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EOM Test 1 > Blood Coagulation > Flashcards

Blood Coagulation Flashcards

1
Q

What is the intrinsic pathway?

A

Activates the clotting cascade by contact with an abnormal surface, relies entirely on substances circulating within the blood

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2
Q

What is the extrinsic pathway?

A

Activates the clotting cascade by substances released from damaged tissue

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3
Q

What is released from damaged tissue and what is its role?

A

Factor III (Tissue factor

Cofactor for Factor VII, required for its activity

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4
Q

What is the pathway and function of Factor VII?

A

Extrinsic pathway

Cleaves Factor X to Xa in the presence of tissue factor (III) and calcium.

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5
Q

What is the pathway and role of HMWK?

A

Intrinsic pathway.

Cofactor for the activation of Kallikerin and Factor XII

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6
Q

What is the pathway and function for Kallikrein?

A

Intrinsic.

Activates Factor XII

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7
Q

What is the pathway and function for Factor XII?

A

Intrinsic.

Activates other XII molecules and prekallikrein (positive feedback)

Also cleaves Factor XI to XIa

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8
Q

What is the pathway and function of Factor XI?

A

Intrinsic.

Once activated, XIa cleaves Factor IX to IXa

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9
Q

What is the pathway and functions of Factor IXa?

A

Intrinsic

Activates its protein cofactor, Factor VIII to VIIIa

Forms a complex with VIIIa, and in the presence of calcium and phospholipid, cleaves Factor X to Xa

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10
Q

What is the pathway and function of Factor VIII?

A

Intrinsic

Once activated, Cofactor for Factor IXa

Activated by Factor IXa and thrombin (IIa)

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11
Q

What is the pathway and function of Factor X?

A

Common.

Xa forms a complex with phospholipid, calcium, and cofactor Factor V

This complex cleaves prothrombin (II) to thrombin (IIa)

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12
Q

What are the functions of Thrombin

A
  • Cleave fibrinogen to fibrin
  • Feeds back to activate VIII and V
  • Activates XIII, which crosslinks fibrin strands
  • Activates Protein C, inactivates V and VIII
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13
Q

What is Protein C and what is its function?

A

Protein C is a protease activated by thrombin that inactivates V and VIII

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14
Q

What intrinsic factors can activate VII?

A

XII

IX

X

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15
Q

What is the structure of fibrinogen?

A

Large complex of 6 proteins (Aa)2(BB)2(y)2

Globular domain at each end, joined by rod-like sections that meet at a globular central domain

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16
Q

What is the role of the negatively charged amino acids in the A and B peptides?

A

Keep the fibrinogen molecules apart.

Make them more soluble

17
Q

What is factor XIII and how does it function?

A

A transglutaminase that crosslinks glutamine and lysine side-chains in adjacent monomers

18
Q

What are the three roles of platelets in coagulation?

A

Physical blockage via aggregation

Contribution of phospholipid surface for CF activation

Contribution of clotting and accessory factors

19
Q

What happens as a result of platelet aggregation?

A

Release of CFs, adenine, serotonin, and growth factors

Flipping of phosphotidylserine to the surface to provide a binding site for CFs

20
Q

What Clotting factors do platelets release upon activation?

A

V

XI

XIII

Fibrinogen

Von Willebrand factor

HMWK

21
Q

What are the functions of von Willebrand factor?

A

Link between platelet surface glycoprotein and ECM

Carrier for VIII

22
Q

What four factors limit the clotting activity to the area of damage?

A
  • Factor concentrations diluted by blood flow
  • active factors removed from circulation by liver
  • Proteases degrade factors
  • Specific plasma inhibitors of clotting factors (AT3)
23
Q

What is antithrombin 3 and what are its functions?

A

Serine protease inhibitor (Serpin)

Strongly inhibits thrombin by forming an irreversible complex with it

Inhibits XII, XI, IX, X

24
Q

What is responsible for dissolving clots?

A

Plasminogen bound to fibrin strands is activated at the right time by tissue plasminogen activator (TPA)

Plasmin cleaves fibrin into small peptides, dissolving the clot

25
Q

How are the proteases in the clotting cascade related to each other?

A

All are serine proteases

Have the same critical active site residues (His, Ser, Asp)

26
Q

What is common between the three contact phase proteases (Kallikrien, XII, and XI)?

A

All have a portion allowing them to bind to negatively charged surfaces

27
Q

What is common between the four proteases that require Ca and a phospholipid?

A

Have a special N-terminal domain containing a large number of Glu residues (called the Gla domain)

28
Q

What is significant about the Gla domain?

A

Glu residues have been modified to contain an extra carboxyl group in their side chains (y-carboxyglutamate) (Gla)

29
Q

What is required for the modification of Glu to Gla?

A

Vitamin K

This reaction requires a Vitamin K-dependent enzyme.

**Not required for activity, required to properly localize factors to substrate

30
Q

What is the genetic defect in Hemophilia A?

A

Factor VIII deficiency, x-linked recessive

31
Q

What is the genetic defect in Hemophilia B?

A

Factor IX deficiency, x-linked recessive

32
Q

What was the traditional treatment for hemophilia and its drawbacks?

A

Administration of purified clotting factor

Expensive

Risk of blood-borne pathogens

33
Q

What are current treatments for hemophilia?

A

A wide variety of recombinant proteins like factors VIII, IX, and VII

34
Q

Aspirin

A

Inhibits platelet aggregation

35
Q

Clopidogrel

A

Inhibits platelet aggregation

36
Q

Coumadin

A

Inhibits factors associated with Vitamin K dependent enzymes

II, IX, X, XII

37
Q

Dabigatran

A

Competitive inhibitor of thrombin

38
Q

Rivaroxaban

A

Inhibits X

EOM Test 1 (17 decks)

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