Hemostasis and Coagulation cascade

Question 1

How to monitor warfarin?

Answer 1

PT/INR (International normalized ratio)

Question 2

Vit K antagonist?

Answer 2

Warfarin

Question 3

Most coagulation factors are serine proteases except?

Answer 3

Factors V and VIII which are glycoproteins

Question 4

What primarily inactivates factors Va and VIIIa

Answer 4

Activated protein C

Question 5

How is protein C activated and how does it work?

Answer 5

Protein C is activated by thrombomodulin found on endothelial cells.
It binds thrombin and the thrombomodulin:thrombin complex activates protein C. With protein S as co-factor, APC inactivates Va and VIIIa

Question 6

Nitric oxide and Prostacyclin?

Answer 6

Released by endothelial cells that make up the inner surface of blood vessels, in the absence of injury.
NO - dilate blood vessels
Prostacyclin- Bind to receptors located on platelets to ultimately prevent platelet activation and aggregation.
Action reversed when blood vessel is damaged.

Question 7

von wilderbrand factor?

Answer 7

When blood vessel is damaged, vwf helps platelets adhere to exposed collagen, causing the platelets to activate and change shape

Question 8

Initiation (Primary hemostasis)

Answer 8

endothelial injury results in transient vasoconstriction.
→ exposure of subendothelial collagen
→ vWF, which is stored in Weibel-Palade bodies of endothelial cells and α-granules of platelets, binds the exposed collagen

Question 9

Example of direct thrombin inhibitor

Answer 9

Dabigatran

Question 10

Direct factor Xa inhibitor examples

Answer 10

Rivaroxaban, Apixaban, Edoxaban

Question 11

Disadvantages of warfarin

Answer 11

Slow onset, Needs to be monitored, many drug and food interactions

Question 12

Activated partial thromboplastin time (aPTT)

Answer 12

measures the time it takes plasma to clot when exposed to substances that activate the contact factors, which assesses the intrinsic and common pathways of coagulation. Normal range is approximately 25 to 35 seconds.

Question 13

Contact factors?

Answer 13

Contact factors include prekallikrein and high molecular weight kininogen (HMWK)

Question 14

What does thrombin time assess?

Answer 14

The thrombin time (TT) assesses the final step in the common pathway (fibrinogen to fibrin), the conversion of fibrinogen to fibrin, following the addition of exogenous thrombin.

Question 15

Factor XIII?

Answer 15

Crosslinks fibrin. This function is not tested by the PT, aPTT, or TT.

Question 16

PT test?

Answer 16

The prothrombin time (PT) measures the time it takes plasma to clot when exposed to tissue factor, which assesses the extrinsic and common pathways of coagulation.

The PT test is performed by recalcifying citrated patient plasma in the presence of tissue factor and phospholipid and determining the time it takes to form a fibrin clot. The formation of a fibrin clot is detected by visual, optical, or electromechanical methods.

The result is measured in seconds and reported along with a control value and/or an INR. the normal range is approximately 11 to 13 seconds.

Question 17

Heparin typically prolongs PT. True/False

Answer 17

False.
Heparin typically prolongs the aPTT alone (because PT reagents contain heparin-binding agents (eg, heparinase, polybrene) that block heparin effect), but at high levels heparin can prolong both tests.

Heparins (unfractionated or low molecular weight) and fondaparinux should in theory prolong the PT because they inhibit thrombin and/or factor Xa.

Question 18

Warfarin typically prolongs the PT alone. True/False

Answer 18

True!

Warfarin typically prolongs the PT alone, but at high levels warfarin can prolong both tests.

Question 19

Causes of prolonged PT

Answer 19

Inherited:
Factor VII deficiency

Acquired: 
Mild vitamin K deficiency
Liver disease
Warfarin*
DIC

Question 20

Causes of prolonged aPTT

Answer 20

Inherited:
Deficiency of factor VIII, IX, or XI
Deficiency of factor XII, prekallikrein, or HMW kininogen (not associated with a bleeding diathesis)
von Willebrand disease (variable)

Acquired:
Heparin, dabigatran, argatroban, direct factor Xa inhibitors (variable)*
Acquired inhibitor of factor VIII, IX, XI, or XII
Acquired von Willebrand syndrome
Lupus anticoagulant (more likely to be associated with thrombosis than bleeding)

Question 21

Causes of prolonged PT and aPTT

Answer 21

Inherited:
Deficiency of prothrombin, fibrinogen, factor V, or factor X
Combined factor deficiencies

Acquired:
Liver disease
DIC
Severe vitamin K deficiency
Anticoagulants (supratherapeutic doses of many anticoagulants, combined heparin and warfarin, direct thrombin inhibitors, anticoagulant rodenticide poisoning)*
Acquired inhibitor of prothrombin, fibrinogen, factor V, or factor X
Amyloidosis-associated factor X deficiency

Question 22

Factor II?

Answer 22

Thrombin

Question 23

What initiates the extrinsic pathway? How?

Answer 23

clotting is initiated when blood is exposed to tissue factor (like when injury occurs)

Tissue Factor (thromboplastin) forms a complex with factor VIIa

Question 24

How is the intrinsic pathway activated?

Answer 24

by exposure of Factor XII (Hageman factor) to
1) subendothelial collagen or
2) HMWK (high molecular weight kininogen)
to produce Factor XIIa

Question 25

What does factor XIIa do?

Answer 25

1) activates factor XI –> XIa
2) activates plasminogen –> plasmin
3) activates kininogen system –> kallikrein and bradykinin

Question 26

What does factor IXa do?

Answer 26

forms a complex with Factor VIII, Tissue Factor (III), calcium to activate factor X –> Xa in the final common pathway

Question 27

So what two ways can factor X get activated?

Answer 27

via Tissue Factor:Factor VIIa and calcium in the extrinsic path
via IXa:Ca, VIIIa, and Tissue Factor in the intrinsic pathway

Question 28

What does Factor Xa do?

Answer 28

with the help of Factor Va and Ca, coverts prothrombin –> thrombin (IIa)

Question 29

What does thrombin do?

Answer 29

1) fibrinogen –> fibrin
2) XIII –> XIIIa
3) activates VIII–> VIIIa in the intrinsic pathway

Question 30

XIIIa?

Answer 30

converts soluble fibrin monomers into insoluble fibrin by enhancing the cross-linking to strengthen the fibrin clot