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Clinical Pathology > UNIT 1 - Lecture 11: Hemostasis Intro > Flashcards

UNIT 1 - Lecture 11: Hemostasis Intro Flashcards

1
Q

What parts of signalment do you want to think about when considering a bleeding disorder?

A

Age, breed, sex-linked

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2
Q

What components of a patient’s history should you think about when considering a bleeding disorder?

A
  1. Are any parents or siblings affected?
  2. Recent drug or vaccine administration
  3. Exposure to potential toxins
  4. Previous surgeries/complications
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3
Q

What are the 2 types of bleeds?

A
  1. Classic platelet-type
  2. Typical coagulation-type
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4
Q

What is a classic platelet-type bleed?

A

Superficial petechial & ecchymotic hemorrhage on skin & mucosa

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5
Q

What is a typical coagulation-type bleed?

A

Deep tissue-type hemorrhages (into body cavities, joints, hematomas)

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6
Q

What does hemostasis mean?

A

Stopping bleeding

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7
Q

What are the 4 components that make up hemostasis?

A
  1. Platelets
  2. Vascular endothelium
  3. Multiple coagulation factors
  4. Other circulating proteins
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8
Q

What is the objective of hemostasis?

A

To maintain balance of coagulation and fibrinolysis

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9
Q

What are the types of hemostasis?

A

Primary, secondary, fibrinolysis (tertiary)

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10
Q

What is the traditional model of hemostasis?

A

Reflects coagulation in the lab;

DOES NOT explain how hemostasis works in the body

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11
Q

What is the in vivo model (cell-based model) of hemostasis?

A

Thrombin generation and fibrin formation occurring on cell surfaces;

Involves plts, endothelial cells, fibroblasts, WBCs, RBCs

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12
Q

What does primary hemostasis result in?

A

Formation of a platelet plug

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13
Q

What are examples of cellular components of primary hemostasis?

A

platelets, endothelial cells

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14
Q

What are examples of proteins involved in primary hemostasis?

A

vWF, subendothelial collagen

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15
Q

What is an example of a facilitator in primary hemostasis?

A

platelet agonists

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16
Q

What are platelets?

A

Anucleated cytoplasmic fragments from megakaryocytes that have a phaspholipid membrane and effector molecules

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17
Q

What is the lifespan of a platelet?

A

~5-7 days

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18
Q

_____% of circulating platelets are contained in the spleen.

A

30-40%

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19
Q

Platelet functions are mediated primarily via _____.

A

cytoplasmic granule contents

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20
Q

What types of granules do platelets have and what does each contain?

A

Alpha granules = contain vWF and coagulation factors

Dense granules = contain platelet agonists that recruit and activate additional platelets

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21
Q

What spp have thrombocytes?

A

Avians, reptiles, fish, and amphibians

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22
Q

What is megakaryopoiesis? Where does it occur?

A

Proliferation and maturation of megakaryocytes;

occurs mostly in the marrow

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23
Q

What is thrombopoiesis?

A

Process of plt production in the marrow (mostly) from megakaryocytes.

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24
Q

What mediates thrombopoiesis?

A

Thrombopoietin (TPO)

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25
Q

What is the relationship between plt/mega #s and circulating [TPO]?

A

inverse relationship

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26
Q

TPO is cleared by _____ and _____.

A

plts, megas

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27
Q

How long does it take for megakaryocytes to be produced and mature to form platelets?

A

~12 days

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28
Q

What is vWF?

A

Large, multimeric glycoprotein that circulates with Factor VIII.

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29
Q

Where is vWF stored?

A

In Weibel-Palade bodies in endothelial cells and platelet alpha-granules

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30
Q

What does vWF do?

A

Acts as a bridge between plts and subendothelium, platelets and fibrin

31
Q

What are the steps to primary hemostasis?

A
  1. Vasoconstriction
  2. Platelet activation
  3. Platelet aggregation
  4. Platelet clot retraction
32
Q

When does vasoconstriction occur?

A

Immediately after vascular injury

33
Q

What is vasoconstriction potentiated by?

A

Endothelium and platelet-derived vasoconstrictors

34
Q

Vasoconstriction is a _____ effect.

A

transient

35
Q

How does platelet activation work in primary hemostasis (what are the 7 steps)?

A
  1. Platelets exposed to subendothelial c.t. constituents
  2. Platelets adhere to vWF –> bridges plts and exposed collagen using glycoprotein receptor Ib-IX-V
  3. Plt converts from smooth disc to spiny sphere with long pseudopodia
  4. Gp-IIb/IIIa increases affinity for fibrinogen
  5. (-) charged phospholipids translocate from inner leaflet to outer leaflet
    1. Bind calcium
    2. Serve as sites of coagulation factor complex assembly
  6. Plts release granule contents
  7. Released granules –> more plts activated
36
Q

Platelet aggregation is mediated by _____.

A

thromboxane A2

37
Q

In plt aggregation, what stabilizes the plt plug (via secondary hemostasis)?

A

fibrin crosslinking

38
Q

What occurs in platelet clot retraction?

A

Plt microfilaments contract and pull the fibrin attached to their surface with them –> retraction of clot

39
Q

What are inhibitors of primary hemostasis?

A
  1. Endothelial cells
  2. Fibrin degradation products (FDPs)
  3. Monoclonal immunoglobulins
  4. Medications
40
Q

What are the 2 ways by which endothelial cells inhibit primary hemostasis?

A
  1. Physical barrier
  2. Release inhibitors of plt aggregation (Nitric oxide, prostacyclin)
41
Q

How do FDPs inhibit primary hemostasis?

A

Compete with fibrinogen for plt receptors –> impair aggregation

42
Q

Secondary hemostasis results in formation of _____.

A

a fibrin clot

43
Q

What are the components of secondary hemostasis?

A
  1. Cells
  2. Enzymatic coagulation factors
  3. Non-enzymatic factors = cofactors
  4. Non-enzymatic factors = substrate: fibrinogen
  5. Calcium
  6. Phosphatidylserine (PS)
44
Q

What is coagulation?

A

Formation of insoluble, cross-linked fibrin by activated coagulation factors, which stabilizes the plt plug

45
Q

What are the enzymatic coagulation factors?

A

II, VII, IX, X, XI

46
Q

Where are enzymatic coagulation factors produced?

A

by hepatocytes

47
Q

What enzymatic coagulation factors are dependent on vitamin K?

A

II, VII, IX, X

48
Q

What anticoagulant proteins require vitamin K?

A

Proteins C and S

49
Q

Cofactors are _____ during coagulation.

A

consumed

50
Q

What is tissue factor (TF)?

A

Transmembrane cellular receptor that is a cofactor for Factors VII and VIIa;

major activator of coagulation in vivo

51
Q

What do factors V and VIII do?

A

They are non-enzymatic cofactors that accelerate coagulation by facilitating surface attachment of coagulation factors

52
Q

What is the final product of coagulation?

A

fibrinogen

53
Q

What is fibrinogen?

A

Positive acute-phase protein produced by hepatocytes

54
Q

What is the half life of fibrinogen in dogs?

A

2-3 days

55
Q

How is fibrinogen consumed during coagulation?

A

It is converted to fibrin by thrombin

56
Q

What is the most important coagulation factor?

A

thrombin

57
Q

What are 3 functions of thrombin?

A
  1. Converts soluble fibrinogen –> fibrin (forms insoluble clot)
  2. Amplifies coagulation process
  3. Induces plt activation and aggregation
58
Q

How does thrombin amplify the coagulation process?

A
  1. Activates Factor XI and co-factors V and VIII
  2. Stabilizes secondary hemostatic plug by activating FXIII
59
Q

What is another name for free (ionized) calcium?

A

Factor IV

60
Q

What is free calcium a cofactor for?

A

IIa, VIIa, IXa, XIIIa

61
Q

What are some anticoagulants we should be aware of?

A
  1. Antithrombin III
  2. Protein C
  3. Protein S
  4. Tissue Factor Pathway Inhibitor (TFPI)
  5. Thrombomodulin
  6. Heparin-like molecules
62
Q

What is fibrinolysis?

A

Clot breakdown; enzymatic degradation of fibrin

63
Q

What cells are involved in fibrinolysis?

A

Endothelial cells and platelets

64
Q

What enzymes are involved in fibrinolysis?

A

tPA, plasminogen, contact pathway factors

65
Q

What cofactors are involved in fibrinolysis?

A

Fibrin, polyphosphates

66
Q

What is the facilitator of fibrinolysis?

A

bradykinin

67
Q

Fibrinolysis is initiated simultaneously with _____ and localized to _____.

A

coagulation, hemostatic plug

68
Q

What does degradation of fibrin and fibrinogen produce?

A

FDPs (fibrin degradation products)

69
Q

What is the sequence of events in fibrinolysis?

A
  1. Release of plasminogen activators
  2. Plasmin production from plasminogen
  3. Clot lysis releasing degradation products
70
Q

What does plasmin do?

A

Degrades blood plasma proteins, including fibrin clots

71
Q

What is the main inhibitor of plasmin?

A

antiplasmin

72
Q

What is the main inhibitor of tPA?

A

PAI-1 and PAI-2

73
Q

What are the 4 inhibitors of fibrinolysis?

A
  1. TAFI
  2. PAI-1 & PAI-2
  3. Antiplasmin
  4. Polyphosphates

Clinical Pathology (22 decks)

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