Blood Coagulation & Wound Healing Flashcards
What do platelets secrete after sticking to collagen in a release reaction?
ADP, serotonin and thromboxane A
The formation of carboxyglutamate is formed by a _____-dependent enzyme (protein carboxylase)
vitamin K
What is primary hemostasis?
the vasoconstriction and platelet response
What do PGH2 and prostacyclin synthetase produce?
prostacyclin (PGI2) to PGF (by endothelial cells)
Fibrin strands adhere to the plug to form an _____ .
insoluble clot
Which regulatory element is activated by thrombin bound to thrombomodulin then degrades factors VIIIa and Va?
Protein C
What causes a bruise?
the accumulation of blood from a broken vessel
Platelets stick to ____ and undergo a ____.
collagen; release reaction
When bound to the fibrin clot, plasminogen _____, which then allows it to be converted into active plasmin.
changes conformation
What is the purpose of von Willebrand factor?
it is associated with subendothelial connective tissue; it serves as a bridge between platelet, glycoprotein GPIb/IX and collagen
Platelets _____ and pump their alpha and dense granules into the area.
de-granulate
Fibrin generation occurs ______ to platelet aggregation.
simultaneously
What are some adhesion molecules?
von Willebrand factor, fibrinogen, integrin, fibronectin
Which signaling molecules cause platelets to undergo platelet release reaction?
ADP and thromboxane A2
What are stored in/secreted by dense granules?
ADP/ATP, serotonin, Ca++, epinephrine, and histamine
Vitamin K is part of the ____ family structure.
quinone
Which factor stabilizes the fibrin clot by facilitating cross-linking?
Factor XIII
___ and ___ are not enough in conditions of high shear.
GPIb; GPIa
Coagulation factors are generally _____ which act by cleaving downstream proteins.
serine proteases
Fibrinogen is _____ into fibrin.
cleaved
This factor is activated by thrombin in presence of calcium. It stabilizes the fibrin clot by covalent cross-linking.
Factor XIII
In a resting platelet, is GPIIb/IIIa active?
NO
Protein C is activated to Protein ___ by thrombin bound to thrombomodulin.
Ca
Coagulation factors circulate as ______.
inactive zymogens
____ acts as a cofactor to Protein C.
Protein S
Plasmin ____ the fibrin polymer down into much smaller molecules to be handled by the body.
degrades
Which pathway is faster? Extrinsic or intrinsic?
extrinsic pathway
Cross-linking of fibrin is catalyzed by ____ or ____.
transglutaminase or factor XIII
Which factors are not cleaved by serine proteases?
V, VIII, XIII
Which factor(s) are cleaved by transglutaminase?
XIII
What are the regulatory elements of the clotting cascade?
von Willebrand factor, protein C, protein S, thrombomodulin, antithrombin III
Which signaling molecules attract platelets?
ADP and thromboxane A2
What regulatory element serves as a connector between platelets, GPIb/IX and collagen?
von Willebrand factor
What is the extrinsic clotting cascade triggered by?
activated by external trauma
This factor binds to exposed collagen at site of vessel wall injury.
Factor XII
What is fibronectin’s role in late repair events?
cell adhesion; essential role in granulation tissue organization; correct assembly of extracellular matrix
Firm adhesion of platelets to the subendothelia is mediated by a glycoprotein called _____.
GPIIb/IIIa
The addition of _____ causes a lag before ADP can be secreted by the platelets to cause aggregation.
collagen
Kallikrein is released by ____ cells.
endothelial
What factor(s) are cleaved by glycoproteins?
V, VIII
Do the extrinsic and intrinsic cascades activate the common pathway (X, thrombin, fibrin)?
YES
___ activates Protein C when bound to thrombin on the surface of endothelial cells.
Thrombomodulin
Activated GPIIb/IIIa binds to vWF at the _____ to promote strong adhesion to vessel wall (primary aggregation).
subendothelial surface
What kind of platelets stick to injury site?
activated platelets
This factor is activated on the surface of activated platelets by tenase complex and by Factor VIIa (w/ tissue factor and calcium)
Factor X
What is platelet aggregation at the site of injury mediated by?
platelet receptors, platelet-derived agonists, platelet-derived adhesive proteins & plasma-derived adhesive proteins
Arachidonic acid is converted into PGG2, PGH2 (endoperoxides) by which enzyme?
cyclooxygenase/prostaglandin synthase
A complex of ___ and ___ is what allows specific interactions with membrane lipids that ultimately lead to the recognizable protein structures in the clotting cascade.
calcium and carboxyglutamte (glu-factors)
Which factor lays down the fibrin mesh to further strengthen the blood clot?
Factor XIII (13)
___, when supplied directly, causes faster aggregation.
ADP
The molecule ___ causes the de-clotting process or clot dissolution.
plasmin
Factor ___ is a subendothelial cell-surface glycoprotein that acts as a cofactor for factor VII.
Factor III (tissue factor)
Which regulatory element is the most important coagulation inhibitor?
Antithrombin III
What are two examples of aggregating agents?
collagen and ADP
What does secondary hemostasis consist of?
A cascade of coagulation serine proteases that culminates from cleavage of soluble fibrinogen by thrombin
Which factor is activated by factor XIIa?
Factor XI
When GPIIb/IIIa binds to fibrinogen, it plays a role in _____ interactions.
platelet-platelet
The initial binding of platelets to von Willenbrand factor is mediated by ______ that are loosely bound (do not promote strong adhesion).
glycoproteins
This factor is activated by thrombin in the presence of calcium.
Factor VII
Factor ____ is activated by thrombin. It is a cofactor in the activation of factor X by IXa.
Factor VIII
Plasminogen is activated by ____.
factors XIa, XIIa, Kallikrein
Which factors are vitamin K-dependent?
IX (intrinsic); VII (extrinsic); X, II (common)
Fibrin cross-linking is joined by creating a ___ bond.
C-NH-C (isopeptide bond)
What are the fat soluble vitamins?
A, D, E, K
What factor does the extrinsic pathway involve?
Factor VII
GPIIb/IIIa integrins on resting platelets bind _____ to its ligands (vWF or fibrinogen).
poorly
Fibronectin can be found in the ___ and ___.
plasma; body cells
Which factor is activated on surface of activated platelets by prothrombinase complex?
Factor II (prothrombin)
Why is vasoconstriction important in hemostasis?
vasoconstriction limits blood flow to form a sticky plug
What is the synthesis pathway of serotonin?
tryptophan > (tryptophan hydroxylase) > 5-HTP > (aromatic AA decarboxylase) > serotonin 5-HT
End-to-end cross-linking connects two domains on ___ fibrin.
the same
Which factor is activated by thrombin and serves as a cofactor in the activation of prothrombin in its “a” form?
Factor V
Which factor is cleaved by thrombin to form a fibrin clot?
Factor I (fibrinogen)
Which signaling molecules cause vasoconstriction?
serotonin and thromboxane A2
Which factors contain carboxyglutamate?
thrombin, VII, IX, and X
In what cells is serotonin made?
enterochromatin cells
Transverse cross-linking connects two ___ domains of fibrin.
opposite
What is the intrinsic factor activated by?
activated by trauma inside the vascular system; activated by platelets, exposed endothelium, chemicals or collagen
Which is a soluble plasma protein: fibrin or fibrinogen?
fibrinogen
Antithrombin controls the activities of ____.
thrombin and factors IXa, Xa, XIa, and XIIa
What factors does the common pathway involve?
I, II, V, X
What causes blood vessels to spasm?
when platelets secrete serotonin
What is fibronectin’s role in the plasma?
stabilizes fibrin clot; platelet adhesion, platelet spreading, platelet aggregation
A _____ blood vessel triggers the release of clotting factors.
damaged
Thrombin cleavage generates ______ that forms a cross-linked fibrin mesh at the site of injury.
insoluble fibrin
Which clotting factor to platelets and damaged tissue release?
Factor VIII
What do PGG2 and thromboxane synthetase produce?
thromboxane A2 to thromboxane B2
What is secondary hemostasis?
the clotting cascade
_____ has a high affinity for calcium ions.
Carboxyglutamate (Glu)
Which factor is activated by factor XIa in the presence of calcium?
Factor IX
Upon the activation of platelets, GPIIb/IIIa undergoes a _____ that reveals a previously-hidden binding site for _____.
conformational change; vWF or fibrinogen
What is the process of blood clotting?
injury or damage > vessel constriction > platelet plug forms > fibrin clot forms
Plasmin is activated by ______.
plasminogen
What factors does the intrinsic pathway involve?
XII, XI, IX, VIII
tPA, uPA, kallikrein, and factor XII all activate ____.
plasminogen, to later form activated plasmin
Which factor is activated by Kallikrein or Kininogen?
XII
Which factors are cofactors?
VIII, V, III (tissue factor)
An ______ can record the aggregation of platelets in platelet-rich plasma in response to an aggregating agent.
aggregometer