hematology\/basics-of-hematology\/hemostasis\/"},"modified":"2021-05-31T15:22:13","modified_gmt":"2021-05-31T13:22:13","slug":"hemostasis","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/hemostasis\/","title":{"rendered":"Hemostasis"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><div class=\"intro\">Hemostasis refers to the process by which bleeding is stopped.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It consists of three main stages:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Local vasoconstriction<\/li><li>Formation of a platelet plug<\/li><li>Blood coagulation (clotting)<\/li><\/ol>\n\n\n\n<p class=\"wp-block-paragraph\"><\/div><\/p>\n\n\n\n<hr class=\"wp-block-separator\"\/>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/meddists.com\/learn\/clinical\/hematology\/basics-of-hematology\/hemostasis\/hemostasis-2\/\"><img loading=\"lazy\" decoding=\"async\" width=\"851\" height=\"1024\" src=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/hemostasis-851x1024.png\" target=\"_blank\" title=\"Hemostasis\" alt=\"\" class=\"wp-image-4476\" srcset=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/hemostasis-851x1024.png 851w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/hemostasis-249x300.png 249w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/hemostasis-768x924.png 768w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/hemostasis-1276x1536.png 1276w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/hemostasis-1701x2048.png 1701w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/hemostasis.png 1329w\" sizes=\"auto, (max-width: 851px) 100vw, 851px\" \/><\/a><figcaption><strong>Figure 1. General outline of hemostasis and the coagulation cascade<\/strong><\/figcaption><\/figure>\n\n\n<span class=\"block-heading\" id=\"header_1\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Description<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n\n<p class=\"wp-block-paragraph\">Generally, hemostasis is divided into three distinct stages:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Local vasoconstriction: vasospasm<\/li><li>Primary hemostasis: platelet activation<\/li><li>Secondary hemostasis: clot formation<\/li><\/ol>\n\n\n<\/span><span class=\"block-heading\" id=\"header_2\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Local vasoconstriction<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n\n<p class=\"wp-block-paragraph\">Once a blood vessel is injured, an immediate response to the injury involves local vasoconstriction to reduce blood flow and a subsequent blood loss from the site of injury.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The vasoconstriction is primarily mediated by <strong>endothelin-1<\/strong>, a potent vasoconstrictor, which is synthesized by the damaged endothelium.<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_3\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Formation of a platelet plug<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<p class=\"wp-block-paragraph\">Platelets circulate through the blood and become activated once they reach a site of vascular injury.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Their main functions include:<ul><li><strong>Adhesion<\/strong><\/li><li><strong>Aggregation<\/strong><\/li><li><strong>Release mediators<\/strong><\/li><\/ul><\/li><li>They carry numerous receptors:<ul><li><strong>Collagen receptors<\/strong> (GP Ia, GP IV)<\/li><li><strong>Thromaxane receptors <\/strong>(TXA2)<\/li><li><strong>ADP receptors<\/strong> (P2Y12)<\/li><li><strong>vWF and fibrinogen receptors<\/strong> (GP Ib, IIb-IIIa)<\/li><\/ul><\/li><li>Exposed subendothelial collagen from the basement membrane under the damaged endothelium is important in the <strong>adhesion<\/strong> of platelets to the vessel.<\/li><li>vWF (von-Willebrand factor), synthesized in the endothelium (and therefore is also exposed in endothelial damage) and in small quantity by megakaryocytes, is also important in <strong>adhesion<\/strong> to the vessel as well as to other platelets (<strong>aggregation<\/strong>).<\/li><li>Once adherent, it will flatten, and <strong>release its mediators<\/strong> from intracellular granules, recruiting additional platelets and forming a platelet plug through active GPIIb\/IIIa receptor with fibrinogen bridges.<\/li><li>Platelets contain three types of intracellular granules:<ul><li><strong>Dense granules<\/strong><ul><li>Less common<\/li><li>Contain ADP, ATP, serotonin, and calcium<\/li><\/ul><\/li><li><strong>Alpha-granules<\/strong><ul><li>More common<\/li><li>Contain vWF, PDGF, and other proteins<\/li><\/ul><\/li><li><strong>Lysosomes<\/strong><\/li><\/ul><\/li><li>The phospholipid surface of platelets participates in the coagulation cascade (discussed below).<\/li><li>In intact vessels, the endothelium releases NO and PGI2 that inhibit platelet activation.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_4\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Blood coagulation<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_4\">\n\n\n<p class=\"wp-block-paragraph\">The coagulation cascade creates an initial, soluble, and weak clot, which later ends up becoming a stable, insoluble, and firm clot; it complements the activity of the platelets, increasing the overall stability and strength of the thrombus.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>It involves a group of proteins (+calcium) known as clotting factors represented by roman numerals, with the important ones ranging from I to XII (except for factor VI which no longer known as a clotting factor).<\/li><li>The clotting factors circulate in a non-active state (zymogens) and become activated under the action of catalysts such as thrombin and tissue factor.<\/li><li>Clotting factors are synthesized by the liver, except for vWF which is synthesized by the endothelium and megakaryocytes.<\/li><li>The goal of the coagulation factors is to create a network consisting of fibrin (the stable, final clot).<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Classically, the coagulation cascade is typically depicted in a rather complex chart such as the following:<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"819\" src=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/clotting-cascade.png\" alt=\"\" class=\"wp-image-4479\" srcset=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/clotting-cascade.png 1024w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/clotting-cascade-300x240.png 300w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/02\/clotting-cascade-768x614.png 768w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><figcaption><strong>Figure 2. Coagulation cascade<\/strong><\/figcaption><\/figure>\n\n\n<\/span><span class=\"block-heading\" id=\"header_5\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Simplified explanation<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_5\">\n\n\n<ul class=\"wp-block-list\"><li>The central component of the cascade is the formation of thrombin (factor II-&gt;IIa) which will then produce fibrin (the ultimate goal), mediated by factor Xa (the &#8220;common pathway&#8221;).<\/li><li>In order to convert prothrombin into thrombin, we require factor Xa together with calcium and factor Va.<\/li><li>The activation of factor X (&#8220;tenase&#8221;) can happen in two ways:<ul><li>The <strong>extrinsic pathway<\/strong> (tissue factor):<ul><li>Involves the exposure of <strong>tissue factor <\/strong>from damaged subendothelial tissues (not endothelial cells).<\/li><li>Tissue factor activates factor VII-&gt;VIIa, which will then complex (VIIa-TF) and activate factor X-&gt;Xa.<\/li><li>Occurs on the surface of subendothelial cells.<\/li><\/ul><\/li><\/ul><ul><li>The <strong>intrinsic pathway<\/strong> (contact activation):<ul><li>Involves <strong>negatively charged surfaces<\/strong> (such as collagen from damaged vessels, bacteria, silica particles, glass surface).<\/li><li>The negative charge will activate factor XII-&gt;XIIa, which will then activate factor XI-&gt;XIa, which in turn will activate factor IX-&gt;IXa.<\/li><li>Factor IXa will complex with factor VIIIa (IXa-VIIIa, its activation is described below), and this complex will activate factor X-&gt;Xa.<\/li><li>Occurs on the surface of platelets.<\/li><\/ul><\/li><li>Both of the pathways form complexes with require <strong>phospholipids <\/strong>and <strong>calcium<\/strong>; the phospholipids are found on the surface of platelets or subendothelial cells, as described above.<\/li><\/ul><\/li><li>The activation of thrombin is done through a <strong>positive feedback system<\/strong>, as thrombin can activate additional factors (which in turn, will end up activating even more thrombin).<ul><li>Factor V-&gt;Va<\/li><li>Factor XI-&gt;XIa<\/li><li>Factor VIII-&gt;VIIIa<\/li><\/ul><\/li><li><strong>Factor VIII <\/strong>is produced in endothelial cells and circulates bound to vWF which stabilizes it and greatly prolongs its half-life, and is released upon activation of the coagulation cascade; it is then activated by thrombin, as mentioned above.<\/li><li><strong><strong>Factor XIII is <\/strong><\/strong>activated by thrombin&nbsp;to form an active transglutaminase enzyme,&nbsp;factor XIIIa.&nbsp;Factor XIIIa&nbsp;introduces cross-links between&nbsp;fibrin-fibrin&nbsp;strands. <\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_6\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Inhibition and fibrinolysis<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_6\">\n\n\n<ul class=\"wp-block-list\"><li><strong>Protein C <\/strong>with its cofactor <strong>protein S <\/strong>inhibit factor Va and VIIIa.<\/li><li><strong>Antithrombin III <\/strong>inhibits factors IX, X, XI.<\/li><li><strong>Plasminogen<\/strong> is activated by <strong>tissue plasminogen activator <\/strong>(or tPA), breaking down the fibrin strands (fibrinolysis).<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_7\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Vit K dependent clotting factors<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_7\">\n\n\n<ul class=\"wp-block-list\"><li>II<\/li><li>VII<\/li><li>IX<\/li><li>X<\/li><li>Protein C and S<\/li><\/ul>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Description<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Local vasoconstriction<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Formation of a platelet plug<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Blood coagulation<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Simplified explanation<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Inhibition and fibrinolysis<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Vit K dependent clotting factors<\/h4><\/div>","protected":false},"excerpt":{"rendered":"<p>Description Generally, hemostasis is divided into three distinct stages: Local vasoconstriction: vasospasm Primary hemostasis: platelet activation Secondary hemostasis: clot formation Local vasoconstriction Once a blood vessel is injured, an immediate response to the injury involves local vasoconstriction to reduce blood flow and a subsequent blood loss from the site of injury. The vasoconstriction is primarily [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":4472,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-4474","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Hemostasis &#8211; Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/hemostasis\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/hematology\\\/hemostasis\\\/\",\"url\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/hematology\\\/hemostasis\\\/\",\"name\":\"Hemostasis &#8211; 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