Week 1: Wednesday Flashcards
what is the role of endothelium
anticoagulant
favors anticoagulant mechanisms
* has smooth surface
* negative charge
what does the endothelium produce
- vasodilators
- inhibitors of coagulation
what is the role of endothelium in procoagulant properties
- vasocontriction
- disruption of endothelial integrity (exposes collagen - activates primary hemostasis; tissue factor - activates secondary hemostasis)
- synthesizes pro-thrombotic factors (Von Willebrand factor)
what is primary hemostasis
- formation of the primary platelet plug
- interaction with endothelium (exposure of collagen)
- provide surface for coagulation factors (secondary hemostasis)
what are platelets
- produced in bone marrow
- lifespan - 6 days
- pre-formed substances in platelet granules (enhance platelet function and attract more platelets to site)
how do plateletes work
- damage to vessel wall (exposure of collagen)
- adhesion
- activation
- aggregation
what is platelet adhesion
- dependent on local blood flow
- static or low speed flow - platelets adhere to collagen of sub-endothelium
- high speed flow - von Willebrand factor mediated platelet adhesion
what is von willebrand factor (VWF)
- synthesized by megakaryocytes and endothelial cells
what is the function of VWF
- mediator of platelet adhesion in rapid blood flow conditions
- decrease of factor VIII clearance
what is platelet activation
- happens secondary to adhesion (collagen) or agonist mediated activation
- thrombin (CF II) is biggest activator
- shape change - pesudopodia
- release of platelet granules (attract, activate more platelets)
what is platelet aggregation
- platelets interact to provide the surface for coagulation factors
- hemostatic plug
- linked to each other by fibrinogen
what are the signs of primary hemostasis
- petechiation, ecchymoses (small bruises)
- spontaneous muscosal bleeding (GI, urogenital, oral/nasal)
- surgical bleeding
what is diagnosis of primary hemostasis
- platelet count
- platelet function tests
- VWF level (most common)
what is secondary hemostasis
- formation of fibrin that crosslinks the primary platelet plug
- fibrinogen (factor I) converted to fibrin by thrombin (factor II)
- stable clot
- coagulation factors
- sequentially active/change other factors in a highly organized process
what are coagulation factors
- proteins (produced in liver; factors III and VIII - endothelium)
- enzymatic and non-enzymatic
- some circulate in inactive form, need to be activated (by other factors; factors II, VII, IX, X - activated by VK)
what is the cell based model of hemostasis
- overlapping phases takes place on different cell surfaces
- initiation
- amplification
- propagation
- starts with exposure of tissue factor
what is tissue factor (TF)
- factor II
- most important factor in initiation of secondary hemostasis
- inactive in intravascular space, active in cytoplasm and extracellular domains
- secondary hemostasus gets activated when TF gets exposed from endothelial damage
what phase in TF
initiation phase
what phases are on the activated platelet surface
- amplification
- propagation
what is the phospholipid bilayer of platelets
- phophatidylserine (PS) and phosphatidylethanolamine (PE) localized to the inner membrane surface
- PS and PE flip to outer surface with platelet activation
what enzymes flip PS and PE to the outer surface and scramble them
- floppase
- flippase
- scramblase
what is the initiation phase of hemostasis
cell based model
- exposure of tissue factor
- trace thrombin
what is the amplification phase of hemostasis
cell based model
- thrombibn travels to platelet
- activates more factors
- activates and attracts more platelets
what is the propagation phase of hemostasis
cell based model
- thrombin converts fibrinogen to fibrin