Clotting Cascade + DSA

Question 1

What is coagulation?

Answer 1

form fibrin clots at the site of BV injury to prevent blood loss

Question 2

How do we only cause the formation of fibrin strands at the site of injury?

Answer 2

Fibrinogen,

the inactive form, circulates in our blood; not fibrin.

Question 3

How does our body know to convert fibrinogen?

Answer 3

Thrombin stimulates the conversion

Question 4

Are we still able to form clots If we are deficient in factor 12?

Answer 4

Yes.

Our extrinsic pathway will make cleave factor 10–> factor 10a

Question 5

Draw out the coagulation cascade

Answer 5

Question 6

What is tissue factor?

Answer 6

Tissue factor (factor 3) is released when endothelial cells are damaged at the site of injury. This activates the intrinsic pathway

Question 7

_____, from the extrinsic pathway will trigger the common pathway via factor 10

Answer 7

Factor 7a

Question 8

What is the extrinsic pathway

Answer 8

The spark that activates 10 and 2, which wil lthen activate the intrinsic pathway.

Question 9

How does thrombin help to activate the intrinsic pathway?

Answer 9

it upregulates factors

5, 7, 8, 11 and 13

(all odd multiples except 8)

Question 10

Hemophilia A–> Factor ___ deficiency

Hemophilia B–>Factor __ deficiency

Hemophilia C–> Factor ___ deficiency

Answer 10

Hemophilia A–> Factor 8 deficiency

Hemophilia B–> Factor 9 deficiency

Hemophilia C–> Factor 11 deficiency

Question 11

3 building blocks for a clot

Answer 11

endothelium,

platelet,

coagulation (fibrin formation)

Question 12

What is primary hemostasis?

Answer 12

Formation of a platelet plug at the site of injury. The activated platelets undergo a conformational change and expose their phospholipid membrane, becomning sticky.

-Vasoconstriction occurs to reduce blood flow.

Question 13

Secondary hemostasis

Answer 13

Adding fibrin to the platelet plug via coagulation, making it stronger and forming a clot

Question 14

Antithrombin

Answer 14

released by thrombin to inhibit coagulation once an effective clot is form.

Question 15

Fibrinolysis

Answer 15

breakdown and remove the clot to restore flow

Question 16

Vitamin K-dependent factors

Answer 16

factor 2, 7, 9 and 10

Question 17

What are Vit K dependent factors important?

Answer 17

Vitamin K dependent factors require the binding of Ca2+ for them to function.

Vitamin K will introduce these binding sites via y-carboxylation of glutaminc acid residues.

Question 18

Vitamin K deficiency would cause what?

Answer 18

Impaired coagulation d/t decreased fx of these factors.

Thus, they would be bleeding a lot

Question 19

Vitamin K deficiienceies are due to what?

Answer 19

liver dz,

malabsorption,

antibiotic,

breast-fed newbrowns,

infants whose moms are on anticonvulsant therapy during pregnancy.

Question 20

Roles of thrombin (3 broad roles)

Answer 20

1. Converts itself from prothrombin to thrombin, forming more (+ feedback)
2. Activates factors 5 and 8.
3. Converts fibrinogen–> fibrin
4. Activates factor 13, forming fibrin polymers
5. Activates platelets
6. Exhibits paracrine activity which influences hemostasis- causes endothelial cells to release NO, prostacylcins, and tissue plasminogen activator, which are anticoagulants as well as ADP and vWF (von williebrand factors)

Question 21

Intrinsic and extrinsic pathways occur at the same time or different times?.

Answer 21

simultaneously

Question 22

Two basic tests to monitor coagulation

Answer 22

prothrombin time (PT)

activated partial thromboplastin time (aPTT).

Question 23

Prothrombin time tests what?

Answer 23

• tests the extrinsic pathway by measuring the clotting time from 7a–> fibrin clot and measures the procoagulant factors
  *

Question 24

PT average time

Answer 24

12-13 seconds

Question 25

What does coumadin (warfarin) do and what test can we run to check coagulation factors?

Answer 25

Coumadin (warfarin) inhibits vitamin K dependent epoxide reductase= inhibit synthesis of **vitamin K dependent coagulation factors (2, 7, 9 and 10, Protein S and C).** The will bleed excessively because they are not forming these clot factors. **Check using the PT test (prothrombin test)**

Question 26

What do you do to people who OD on coumadin?

Answer 26

**Give Vitamin K**

Question 27

Person with vit K deficiency will have deficiencies in what factors?

Answer 27

**2, 7, 9 and 10, Protein S and C**

Question 28

aPTT

Answer 28

**tests the intrinsic pathway: Clotting time from factor 12--\> fibrin clot**

Question 29

What is the average time for 30-50 seconds?

Answer 29

**aPTT.**

Question 30

What can **aPTT** detect?

Answer 30

1. **Hemophilia** (8, 9 and 10) 2. **Heperin therapy**--\> heparin is an anticugulant that inhibits factors **9 and 10a, and thus 2a.**

Question 31

What does warfarin do?

Answer 31

Decreases the amount of **vitamin K-dependent expoxide reductase**, which reduces vitamin K after it has been oxidized. Thus, it decreases the amount of usable vitamin K

Question 32

Which factors have the shortest and longest half-lives?

Answer 32

**Shortest- factor 7** ## Footnote **Longest- Factor 2 and 10**

Question 33

What activates the extrinsic pathway?

Answer 33

External trauma, causing blood to escape the vascular system quickly

Question 34

What activates the intrinisic pathway?

Answer 34

Trauma *inside* the **vascular system**, **platelets**, **exposed endothelium**, **chemicals** or **collagen**. Thus, it is slower than extrinsic

Question 35

What is the key difference between primary and secondary hemostasis?

Answer 35

Primary makes a weak platelet plug and secondary makes it stronger by adding fibrin mesh onto it.

Question 36

Warfarin is a racemic mixture. Which is more active?

Answer 36

**S warfarin**

Question 37

\_\_\_\_\_\_\_ is a medication used to prevent harmful blot clots.

Answer 37

Warfarin (coumadin)

Question 38

What do **Protein C and S** do?

Answer 38

They are anti-coagulants, inactivating factor **5a and 8a**

Question 39

**Protein C/S defiency** will cause

Answer 39

**Increased risk of venous thrombosis.**

Question 40

What are thrombolytics?

Answer 40

Thrombolytics convert plasminogen--\> plasmin, which cleaves thrombin and fibrin clots. It can be used to treat strokes

Question 41

What is heparin?

Answer 41

Anticoagulant, which prevents the formation of blood clots, but does not actively lyse them.

Question 42

What does aspirin do?

Answer 42

Irreversibly inhibits cyclooxygenase, which prevents platets aggregation and prevents formation of clots.

Question 43

Is heparin a thrombolytic?

Answer 43

No. Thrombolytics will convert plasminogen--\> plasmin, which cleaves thrombin and fibrin clots. Heparin does not actively lyse clots; it prevents their formation by inactivating 2a and 7a.