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- Non-Platelet derived
What is the strongest/largest non-platelet derived Agonist? Thrombin
Name some PLT Derived Agonists: - ADP
- Serotonin
- Platelet Activating Factor
- Thromboxane A2 (TXA2)
Name some Non-PLT Derived Agonists: - Thrombin
- Collagen
- Epinephrine
During PLT Secretion, the activated PLT's will secrete granules that aid in - Alpha
primary hemostasis. What are these granules called? - Dense
List 3 AlphaGranules: - Thrombospondin
- vWF
- PLT-Derived Growth Factor [PDGF]
List 3 DenseGranules: - ADP
- Calcium
- Serotonin
This Alphagranule promotes PLT-to-PLT interaction Thrombospondin
This Alphagranule aids in PLT adhesion vWF
This Alphagranule promotes smooth muscle growth PLT-Derived Growth Factor [PDGF]
This Densegranule promotes PLT Aggregation ADP
This Densegranule regulates PLT activation/aggregation Calcium
This Densegranule promotes vasoconstriction Serotonin
Platelet Secretion works on what type of feedback system? Positive
This stage is characterized by PLT's attaching to one another. Newly PLT Aggregation
arriving PLT's will adhere to the tissue and become activated by contact
with agonist:
This substance secreted from dense granules will aid in the attraction and ADP
activation of new PLT's to the aggregate:
Once the activated PLT's aggregate enough into a large clump, this Platelet Plug (Takes 10 mins)
structure is formed which stops the bleeding:
Primary ___________ is stabilized and anchored firmly to the vessel wall
by the process of secondary hemostasis
Due to the fragility of the PLT Plug, what happens to it during Secondary Rapid reinforcement of Plt Plug takes place with a fibrin clot.
Hemostasis:
What is the role of Coagulation Factors in Secondary Hemostasis? Inactive Coag factors are sequentially activated in order to
produce a fibrin clot.
What is the name of inactive coagulation factors? Zymogens
Inactive Zymogens in circulation are sequentially activated into Fibrin Clot
their active enzyme form, this ultimately results in the formation of a?
Play the major role in secondary hemostasis Coagulation factors
Plasma contains 15 coagulation factors or clotting factors
Almost all are made in the liver
Are proteins
Coagulation factors are normally present in plasma in their inactive form Zymogens
____________________.
• ___________________ require activation to active forms to catalyze
the next reaction in the sequence
Coagulation Factors can be divided up into 3 main groups. These are: 1 - Fibrinogen Group
2 - Prothrombin Group
3 - Contact Group
What factors are in the Fibrinogen Group: I [Fibrinogen]
-All factors are consumed during process of coagulation (present in V
plasma; absent in serum)
VIII
XIII
What Factor in the Fibrinogen Group is heat labile (unstable) ? V
All coag factors of the fibrinogen group are consumed when? During the process of coagulation.
Therefore they are present in plasmaand absent in serum
What happens to a sample or specimen if it is heated too much or for too It will denature Factor V and will falsely elevate the Bleeding
long: time result
What factors are in the Prothrombin Group? II [Prothrombrin]
VII
IX
X
What factors make up the Contact XI
group? XII
PK
HK
What must occur before the Contact Group can be activated? Requires contact with a surface for activation
The initiation of the Coagulation Cascade can occur through 2 pathways. - Intrinsic [Contact with endothelium]
What are they? - Extrinsic [Tissue Factor/Vessel Injury]
How does the coagulation cascade differ in vitro and in vivo? In vitro: Initiation of the cascade occurs via the 2 pathways
independently
In Vivo: Basically the cascade occurs simultaneously in both
pathways
Which Group is Vitamin K dependentand what factors are in that group? - Prothrombin group
- II, VII, IX, X
Prothrombin Group factors are not consumed during coagulation except? II (prothrombin)
Present in plasma and serum (except ___)
This group Includes factors Contact Group
1. XI
2. XII
3. Prekallikrein (PK)
4. High molecular weight kininogen
• Not consumed during coagulation Contact Group
Present in serum and plasma
• Requires contact with a surface for activation
What is the only factor that will not cause a bleeding disorder? XII
Which factor plays the primary role of blood coagulation in vivo? XI
This pathway requires a substance not normally present in blood to Extrinsic Pathway
become activated:
What substance is normally the start of the Extrinsic Pathway? Tissue Factor or [Tissue Thromboplastin]
When is Tissue Factor exposed? During an injury to the blood vessel. It is located on the
vessel wall beneath a layer of endothelial cells and released
into circulation when exposed.
Tissue Factor will form a complex with what factor to activate the Factor VII
Extrinsic Pathway?
When and in which pathway is the blood clot formed? At the end of the common pathway
Which pathway involves substances that are normally present in Intrinsic pathway
circulation [Specifically Plasma]?
Exposure of these substances will lead to the activation of Factor XII and - Collagen
Factor XI of the Contact Group: - Subendothelium
The activation of Factor XIIand Factor XIwill lead to the activation of Intrinsic PAthway
what pathway?
The Common Pathwaybegins when the Intrinsic and Extrinsic pathways Factor X
converge and both activate what factor?
Activated Factor X will lead to the activation of? Factor II/Thrombrin
How does FactorII/Thrombin assist in strengthening and reinforcing the - FII/Thrombin will cleave FI/Fibrinogen resulting in the
platelet plug? formation of fibrin strands.
- At the same time, FII/Thrombin will also cleave a peptide
from Factor XIII which activates FXIII. Activated FXIII will link
the fibrin strands created from the cleaved Fibrinogen
resulting in Fibrin polymers. These Fibrin polymers help
create the blood clot.
What factors comprise the Extrinsic Pathway: VII
III
What factors, in order, make up the Common Pathway: X
V
II
I
XIII
What factors, in order, comprise the Intrinsic Pathway: PK
HK
XII
XI
IX
VIII
Once the blood clot formed at the end of the Common Pathway has Fibrinolysis
stopped the bleeding and is no longer needed, the Fibrin used in the clot
must be broken down and removed. What is the name of this process?
Fibrinolysis Overview: - Essentially the process of the removal of unwanted fibrin
deposits
- Fibrin is cleaved enzymatically into soluble fragments
- These fragments are then removed by macrophages
- Fibrinolysis is initiated by the formation of fibrin
This inactivated enzyme that circulates in plasma will bind to fibrin as Plasminogen [PLG]
clotting begins:
Plasminogenrequires the help of 2particular activators in order for it to -tPA [Tissue Plasminogen Activator]
be converted into Plasmin - uPA [Urokinase Type Plasminogen]
When tPA and uPA act upon and activate Plasminogen, it is then Plasmin
converted into this?
This enzyme slowly initiates fibrinolysisthrough a slow process Plasmin
of cleaving fibrinvia digestion:
Plasmin will initiate fibrinolysis by slowing doing what? Cleaving fibrin into smaller fragments
The degradation of Fibrin in Fibrinolysis results in these distinct protein Fibrin Degradation or Split Products[FDP/FSP] - X, Y, D, E
fragments called:
Which FDP fragments can exert an anti-thrombin effect by inhibiting D Dimer [2 D Fragments]
hemostasis?
The Coagulation system is kept in balance by: Activators and Inhibitors of clotting and fibrinolysis
The Regulatory Mechanisms OR Inhibitorsof the Coagulation - Limit the amount of fibrin clot formed to avoid ischemia
Cascadeserve two main functions in Secondary Hemostasis inhibition. (inadequate blood supply to tissues)
What are they? - Localize clot formation to the site of tissue or vessel injury,
preventing thrombosis.
This glycoprotein found on endothelial surfaces is an inhibitor serves as Tissue Factor Pathway Inhibitor [TFPI]
an anticoagulant by inhibiting Factors VIIa and Xa
Suppresses the Extrinsic and common Pathway:
These two inhibitors are both Vitamin K Activated Protein C & S
dependent inhibitors and together they inactivate Factors Va & VIIIa:
Major inhibitory mechanism in controlling blood coagulation Protein C
This group of inhibitors are known as "Serpins" and will inhibit the target Serine Protease Inhibitors
by trapping the enzyme with the Serpin and resulting in loss of activity:
This Serpin inhibitor is a protein synthesized by the liver & will bind and Antithrombin [AT]
directly inactivates thrombin and other factors*: Also inhibits IX, X, XI, XII, kallikrein, and plasmin
What is the most importantSerine Protease Inhibitors? Antithrombin [AT]
What Anticoagulant paired with Antithrombinwill have the most Heparin
effectiveness when inhibiting thrombin?
This plasma Serpin inhbitor will inhibit Factor Xa in a ProteinZ- ZPI
Dependentmanner:
Tissue Plasminogen Activator (TPA) produced by endothelial cells will aid Fibrinolysis
in activation of?
TPA is also a thrombolytic agent (clot-busting drug)
• Approved for use in certain patients having a heart attack or stroke