4 Mechanisms of Hemostasis Flashcards

1
Q

What is the mechanism by which bleeding is controlled after injury?

A

Hemostasis

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2
Q

Pathological states of hemostasis can lead to what 2 things?

A

thrombosis or hemorrhage

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3
Q

What cells play a vital role in hemostasis?

A

endothelial

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4
Q

damage to endothelium leads to what?

A

platelet adherence, aggregation and adherence

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5
Q

What happens at platelet activation?

A

release granules, increased intracellular Ca and decreased cAMP

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6
Q

What provides the phospholipid substrate on much of fluid phase coagulation occurs?

A

platelets

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7
Q

Plasma coagulation causes?

A

solubule FIBRINOGEN becomes insoluble cross-linked polymer FIBRIN

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8
Q

What type of enzymes need to be activated for fluid phase coagulation?

A

serine proteases

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9
Q

Where are coagulation factors produced?

A

liver

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10
Q

Breakdown of a clot requires what?

A

plasmin generation from plasminogen (fibrinolysis)

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11
Q

Decreasing clot formation is initiated by what?

A

antithrombin

Protein C and S pathways

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12
Q

Where does much of the interaction of plasma proteins occur?

A

on the surface of platelets

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13
Q

Coagulation occurs by interactions of what three things?

A

plasma proteins
platelets
tissue factor

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14
Q

What happens to arterioles right after injury?

A

vasoconstriction- brief, reflex mechanisms

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15
Q

What part of hemostasis is formation of platelet plug? fibrin clot?

A

Primary Hemostasis and Secondary Hemostasis

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16
Q

How long do platelets circulate in the blood?

A

7-10 days

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17
Q

What provides an enormous expansion of the surface area/volume ratio in platelets?

A

open canalicular system

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18
Q

What recruits adjacent platelets to form a plug?

A

alpha and dense granules

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19
Q

What are 5 basic events in series of platelet reaction?

A
  1. adhesion
  2. activation
  3. Release Reaction
    4, clot formation and retraction
  4. support plasma coagulation
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20
Q

Platelet adhesion requires what factor?

A

plasma protein von Willebrand factor (vWf) and of course the membrane receptor for it (Ib-IX-V)

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21
Q

Where is von willebrand factor produced and stored?

A

produced and stored in endothelial cell and megakaryocytes

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22
Q

T-F - platelets have vWf in there alpha granules?

A

True

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23
Q

what are the 3 functions of vWf?

A

bind platelet receptor
bind collagen
stabilize factor VIII

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24
Q

What binds to glycoprotein IIb-IIIa?

A

fibrinogen

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25
Q

T-f- after activations platelets do not change shape?

A

False-become spherical spiny due to ADP receptors

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26
Q

What do dense granules contain?

A

ATP, ADP, calcium, serotonin

27
Q

What do alpha granules contain?

A

coagulation factors
growth modulators
adhesive proteins

28
Q

T-F - platelet granules also contain lysozymes

A

True

29
Q

What does release of granule contents cause?

A

vasoconstriction, modulation of growth of vessel, cell adhesion, fluid phase coagulation

30
Q

What generates arachidonic acid?

A

phospholipids acted upon by Phospholipase C.

31
Q

What converts arachidonic acid to cyclic endoperoxide?

A

cyclo-oxygenase

32
Q

What becomes of the endoperoxides?

A

prostoglandins

or Thromboxane A2

33
Q

The secretion of platelet alpha granules leads to high concentrations of fibrinogen, factors V, VIII, XI, XIII which lead to and enhance what?

A

fibrin formation and stabilization

34
Q

True or False- platelets have similarities of embryonic muscle?

A

True- actin myosin in platelets which organize filopodia

35
Q

What do the platelet filopodias bind to?

A

fibrin and then contract to pull close together- drawing together the edges of the injured tissue.

36
Q

What inhibits platelet aggregation

A

prostacyclin- made by endothelial cells

NO- also made from endothelial cells

37
Q

Abnormal bleeding does not occur above what platelet count? troublesome bleeding?

A

> 100x10^9

<50x10^9

38
Q

What factor is the main factor of activation from prothrombin to thrombin

A

Factor Xa

39
Q

The final product of the coagulation cascade is fibrinogen to fibrin which is then cross linked by which factor?

A

XIII

40
Q

What initiates the coagulation cascade in vivo?

A

tissue factor

41
Q

What type of cell produces most of the coagulation factors? Exceptions?

A

hepatocytes—

  • -exception VIII- liver endothelial cells
    • exception vWf- endothelial cells and megakaryocytes
42
Q

What must PROTHROMBIN(II), VII, IX, X, protein C and S have in order to be fully functional?

A

Vitamin K

43
Q

Where does most of the Vitamin K we need come from?

A

gastrointestinal tract by bacteria

44
Q

What step is vitamin K needed?

A

second step- acts as a cofactor for an enzyme that inserts a second carboxyl group into gamma carbon on glutamic residues

45
Q

What are the 5 roles of thrombin?

A
  1. cleavage of fibrinogen to fibrin
  2. activate clotting factors (V,VIII,XI,XIII)
  3. activation of platelets
  4. activation of endothelial cells
  5. binds thrombomodulin and activates Protein C
46
Q

What laboratory measurements evaluates the INTRINSIC and common pathways of coagulation?

A

activated partial thromboplastin time (APTT)

-clotting time of a mixture of citrated plasma, phospholipid, calcium and an agent to increase contact activation

47
Q

What laboratory measurement evaluates the EXTRINSIC and common pathways of coagulation?

A

Prothrombin Time

-clotting time of citrated plasma, tissue thromboplastin, and calcium ions.

48
Q

A deficiency in factors VII, X, V, prothrombin and fibrinogen can be seen through what laboratory measurement?

A

PT

49
Q

T or F- APTT can measure a deficiency in Factors VII and XIII?

A

False

50
Q

What are 3 basic control mechanisms of regulating clot formations?

A
  1. Blood Flow
  2. hepatic clearance of activated factors
  3. Plasma Inhibitors
51
Q

What inhibits thrombin by forming a 1:1 complex between arginine residue of itself with a serene residue in active site of thrombin?

A

antithrombin–also note that it inhibits XIa,Xa, IXa.

52
Q

free thrombin at endothelial cell surface is bound by what? what does it activate?

A

thrombomodulin- this complex activates protein C and Protein C with S degrades Va and VIIIa AND NO LONGER SUPPORT THROMBIN AND Xa FORMATION

53
Q

What enhances fibrinolysis by degrading endogenous inhibitor of endothelial cell plasminogen activator?

A

APC (activated protein C) and Protein S

54
Q

What inhibits extrinsic pathway tissue factor/factor VIIa/ factor Xa/ calcium complex?

A

Tissue factor pathway inhibitor (TFPI)

55
Q

The ability to lyse or dissolve a clot primarily comes from what protein?

A

Plasmin- From plasminogen produced in liver

56
Q

T-F –plasmin can cleave fibrinogen or fibrin?

A

True

57
Q

Cleavage of fibrin produces what>

A

D-dimers

58
Q

What does plasminogen activator T-PA have a high affinity for?

A

Fibrin

59
Q

What inhibits activation of plasmin?

A

PAI-1 plasminogen activator inhibitor

- synthesized by endothelial cells, hepatocytes, fibroblasts and platelets

60
Q

What is plasmin activity physiologically regulated by>

A

alpha 2 antiplasmin–binds lysine binding site on plasmin

61
Q

Normal unperturbed epithelium supports what 3 things?

A
  1. antithrombin inactivation of thrombin (by heparinoids)
  2. APC formation (by thrombin/thrombomodulin complex
  3. Prostacyclin- inhibit platelet adherence/aggregation
62
Q

Patients with deficiencies in factor VIII or IX have what bleeding disorder?

A

hemophilia

63
Q

What do patients with deficiency of Protein C or antithrombin have?

A

increased risk of clotting because missing normal checks of clotting process.