Blood Coagulation Cascade and Reg Factors

Question 1

Define hemostasis

Answer 1

Prevent blood loss

• Damage? Stop bleeding
• Normal conditions? Maintain fluidity

Question 2

Define thrombosis

Answer 2

Form a clot or thrombus inside an intact blood vessel

Question 3

Hemostasis and thrombosis involved what components?

Answer 3

Vascular endothelium
Platelets
Coag system
Fibrinolytic system

Question 4

Coagulation cascade has what pathways involved?

Answer 4

Extrinsic
Intrinsic
Common

Question 5

Vitamin K depedent factors are?

Answer 5

2, 7, 9 and 10

Question 6

Contact activated factors are?

Answer 6

12, prekallikrien, high molecular weight kininogen

Question 7

Thrombin sensitive factor

Answer 7

1, 5, 8, 11, 13

Question 8

Hematostasis events

Answer 8

Localized vascular spasms
Primary hemostasis (loose plug)
Secondary hemostasis
Clot dissolution

Question 9

Localized Vasoconstriction

Answer 9

Mediated by reflex neurogenic mechanisms –> increase Ca within SMC

Question 10

Primary Hemostasis

Answer 10

Platelet adhesion
Platelet activation
Platelet aggregation
Form primary platelet plug

Question 11

Platelet Adhesion

Answer 11

via von Willebrand Factor binds to GPIb (bridge between platelet and collagen)

Question 12

Platelet Activation

Answer 12

release TxA2 which leads to platelet aggregation and activating vasoconstrictors

Question 13

Platelet Aggregation

Answer 13

TxA2, PAF, ADP call other platelets to aggregate via fibrinogen

Question 14

Secondary Hemostasis

Answer 14

Extrinsic Pathway (rapid response via initial coag)
Inhibited by TFPI but the thrombin activates the intrinsic pathway

Question 15

Intrinsic pathway does what?

Answer 15

Activates Thrombin-sensitive factors 5, 8 and 11 which boost thrombin production

• Promotes platelet activation
• Converts fibrinogen into fibrin
• Activated Factor 8

Question 16

What does Thrombin do?

Answer 16

Promotes platelet activation and aggregation via proteases activated receptors
Catalyze fibrinogen to fibrin
Activates factor 8 which stabilizes platelet aggregation

Question 17

OVERALL Secondary hemostatis is to do what?

Answer 17

Stabilize the initial soft clot

Takes longer than primary

Question 18

Platelet Function

Answer 18

CONTAIN ONLY COX1
Bind exposed collagen
Increased Ca and PKC activation = more platelets
TxA2 stimulates new platelets and more aggregation

Question 19

Dense granules are?

Answer 19

ADP and ATP, ionized calcium

Released first

Question 20

Alpha granules are?

Answer 20

von Willebrand factor
Fibrinogen
Factor V and VIII

Question 21

ADP does what?

Answer 21

Activates P2Y1 which activate phospholipase C –> increase Ca
P2Y12 inhibits adenylyl cyclase –> bind fibrogen

Question 22

Pro-coagulant Properties

Answer 22

Promote adhension (VWF)
Anti-fibronlytic
Release of tissue factors (trigger entrinsic)

Question 23

Anticoagulant properties are?

Answer 23

Inhibit activation and aggregation (ADP, NO)
Release anticoagulants (TFPI)
Fibrinolytic properties

Question 24

Extrinsic Pathway MOA?

Answer 24

TF forms complex with VII which activates X which creates thrombin

Question 25

Intrinsic Pathway MOA?

Answer 25

Form HMWK, PK and Factor XII | XII --> XI --> IX + VIII (tenase) + Ca --> X

Question 26

Common Pathway

Answer 26

X + V = prothrombinase complex --> prothrombin --> thrombin | Thrombin: fibrinogen --> fibrin & Factor XIII --> crosslinking

Question 27

PAR1 and PAR4 activation leads to

Answer 27

platelet activation

Question 28

Pro-Thrombin effects are?

Answer 28

``` Activated PAR 1 and PAR4 Factor V, VIII, XI Fibrinogen to fibrin Factor XIII Activation of TAFI ```

Question 29

Anti-Thrombin effects are?

Answer 29

Activated Protein C | APC degrades factor Va/Viii

Question 30

Mutation in Factor V does what?

Answer 30

Prevents breakdown via APC --> thrombophilia

Question 31

Antithrombin

Answer 31

Targets intrinsic pathway factors (X and II) | Heparin increases catalytic activity

Question 32

TFPI

Answer 32

Inhibits Factor X which inhibits vWF --> No more X

Question 33

Tissue Plasminogen Activator

Answer 33

Cleaves fibrin from plasmin and degrades fibrin

Question 34

Vitamin K

Answer 34

Required to activate Factors II, VII, IX, X + protein S/C

Question 35

Calcium and phospholipids required for

Answer 35

Tenase (VIII + IX) and prothrombinase complexes | aka clotting

Question 36

Blood test for extrinsic pathway?

Answer 36

Prothrombin time

Question 37

Blood test for intrinsic pathway?

Answer 37

Activated partial Thromboplastin Time

Question 38

Prothrombin Time Test

Answer 38

Blood sample + calcium chelator TF + phospholipids are added Finally calcium to initiate the test Range is 12-14 seconds (>20 = deficiency)

Question 39

Activated Partial Thromboplastin TIme

Answer 39

Negative phospholipids + particulate is added to citrated plasma Add Ca and test is initiated Clot formation time is measured Range is 26-33 sec

Question 40

If you have prolonged aPTT and PT you have a defect in?

Answer 40

Common coagulation pathway

Question 41

Hemophilia A

Answer 41

Fact VIII deficent

Question 42

Hemophilia B

Answer 42

Fact IX

Question 43

Hemophilia C

Answer 43

Fact XI