Mehta

Question 0

Heparane sulfate (HS)

Answer 0

An anticoagulant

Enhances activity of antithrombin

Question 1

Prostaglandin PG12

Answer 1

An anticoagulant

Prevents platelet activation

Question 2

Ecto ADPase (CD39)

Answer 2

An anticoagulant
Degrades ADP
Prevents platelet aggregation

Question 3

Plasminogen Activator Inhibitor-1 (PAI-1)

Answer 3

Inhibits formation of plasmin
Anticoagulant
Opposes thrombus dissolution

Question 4

Plasminogen Activator (TPA)

Answer 4

A protease
Converts plasminogen to plasmin
Dissolves clots

Question 5

Thrombomodulin (TM)

Answer 5

An anticoagulant

Activates protein C to degrade factors V and VIII

Question 6

Nitric Oxide (NO)

Answer 6

Relaxes smooth muscle cells to prevent platelet aggregation

Question 7

Store and release Von Willbrand Factor (vWF)

Answer 7

Facilitates platelet aggregation

Question 8

Thrombosis is due to abnormalities in:

Answer 8

1. Blood flow or hemodynamics
2. Blood vessel wall
3. Blood constituents
4. Genetic
5. Acquired

Question 9

Hemorrhage is due to abnormalities in:

Answer 9

1. Synthesis or function of clotting and anti-clotting factors
2. Generation and function of platelets
3. Genetic diseases
4. Acquired

Question 10

Define thrombus.

Answer 10

Abnormal clot that develops in a blood vessel.

Question 11

Define embolus.

Answer 11

A clot that flows freely in the blood.

Question 12

Define infarct.

Answer 12

Necrotic tissue area formed due to obstruction of blood due to a thrombus or embolus.

Question 13

Define hemostasis.

Answer 13

Hemostasis is prevention of blood loss upon injury to the blood vessel and reestablishment of blood flow.

Question 14

List the 5 overlapping responses in the hemolytic cascade.

Answer 14

1. Vasoconstriction: narrows the blood vessels
2. Platelet adhesion and aggregation: lead to the formation of plug at the site of injury or disturbance
3. Coagulation: converts plasma from a liquid to a gel. This forms the clot.
4. Blood vessel repari: endothelial cells divide, fibroblasts migrate to the site of injury, collagen is synthesized and the vessel is healed.
5. Clot dissolution: a series of biochemical events, resulting in the dissolution of the the clot/plug.

Question 15

List and describe the classes of the clotting and anti-clotting factors

Answer 15

1. Enzymes: circulate in inactive form, get activated to initiate clotting. Most are serine proteases.
2. Cofactors: bind and stabilize clotting factors buy have no enzymatic activity.
3. Control proteins: regulate coagulation and anti-coagulation.
4. Substrates: Fibrinogen and fibrin

Question 16

Hemophilia A

Answer 16

Factor VIII deficiency

Question 17

Hemophilia B

Answer 17

Factor IX deficiency

Question 18

Hemophilia C

Answer 18

Factor XI deficiency

Question 19

Name the direct anti-clotting factor agents that are direct thrombin inhibitors.

Answer 19

These factors bind thrombin to inhibit activity.

1. Hirudin
2. Argatroban
3. Melagatran
4. Orgaran

Question 20

Name all direct anti-clotting factor agents that are indirect thrombin inhibitors.

Answer 20

These factors inhibit thrombin generation.

1. ANTI-Xa antibodies
2. TFP1
3. Soluble thrombomodulin

Question 21

Name all the indirect anti-clotting factor agents that are ATIII dependent.

Answer 21

These factors will increase ATIII activity.

1. Heparin
2. Heparin fragments

Question 22

Name all the indirect anti-clotting factors that are Vitamin K antagonists.

Answer 22

These factors inhibit the synthesis of clotting factors. These are the most common drugs.

1. Warfarin
2. Coumarin
3. Dicoumarol

Question 23

vWF

Answer 23

Facilitates platelet aggregation by binding to GP1b-IX-V.

Initiates adhesion of platelets to collagen and platelets to cell receptors.

Question 24

G-protein coupled receptors (GPCR)

Answer 24

Present on the platelet surface; binds PGI2, TXA2, Thrombin, and ATP.

Question 25

PGI2

Answer 25

Inhibits platelet aggregation and is coupled to receptor Cs (increases cAMP).

Question 26

TXA2

Answer 26

Induces platelet aggregation and is coupled to receptors Gq or Gi.

Question 27

ADP

Answer 27

Activates platelets by binding to 2 receptors, Gi or Gq and causes aggregation.

Question 28

Integrin alpha2beta1

Answer 28

Mediates adhesion of platelets to collagen on exposed vessel surfaces and strengthens and stabilizes the bonds. It causes platelets to exocytose, releasing TXA2, ADP, and thrombin, thus causing platelet aggregation.

Question 29

Integrin alphaIIb-beta3

Answer 29

Mediates adhesion between platelets via fibrinogen. | Establishes cross-linking of integrins.

Question 30

Tissue factor (Factor III)

Answer 30

Initiates extrinsic pathway when it is exposed during injury or inflammation. Is present on sub-endothelial tissues.

Question 31

Thrombin

Answer 31

A coagulation factor/protease that activates platelets and binds to GPCR (Gi or Gq). Protease that cleaves fibrinogen into fibrin.

Question 32

Factor XIII.

Answer 32

Activated by trace thrombin and becomes part of the tenase complex. Is a transglutaminase (NOT a serine protease). Synthesized in the liver and circulates as a zymogen. Crosslinks fibrin chains, strengthening the bonds.

Question 33

TPA

Answer 33

Plasminogen activator. Protease that converts plasminogen to plasmin and dissolves clots (must be bound to fibrin to be activated). Two types: tissue (TPA and UPA).

Question 34

Plasmin

Answer 34

Dissolves the clot (serine protease) by digesting cross-linked fibrin monomers. Only has high affinity to TPA bound to fibrin, so only has affinity for clot. Digests polymerized fibrin to produce D-dimers and E-fragments (the presence of D-dimers in circulation is used as a clinical test to rule out deep venous thromboses and pulmonary embolism).

Question 35

Gamma carboxylation clotting factors

Answer 35

Prothrombin, VII, IX, X, XI, XII and protein C and S | Mediated by Vitamin K

Question 36

Protein C

Answer 36

Class C anticoagulation factor Degrades factors V and VIII Inhibits the formation of prothrombinase, and hence the formation of thrombin. Must have the cofactor protein S.

Question 37

NSAIDS

Answer 37

Block prostaglandin synthase (COX-1 and COX-2) in endothelial cells and platelets. In platelets, they inhibit the production of TXA2 from PGH2, thus inhibiting aggregation of platelets.

Question 38

Hemophilia A

Answer 38

Factor VIII deficiency

Question 39

Hemophilia B

Answer 39

Factor IX deficiency. | Coagulation time is prolonged

Question 40

Hemophilia C

Answer 40

Factor XI deficiency. | Coagulation time is prolonged.

Question 41

Deep venous thrombosis.

Answer 41

Life threatening, severe clotting throughout the body. | Due to homozygous deletion of protein C.

Question 42

Name the three domains of serine proteases.

Answer 42

1. GLA (gamma carboxylase acts on this) 2. Kringle (regulatory role) 3. Catalytic