Hemostasis

Question 1

Primary Hemostasis

Answer 1

rapid vasoconstriction and formation of the platelet plug minimizing blood loss after injury

Question 2

Secondary Hemostasis

Answer 2

An explosive, localized increase in thrombin generation and fibrin clot formation that anchors and stabilizes the platelet plug

Question 3

2 Functions of Thrombin

Answer 3

Potent platelet activator

Converts soluble fibrinogen to insoluble fibrin clot

Question 4

Plasmin

Answer 4

a protease that gradually breaks down the fibrin clot

converted from plasminogen

Question 5

3 Prothrombotic Components

Answer 5

Platelets/von Willebrand Factor (primary platelet plug)
Coagulation Cascade
Fibrinolysis inhibitors

Question 6

3 Antithrombotic Components

Answer 6

Endothelium
Fibrinolysis (plasmin)
Coagulation inhibitors

Question 7

What occurs in Adhesion phase of primary hemostasis?

Answer 7

mediated by the binding of the platelet glycoprotein Ib-V-IX complex to vWF
platelets then activated by a variety of agonists (thrombin, collagen, ADP, etc.)

Question 8

What occurs in Aggregation phase of primary hemostasis?

Answer 8

cross-linking of activated platelets primarily mediated by fibrinogen binding to activated glycoprotein IIb/IIIa complex

Question 9

What occurs in Secretion phase of primary hemostasis?

Answer 9

platelet granules release substances that recruit/activate additional platelets

Question 10

Normal range of platelets in blood

Answer 10

150,000-400,000/microL

Question 11

What occurs when a platelet is activated?

Answer 11

• shape change
• conformational activation of the Gp IIb/IIIa complex
• granule release
• eventually thrombus retraction

Question 12

Describe Thrombopoietin (TPO)

Answer 12

controls the production of platelets
negative feedback, platelets bind to TPO
If more TPO is unbound, will signal to make more platelets

Question 13

Describe platelet storage

Answer 13

about 30% of circulating platelets are sequestered in the spleen (reserve force)
spleen also removed platelets from blood after 7-10 days

Question 14

Two major functions of von Willebrand Factor

Answer 14

• the major carrier protein for factor VIII (significantly prolongs the plasma half-life for this factor)
• vWF mediates platelet tethering and adhesion

Question 15

what receptor on platelets does vWF bind to?

Answer 15

Gp Ib-V-IX

Question 16

Function of ADAMTS13

Answer 16

cleaves partially unfolded ultra-large vWF multimers that have bound to platelets into smaller, less sticky multimers
-if there is an inherited or acquired deficiency in ADAMTS13, large vWF-platelet aggregates can form in the circulation and occlude small blood vessels (occurs in thrombotic thrombocytopenic purpura (TPP))

Question 17

What characterizes von Willebrand Disease?

Answer 17

mutations in the vWF gene that impairs multimer formation, or that lead to excessive cleavage of multimers by ADAMTS13 that can lead to bleeding disorder

Question 18

2 strong platelet agonists

Answer 18

• Collagen (extracellular matrix)

- Thrombin (generated by TF exposure at site of injury)

Question 19

4 weak platelet agonists

Answer 19

• Epinephrine
• ADP
• Serotonin
• Thromboxane A2 (produced from platelet arachidonic acid via COX-1 pathway)

Question 20

Important step for platelet aggregation

Answer 20

conformational change in the Gp IIb/IIIa receptor that allows the receptor to bind fibrinogen (glues platelets together)

Question 21

Phosphatidylserine exposure on outer platelet membrane leads to?

Answer 21

assembly of the membrane-bound coagulation enzyme complexes IXa-VIIIa, Xa-Va

Question 22

Another name for Thrombin and its function in cascade?

Answer 22

Factor IIa, serine protease that converts fibrinogen to fibrin

Question 23

Two arms of the coagulation cascade

Answer 23

Intrinsic and Extrinsic

Question 24

Which lab test measures the Extrinsic pathway?

Answer 24

Prothrombin time (PT)

Question 25

Which lab test measures the Intrinsic pathway?

Answer 25

activated partial thromboplastin time (aPTT)

Question 26

Remember this about the intrinsic and extrinsic pathway separation.

Answer 26

useful for lab testing but not for describing the response in vivo

Question 27

Vitamin K dependent proteases

Answer 27

II (prothrombin), VIIa, IXa, Xa, Protein C

Question 28

Function of factor XIII

Answer 28

activated by thrombin and crosslinks fibrin to stabilize the thrombus

Question 29

List the cofactors in cascade

Answer 29

Tissue factor (TF), factor V, factor VIII, protein S