Introduction to Hemostasis II Flashcards
Factor IIa (thrombin) activates more ________, leading to amplification.
V, VIII, and XI
Serpins are ________.
serine protease inhibitors
Heparin is a cofactor for ________.
anti-thrombin, increasing its output 1,000-fold
Molecularly, heparin is a ________.
highly suflated glycosaminoglycan
Regular (long-chain) heparin inhibits both _______, while shortened heparin inhibits only ______.
factor Xa and thrombin; factor Xa
Protein C is a ___________.
vitamin-K-dependent serine protease that inactivates factor Va and VIIIa; its cofactor is protein S
Protein C is activated by _________.
thrombin
What serine proteases are dependent on vitamin K?
II, VII, IX, X, C, and S
Factor V Leiden is a __________.
mutated form of factor V that is resistant to deactivation by APC (activated protein C)
TFPI inhibits ________.
the extrinsic pathway
The main enzyme responsible for fibrinolysis is ________.
plasmin, another serine protease
Plasmin is activated by _________.
t-PA (tissue plasminogen activator) and urokinase
Fibrin has binding sites for _________.
plasminogen
Elevated D-dimers indicate _______.
clot formation (as D-dimers are released by the action of plasmin)
Tissue-plasminogen activators and urokinases are inactivated by _________.
plasimogen-activator inhibitor 1 (PAI-1)
In the suite of anticoagulation proteins, the liver produces _________, while the endothelium produces ________.
protein C, protein S, antithrombin, heparin cofactor 2, and alpha-2-macroglobulin; thrombomodulin and tissue-factor pathway inhibitor
The only parts of the anticoagulation pathway that are vitamin-K dependent are ________.
protein C and protein S
What inactivates Va and VIIIa?
Protein C (with protein S and thrombomodulin)
What does antithrombin inactivate?
Serine proteases: thrombin (IIa), VIIa, IXa, Xa, XIa, XIIa, and kallikrein
Heparin is __________.
a cofactor for antithrombin
The shortened form of heparin is able to speed up the inactivation of _____, but not of ________.
Xa; thrombin (however, longer forms of heparin can speed up the inactivation of thrombin)
When is thrombomodulin expressed on endothelial cells?
All the time, though it is downregulated in response to inflammatory agents (likely one of the causes of pro-coagulatory states seen in inflammation)
What does thrombomodulin do?
It serves as a cofactor in the activation of protein C by thrombin and also inactivates thrombin by itself (thrombin plus thrombomodulin also activates thrombin-activatable fibrinolysis inhibitor)
Protein C and protein S assemble _______.
on an anionic membrane surface
Fatal neonatal thrombotic events occur in ________.
homozygous deficiency of protein C
Factor V Leiden is _________.
a point mutation in factor V that results in APC-resistant Va
Because protein C is also a vitamin K dependent serine protease, giving warfarin will __________.
lead to a temporarily hypercoagulable state
How does tissue-factor protein inhibitor work?
It binds to the newly formed Xa and inactivates VIIa in the VIIa-TF complex.
Where is TFPI found?
It is constitutively made by endothelial cells and circulates in the blood; however, most is bound to lipoproteins.
Plasmin breaks down both ___________.
fibrinogen and fibrin, leading to lots of products collectively called “fibrin degradation products,” or FDP
What five things activate plasmin?
Primarily tissue plasminogen activator, but also urokinase, kallikrein, XIIa, and XIa
t-PA is produced by __________.
endothelial cells, and it has a very short half life; it is released by damaged endothelial cells
t-PA activates plasminogen better in the presence of _________.
fibrin
PAI-1 is produced in the ______ and inhibits _________.
platelets (along with other cells); t-PA
How does TAFI work?
Thrombin-activatable fibrinolysis inhibitor is attached to fibrin by XIIIa; once there, it cleaves off parts of fibrin where plasmin would normally bind
PGI2 and NO both __________.
decrease platelet adhesion
Where is vWF released from?
Damaged endothelial cells
Undamaged endothelium acts to prevent clots by ____________.
constitutively expressing TFPI, t-PA, u-PA, thrombomodulin, PGI2, and NO; endothelium also metabolizes ADP (a platelet stimulator) to AMP and Pi
Bind to extravascular proteins (like collagen and fibronectin) causes platelets to ________.
express phosphatidylserine as a substrate for coagulation
Activated platelets express ______ that binds fibrinogen.
GPIIb/IIIa
