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Coagulation Disorders Flashcards

Exam 4

1
Q

Describe the brick-and-mortar explanation of thrombogenesis

A

Brick and mortar (thrombi) = mortar (fibrin) + bricks (platelet plugs)

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2
Q

What are the 4 phases of thrombogenesis?

A
  1. Adhesion
  2. Aggregation
  3. Secretion
  4. Cross-linking of adjacent platelets
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3
Q

What are the 2 parts to platelet adhesion?

A
  • vWF binds to GP 1b receptor
  • collagen binds to GP 1a receptor
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4
Q

What mediators are secreted during thrombogenesis?

A

5-HT, ADP, TXA2

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5
Q

Prostacyclin (PGI2) inhibits what?

A

clot formation/platelet aggregation

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6
Q

NSAIDs inhibit _____ and are (anti or pro) - _____ clot

A

PGI2, pro

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7
Q

Aspirin inhibits _____ and is (anti or pro) - _____ clot

A

TXA2, anti

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8
Q

________ holds the clots together

A

Fibrin

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9
Q

______ converts fibrinogen to fibrin

A

thrombin

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10
Q

____ converts prothrombin to thrombin

A

Xa

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11
Q

How is the extrinsic coagulation pathway initiated?

A

Tissue damage exposes tissue factor

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12
Q

How is the intrinsic coagulation pathway initiated?

A

Platelets interact with damaged endothelium

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13
Q

The ______ pathway describes the activation of thrombin, and formation of the fibrin clot

A

common

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14
Q

What are the 3 inhibitors in the coagulation pathway? What do they inhibit?

A

1) TFP1 - factor 7
2) Antithrombin - thrombin (factor 2a) and 10
3) Protein C (factors 5 and 8)

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15
Q

What are the 5 things that thrombin activates in the coagulation cascade?

A

factors 5, 8, 11, 13, and protein C

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16
Q

Describe the steps to the intrinsic coagulation pathway

A

1) damaged endothelium
2) activation of factor XII → XI →IX → X
3) Xa converts prothrombin → thrombin (common pathway)

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17
Q

Describe the steps to the extrinsic coagulation pathway

A

1) trauma activates factor VII and exposes tissue factor
2) tissue factor and VIIa → activates factor X
3) Xa converts prothrombin → thrombin (common pathway)

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18
Q

Describe the common pathway of coagulation

A

1) Xa converts prothrombin (II) → thrombin (IIa)
2) thrombin (IIa) converts fibrinogen (I) to fibrin (Ia)
3) XIIIa (activated by thrombin) converts fibrin (Ia) → cross-linked fibrin clot

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19
Q

How is protein C activated?

A

Thrombin activates inactive protein C + thrombomodulin and protein S converts it into active protein C

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20
Q

What is Virchow’s triad?

A

1) stasis (decreased blood flow)
2) endothelial injury (damage to inside of blood vessel)
3) hypercoagulability

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21
Q

Virchow’s triad can result in _____

A

Deep Vein Thrombosis (DVT)

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22
Q

What are the 2 types of DVT risk factors?

A

Inherited and acquired

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23
Q

What are the 5 types of inherited DVT risk factors?

A
  • Antithrombin III deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Sickle cell anemia
  • Activated protein C resistance
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24
Q

What are the 6 types of acquired DVT risk factors?

A
  • Bedridden
  • Surgery/trauma
  • Obesity
  • Estrogen use
  • Malignancies
  • Chronic venous insufficiency
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25
____ is the over stimulation of the blood clotting mechanism
DIC - Disseminated coagulation
26
Differentiate between red and white thrombi
White - high pressure arteries; platelets + thrombin Red - low pressure vein, long tail, red cells around white thrombus
27
What are the 3 results of DIC?
- Generalized blood coagulation - Excessive consumption of factors and platelets - Leads to spontaneous bleeding
28
What are the 4 causes of DIC?
- Massive tissue injury - Malignancy - Bacterial sepsis - Abruptio placentae
29
What is the mortality rate of DIC?
10-50% mortality
30
How is DIC treated?
Plasma transfusions and treat the underlying cause
31
What are the 2 major systems of coagulation regulation?
- Fibrin inhibition - Fibrinolysis
32
What are the 4 classes of coagulation modifier drugs?
1. anticoagulants 2. anti-platelets 3. thrombolytic drugs (fibrinolytic) 4. hemostatic or antifibrinolytic drugs
33
______ inhibit the action or formation of clotting factors
Anticoagulants
34
_____ inhibit platelet aggregation, preventing platelet plugs
Anti-platelet drugs
35
_______ lyse (break down) existing clots
Thrombolytic drugs (Fibrinolytic)
36
______ promote blood coagulation
Hemostatic or Antifibrinolytic drugs
37
______ prevent venous thrombosis
anticoagulants
38
______ prevent arterial thrombosis
antiplatelets
39
What are the direct acting anticoagulants?
Hirudin (Lepirudin) and warfarin (Coumadin)
40
What are the indirect thrombin inhibitors?
Heparin - LMWH and HMWH Fondaparinux (Arixtra)
41
LMW heparin is _____ specific for factor Xa and has _____ effect on thrombin than HMW heparin
more, less
42
What is the lab test used to monitor heparin levels?
activated partial thromboplastin time (aPTT)
43
Transient thrombocytopenia is also known as _____ and is a toxic effect of _____
Heparin induced thrombocytopenia (HIT) heparin
44
What is the normal aPTT? What does it measure?
- normal 35-45 sec - measures activity of the *intrinsic system* and common pathway - Phospholipid added to induce intrinsic pathway
45
How is heparin reversed?
- D/C drug - Protamine sulfate
46
Compare the MOA of the 3 indirect thrombin inhibitors
HMWH - AT III, Xa, and thrombin LMWH - Xa and AT III Fondaparinux (Arixtra) - AT III
47
Differentiate between PT and INR
PT - time to clot INR - time to clot compared to control INR = PT(test)/PT(normal)
48
What does Prothrombin time (PT) measure?
Assess the function of the extrinsic system and common pathway of the coagulation cascade - Addition of tissue factor (factor III)
49
What is the MOA of Hirudin (Lepirudin – recombinant)?
Direct thrombin inhibitor - Bind to both active and substrate recognition sites of thrombin
50
Warfarin has an oral bioavailability of ____ and protein binding of ____
- 100% oral availability - Protein binding = 99%
51
What is the MOA of warfarin?
Direct thrombin inhibitor - Blocks the γ-carboxylation of several glutamate residues (vitamin K dependent)
52
What is the normal vs therapeutic target for INR?
normal 0.8-1.2; warfarin target 2-3
53
How is warfarin reversed?
- Stop drug - Large dose vitamin K - FFP - Factor IX concentrates
54
How do fibrinolytics work?
Catalyze the formation of serine protease plasmin and rapidly lyse thrombi
55
What are the 3 fibrinolytics?
Streptokinase Urokinase Tissue plasminogen activators (t-PA)
56
What is the recombinant form of Tissue plasminogen activators (t-PA)?
Alteplase
57
What do fibrinolytic drugs treat?
MI and PE
58
What are the 3 antiplatelet aggregation drugs?
aspirin clopidogrel abciximab
59
MOA of aspirin
Inhibition of TXA2 synthesis, COX-1 Selective
60
MOA of clopidogrel
Irreversibly inhibit ADP receptor on platelets
61
MOA of Abciximab
IIb/IIIa Receptor Blocker - Activation of this receptor complex in the final common pathway
62
What are the 5 drugs used to treat bleeding disorders?
1. Vitamin K 2. Plasma Fractions 3. Desmopressin Acetate 4. Aminocaproic acid 5. Tranexamic Acid (TXA)
63
Vitamin K confers activity on what?
- Prothrombin - Factors VII, IX, and X
64
What are plasma fractions used to treat?
Deficiencies in plasma coagulation factors - Hemophilia, AT III deficiency, etc.
65
What is vitamin K used to treat?
Warfarin OD and vitamin K deficiency
66
What are the 2 hemostatic drugs that replenish factors?
Vitamin K and plasma fractions
67
What are the 2 drugs that are fibrinolytic inhibitors?
Aminocaproic acid Tranexamic Acid (TXA) - both inhibit plasminogen → plasmin
68
What is the MOA of Desmopressin Acetate?
Increases factor VIII activity
69
What does Desmopressin Acetate treat?
- Mild hemophilia A - von Willebrand disease
70
What does Aminocaproic acid treat?
- Adjunctive hemophilia therapy - Bleeding from fibrinolytic therapy - Intracranial aneurysms - Post surgical bleeding
71
What does Tranexamic acid (TXA) treat?
Decreased risk of death in major bleeding - Trauma, heavy menstrual bleeding, postpartum, epistaxis
72
Draw the pathway for fibrinolysis including the mediators involved.
73
What are the 2 direct thrombin inhibitors that bind only to thrombin active sites?
- Argatroban - Dabigatran (Pradaxa)
74
What are the 2 factor Xa inhibitors? What are they used to treat?
Rivaroxaban, Apixaban Stroke and VTE

Pharm 2024 (32 decks)

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