Unit 5 Flashcards
What does primary hemostasis include
Platelet production, destruction, function
What is Secondary Hemostasis
Coagulation cascade
Fibrinolysis
What is a clot
Soluble protein fibrinogen converts to insoluble fibrin
What does a clot do
Reinforces platelet plug
What is fibrinolysis
Dissolution of the fibrin clot
What does hemostasis depend on
1.Structure and integrity of blood vessels
2.Platelet concentration and function
3.Clotting factors
What are the 3 layers of tissue in blood vessels
- Tunica Intima
- Tunica Media
- Tunica Adventitia
What is the Tunica Intima
-A continuous, single layer of flattened epi cells
-Provides a protective environment for cellular elements of blood
What is Tunica Media
Composed of smooth muscle cells that can contract or expand to dilate or constrict lumen
What is Tunica Adventitia
Composed of collagen-anchors vessels to surrounding tissues
Why are normal epi cells negatively charged
Repel platelets and clotting proteins
What do injured Epi cells produce
-von Willebrand Factor
-Platelet activating factor
What does VWF do
-Aids in platelet adhesion to injured sites
-Carries a certain clotting protein (VIII)
What does exposure of tissue factor do
Exposes the receptor for clotting factor VII and will initiate the extrinsic coag pathway
Why are injured epi cells thrombogenic
with collagen exposure they become sticky which creates contact activation
what is contact activation
a protein complex forms on collagen which initiates the intrinsic coag pathway
What do blood vessels do after an injury
VASOCONSTRICTION
1. narrow the lumen to reduce blood loss
2. force platelets and plasma proteins into closer proximity to the vessel wall
3. stimulate and prolong platelet release of serotonin
What happens in Primary Hemostasis
Platelets:
-Adhere to injured vessel wall
-Aggregate to each other
- Form the primary hemostatic plug
How do mature MKs mature
Endomitosis
What is endomitosis
-Doubling of nuclear DNA content without dividing
-increase in cell size
-single nucleus goes from a round to highly lobulated nucleus
1 megakaryocyte = how many platelets
1,000-3,000
What is TPO
Thrombopoietin
What does TPO do
-Major factor regulating platelet development
-Influences MK and platelet production
Where is TPO produced
At a constant rate primarily in the liver
How does TPO work
Binds to MKs and MK precursors and stimulate
Binds to circulating platelets (prevent excessive production)
What is a result of an increased level of free active TPO
Thrombocytopenia
Normal reference range for PLT
150-450
How long do PLTs survive
9-12 days
What does GP-Ib do
Adheres PLT to damaged vessel
Major receptor for VWF
What does GP-IIb/IIIa do
Aggregates surrounding PLTs
Major receptor for fibrinogen
What do alpha granules of PLTs contain
Hemostatic proteins:
Clotting factors
VWF
Non-hemostatic proteins:
Growth factors for wound healing
What do dense bodies of PLTs contain
Serotonin
*induce/prolong vasoconstriction
Platelet aggregation agonists
*non-metabolic ADP *Epinephrine
Calcium
*important for secondary hemostasis
What are the strong agonists for PLTs
Collagen
Thrombin
What is collagen used for in PLTs
Exposed upon vascular injury
*VWF binds to collagen
*PLT GP-Ib binds to VWF (adhesion)
What does Thrombin used for in PLTs
Tissue Factor is exposed upon vascular injury
*Small amounts of thrombin are produced
*Thrombin attracts and activates PLTs
*Activated PLTs amplify thrombin production
*Leads to a stabilized fibrin clot
Platelet-derived Agonists can produce what other substances upon activation
Thromboxane A2 (TxA2)
Platelet activating factor (PAF)
What do PLT-derived agonists release from their granules
ADP
Epinephrine
Serotonin
What does aspirin do
COX inhibitor which prevents PLT aggregation
How is Thromboxane A2 produced
-COX catalyzes the conversion of Arachidonic acid into Prostaglandin H2
-Prostaglandin H2 is then converted to TXA2
What does TXA2 do
activates GP IIb/IIIa which promotes PLT aggregation
What does VWF carry
Clotting Factor VIII
What step of PLT function requires Calcium
Aggregation
What does fibrinogen do
Acts like a bridge and connects adjacent platelets
What does In Vivo testing for
bleeding time
What In Vitro testing for
platelet function analyzer
platelet function analyzer (PFA) detects what
Closure time: the amount of time it took for the PLT plug to form
The 3 pathways in 2nd Hemostasis
Intrinsic
Extrinsic
Common Pathway
What is evaluated in In Vitro testing
PT
aPTT
TT
What does PT evaluate
extrinsic and common pathway
What does aPTT evaluate
intrinsic and common pathway
What doe TT evaluate
Common pathway
What is a zymogen
Inactive form of an enzyme
What produces zymogens
mostly the liver
What Coag Factors are in the intrinsic pathway
PK
HK
XII
XI
IX
VIII
What are the names for PK
Prekallikrein
Fletcher Factor
What are the names for HK
High Molecular Weight Kininogen
Fitzgerald Factor
What is the common name for XII
Hageman Factor
What is the common name for XI
Antihemophilic Factor C
What is the common name for IX
Antihemophilic Factor B
Christmas Factor
What is the common name for VIII
Antihemophilic Factor A
**carried in circulation by VWF
What are the contact factors
PK
HK
XII
XI
What activates Contact Factors
Collagen when exposed
What is in the extrinsic pathway
Tissue Factor
VII
What is tissue factor also known as
thromboplastin
What makes up Extrinsic Tenase
VIIa:Ca2+
What does extrinsic tenase do
Assembles TF expressing cells
Activate IX
What is Factor X also known as
Stuart-Prower Factor
What is Factor V also known as
Labile Factor
What factor deteriorates at room temperature
Factor V: Labile Factor
What is Factor II
Prothrombin
What is the active form of Factor II
Thrombin
What is Factor I
Fibrinogen
What is the active form of Factor I
Fibrin
What makes up Prothrombinase
Xa
Va
Ca2+
PL (phospholipid)
What is Fibrinogen
Acute phase protein synthesized by the liver
What is the role of fibrinogen
Acts a bridge between aggregated platelets
Precursor to fibrin mesh
What are the 3 stages of conversion of fibrinogen to fibrin
- Proteolysis
- Polymerization
- Stabilization
What happens in Proteolysis
Cleavage of Factor I into active Ia by thrombin
Results in fibrin monomer
What happens in Polymerization
Spontaneous self-assembly into fibrin polymers
What happens in stabilization
Intro of covalent bonds into fibrin polymers by XIIIa
What will create the stable, crosslinked fibrin clot
Zymogen Factor XIII
What activates XIII
thrombin
What are the roles of thrombin
Activates: Fibrinogen, VIII, XIII
Stimulates endothelial cells to release VWF
A platelet agonist
What is the sequence after vessel injury
Vasoconstriction
Platelet adhesion
Platelet aggregation
Coagulation cascade
Fibrin Stabilization
What are the Vitamin K dependent factors
II
VII
IX
X
What does Vit K do
y-carboxylation of glutamic acid
Adding carboxy group to negatively charged phosohlipid membrane via Ca2+
What does Coumadin inhibit
Activity of epoxide reductase and prevents Vit K function
How does Coumadin affect Vit K
Proteins are synthesized
y-carboxylation does not occur
Clotting factors can’t bind to phospholipid surface via Ca2+
Rendered nonfunctional
What are naturally occurring inhibitors
Antithrombin
Tissue factor pathway inhibitor
Protein C & S
