Coag Flashcards
2 examples of anticoagulant factors:
Prostacyclin
Vascular Plasminogen Activator
Anticoagulant Factors are released from _______.
Endothelial cells.
2 Procoagulant Factors:
Platelets
Plasma proteins
The inactive state is called ______.
Zymogen
A membrane-bound protein is called the ______.
Tissue Factor
_______ tend to be released when the lining of the vascular vessel gets disrupted.
Procoagulant Factors
3 phases of Cell-Based Coagulation
Initiation
Amplification
Propagation
The activity of the ______ complex is the most significant event to initiate coagulation.
FVIIa/TF
7a/Tissue Factor
In the initiation phase of cell base coagulation, the _____ is both a receptor and cofactor for FVII (F7).
Tissue factor
When the zymogen FVII (F7) binds to the tissue factor it becomes _____ and forms the _____ complex.
7a
F7a/TF
In the initiation phase, the F7a/TF complex activates what zymogens?
F9 and F10
TF-bearing cells appear to bind Factor 7a and low levels of Factors 9a and 10a even ______ but are separated from the Phase II: Amplification compounded by the normally intact blood vessel wall.
In the absence of injury
In the initiation phase of Cell Based Coagulation factor ___ formed on the TF-bearing cell interacts with cofactor ____ to form a prothrombinase complex.
10a
5a
The thrombin generated on the TF-bearing cell serves as the “signal” for Phase ______ to begin.
Phase 2: Amplification
The prothrombinase complex generates a _______ on the surface of TF-bearing cells.
Small amount of “priming” thrombin.
Fibroblasts and monocytes are examples of _____.
Tissue factor bearing cells
If tissue injury has occurred and activated platelets are around, Factor ___ will diffuse to those platelets, bind to their surface, and (in conjunction with Cofactor ___) activate zymogen Factor ___ to Factor ___.
9a
8a
10
10a
_______ are released by endothelial cells.
Anticoagulant Factors
TF-bearing cells appear to bind Factor ___ and low levels of Factors ___ and ___ even in the absence of injury but are separated from the Phase II: Amplification compounded by the normally intact blood vessel wall.
7a
9a and 10a
The _____ generated on the TF-bearing cell serves as the “signal” for Phase 2: Amplification to begin.
Thrombin
In the initiation phase of Cell Based Coagulation factors ____ remain on the TF-bearing cell, while factor ____ diffuses away.
10a and 5a
9a
In the initiation phase of Cell Based Coagulation Factor 10a formed on the TF-bearing cell interacts with Cofactor 5a to form a _____ complex.
Prothrombinase
The activity of the FVIIa/TF complex is the most significant event to _______.
Initiate coagulation
In phase 2 of Cell Based Coagulation, when sufficient _____ is generated on or adjacent to TF-bearing cells, ____ are activated.
Thrombin (F2a)
Platelets
The small amount of TF-bearing cell-generated thrombin does what 4 things during Phase 2?
Activates platelets
Activates F5a from F5
Activates F8a and dissociates it from von Willebrand Factor (vWF)
Activates F11a from F11
Rate of thrombin generation takes leading role in ____ circulation.
Venous
When vascular injury occurs, platelets leave the blood vessel, bind to _______ and are activated by a combination of those factors and the _______.
This occurs during Phase _____.
Collagen, vWF, blood vessel wall receptors
“Priming” dose of thrombin
3
The adherence of platelets to the damaged tissue is the first step in the formation of the platelet “plug” necessary for ______.
Primary hemostasis
In phase 3, the newly activated platelets bind Factors _____ and the Factor ____ freshly liberated by the Factor 7a/TF complex.
5a
8a
9a
In phase 3, the freshly-generated Factor ___ binds to the freshly activated platelet.
11a
In phase 3, the freshly-generated Factor 11a binds to the _____, effectively bypassing the need for Factor ____.
Freshly activated platelet
12a
in Phase 3, membrane-bound Factor ____ keeps on activating Factor 9 to Factor 9a.
11a
in Phase 3, membrane-bound Factor 11a keeps on activating Factor ___ Factor ___.
9
9a
Factor 8a and co-factor 9a form what is called the _____.
Platelet tenase complex (PTC)
The production of vast amounts of thrombin on the surface of activated platelets is the first step in _____.
Phase 3: Propagation
_____ agents are used to prevent DVT.
Anti-thrombin
The Platelet Tenase Complex is formed by:
F8a and co-factor 9a
The PTC activates even more Factor ___ to Factor ___.
10
10a
Factor ___ combines with Factor ___ to form the prothrombinase complex.
10a
5a
Platelets take leading role followed by fibrin formation in ____ circulation.
Arterial
Factor 10a combines with Factor 5a to form the _____ complex.
Prothrombinase
The prothrombinase complex causes the:
Explosive burst of thrombin that helps produce a stable fibrin clot
Most of the thrombin produced is generated ____ the initial fibrin clot is formed.
After
______ is most prominent following severe crushing type injuries.
Vascular constriction
____ is considered in vitro.
CPB circuit
____ is considered in vivo.
Patient
Patients that lack Factor ___ have no problem clotting.
12
____ circulation requires rapid response system to seal off any bleeding sites.
Arterial
_____ + _____ = activation of the platelet.
Transmembrane signaling
High shear stress
_____ agents are used to prevent arterial thrombosis.
Anti platelet
What 7 things occur when an arterial blood vessel is damaged?
Vascular constriction
Platelet adhesion
Platelet activation (formation of platelet plug)
Activation of cell-based coagulation cascade (formation of fibrin clot)
Clot retraction
Activation of fibrinolytic cascade
Vessel repair/regeneration
Vascular constriction involves _____ and is most prominent following ______.
Smooth muscle
Severe crushing injuries
In arterial circulation, ____ take leading role followed by ____.
Platelets
Fibrin formation
Sub-endothelial collagen also binds with platelet receptor GP4 which causes _____.
Activation of the platelet
____ circulation has an acceptable slower response.
Venous
In venous circulation rate of ____ takes leading role.
Thrombin
Smooth muscle layers of arteries
Outer longitudinal
Inner circular
Capture that occurs in platelet adhesion depends on: (2)
Sub-endothelial molecules of von Willebrand’s Factor (vWF) and collagen
Platelet surface receptor Glycoprotein Ib
GPIb binds easily with vWF, but it has a ____ affinity interaction, which slows but does not stop the platelet.
Low
Cyclooxygenase activity irreversibility inhibited by Aspirin because there is no _____ formation.
Thromboxane
Interaction between platelet GPIb and the vWF molecule causes ______.
Transmembrane signaling
Which platelet agonists have vasoconstricting effects?
Thromboxane A2 (TXA2) Serotonin
Transmembrane signaling coupled with high shear stress results in activation of ____.
Platelet
_____ binds with platelet receptor GP1a/2a.
Sub-endothelial collagen
During platelet activation, the platelet loses its normal ____ shape.
Discoid
Platelet receptor _____ undergoes conformation change.
GP2b/3a
After the platelet receptor GP2b/3a undergoes conformational change it is able to bind to ____.
vWF
GP2b/3a and vWF have a ____ affinity bond that secures the activated platelet to the ____.
High
Sub-endothelium
Sub-endothelial collagen binds with platelet receptor ____. At medium shear stress strong enough to bind platelet to sub-endothelium.
Gp1a/2a
5 goals of platelet activation:
Recruitment of additional platelets
Vasoconstriction of smaller arteries
Local release of ligands needed for stable platelet-platelet matrix
Localization and acceleration of platelet-associated fibrin formation
Protection of clot from fibrinolysis
Activated platelets release _____, which recruit additional platelets.
Platelet agonists
3 platelet agonists
Thromboxane A2
Serotonin
ADP
_____ inactivate F5a and F8a cofactors.
Proteins C and S
Thromboxane is an important _____ and _____.
Platelet agonist
Vasoconstrictor
_____ is formed in cytosol following cyclooxygenase cleavage of arachidonic acid.
Thromboxane A2
____ anchors the platelet.
GP2b/3a
ASA paralyzes the production of ____.
thromboxane A2
Why should platelet gel should never be applied directly to new bypass graphs?
Vasoconstriction effects
Serotonin is released from platelet granules. It is a _____ and _____.
Platelet agonists
Vasoconstrictor
____ is released from platelet granules and is a platelet agonists with no known vasoactive roles.
ADP
Cyclooygenase activity irreversibility inhibited by ____ because there is no thromboxane formation.
Aspirin
Sub-endothelial collagen also binds with platelet receptor _____ which causes activation of the platelet.
GP4
____ is the site of action of newer anti-platelet agents.
GP2b/3a
The formation of the platelet plug begins with the surface receptor GP2b/3a undergoing a _____ dependent conformational change making it able to bind with _______.
Calcium
Fibrinogen or vWF
The production of _____ signals the Fibrinolytic phase of coagulation.
Plasmin
Fibrinogen and vWF are stored in ____ within the platelet that are released ____.
Alpha-granules
Following activation
Fibrinogen and vWF bonds form between _____ binding them together in a _____.
Platelet
Tight matrix
_____ is released by endothelial cells and activated by thrombin and venous occlusion.
tPA
More than _____ GP2b/3a receptors present on platelet surface, with additional receptor molecules available within ____.
50,000
Cytoplasm
Even as the fibrin clot is being formed, the ____ system is being initiated to disrupt the clotting process and the clot itself.
Termination
_____ are measured to help determine the amount of fibrinolysis occurring.
FDPs
Four autologous anticoagulants help control the spread of coagulation activation:
Tissue Factor Pathway Inhibitor (TFPI) Protein C (PC) Protein S (PS) Antithrombin III (AT or AT-III)
____ forms a quarternary complex called the TF/F7a/10a/TFPI which I activates various factors and limits coagulation.
TFPI
What does the quarternary complex called the TF/F7a/F10a/TFPI formed by TFPI?
Inactivates various factors and limits coagulation
______ are regulated by Plasminogen Activator Inhibitors 1&2.
uPA and tPA
Endothelial cells have a negative charge that repels _____.
Platelets (positive charge)
Endothelial release of ADPase inactivates platelet released ADP limiting ability ______.
Recruit other platelets
TFPI forms a quarternary complex called the ____ which inactivates various factors and limits coagulation.
TF/F7a/F10a/TFPI
____ is a vitamin K-dependent plasma glycoprotein which helps break down F10a and F8a.
Protein C
Proteins C and S inactivate ____ and ____ cofactors.
F5a
F8a
Protein C is activated by ____ and its activity is increased by ____.
Thrombin
Protein S
Protein C and Protein S are _____ dependent plasma glycoproteins.
Vitamin K
_____ inhibits thrombin and the “serine protrudes”.
Anti-thrombin
_____ is produced from the zymogen plasminogen by the action of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA).
Plasmin
Serine Proteases include Factors _____ (4).
4a
10a
11a
12a
tPA is released by _____ and activated by _____ and _____.
Endothelial cells
Thrombin and venous occlusion
tPA and plasminogen bind to the growing fibrin polymer as _____ is converted to _____.
Fibrinogen (F1)
Fibrin (F1a)
____ and ____ bind to the growing fibrin polymer as fibrinogen (F1) is converted to fibrin (F1a).
tPA
Plasminogen
In the last step of fibrinolysis, _____ is activated to _____ which cleaves fibrin strands.
Plasminogen
Plasmin
In the last step or fibrinolysis, plasminogen is activated to Plasmin which cleaves _____ strands.
Fibrin
FDPs are measured to help determine the amount of _____ occurring.
Fibrinolysis
_____ anticoagulants prevent clotting and require intact endothelial cell barrier.
Endogenous
Endothelial release of ____ and ____ inhibit platelet adhesion and aggregation.
Nitric oxide
Prostacyclin (PGI2)
4 effects that coagulation has on cardiac surgery and cardiopulmonary bypass
Bleeding
Circuit integrity
Inflammation
Disease state of patient
____ foreign surface stimulates coagulation cascade.
Large
Coagulation cascade will stimulate ____ activities.
Inflammation
5 effects of bypass/surgery on coagulation:
Activates intrinsic and extrinsic coagulation pathways Activates neutrophils and monocytes Exposes sub-endothelium Activates platelets Vascular endothelial cell activation.
Large negatively charged surface activates ____ pathway, which also activates _____ which activates _____.
Intrinsic
Fibrinolysis
Complement
Endothelial release of ____ inactivates platelet released ADP limiting ability to recruit other platelets.
ADPase
Activation of complement cascade results in ____ activation.
Leukocyte
Exposed sub-endothelium stimulates ______.
Coagulation
Platelet activation during bypass can occur due to ____ and activates _____.
Contact with foreign surface of circuit
Intrinsic and extrinsic pathways
Endothelial cells have a ____ charge.
Negative
Cleaved fibrin strand produces _____.
Fibrin Degradation Products
FDPs or Fibrin Split Products
Plasmin is produced from the zymogen plasminogen by the action of _____ and _____.
uPA and tPA
uPA and tPA are regulated by _______.
Plasminogen Activator Inhibitors 1&2 (PAI-1 & PAI-2)
Coronary suction introduces _____ from damaged cells which activates the ____ pathway.
Tissue factor
Extrinsic
The production of plasmin signals the ____ phase of coagulation.
Fibrinolytic
Endothelial release of nitric oxide and prostacyclin inhibit ________ (2).
Platelet adhesion and aggregation
Plasmin is produced from the zymogen _____ by the action of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA).
Plasminogen
More than 50,000 _____ receptors present on platelet surface, with additional receptor molecules available within cytoplasm.
GP2b/3a
