MLAB 1227- Coagulation Keri Brophy-Martinez Overview of Hemostasis: Part One

Hemostasis Heme= blood stasis= to halt Process of retaining blood within the vascular system Repairs injury to blood vessels Stops or prevents blood loss

Balance of Hemostasis Procoagulant Factors Regulatory Factors Fibrin Fibrinogen Procoagulant Factors Regulatory Factors Fibrin Balance of Hemostasis *Balance of bleeding (hemorrhaging) and clotting (thrombosis) *Imbalance in one direction can lead to: bleeding : hypocoagulable state OR thrombosis: hypercoagulable state

Hemostasis Components Vascular System Platelet System Controls rate of blood flow Platelet System Interaction of vasculature and platelets form a temporary plug Coagulation System Forms a stable insoluble plug (i.e) fibrin forming Fibrinolytic System Fibrin lysing Coagulation Inhibition System Natural inhibitors Control fibrin formation and fibrin lysis

Hemostasis Failure or deficiencies in any of the five systems involved with hemostasis can leads to varying degrees of uncontrolled hemorrhaging or clotting

Hemostasis The hemostatic components remain inert in the presence of intact vascular tissue or endothelium Following injury, each component must function optimally.

Hemostasis: Overview Consists of three stages Primary Hemostasis Process of blood clotting in response to injury or desquamation of dying /damaged endothelial cells Blood vessels (vasculature) and platelets are the main “players.” Primary Hemostatic plug is formed Platelet plug temporarily arrests bleeding. Insoluble fibrin strands deposit on the initial plug to reinforce and stabilize. The fibrin originates from soluble plasma proteins. Secondary Hemostasis Actions of the protein coagulation factors form fibrin in response to injury Fibrin is stabilized by Factor XIII At this time, blood has changed into a solid state Fibrinolysis Clot is removed following healing of wound

Stages of Hemostasis http://tinyurl.com/8w8redf

Vascular System Components Arteries/ Arterioles Carry blood from the heart to capillaries Thickest walls of the vasculature Veins/Venules Return blood from capillaries to the heart Thinnest walls of vasculature Capillaries No vessel wall Do not contribute to hemostasis

Vascular System: Anatomy of the Blood Vessels Structure Endothelium Single layer of endothelial cells, lining vessels Coated by glycocalyx (protein and mucopolysaccarides) Protects basement membrane Negatively charged, repels circulating proteins and platelets Secretes substances to keep the blood vessel in a nonreactive environment

Vascular System: Anatomy of the Blood Vessels Structure con’t Subendothelium Smooth muscle and connective tissue with collagen fibers Basement membrane Collagen– stimulates platelets Tissue Factor (TF)- activates coagulation & fibrin formation Connective tissue Elastic fibers- provide support around vessels

Vascular System: Blood Vessels Daily Function Endothelium Controls vessel permeability Controls blood flow rate Produces and releases substances that inhibit OR stimulate platelets, coagulation and fibrinolysis

Hemostatic Trigger Once vessel damage occurs, action begins! Arteries and arterioles vasoconstrict Smooth muscle cells contract to reduce blood flow The endothelium becomes thrombogenic Platelets and coagulation proteins are activated VWF is secreted Fibrinolysis initiated

How Does the Endothelium Become Thrombogenic? Actions Von Willebrand’s Factor is made and released to assist the platelets in primary hemostasis Produce tissue factor needed for secondary hemostasis Collagen is exposed which secretes platelet activating factor which in turn activates platelets Subendothelium promote the binding of leukocytes Plaminogen activator inhibitor is released to inhibit fibrinolysis

Resting “Normal”

Vascular System: Function Following Injury Initiate hemostasis: FIRST RESPONSE Vasoconstriction of the arterioles Minimizes blood flow to injured area Prevents blood loss Delivers platelets and plasma proteins to the vessel wall Immediate Short-lived

Vasoconstriction Mechanism Neurogenic factors Regulatory substances Prolong vasoconstriction Serotonin ( product of platelet activation & endothelium) Thromboxane A2 ( product of platelet activation & endothelium) Endothelin-1 (product of damaged endothelial cells)

Roles of the Healthy Endothelium Prostaglandin (PGI2)/ Prostacyclin and Nitric Oxide Vasodilates to increase blood flow to bring fresh supplies of clotting substances Inhibits platelet aggregation & recruitment Causes redness at the injury site

Additional Roles Contraction of venules Inflammatory response Causes gaps between them which pushes fluids causing edema or swelling Inflammatory response

References McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 29." Clinical Laboratory Hematology. Boston: Pearson, 2010. eMedTV. (2009, August 12). How Does Blood Clot.[Video file]. Retrieved from http://www.youtube.com/watch?v=--bZUeb83uU