5.3 Lecture - Hemostasis: Vascular Constriction & Platelet Properties

• Hemostasis is achieved through vascular constriction, platelet plug formation, blood clot formation, and fibrous tissue growth when a blood vessel is cut.

Vascular Constriction

• Myogenic spasm, factors from traumatized tissue, and nervous reflexes lead to vascular constriction.
• Myogenic spasm is mediated by local humoral factors, like thromboxane A2 released from platelets, causing the most vasoconstriction.
• Autocoids are hormone-like substances that act locally.
• Nervous reflexes are initiated by pain nerve impulses from the traumatized vessel or nearby tissues.

Properties of Platelets

• Platelets lack nuclei and cannot reproduce.
• They contain actin and myosin molecules for contraction.
• Residuals of the endoplasmic reticulum and Golgi apparatus within platelets synthesize enzymes and store calcium.
• Platelets have mitochondria and enzyme systems for ATP formation.
• Platelets produce prostaglandins and contain the protein fibrin-stabilizing factor.
• Platelets have a growth factor that stimulates vascular cell growth.
• Glycoproteins on the platelet cell membrane prevent adherence to normal endothelium but cause adherence to injured areas.
• Platelets are active in the blood for 8 to 12 days, then eliminated by the macrophage system.

Platelet Plug Formation

• Platelet plugs seal ruptures in small blood vessels that occur frequently.
• When damage occurs, platelets swell, form irregular shapes with pseudopods, contract, and release multiple active factors, becoming sticky.
• Platelets adhere to collagen and von Willebrand factor in the tissue.
• Platelets secrete ADP, platelet-activating factor, and thromboxane A2.

Blood Coagulation

• Blood coagulation involves over 50 substances, with the formation of prothrombin activator being rate-limiting.
• Prothrombin activator, along with calcium, converts prothrombin into thrombin.
• Prothrombin, a plasma protein formed in the liver, easily splits into thrombin.
• Fibrinogen, also formed in the liver, is acted upon by thrombin to create fibrin in the liver.
• The clot is a meshwork of fibrin fibers trapping blood cells, platelets, and plasma.

Clot Retraction

• Once a clot forms, it contracts and expresses fluid called serum, which lacks clotting factors and cannot clot.
• Clot retraction and constriction require platelet function; thrombocytopenia can cause failure of clot retraction.
• Thrombin acts on many other blood clotting factors besides fibrinogen.
• The conversion of prothrombin to thrombin by prothrombin activator can begin the positive feedback loop.
• Once a critical amount of prothrombin is formed, a positive feedback loop develops, promoting more clotting.
• Prothrombin activator is formed through the extrinsic and intrinsic pathways, which interact constantly.

Extrinsic Pathway

• Thrombin acts on factor V to greatly accelerate the clotting process, creating more prothrombin activator.

Intrinsic Pathway

• The intrinsic pathway begins with trauma to the blood or exposure of the blood to collagen.
• Trauma to the blood causes activation of factor XII and the release of platelet phospholipids.
• Factor VIII, along with platelet phospholipids and factor III, activates factor X.
• If any part of either pathway is missing, the activation of factor X is slowed.

Common steps

• The last step in both pathways is the same: activated factor X combines with factor V to form prothrombin activator.
• Calcium is required for all blood clotting reactions except the first two steps of the intrinsic pathway.
• A positive feedback loop mechanism of thrombin is a commonality.

Anticoagulants

• The most important anticoagulants remove thrombin.
• Fibrin fibers remove thrombin from circulation.
• Antithrombin III combines with thrombin to block its effects.
• Heparin increases antithrombin III's effects.
• Heparin is produced by mast cells in tissues, especially around capillaries of the lungs and liver.

Plasmin System

• Plasmin digests fibrin fibers and other protein coagulates, causing clot lysis or hypercoagulation.
• Plasminogen is trapped in a clot during formation.
• Tissue plasminogen activator (TPA) is released after bleeding stops, converting plasminogen to plasmin.
• The plasmin system removes minute clots from tiny peripheral blood vessels.

Liver and Vitamin K

• Almost all clotting factors are formed by the liver; liver disease can increase bleeding.
• Vitamin K is synthesized in the intestinal tract by bacteria, so deficiency is rare in healthy people.
• GI disease can cause a deficiency.
• Bile from the liver aids in fat digestion and absorption; obstruction of bile tracts or liver disease can cause poor vitamin K absorption, decreasing thrombin and other clotting factors.

Hemophilia

• Hemophilia occurs almost exclusively in males and is caused by an abnormality of factor VIII (85% of cases) or factor IX (15% of cases).
• It is recessive and transmitted on the X chromosome; females rarely have the disease.
• A loss of one component of factor VIII causes hemophilia; a loss of the other component causes von Willebrand's disease.

Thrombocytopenia

• Thrombocytopenia is a low platelet count; normal is between 240,000 and 450,000 per microliter.
• Platelet count below 30,000 increases bleeding risk, and below 10,000 is usually fatal.

Thrombus and Embolus

• A clot in a vessel is called a thrombus.
• A free-flowing clot is known as an embolus.
• Causes of thrombus and embolus include a rough endothelial surface of a vessel and very slow blood flow.

Bedrest and Clots

• Bedrest, with calves and feet elevated on pillows, causes slow blood flow to the lower extremities and can result in a thrombus

Disseminated Intravascular Coagulation (DIC)

• DIC often results from large amounts of traumatized or dying tissue releasing tissue factor, causing microclots.
• DIC can lead to bleeding due to the consumption of clotting factors by widespread clotting.

Blood Coagulation Tests

• Bleeding time measures how long bleeding lasts, ordinarily 1-6 minutes; lack of clotting factors, especially platelets, can prolong it.
• Clotting time varies depending on the method, so it's no longer commonly used.
• Prothrombin time measures the extrinsic and final common pathways by measuring thrombin concentration.
• The international normalized ratio (INR) was created to standardize prothrombin time measurement.

Overview of hemostasis achieved through vascular constriction, platelet plug formation, blood clot formation, and fibrous tissue growth. Also describes the properties of platelets including spasm, traumatized tissue, nerve reflexes and autocoids.