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MHD/Pharm Block 4 > MHD: Normal Hemostasis > Flashcards

MHD: Normal Hemostasis Flashcards

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1
Q

What is the major event of normal hemostasis?

A

The formation of a hemostatic plug when blood vessels are ruptured or injured

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2
Q

What is abnormal hemostasis?

A

Pathological activation of clotting factors leading to formation of a clot when there are no ruptured vessels.

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3
Q

Hemostasis depends on interactions between what 3 entities?

A

Blood vessel wall
Platelets
Coagulation and fibrinolytic systems

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4
Q

What is the first step of primary hemostasis?

A

Vasoconstriction occurs reflexively in order to try to minimize blood loss

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5
Q

What is the vasoconstrictive agent involved with the first step of primary hemostasis?

A

Endothelin, released by the endothelial cells near the site of injury

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6
Q

After vasoconstriction, what are the next steps of primary hemostasis?

A

Platelet adherence to newly exposed collagen
Activation: degranulation release of ADP, TXA2, 5HT
Aggregation: degranulation recruits additional platelets to form hemostatic plug

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7
Q

What are the two types of platelet granules?

A 
Light granules (Alpha): contain proteins including PF4, PDGF
Dense granules (Beta): contain ADP, Ca2+, histamine, 5HT, and Epi
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8
Q

What is the general function of primary hemostasis? What about secondary hemostasis?

A

Primary Places Plug

Secondary Stabilizes

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9
Q

What factor is released to initiate secondary hemostasis?

A

Tissue factor released from the endothelial cells at the site of injury

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10
Q

What two events occur simultaneously during secondary hemostasis?

A

Release of tissue factor

Coagulation proteins form complexes on platelet surface

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11
Q

What is the product of the coagulation cascade?

A

Thrombin is formed, which then converts fibrinogen to fibrin

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12
Q

What process forms the stabilized permanent hemostatic plug?

A

Fibrin polymerization

Cross linking of fibrin forms a stable platelet t-thrombin plug

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13
Q

Describe the cells contained in the permanent hemostatic plug.

A

RBCs and WBCs become trapped in the plug in addition to the platelets that make up the majority of the plug

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14
Q

What two outcomes of hemostasis are controlled by the endothelium?

A

Normally, endothelium has an antithrombotic effect

If there is injury to the endothelium, then there is a prothrombotic effect

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15
Q

Describe the antiplatelet effect of the endothelium

A

Prevents contact between collagen and platelets/coagulation proteins
Secretion of prostacyclin and nitric oxide

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16
Q

Describe the anticoagulant effect of the endothelium

A 
Endothelial membranes express antithrombin (heparin cofactor) and thrombomodulin.
Thrombomodulin combines with thrombin to activate protein C
Protein S (cofactor for C) is also secreted
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17
Q

Describe the fibrinolytic effect of the endothelium

A

The endothelial cells secrete plasminogen activators (t-PA) which converts plasminogen to plasmin, thus promoting fibrinolysis

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18
Q

What factors of the clotting pathway are degraded by activated protein C?

A

Va and VIIIa

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19
Q

Describe the prothrombotic effect of the endothelium

A

Following injury, endothelia secrete von Willebrand factor (VWF), which allows platelets to attach to newly exposed collagen

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20
Q

What 3 molecules are released by endothelia for during the prothrombotic response to injury?

A

VWF
Tissue factor
Cytokines

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21
Q

What is the definition of a platelet?

A

Discoid, anuclear cells that play a major role in hemostasis

22
Q

Describe the composition of the plasma membrane of platelets

A

Contains many glycoprotein receptors

23
Q

What are the three reactions that platelets undergo after exposure to subendothelial proteins?

A

Adhesion
Activation
Aggregation

24
Q

Describe the process of platelet adhesion

A

GPIb on platelet membrane connects to collagen via VWF

25
Q

Describe the process of platelet activation

A

GPIIb/IIIa receptor activation leads to release of granular content including ADP, Ca2+, and TXA2
The phospholipid complex (exposed negatively charged phospholipids on platelet surface) leads to activation of the intrinsic pathway

26
Q

Describe the process of platelet aggregation

A

ADP and TXA2 are released from platelets to recruit, activate and aggregate platelets
5HT and TXA2 vasoconstrict
Thrombin formed via intrinsic pathway

27
Q

What factor is thrombin in the coagulation cascade?

A

Factor IIa

converts fibrinogen to fibrin

28
Q

What enzyme stabilizes the fibrin clot?

A

Transamidase (Factor XIIIa) and TAFIa stabilize the fibrin clot

29
Q

What are the three components of the clotting cascade?

A

Intrinsic pathway
Extrinsic pathway
Common pathway

30
Q

What is the common factor activated by both the intrinsic and extrinsic pathway of the clotting cascade?

A

Factor X is activated to Xa by both pathways

31
Q

List the order of factors activated during the intrinsic pathway?

A 
XII (Hageman factor) --> XIIa
XI ---> XIa (activated by thrombin)
IX --> IX a (activated by XIa)
VIII --> VIIIa (activated by thrombin)
VIIIa then activates X to Xa
32
Q

What factors are involved with the extrinsic pathway?

A

VII gets activated to VIIa by Tissue factor

VIIa then activates X to Xa

33
Q

What factors are involved with the common pathway?

A

5, 2, 1
Thrombin activate V to Va
Va and Xa activate II (Prothrombin) to IIa (Thrombin)
IIa converts fibrinogen (I) to fibrin (Ia)

34
Q

What lab test measures intrinsic pathway factors?

A

APTT (XII, XI, IX, VIII)

35
Q

What lab test measures extrinsic pathway factors

A

PT/INR

36
Q

Which pathway does heparin act on ?

A

Intrinsic pathway

37
Q

Which pathway does warfarin act on ?

A

Extrinsic pathway

38
Q

What type of enzyme are almost all clotting factor proteins?

A

Serine proteases (All except XIIIa, which is a transamidase)

39
Q

Which factors are members of the fibrinogen group?

A

I, V, VIII, XIII

“5+8 x 1 = 13”

40
Q

Which factors are members of the prothrombin group?

A

II, VII, IX, X

41
Q

What structural similarity exists between the members of the prothrombin group?

A

II, VII, IX, X all contain gamma carboxy glutamic acid for binding of calcium

42
Q

Which factors are members of the contact group?

A

XI, XII

Also: Prekallikrein (Fletcher factor), and HMW Kininogen (Fitzgerald factor)

43
Q

What are the two major inhibitors of the coagulation system?

A 
Antithrombin III (AT)
Tissue factor pathway inhibitor (TFPI)
44
Q

What drug is associated with ATIII function?

A

ATIII mediates the anticoagulant action of heparin

Heparin-ATIII inactivates thrombin and other factors

45
Q

What is the function of the fibrinolytic system?

A

These enzymes are responsible for breaking down clots

46
Q

What is the main fibrinolytic enzyme?

A

Plasmin: breaks fibrin into fibrin split products

47
Q

What are the main inhibitors of the fibrinolytic system?

A

Plasminogen activator inhibitor (PAI)
α2-antiplasmin
α2-macroglobulin
Thrombin activatable fibrinolytic inhibitor (TAFI)

48
Q

What substances activate plasminogen to plasmin?

A

Tissue plasminogen activator (tPA)

Urokinase

49
Q

Define thrombosis

A

Pathologic transition of the state of blood from fluidity to non-fluidity

50
Q

What is the difference between a thrombus and an embolus?

A

Thrombi are stationary. They can progress and break into mobile pieces throughout the circulation which are called Emboli.

51
Q

What are the factors leading to thrombosis?

A

Virchow’s triad: endothelial injury, abnormal blood flow, hypercoagulability

52
Q

What are the main genetic causes of hypercoagulable states?

A 
Molecular thrombophilias (Factor V Leiden)
Inhibitor deficiency

MHD/Pharm Block 4 (25 decks)

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