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Pharm 2024 > Coagulation Disorders > Flashcards

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
Q

____ is the over stimulation of the blood clotting mechanism

A

DIC - Disseminated coagulation

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26
Q

Differentiate between red and white thrombi

A

White - high pressure arteries; platelets + thrombin
Red - low pressure vein, long tail, red cells around white thrombus

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27
Q

What are the 3 results of DIC?

A
  • Generalized blood coagulation
  • Excessive consumption of factors and platelets
  • Leads to spontaneous bleeding
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28
Q

What are the 4 causes of DIC?

A
  • Massive tissue injury
  • Malignancy
  • Bacterial sepsis
  • Abruptio placentae
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29
Q

What is the mortality rate of DIC?

A

10-50% mortality

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30
Q

How is DIC treated?

A

Plasma transfusions and treat the underlying cause

31
Q

What are the 2 major systems of coagulation regulation?

A
  • Fibrin inhibition
  • Fibrinolysis
32
Q

What are the 4 classes of coagulation modifier drugs?

A
  1. anticoagulants
  2. anti-platelets
  3. thrombolytic drugs (fibrinolytic)
  4. hemostatic or antifibrinolytic drugs
33
Q

______ inhibit the action or formation of clotting factors

A

Anticoagulants

34
Q

_____ inhibit platelet aggregation, preventing platelet plugs

A

Anti-platelet drugs

35
Q

_______ lyse (break down) existing clots

A

Thrombolytic drugs (Fibrinolytic)

36
Q

______ promote blood coagulation

A

Hemostatic or Antifibrinolytic drugs

37
Q

______ prevent venous thrombosis

A

anticoagulants

38
Q

______ prevent arterial thrombosis

A

antiplatelets

39
Q

What are the direct acting anticoagulants?

A

Hirudin (Lepirudin) and warfarin (Coumadin)

40
Q

What are the indirect thrombin inhibitors?

A

Heparin - LMWH and HMWH
Fondaparinux (Arixtra)

41
Q

LMW heparin is _____ specific for factor Xa and has _____ effect on thrombin than HMW heparin

A

more, less

42
Q

What is the lab test used to monitor heparin levels?

A

activated partial thromboplastin time (aPTT)

43
Q

Transient thrombocytopenia is also known as _____ and is a toxic effect of _____

A

Heparin induced thrombocytopenia (HIT)
heparin

44
Q

What is the normal aPTT? What does it measure?

A
  • normal 35-45 sec
  • measures activity of the intrinsic system and common pathway
    • Phospholipid added to induce intrinsic pathway
45
Q

How is heparin reversed?

A
  • D/C drug
  • Protamine sulfate
46
Q

Compare the MOA of the 3 indirect thrombin inhibitors

A

HMWH - AT III, Xa, and thrombin
LMWH - Xa and AT III
Fondaparinux (Arixtra) - AT III

47
Q

Differentiate between PT and INR

A

PT - time to clot
INR - time to clot compared to control
INR = PT(test)/PT(normal)

48
Q

What does Prothrombin time (PT) measure?

A

Assess the function of the extrinsic system and common pathway of the coagulation cascade
- Addition of tissue factor (factor III)

49
Q

What is the MOA of Hirudin (Lepirudin – recombinant)?

A

Direct thrombin inhibitor - Bind to both active and substrate recognition sites of thrombin

50
Q

Warfarin has an oral bioavailability of ____ and protein binding of ____

A
  • 100% oral availability
  • Protein binding = 99%
51
Q

What is the MOA of warfarin?

A

Direct thrombin inhibitor - Blocks the γ-carboxylation of several glutamate residues (vitamin K dependent)

52
Q

What is the normal vs therapeutic target for INR?

A

normal 0.8-1.2; warfarin target 2-3

53
Q

How is warfarin reversed?

A
  • Stop drug
  • Large dose vitamin K
  • FFP
  • Factor IX concentrates
54
Q

How do fibrinolytics work?

A

Catalyze the formation of serine protease plasmin and rapidly lyse thrombi

55
Q

What are the 3 fibrinolytics?

A

Streptokinase
Urokinase
Tissue plasminogen activators (t-PA)

56
Q

What is the recombinant form of Tissue plasminogen activators (t-PA)?

A

Alteplase

57
Q

What do fibrinolytic drugs treat?

A

MI and PE

58
Q

What are the 3 antiplatelet aggregation drugs?

A

aspirin
clopidogrel
abciximab

59
Q

MOA of aspirin

A

Inhibition of TXA2 synthesis, COX-1 Selective

60
Q

MOA of clopidogrel

A

Irreversibly inhibit ADP receptor on platelets

61
Q

MOA of Abciximab

A

IIb/IIIa Receptor Blocker - Activation of this receptor complex in the final common pathway

62
Q

What are the 5 drugs used to treat bleeding disorders?

A
  1. Vitamin K
  2. Plasma Fractions
  3. Desmopressin Acetate
  4. Aminocaproic acid
  5. Tranexamic Acid (TXA)
63
Q

Vitamin K confers activity on what?

A
  • Prothrombin
  • Factors VII, IX, and X
64
Q

What are plasma fractions used to treat?

A

Deficiencies in plasma coagulation factors - Hemophilia, AT III deficiency, etc.

65
Q

What is vitamin K used to treat?

A

Warfarin OD and vitamin K deficiency

66
Q

What are the 2 hemostatic drugs that replenish factors?

A

Vitamin K and plasma fractions

67
Q

What are the 2 drugs that are fibrinolytic inhibitors?

A

Aminocaproic acid
Tranexamic Acid (TXA)
- both inhibit plasminogen → plasmin

68
Q

What is the MOA of Desmopressin Acetate?

A

Increases factor VIII activity

69
Q

What does Desmopressin Acetate treat?

A
  • Mild hemophilia A
  • von Willebrand disease
70
Q

What does Aminocaproic acid treat?

A
  • Adjunctive hemophilia therapy
  • Bleeding from fibrinolytic therapy
  • Intracranial aneurysms
  • Post surgical bleeding
71
Q

What does Tranexamic acid (TXA) treat?

A

Decreased risk of death in major bleeding
- Trauma, heavy menstrual bleeding, postpartum, epistaxis

72
Q

Draw the pathway for fibrinolysis including the mediators involved.

A
73
Q

What are the 2 direct thrombin inhibitors that bind only to thrombin active sites?

A
  • Argatroban
  • Dabigatran (Pradaxa)
74
Q

What are the 2 factor Xa inhibitors? What are they used to treat?

A

Rivaroxaban, Apixaban
Stroke and VTE

Pharm 2024 (32 decks)

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