Coagulation Flashcards

1
Q

Where are coagulation factors produced?

A

Liver, factor 8 also can be made in endothelial cells

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2
Q

Zymogens coagulation factors (5)

A

2, 7, 9, 10, 11

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3
Q

Vitamin K dependent

A

2, 7, 9, 10

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4
Q

Procofactors (3)

A

TF, 5, 8

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5
Q

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

A

Tissue factor (TF)

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6
Q

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

A

7a

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7
Q

TF-7a complex cleaves these two factors

A

9a, 10a

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8
Q

What cleaves prothrombin to thrombin

A

10a

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9
Q

F2a

A

thrombin

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10
Q

What cleaves fibrinogen to fibrin?

A

Thrombin

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11
Q

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

A

Thrombin

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12
Q

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

A

8a

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13
Q

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

A

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

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14
Q

What factor is critical for crosslinking? What activates it?

A

13a, thrombin

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15
Q

List the 3 main functions of thrombin

A
  1. cleaves 5, 8, 11, 13
  2. Cleaves fibrinogen to fibrin
  3. Restructures platelet phospholipid membrane
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16
Q

Which two complexes bind to platelet?

A

5-10, 8-9

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17
Q

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

A

Gla residues (gamma-carboxyglutamate)

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18
Q

What is the role of the vitamin K dependent carboxylase?

A

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

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19
Q

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

A

PS (phosphotidylserine)

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20
Q

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

A

Reduced to Oxidized

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21
Q

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

A

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

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22
Q

Prothombin time evaluates which pathway?

A

Extrinsic pathway

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23
Q

What is the only factor involved in the extrinsic pathway?

A

TF

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24
Q

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

A

citrate (can bind to calcium)

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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 is the common mutation in hemophilia A?
inversion of intron 22
68
In terms of laboratory test limitations, what does a D-dimer require?
A highly sensitive assay
68
Explain "all D-dimer assays are not created equal"
different methods, machines, antibodies and FDA approval
68
What factor has a major role in PTT?
F8