24. Clotting Cascade

Question 1

In the extrinsic pathway- Tissue factor, which is released by endothelium after tissue damage, interacts with what which triggers the clotting/coagulation cascade?

Answer 1

Interacts with factor VII (7) allowing it to come in contact with factor III to produce VIIa

Question 2

Factor III, VIIa, and Ca2+ bind to factor X, activating factor X to Xa which will?

Answer 2

feed the common pathway which is Xa with Va and Ca2+ avticates II (prothrombin) to become IIa(thrombin). IIa, I (fibrinogen) and Ca, activate Ia (fibrin) which with activated XIIIa (13a) crosslinks fibrin

Question 3

In the intrinsic pathway, factor XII is activated by negative platelet and HMWK to form XIIa. This activates XIa which activates IXa. IXa then does what?

Answer 3

Factor VIII to VIIIa activated via IIa (thrombin), which with IXa and Ca form the tenase complex. Tenase converts factor X to Xa, which goes to common pathway

Question 4

PPT or partial prothrombin time is the time is takes from?

Answer 4

(intrinsic pathway) XII to fibrin clot usually 20-35 seconds

Question 5

PT or prothrombin time is the time is takes for?

Answer 5

extrinsic pathway to make fibrin clot usually 10-13 seconds

Question 6

Warfarin decreases vitamin K which is needed to activate Factor II, VII, IX, and X. What changes when someone is on warfarin and is taken off 48 hours before- establishing a normal PT?

Answer 6

The time required for full expression of Factor II, VII, IX, and X along with Protein C and S

Question 7

What are the shortest half life and longest halflifes of vitamin K dependent factors?

Answer 7

Factor VII : 4-6 hours shortest
Protein C: 7 hours- shorter
Factor II: 60 h LONGEST
Factor X: 40-60h

Question 8

The extrinsic pathway is quicker than intrinsic, activated by external traumaand involves factor VII, while the intrinsic pathway? (3)

Answer 8

Is slower than extrinsic
activated by trauma inside and platelets
involves factors XII, XI, IX, VIII

Question 9

What does the common pathway share?

Answer 9

Factors I, II, V, and X

Question 10

The key difference between primary and secondary hemostasis is that primary hemostasis makes a weak platelet plug at the injury site, while secondary hemostasis?

Answer 10

makes is strong by generating a fibrin mesh on it

Question 11

Thrombin activates XIII to XIIIa and fibrinogen to fibrin + Ca allows fibrin crosslinkning. What are the 3 other important roles of thrombin?

Answer 11

Activates itself from prothrombin to thrombin
Activates platelets
Activates Factors V and VIII to Va and VIIIa

Question 12

Vitamin K is needed for long term control over INR. To activate Vit K, the first step uses 2,3 epoxide reductase to convert vitamin K to its quinone form. What is the second step?

Answer 12

Quinone reductase reduces the quinone form of Vit K to active form Vitamin K quinol form

BOTH of these steps (MAINLY epoxide reductase) can be blocked by Warfarin

Question 13

Warfarin works by decreasing the activity of Vit K dependent epoxide reductase, lengthening the time to form a clot. Vitamin K is a cofactor in synthesizing what factors?

Answer 13

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

Question 14

Once VitK is in the active quinol form, it reacts with 10+ glutamyl carboxyglutamate, to activate the factors. What is the main used of vitamin K?

Answer 14

to help patients with over coagulation

Question 15

Warfarin has both S/R diastereomers. What is most effective and by how much, what does it activate?

Answer 15

S warfarin is more activate than R warfarin, 2-5 times more active, activating cytochrome P2C9 (CYP2C9)

Question 16

Orally ingested warfarin is completely absorbed and has peak plasma concentrations at 3 hours. What is important to remember about interactions with warfarin?

Answer 16

There are many drug, food, and environmental, herbal interactions associated with warfarin

Question 17

Protein C and S inactivate Factor Va and VIIIa to limit thrombin. A genetic deficiency in protein C causes?

Answer 17

a significantly increased risk of venous thrombosis d/t increased coagulation

Question 18

Hemophilia A also called factor VIII deficiency is a genetic disorder caused by missing or defective factor VIII (8). This is usually passed down from parents to children, with 1/3 being from a spontaneous mutation. What happens when there is no factor VIII?

Answer 18

No factor 8 will lead to no intrinsic activation of factor X, with little to none X, there will be no clotting cascade- BLEED FOREVER

Question 19

PT measures extrinsic pathway with a normal time of 12-13 seconds. What factors are associated with extrinsic?

Answer 19

VII 7

Question 20

PTT measures intrinsic pathway with a normal time of 30-50 seconds. What factors are associated with intrinsic?

Answer 20

XII, XI, IX, VIII (12,11,9,8)

Question 21

What is the INR? (internation reference tissue factor)

Answer 21

Ratio of patient’s prothrombin time to a normal sample, raised to the power of ISI value (internation sensistivity index) for the analytical system being used

Question 22

By looking at PT and PTT, a practitioner can gain clues as to what bleeding disorder may be present. If PT is prolonged and PTT is normal. What could this clue to?

Answer 22

Liver disease, decreased VitK, decreased factor VII

Question 23

If a patient has recurrent DVT but PTT, PT and thrombin times are normal, what can be the cause?

Answer 23

Deficiency of Protein S (Protein C) becuase they cause anticoagulation