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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
What is the relationship between plt/mega #s and circulating [TPO]?
inverse relationship
26
TPO is cleared by _____ and \_\_\_\_\_.
plts, megas
27
How long does it take for megakaryocytes to be produced and mature to form platelets?
~12 days
28
What is vWF?
Large, multimeric glycoprotein that circulates with Factor VIII.
29
Where is vWF stored?
In Weibel-Palade bodies in endothelial cells and platelet alpha-granules
30
What does vWF do?
Acts as a bridge between plts and subendothelium, platelets and fibrin
31
What are the steps to primary hemostasis?
1. Vasoconstriction 2. Platelet activation 3. Platelet aggregation 4. Platelet clot retraction
32
When does vasoconstriction occur?
Immediately after vascular injury
33
What is vasoconstriction potentiated by?
Endothelium and platelet-derived vasoconstrictors
34
Vasoconstriction is a _____ effect.
transient
35
How does platelet activation work in primary hemostasis (what are the 7 steps)?
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
Platelet aggregation is mediated by \_\_\_\_\_.
thromboxane A2
37
In plt aggregation, what stabilizes the plt plug (via secondary hemostasis)?
fibrin crosslinking
38
What occurs in platelet clot retraction?
Plt microfilaments contract and pull the fibrin attached to their surface with them --\> retraction of clot
39
What are inhibitors of primary hemostasis?
1. Endothelial cells 2. Fibrin degradation products (FDPs) 3. Monoclonal immunoglobulins 4. Medications
40
What are the 2 ways by which endothelial cells inhibit primary hemostasis?
1. Physical barrier 2. Release inhibitors of plt aggregation (Nitric oxide, prostacyclin)
41
How do FDPs inhibit primary hemostasis?
Compete with fibrinogen for plt receptors --\> impair aggregation
42
Secondary hemostasis results in formation of \_\_\_\_\_.
a fibrin clot
43
What are the components of secondary hemostasis?
1. Cells 2. Enzymatic coagulation factors 3. Non-enzymatic factors = cofactors 4. Non-enzymatic factors = substrate: fibrinogen 5. Calcium 6. Phosphatidylserine (PS)
44
What is coagulation?
Formation of insoluble, cross-linked fibrin by activated coagulation factors, which stabilizes the plt plug
45
What are the enzymatic coagulation factors?
II, VII, IX, X, XI
46
Where are enzymatic coagulation factors produced?
by hepatocytes
47
What enzymatic coagulation factors are dependent on vitamin K?
II, VII, IX, X
48
What anticoagulant proteins require vitamin K?
Proteins C and S
49
Cofactors are _____ during coagulation.
consumed
50
What is tissue factor (TF)?
Transmembrane cellular receptor that is a cofactor for Factors VII and VIIa; ## Footnote **major activator of coagulation in vivo**
51
What do factors V and VIII do?
They are non-enzymatic cofactors that accelerate coagulation by facilitating surface attachment of coagulation factors
52
What is the final product of coagulation?
fibrinogen
53
What is fibrinogen?
Positive acute-phase protein produced by hepatocytes
54
What is the half life of fibrinogen in dogs?
2-3 days
55
How is fibrinogen consumed during coagulation?
It is converted to fibrin by thrombin
56
What is the most important coagulation factor?
thrombin
57
What are 3 functions of thrombin?
1. Converts soluble fibrinogen --\> fibrin (forms insoluble clot) 2. Amplifies coagulation process 3. Induces plt activation and aggregation
58
How does thrombin amplify the coagulation process?
1. Activates Factor XI and co-factors V and VIII 2. Stabilizes secondary hemostatic plug by activating FXIII
59
What is another name for free (ionized) calcium?
Factor IV
60
What is free calcium a cofactor for?
IIa, VIIa, IXa, XIIIa
61
What are some anticoagulants we should be aware of?
1. Antithrombin III 2. Protein C 3. Protein S 4. Tissue Factor Pathway Inhibitor (TFPI) 5. Thrombomodulin 6. Heparin-like molecules
62
What is fibrinolysis?
Clot breakdown; enzymatic degradation of fibrin
63
What cells are involved in fibrinolysis?
Endothelial cells and platelets
64
What enzymes are involved in fibrinolysis?
tPA, plasminogen, contact pathway factors
65
What cofactors are involved in fibrinolysis?
Fibrin, polyphosphates
66
What is the facilitator of fibrinolysis?
bradykinin
67
Fibrinolysis is initiated simultaneously with _____ and localized to \_\_\_\_\_.
coagulation, hemostatic plug
68
What does degradation of fibrin and fibrinogen produce?
FDPs (fibrin degradation products)
69
What is the sequence of events in fibrinolysis?
1. Release of plasminogen activators 2. Plasmin production from plasminogen 3. Clot lysis releasing degradation products
70
What does plasmin do?
Degrades blood plasma proteins, including fibrin clots
71
What is the main inhibitor of plasmin?
antiplasmin
72
What is the main inhibitor of tPA?
PAI-1 and PAI-2
73
What are the 4 inhibitors of fibrinolysis?
1. TAFI 2. PAI-1 & PAI-2 3. Antiplasmin 4. Polyphosphates

Clinical Pathology (22 decks)

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