Introduction to Hemostasis II

Question 1

Factor IIa (thrombin) activates more ________, leading to amplification.

Answer 1

V, VIII, and XI

Question 2

Serpins are ________.

Answer 2

serine protease inhibitors

Question 3

Heparin is a cofactor for ________.

Answer 3

anti-thrombin, increasing its output 1,000-fold

Question 4

Molecularly, heparin is a ________.

Answer 4

highly suflated glycosaminoglycan

Question 5

Regular (long-chain) heparin inhibits both _______, while shortened heparin inhibits only ______.

Answer 5

factor Xa and thrombin; factor Xa

Question 6

Protein C is a ___________.

Answer 6

vitamin-K-dependent serine protease that inactivates factor Va and VIIIa; its cofactor is protein S

Question 7

Protein C is activated by _________.

Answer 7

thrombin

Question 8

What serine proteases are dependent on vitamin K?

Answer 8

II, VII, IX, X, C, and S

Question 9

Factor V Leiden is a __________.

Answer 9

mutated form of factor V that is resistant to deactivation by APC (activated protein C)

Question 10

TFPI inhibits ________.

Answer 10

the extrinsic pathway

Question 11

The main enzyme responsible for fibrinolysis is ________.

Answer 11

plasmin, another serine protease

Question 12

Plasmin is activated by _________.

Answer 12

t-PA (tissue plasminogen activator) and urokinase

Question 13

Fibrin has binding sites for _________.

Answer 13

plasminogen

Question 14

Elevated D-dimers indicate _______.

Answer 14

clot formation (as D-dimers are released by the action of plasmin)

Question 15

Tissue-plasminogen activators and urokinases are inactivated by _________.

Answer 15

plasimogen-activator inhibitor 1 (PAI-1)

Question 16

In the suite of anticoagulation proteins, the liver produces _________, while the endothelium produces ________.

Answer 16

protein C, protein S, antithrombin, heparin cofactor 2, and alpha-2-macroglobulin; thrombomodulin and tissue-factor pathway inhibitor

Question 17

The only parts of the anticoagulation pathway that are vitamin-K dependent are ________.

Answer 17

protein C and protein S

Question 18

What inactivates Va and VIIIa?

Answer 18

Protein C (with protein S and thrombomodulin)

Question 19

What does antithrombin inactivate?

Answer 19

Serine proteases: thrombin (IIa), VIIa, IXa, Xa, XIa, XIIa, and kallikrein

Question 20

Heparin is __________.

Answer 20

a cofactor for antithrombin

Question 21

The shortened form of heparin is able to speed up the inactivation of _____, but not of ________.

Answer 21

Xa; thrombin (however, longer forms of heparin can speed up the inactivation of thrombin)

Question 22

When is thrombomodulin expressed on endothelial cells?

Answer 22

All the time, though it is downregulated in response to inflammatory agents (likely one of the causes of pro-coagulatory states seen in inflammation)

Question 23

What does thrombomodulin do?

Answer 23

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)

Question 24

Protein C and protein S assemble _______.

Answer 24

on an anionic membrane surface

Question 25

Fatal neonatal thrombotic events occur in ________.

Answer 25

homozygous deficiency of protein C

Question 26

Factor V Leiden is _________.

Answer 26

a point mutation in factor V that results in APC-resistant Va

Question 27

Because protein C is also a vitamin K dependent serine protease, giving warfarin will __________.

Answer 27

lead to a temporarily hypercoagulable state

Question 28

How does tissue-factor protein inhibitor work?

Answer 28

It binds to the newly formed Xa and inactivates VIIa in the VIIa-TF complex.

Question 29

Where is TFPI found?

Answer 29

It is constitutively made by endothelial cells and circulates in the blood; however, most is bound to lipoproteins.

Question 30

Plasmin breaks down both ___________.

Answer 30

fibrinogen and fibrin, leading to lots of products collectively called “fibrin degradation products,” or FDP

Question 31

What five things activate plasmin?

Answer 31

Primarily tissue plasminogen activator, but also urokinase, kallikrein, XIIa, and XIa

Question 32

t-PA is produced by __________.

Answer 32

endothelial cells, and it has a very short half life; it is released by damaged endothelial cells

Question 33

t-PA activates plasminogen better in the presence of _________.

Answer 33

fibrin

Question 34

PAI-1 is produced in the ______ and inhibits _________.

Answer 34

platelets (along with other cells); t-PA

Question 35

How does TAFI work?

Answer 35

Thrombin-activatable fibrinolysis inhibitor is attached to fibrin by XIIIa; once there, it cleaves off parts of fibrin where plasmin would normally bind

Question 36

PGI2 and NO both __________.

Answer 36

decrease platelet adhesion

Question 37

Where is vWF released from?

Answer 37

Damaged endothelial cells

Question 38

Undamaged endothelium acts to prevent clots by ____________.

Answer 38

constitutively expressing TFPI, t-PA, u-PA, thrombomodulin, PGI2, and NO; endothelium also metabolizes ADP (a platelet stimulator) to AMP and Pi

Question 39

Bind to extravascular proteins (like collagen and fibronectin) causes platelets to ________.

Answer 39

express phosphatidylserine as a substrate for coagulation

Question 40

Activated platelets express ______ that binds fibrinogen.

Answer 40

GPIIb/IIIa