{"id":911,"date":"2024-01-28T18:19:09","date_gmt":"2024-01-28T23:19:09","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&p=911"},"modified":"2026-01-03T16:16:56","modified_gmt":"2026-01-03T21:16:56","slug":"hemostasis-blood-clotting","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/hemostasis-blood-clotting\/","title":{"raw":"Hemostasis (Blood Clotting)","rendered":"Hemostasis (Blood Clotting)"},"content":{"raw":"Hemostasis Overview:<\/strong>\r\n\r\nWhen a blood vessel wall is cut, hemostasis is initiated in order to create a natural band-aid that stops the bleeding and loss of blood.\u00a0 Hemostasis is a fast process taking minutes to occur.\u00a0 The word hemostasis originates from the Latin and Ancient Greek words, hemo-<\/em> referring to blood, and -stasis<\/em> meaning motionless.\u00a0 There are three major stages of hemostasis:\r\n
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  1. Vascular Spasm:\u00a0<\/strong> When damaged, blood vessel wall endothelial cells release a variety of chemical messengers (e.g. ADP, Tissue Factor,<\/strong> and endothelins).<\/strong>\u00a0 Endothelin peptides are potent vasoconstrictors, triggering the smooth muscle layer of the blood vessel to contract, narrowing the blood vessel.\u00a0 This serves to minimize blood loss.<\/li>\r\n \t
  2. Platelet Plug Formation:<\/strong>\u00a0 In this next stage, platelets<\/strong> are attracted to the wounded site, becoming activated and adhering to the exposed collagen of the damaged vessel, forming an unstable plug within seconds to minutes.\u00a0 Prior to becoming activated, 30% of platelets are typically located in the spleen and 70% of platelets are circulating the blood stream.\u00a0 When inactive, the platelets have smooth unsticky surfaces.\u00a0 Once activated, platelets become more spikey and sticky capable to adhering to the cut edges of blood vessels and releasing from granules their own chemical messengers which include: ADP, thromboxane<\/strong> A2<\/sub><\/strong>, serotonin, clotting factor proteins,<\/strong> Ca++<\/sup><\/strong>, prostaglandins,<\/strong> platelet-activating cytokines, and Platelet Derived Growth Factor (PDGF).<\/strong>\u00a0 ADP attracts more platelets to the area.\u00a0 Serotonin is a vasoconstrictor.\u00a0 Thromboxane A2<\/sub> stimulates more vasoconstriction and also recruits and activates more platelets. This recruitment and activation of more platelets is termed a positive feedback loop,<\/strong> which will end when the wound is sealed.<\/li>\r\n \t
  3. Coagulation:<\/strong>\u00a0 In this step, the plasma protein fibrinogen<\/strong> (water-soluble protein) is converted to fibrin<\/strong> (long ropy water-insoluble) proteins which wrap around and through, stabilizing the platelet plug. At this stage, clot retraction<\/strong> occurs, as platelets contract pulling the torn edges of the blood vessel closer together.<\/li>\r\n<\/ol>\r\nDuring the Coagulation<\/strong> stage to occur, there are two pathways that simulataneously occur, the Extrinsic and Intrinsic Pathways.\r\n
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    • Extrinsic Pathway<\/strong>:\u00a0 In this pathway, extrinsic factors (e.g. Tissue Factor)<\/strong> are released from blood vessel wall endothelial<\/strong> cells that in a cascade of activation involving calcium<\/strong> and clotting factors,<\/strong> serve to activate Prothrombin Activator<\/strong> (Factor X).\u00a0 Prothrombin Activator converts the inactive prothrombin into the activated thrombin<\/strong> enzyme.\u00a0 Thrombin is then able to convert fibrinogen to fibrin,<\/strong> which is required for stabilizing the platelet plug.<\/li>\r\n \t
    • Intrinsic Pathway<\/strong>:\u00a0 This pathway's purpose is to also activate Prothrombin Activator in order to produce fibrin for stabilizing the platelet plug.\u00a0 The intrinsic pathway, begins when platelets degranulate releasing intrinsic factors (e.g. Platelet Factor)<\/strong> that begin a cascade of activation involving calcium and clotting factors.\u00a0 These clotting factors again serve to activate Prothrombin Activator (Factor X).\u00a0 This process is slower than the extrinsic pathway though is necessary.\r\n\r\n[caption id=\"attachment_4217\" align=\"alignnone\" width=\"1024\"]\"A A basic diagram of the series of events that occur after a wound, starting with the attraction of platelets to the wound site, the cascade reactions, activation of clotting factors, and ending with the conversion of fibrinogen into fibrin and scab formation. (Note: Not all 13 clotting factors are explicitly pointed out; blue clotting factors are inactive, green are active, and black is the activated fibrinogen)[\/caption]<\/li>\r\n<\/ul>\r\n \r\n\r\nFibrinolysis:<\/strong>\u00a0 Once healing has begun, the fibrin and platelet plug are removed as new blood vessel wall cells are regenerated.\u00a0 The digestion of fibrin is termed fibrinolysis.\u00a0 During fibrinolysis, tPA<\/strong> (Tissue-Type Plasminogen Activator) converts the inactive plasminogen<\/strong> to the active plasmin<\/strong> protease enzyme, which degrades fibrin.\u00a0 At the same time, macrophages are removing cellular debris.\r\n\r\nHealing:<\/strong>\u00a0 Platelets release PDGF to stimulate vessel regeneration.\u00a0 In addition fibroblasts release mitogens and cell division allows for the replacement of damaged cells.\u00a0 Large wounds may incorporate more collagen and fewer functional cells giving rise to scar tissue.\r\n\r\nHemostasis and Platelet Regulation<\/strong>:\r\n\r\nEndothelial cells release prostacyclin, <\/strong>a signalling molecule that acts as both a vasodilator and platelet-inihibitor, to ensure platelet aggregation is not excessive.\u00a0 Too many platelets could lead to large thrombi<\/strong> formations which may result in platelet-RBC-fibrin clots that break off and travel, becoming emboli,<\/strong> that lodge downstream in smaller blood vessels creating sites of ischemia and hypoxia.\r\n\r\nToo few platelets can also lead to problems.\u00a0 Thrombocytopenia<\/strong> is a condition in which there are low levels of platelets, possibly due to nutrition deficiency, an underlying illness, or medicine-induced.\u00a0 Most common signs and symptoms involve prolonged or excessive bleeding (e.g. frequent nosebleeds, heavier menstruation, bruising, petechiae (tiny red spots caused by capillary hemorrhages).\r\n\r\nHemophilia<\/strong> is defined as an impaired ability to make blood clots, typically due to inherited mutations in one or more clotting factors involved in the intrinsic or extrinsic pathways.\u00a0 The most common cause of hemophilia is due to recessive genetic disorders involving mutations in either Factor VIII or Factor IX genes, both of which are on the X chromsome, meaning that more XY males are affected by hemophilia than XX females.\u00a0 Signs and symptoms of untreated hemophilia can involve severe and frequent bleeds internally in soft tissues and joints, even without trauma, in addition due to external cuts.\r\n\r\n \r\n\r\nSummary<\/strong>\r\n