Clotting Cascade

Question 1

Thrombin function

Answer 1

Recruit even more platelets and cause fibrins to form a mesh work over the platelet aggregation

Question 2

CASE 1 68yo male on warfarin therapy for 5 mos for many past strokes, he has fallen and fractured his hip. Warfarin is discontinued 48hrs before surgery for what reason

Answer 2

48hrs is the time required for full expression of the Factor 2,7,9,10 genes

Question 3

Reason warfarin should be discontinued 48hrs prior to surgery

Answer 3

Warfarin DECREASES VIT K

VIT K is needed for gamma-glutamylcarboxylase since it inhibits epoxied hydrolase

Question 4

What does Gamma-glutamylacarboxylase do

Answer 4

Catalysts many Ca bonding proteins (FACTORS 2, 7, 9, 10 + PROTEIN C and PROTEIN S) = coagulation
(Synthesis of these take 48hrs, and breakdown of them also takes 48hrs by warfarin)

Question 5

Factor 2 half-life

Answer 5

60hrs

Question 6

Factor 9 half-life

Answer 6

24hrs

Question 7

Factor 10 half-life

Answer 7

40-60hrs

Question 8

What activated the extrinsic pathway

+ which important factor

Answer 8

External Trauma when blood escapes the vascular system
FASTER
*FACTOR 7

Question 9

What activates the intrinsic pathway + which important factor

Answer 9

Trauma inside vascular system
(Platelets, exposed endothelium, chemicals, collagen —> activate)
SLOWER
*Factor 8, 9, 11, 12

Question 10

INTRINSIC PATHWAY STEPS

Answer 10

1. Kallikrein activates F12 (hageman factor)
2. F12a activates F11
3. F11a activates F9*
4. Thrombin activates F8*
5. F10 is added *
   =TENASE COMPLEX

Question 11

Thrombin is what factor

Answer 11

Factor 2

Question 12

Intrinsic TENASE complex includes

Answer 12

F8a
F9a
F10

Question 13

EXTRINSIC PATHWAY steps

Answer 13

1. Tissue injury activates Thromboplastin
2. Thromboplastin activates F7*
3. Tissue Factor is added
4. F10 is added
   = TENASE COMPLEX

Question 14

Extrinsic TENEASE complex

Answer 14

F7a
F10
Tissue Factor

Question 15

COMMON PATHWAY steps

Answer 15

1. Factor 10 on TENASE complex is activated by CA+2
2. F10a uses Ca+2 + F5a to activate Prothrombin (F2) to Thrombin (F2a)
3. F2a activates F5
4. F2a uses Ca+2 to activate F8 + make FIBRIN *

Question 16

Primary Hemostasis

Answer 16

Platelets aggregate to form platelet plug (block hole)
WEAK
-vascular contraction 
-glycoproteins R on platelets
- collagen +fibrinogen

Question 17

Secondary Hemostasis

Answer 17

Fibrin Mesh forms of the platelet plug by coagulation cascade

• STRONG
• fibrin
• subendothelial collagen
• Thromboplastin
• coagulation factors
• fibrinogen

Question 18

MAJOR ROLE OF THROMBIN *

Answer 18

1. Fibrinogen to Fibrin

2. F13 to F13a

Question 19

How is the Fibrin cross linked

Answer 19

F13a and Ca+2 cause the fibrin to cross link

Question 20

3 other roles of thrombin

Answer 20

1. F5a
2. F8a
3. Activation of platelets

Question 21

2 anticoagulants and what there major effect is

Answer 21

1. Hydroxycoumarins
2. Indanediones
   * INHIBIT VIT K

Question 22

Hydroxycoumarins example

Answer 22

Warfarin

Question 23

Activation of VIT K steps (2 steps)

Answer 23

1. 2,3-epoxied reductase + NADH : 2,3-epoxide—> QUINONE
2. Quinone reductase : quinone —> QUINOL * in liver
   * LIVER : quinone —> quinol (active)

Question 24

What does the VIT K (QUINOL) do

Answer 24

Uses gamma-glutamyl carboxylase* to ACTIVATE Factors 2, 7, 9, 10, Protein C and Protein S

Question 25

How does Warfarin inhibit coagulation

Answer 25

It INHIBITS the 2,3-Epoxide Reductase which blocks the conversion of VIT K cycle to convert GLUTAMATAE RESIDUES ——> gamma-carboxyglutamate residues (Factors 2,7,9,10, proteins C +S)* + PROTHROMBIN*

Question 26

For patient with elevated PT or mucosal bleeding what shouldI give them

Answer 26

400mg VIT K or daily 50mg-100mg

Question 27

Peak plasma warfarin happens when

Answer 27

3hrs after Ingested

Question 28

S-Warfarin

Answer 28

Binds to albumin tighter | *5x more potent

Question 29

R-warfarin

Answer 29

Highly binds to proteins | Not as potent

Question 30

Which types of drugs will inhibit or increase the ability of warfarin to work

Answer 30

Drugs that compete to bind to albumin or drugs that inhibit warfarin metabolism

Question 31

Protein C and Protein S function

Answer 31

ANTICOAGULATION ——I F5a + F8a = LOWER THROMBIN FORMATION*

Question 32

Low Protein C cases

Answer 32

Significant risk for venous thrombosis

Question 33

With Patient taking Warfarin what should you look our for

Answer 33

Any bleeding Diet should have VIT K (green leafy veggies) Carry ID card

Question 34

Hemophilia A

Answer 34

X F8 most severe + more common | * cant form Fibrin clot (Hemostasis) + no TENASE COMPLEX

Question 35

Hemophilia B

Answer 35

X F9 | Also called Christmas Disease