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Flashcards in Coagulation Deck (71):
1

Where are coagulation factors produced?

Liver, factor 8 also can be made in endothelial cells

2

Zymogens coagulation factors (5)

2, 7, 9, 10, 11

3

Vitamin K dependent

2, 7, 9, 10

4

Procofactors (3)

TF, 5, 8

5

When you have an injury to endothelial cells, you activate primary hemostasis and expose

Tissue factor (TF)

6

You have a very small amount of this factor in its activated cleaved form that binds to TF to form a complex with calcium

7a

7

TF-7a complex cleaves these two factors

9a, 10a

8

What cleaves prothrombin to thrombin

10a

9

F2a

thrombin

10

What cleaves fibrinogen to fibrin?

Thrombin

11

What restructures the platelet's phospholipid membrane so that factors can bind and interact?

Thrombin

12

In the presence of calcium, 9a forms a complex with this factor

8a

13

9a-8a complex actives more of this factor, which subsequently forms a complex with what factor? (in presence of calcium)

10a, forms a complex with 5a. Cleaves prothrombin to thrombin much more aggressively

14

What factor is critical for crosslinking? What activates it?

13a, thrombin

15

List the 3 main functions of thrombin

1. cleaves 5, 8, 11, 13
2. Cleaves fibrinogen to fibrin
3. Restructures platelet phospholipid membrane

16

Which two complexes bind to platelet?

5-10, 8-9

17

These residues are responsible for the high-affinity binding of calcium ions and interaction with platelet membrane

Gla residues (gamma-carboxyglutamate)

18

What is the role of the vitamin K dependent carboxylase?

carboxylates glutamic acid resides to gamma carboxy glutamic acid (gla)

19

Thrombin restructures platelet membrane to expose the net negative charge of this component

PS (phosphotidylserine)

20

In forming a carboxylated prozmogen, Vitamin K converts from what state?

Reduced to Oxidized

21

Epoxide reductase converts oxidized vitamin K to its reduced form. What are two blockers of this step? What are the consequences of this blockage

Coumadin and warfarin. If cant bring Vitamin K back to reduced form, it cant carboxylate and can't function/clot as well. Have thinner blood

22

Prothombin time evaluates which pathway?

Extrinsic pathway

23

What is the only factor involved in the extrinsic pathway?

TF

24

In prothrombin time, the specimen is collected in this to remove calcium

citrate (can bind to calcium)

25

This was created to standardize the PT results across labs, since TF reagants are variably thrombogenic

International Normalized Ratio (INR)

26

What's a normal INR? What's a typical therapeutic INR?

normal=1, therapeutic=2-3

27

Partial thromboplastin time evaluates which pathway? What does it not include?

Intrinsic, no TF

28

PTT is used for monitoring

unfractured heparin

29

phospholipids - TF = ?

partial thromboplastin (PTT)

30

What gets added first in PTT?

Silica

31

What does silica activate

F12

32

Not a big deal if deficient in these factors

12, 11

33

Which two anticoagulants are Vitamin K dependent?

Protein C and S

34

Serpin

serine protease inhibitor = antithrombin

35

inactivates all serine protease coagulation factors by irreversible binding

antithrombin

36

AT acts on all coagulation factors with the exception of these two

profactors 5 and 8

37

antithrombin by itself is a very slow inhibitor. What does it need to work better?

Heparin

38

How much does heparin increase AT activity?

induces conformation change in AT resulting in a 10,000 fold increase in activity

39

What are heparin sulfate molecules and where are they found?

Branches that come off on thriving endothelial cells nearby. AT comes by and binds, building a wall upstream and downstream that prevents extension of clot

40

What is the key molecules that AT-heparin complex binds to?

Thrombin

41

What are the two main systems for anticoagulation?

Heparin-AT system, Protein C and Protein S system

42

What does activated Protein C cleave/deactivate?

F8 and F5 (note: it cleaves F8a to F8, thus deactivating it. just shorthanding the notes)

43

TF complex is located on

tissue bearing cell

44

F10-5 and F9-8 complex are located on

platelets

45

Protein C receptor

EPCR (endothelial protein C receptor)

46

EPCR is in close proximity to

Thrombomologin (TM)

47

In anticoagulation, thrombin interacts with _____ allowing it to cleave ________

Thrombin interacts with TM, bringing it close to EPCR, allowing it to cleave and activate Protein C
(TM and EPCR are close to one another)

48

Activated protein C interacts on membrane with this cofactor

Protein S

49

Protein C and S downregulate

F8 and F5.

50

What are you deficient in potentially if hypercoagulant?

Protein C and S.

51

1. Primary hemostasis (platelet plug)
2. Secondary hemostasis (fibrin clot)
3. natural anticoagulant system
4. ????

4. fibrinolytic system

52

when is the fibrinolytic system activated?

as soon as you activate primary hemostasis. as you start to form, you immediately start to break it down. not just cleaning up mess

53

in the fibrinolytic system, an increase pressure from endothelial cells causes a release in what?

tPA= tissue plasminogen activator

54

What does tPA do?

cleaves plasminogen to plasmin

55

what activates plasminogen?

tPA

56

What is function of plasmin?

Breaks up fibrin into fibrin degradation products

57

what does tPA interact with DIRECTLY ON THE CLOT?

Plasminogen IN the clot. We want clot localized

58

After plamin chews up fibrin, it releases fibrin degradation products and it will release itself. What binds to plasmin?

Alpha 2 antiplasms (a2

59

What are inhibitors of fibrinolysis called?

Plasminogen Activator Inhibitors (PAIs)

60

What activated PAIs?

Thrombin

61

What is a D-dimer

specific fragments of fibrinogen. Plasmin snips off pieces of fibrin

62

An increase in D-dimer indicates

clotting activity

63

A normal DD would rule out the presence of

significant clots i.e. pulmonary embolus or deep vein thrombosis (blood clot in vein)

64

In terms of laboratory test limitations, what does a D-dimer require?

A highly sensitive assay

65

Explain "all D-dimer assays are not created equal"

different methods, machines, antibodies and FDA approval

66

What factor has a major role in PTT?

F8

67

What is the common mutation in hemophilia A?

inversion of intron 22

68

What factor has a major role in PTT?

F8

69

Explain "all D-dimer assays are not created equal"

different methods, machines, antibodies and FDA approval

70

In terms of laboratory test limitations, what does a D-dimer require?

A highly sensitive assay

71

What is the common mutation in hemophilia A?

inversion of intron 22