Flashcards in LG2.14 Introduction to Coagulation Part 1 Deck (35):
What are the 4 major events that occur in hemostasis?
2) Platelet Actions: Adhesion, Activation, Release or Secretion, Aggregation
3) Fibrin Clot formation/coagulation
What is hemostasis?
Hemostasis is the process of normal blood clotting, the subsequent dissolution of the clot, and subsequent repair of the injured tissue.
What are the major components of the hemostatic system?
a. Vascular endothelium
c. Coagulation system
d. Fibrinolytic system
What does Nitric Oxide do?
Inhibits platelet adhesion and aggregation by elevating levels of cGMP
What does Prostacyclin do?
Inhibits platelet aggregation by increasing levels of cAMP
What does Thrombomodulin do?
Binds thrombin which then cleaves protein C to yield activated protein C
What substances does the Endothelial cells produce that are potent vasodilators and inhibitors of platelet functions?
-prostacyclin (prostaglandin I2, PGI2)
-nitric oxide (NO).
What does Tissue Plasminogen activator (TPA) do?
What is Primary Hemostasis?
Formation of a Platelet Plug
What is the steps of Primary hemostasis?
i. Platelet Adhesion
ii. Shape change
iii. Granule release (ADP,TXA2)
v. Aggregation (hemostatic plug)
What is secondary hemostasis?
Formation of a fibrin Clot
What is the steps of secondary hemostasis?
i. Tissue factor
ii. Phospholipid complex expression
iii. Thrombin generation
iv. Fibrin polymerization
What is Prothrombin converted to?
What is thrombin covert?
Fibrinogen to Fibrin
What is the function of vWF?
function is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites.
What does vWF stand for?
von Willebrand Factor
What is the function of ADP?
A mediator of further platelet activation, leads to a conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen
What does TXA2 stand for?
What is the function of TXA2?
A prostaglandin, Vasoconstriction
What is Gp IIB/IIa?
-Is an integrin complex found on platelets. It is a receptor for fibrinogen and von Willebrand factor and aids in platelet activation.
-The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence.
-Platelet activation by ADP leads to a conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen.
What is Fibrinogen?
Form bridges between platelets, by binding to their GpIIb/IIIa surface membrane proteins; however, its major function is as the precursor to fibrin
What is PAI stand for?
Plasminogen activator inhibitor
What is FDP stand for?
Fibrin degradation products
What does t-PA stand for?
tissue plasminogen activator
How is Plasminogen involved in clotting?
Plasminogen is a zymogen of plasmin. It is manufactured in the liver and circulates in the blood in a form that is activation-resistant. Upon binding to fibrin, it can readily be converted to plasmin by plasminogen activators
What does activated GpIIb/IIa receptors provide?
The GpIIb/IIIa receptors on activated platelets form bridging crosslinks with fibrinogen, leading to platelet aggregation.
What do alpha granules contain?
• α granules contain fibrinogen, clotting factors V and VIII
What do dense bodies contain?
ADP, ionized calcium and serotonin
How are platelets involved in clotting?
-Platelets are anucleate cell fragments shed into the bloodstream by marrow megakaryocytic.
-They play a critical role in normal hemostasis by forming a hemostatic plug that seals vascular defects, and by providing a surface that recruits and concentrates activated coagulation factors.
What do platelet receptos GP1a-IIa and GP VI bind directly to?
What do platelets bind indirectly to collagen via GPib and vWF bind indirectly to?
What is ECM?
What happens directly after vascular injury?
After vascular injury, platelets encounter ECM constituents (collagen is most important) and adhesive glycoproteins such as vWF. This sets in motion a series of events that lead to (1) platelet adhesion, (2) platelet activation and (3) platelet aggregation.
What does activation of thrombin cause?
Activation of thrombin promotes fibrin deposition, cementing the platelet plug in place.