Clotting Flashcards
(65 cards)
1
Q
Hemostasis is:
A
- the arrest of bleeding from an injured blood vessel
2
Q
Steps of Hemostasis:
A
- Arteriolar vasoconstriction
- Primary hemostasis
- Secondary hemostasis
- Regulation of thrombus formation
- Antithrombotic actvity
3
Q
Arteriolar (local) vasoconstriction is due to:
A
- release of endothelin from endothelium cells lining blood vessels
4
Q
Primary hemostasis is:
A
- formation of the platelet plug
5
Q
Normal platelet count:
A
150K - 350K
6
Q
Thrombocytopenia:
A
too few platelets
7
Q
Thrombocytosis:
A
too many platelets
8
Q
Does platelet size matter?
A
- Yes
- larger platelets are more prothrombotic (likely to stick)
9
Q
The normal endothelial monolayer is anti-thrombogenic.
What happens when the endothelial monolayer is injured?
A
- Platelets in the bloodstream recognize collagen and von Willebrand factor (vWF) in the basement membrane and adhere to it.
10
Q
Steps in formation of the platelet plug (primary hemostasis):
A
- adherence
- activation
- granule release
- shape change
- aggregation
11
Q
von Willebrand factor is:
A
- a large circulating protein (multimer) that plays an important role in both primary and secondary hemostasis.
12
Q
von Willebrand factor is produced by:
A
endothelial cells and megakaryocytes
13
Q
Role of von Willebrand factor at a site of blood vessel injury (2):
A
- adheres to exposed collagen
- facilitates platelet tethering to sub-endothelial basement membrane
14
Q
Steps in how von Willebrand factor (vWF) functions:
A
- vWF circulates in the blood in a closed conformation.
- At the site of injury, vWF binds to exposed collagen.
- vWF elongates into an open conformation revealing platelet binding sites.
- Platelets bind to vWF, become active, and aggregate onto elongated vWF.
15
Q
What happens to platelets when they bind to elongated vWF and become activated?
A
- they release granules containing:
- adhesive proteins
- prothrombotic factors
- cytokines
- growth factors
- platelet agonists
16
Q
The five components contained in platelet granules and that are released upon platelet activation:
A
- adhesive proteins
- prothrombotic factors
- cytokines
- growth factors
- platelet agonists
17
Q
Low platelet counts result in:
A
- petechiae
- reddish purple discolorations on the skin that do not blanche on applying pressure.
18
Q
Petechiae are:
A
- reddish purple discolorations on the skin that do not blanche on applying pressure.
- 1-3mm in size.
- result from low platelet counts.
19
Q
Secondary hemostasis is:
A
- the process by which cross-linked fibrin is formed.
20
Q
Why is secondary hemostasis necessary?
A
- initial platelet plug is not very strong and requires a “sealant”
- “sealant” = cross-linked fibrin
21
Q
Most coagulation factors are:
A
- serine proteases that circulate as zymogens in the blood stream plasma
22
Q
Nomenclature: what is the name of Factor 10 when in its active form?
A
- Factor 10a
- “a” is added to the end of active factors
23
Q
The three pathways of secondary hemostasis:
A
- extrinsic pathway
- intrinsic pathway
- common pathway
24
Q
What is Tissue Factor?
A
- a transmembrane protein synthesized and expressed by endothelial cells and monocytes.
- triggers first step in extrinsic pathway coagulation.
NOT NORMALLY EXPRESSED - ONLY IN INJURY
25
Tissue factor is synthesized and expressed by:
* endothelial cells and monocytes
* only exposed and unregulated in injured tissue
26
Factor 2 is:
* prothrombin
* when activated (Factor IIa), thrombin
27
Factor 2a (thrombin) role:
* cleaves fibrinogen into fibrin
28
Extrinsic pathway of secondary hemostasis includes:
* Factor 7
* Tissue factor
29
Steps in Extrinsic Pathway from injury to fibrin formation in secondary hemostasis:
**TF - 7 - 9 - 10 - 2 - F**
1. Vessel wall injury exposes Tissue Factor.
2. Endothelial cells increase Tissue Factor expression.
3. Circulating Factor 7 binds exposed tissue factor and becomes activated.
4. Factor 9 recruited and binds to TF/Factor 7.
5. Factor 10 recruited and activated.
6. Common Pathway: Factor 10 activates Factor 2 (prothrombin).
7. Common Pathway: Factor 2a (thrombin) cleaves fibrinogen to form fibrin.
30
Common Pathway of secondary hemostasis:
**10 - 2 - F**
1. Factor 10 activated.
2. Factor 10 activates Factor 2 (prothrombin).
3. Factor 2a (thrombin) cleaves fibrinogen to form fibrin.
31
What is Factor 8?
* anti-hemophilic factor
* circulates in the plasma with vWF
* soluble co-factor
* accelerant/catalyst for factor IXa
32
What is Factor 5 and its role in secondary hemostasis?
* soluble co-factor
* no enzymatic activity
* accelerant/catalyst for Factor 10a
33
Factor 8 and Factor 5 are both activated by:
Thrombin
34
What does vWF do to factor 8?
* binds to and stabilizes factor 8
* extends half-life of Factor 8 from 8 minutes to 8 hours.
35
What is the role of Factor 8a in secondary hemostasis?
* no enzymatic activity
* soluble co-factor that functions as an accelerant/catalyst for Factor 9a
36
What are the two amplification steps in secondary hemostasis?
1. Factors 8/9 accelerate Factor 10 activation and production.
2. Factors 5/10 accelerates conversion of prothrombin to thrombin.
## Footnote
**Factor X cleaves fibrinogen into fibrin.**
37
Hemophilia A is due to deficiency in:
Factor 8
38
Hemophilia B is due to deficiency in:
Factor 9
39
What are the Vitamin-K dependent coagulation factors?
2, 7, 9, 10
40
What does vitamin K do?
* Converts glutamates on the N-terminus of Factors 2, 7, 9, and 10 to γ-carboxyglutamate (GLA).
* Carboxylation.
* Adds negative charge.
* Allows factors to bind to Ca2+ on platelets.
41
Factors 2, 7, 9, or 10 + Oxidized Vitamin K =
N-terminus Glutamate → γ-carboxyglutamate (GLA)
42
How do Factors 2, 7, 9, and 10 bind to platelets?
* Active platelets have negative charge.
* Ca2+ binds to active platelets.
* Carboxylated Factors 2, 7, 9, and 10 bind to Ca2+.
* **VITAMIN K DEPENDENT**
43
Function of Warfarin:
* Blocks Vitamin K epoxide reductase (VKOR), which prevents regeneration of reduced Vitamin K for the clotting process.
* Clotting blocked.
44
Extrinsic pathway diagram:
45
Intrinsic pathway diagram:
46
Is the intrinsic pathway activated by Tissue Factor?
* No. It is Tissue Factor independent.
* Activated by negative charge.
47
What is the only factor in the intrinsic pathway associated with a bleeding phenotype?
Factor 11
48
Steps in intrinsic pathway of secondary hemostasis:
**12 - HMKG - 11 - 9 - 10 - 2 - Fibrin**
1. Factor 12 in bloodstream activated by negative charge.
2. Factor 12 recruits and binds HMKG, which releases its bound PKK.
3. Factor 11 binds to HMKG.
4. Factor 9 binds to Factor 11.
5. Common pathway (10-2-fibrin).
49
Hemophilia C is due to deficiency in:
Factor 11
50
Role of Factor 11 in intrinsic clotting pathway:
* functions in propagation of clotting with Factor 9a
51
What two clotting factors are not enzymes?
* **Factor 5**.
* co-factor to Factor 10a.
* **Factor 8.**
* ****co-factor to Factor 9a.
52
Thrombin activates what clotting factors further?
**13, 5, 8-11**
Factors 5, 8, 9, 10, 11, and 13
53
Steps in thrombin cleavage of fibrinogen to fibrin fibril formation:
1. Thrombin cleaves fibrinopeptide A from fibrinogen to form fibrin I.
2. Fibrin I cross-links to form protofibrils.
3. Thrombin cleaves fibrinopeptide B from fibrinogen to form fibrin II.
4. Fibrin II causes lateral aggregation of protofibrils.
54
Role of Factor 13 in the clotting process:
* Forms extensive covalent bonds (cross-linking) between the fibrin chains.
* Activated by thrombin.
55
Thrombomodulin is:
* an anti-coagulant
* a receptor with high affinity for Factor 2 (thrombin)
56
Thrombomodulin is a co-factor for:
* thrombin-dependent activation of protein C
57
Protein C and Protein S are:
1. anticoagulants
2. vitamin K-dependent inhibitors of Factor 5a and 8a
58
Protein C and S are activated by:
the thrombin-thrombomodulin interaction
59
Function of Activated Protein C (APC):
* Cleaves Factor 5a and 8a
* turns off clot formation.
60
What is the phenotype of Factor 5 Leiden Mutation?
* Arginine - Glutamine substitution in Factor 5 makes it resistant to cleavage by APC.
* Excessive clotting and DVT.
61
What is the single amino acid substitution in Factor 5 Leiden Mutation?
Arginine - Glutamine
62
Fibrinolysis is:
* the process that prevents blood clots from growing and becoming problematic.
* Breakdown of clots.
63
What is the primary protein involved in fibrinolysis?
plasminogen (active form = plasmin)
64
Plasminogen is:
* a circulating blood protein incorporated into clots that is activated into plasmin.
* Plasmin degrades fibrin.
65
Plasminogen is activated by:
* Tissue plasminogen activator (tPA)
* Thrombin
