Hemostasis Physiology Review Flashcards
What is the opposite to hemostasis?
hemorrhage
What is hemostasis?
Process which causes bleeding to stop
What is the goal of hemostasis?
Goal is to keep blood within a damaged blood vessel
What is the balance between clotting and bleeding?
normal hemostasis
What are 3 components of hemostasis?
vasculature
coagulation proteins
platelets
primary hemostatis is ???
formation of the platelet plug
What is secondary hemostasis?
clotting factors, proteolytically activated, activation of fibrin
What are the 4 phases of the hemostatic process
- Initiation and formation of the platelet plug
- Propagation of the clotting process by the coagulation cascade
- Termination of clotting by antithrombotic control mechanisms
- Removal of the clot by fibrinolysis
The hemostatic system players include ____, _____ and ____
blood proteins
platelets
the vessel wall
______: inhibits platelet activation & aggregation
Secretion of Prostacyclin (PGI₂):
________: vasodilation, inhibits platelet activation & aggregation
Secretion of Nitric Oxide (NO)
Secretion of what other factors that discourage coagulation include ????
Heparin sulfate
thrombomodulin
tissue factor pathway inhibitor
Name 4 ways in which when injured, endothelial cells become procoagulant
Down regulation of thrombomodulin
Expression of tissue factor
Expression of PAI-1 (plasminogen activator inhibitor)
Release of von Willebrand Factor
Endogenous PLTs circulate for_____ before being cleared from circulation
~10 days
About ____ of PLTs released from the bone marrow or transfused are pooled in the spleen
1/3
What is the normal platelet count?
150K to 450K
Why is the normal platelet count range so wide?
due to storage of platelets in the spleen
Platelet anatomy:____ and _____ function to promote clotting
Internal granules and External receptors
What are the 2 ways platelets promote clotting?
1 – At the site of an active bleed, PLTs bind to exposed collagen to form the primary plug
The very first response to an injured vessel
2 – After forming the initial plug, additional PLTs are recruited to expand and propagate the clot
What are the platelets steps of clotting?
- Adhere to site of blood vessel damage and form a physical barrier - plug
-Start the clotting cascade – fibrin deposition
-Undergo activation – secretion and granule content release
-Release thromboxane – activates other platelets
Von Willebrand factor is synthesized and stored in ____ and ____
1) endothelial cells and
2) platelets
What is the primary function of Von Willebrand factor?
Primary function is binding to other proteins
NOT an enzyme so does not require a catalytic event
What are the 3 coagulation functions of von willebrand factor?
- Binds to endothelium and promotes platelet adhesion to sites of vessel injury (through Gp1b-platelet glycoprotein Ib)
- Plasma carrier for Factor VIII, prevents its degradation
Factor VIII is released from vWF by thrombin - Binds to collagen when exposed
What are some principles of secondary hemostasis?
Clotting factors circulate inactive
Activate each other (cascade effect)
The extrinsic pathway is activated by _____
tissue factor found OUTSIDE the blood
The intrinsic pathway is activated by _____
factors required for activation are found INSIDE the blood
What are the 3 essential steps needed in the mechanism of blood coagulation?
- Prothrombin Activator is formed
- Prothrombin Activator
converts Prothrombin to Thrombin - Thrombin acting as an enzyme converts Fibrinogen to Fibrin
**Which factors and proteins are Vit K dependent?
Factors II, VII, IX, X, protein C, protein S
Under what conditions would you see Vit K decrease?
fat malabsorption/malnutrition
antibiotic therapy (esp. cephalosporins)
in the newborn
_____ is a vitamin K antagonist
Warfarin (coumadin)
The extrinsic pathway begins with ????
Release of tissue thromboplastin from traumatized tissue
Activation of Factor VII (VIIa)
Activation of Factor X (Xa) forming Prothrombin Activator (common pathway)
The activation of factor X forms ______. This splits _____ into _____.
prothrombin activator.
prothrombin into thrombin (common pathway)
What are the 5 beginning steps to the intrinsic pathway?
Exposure to collagen causes activation of Factor XII (XIIa)
Causes activation of Factor XI (XIa)
Causes activation of Factor IX (IXa) with help of Ca+
Factor IXa, Factor VIIIa, and calcium form a complex to activate Factor X
Activation of Factor X forms Prothrombin Activator (common pathway)
exposure to _____ causes activation of factor XII
collagen
the common pathway is produced continuously in the ____
liver
what is considered the common pathway?
conversion of prothrombin to thrombin
____- is required for activation of Prothrombin
Vit K
_____ or _____ prevents normal Prothrombin formation
Lack of Vit K
or
presence of Liver Dz
What is the essential step three in clot formation?
Fibrinogen Fibrin Clot formation
_____ is protein formed in the liver
Fibrinogen
_____ works as an enzyme on fibrinogen to convert it to fibrin
Thrombin
____ molecules polymerize with other _____ molecules to form long ____ threads that produce the retinaculum of the clot.
Fibrin
Fibrin
Fibrin
What is another name for Factor I?
Fibrinogen/ Fibrin
____ is the most abundant coagulation protein
factor I
Fibrinogen is converted to fibrin by ____, then stabilized by polymerization and cross-linking (factor XIIIa)
thrombin
What are the 3 main roles of Factor I in coagulation?
1) Transforms the unstable platelet plug into a stable, permanent plug
2) Induces platelet aggregation
3) Starts the fibrinolysis process
_____ and ____ are glycoproteins mainly synthesized in the liver
Protein C and protein S
____ and ____ are important components of the natural anticoagulant system in the body. Are they Vit K dependent?
protein C and protein S
Yes, they are Vit K dependent
When protein C and S are activated, have almost direct effect on conversion of _____ to ____
Prothrombin to thrombin
____ inactivates Thrombin and IXa, Xa, XIa and XIIa
Anti-Thrombin (III)
_____ inhibition accelerated 1,000-fold with heparin
Anti-Thrombin (III)
Active protein C works on which 2 factors?
factor 5 and 8
What does a negative dedimer test indicate? What does a positive dedimer test indicate?
there are no clots present
clots are present
Which enzyme converts fibrinogen into fibrin during the blood clotting process?
thrombin
What is the name of the protein released by platelets and injured tissues (extrinsic pathway) that initiates the formation of a blood clot?
tissue factor
Which coagulation factors are Vit K dependant?
factor 2,7, 9, 10 and protein C and S
????/ best describes the function of the activated protein C complex.
Inhibition of factors Va and VIIIa
Which of the following best describes the function of tPA?
Conversion of plasminogen to plasmin
