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PHRM 844 > Anticoag - Wendt > Flashcards

Anticoag - Wendt Flashcards

1
Q

What are the major components PRIMARY hemostasis?

A

Vasoconstriction and platelet activation

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2
Q

What are the major components of SECONDARY hemostasis?

A

Platelet activation and antithromotic control mechanisms

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3
Q

What converts fibrinogen to fibrin?

A

Thrombin

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4
Q

What are the 4 phases of hemostasis?

A

1 Vasospasm
2 Platelet plug formation
3 Fibrin clot formation
4 Fibrinolysis

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5
Q

What is the definition of hemostasis?

A

Arrest of bleeding from a damaged blood vessel

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6
Q

What is the definition of coagulation?

A

Multi-step process to “plug” the leaking vessel

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7
Q

Platelets have organelles and secretory granules but what are they missing?

A

A nucleus

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8
Q

What are the 3 steps of thrombus formation?

A

1 Adhesion and shape change
2 Secretion reaction
3 Aggregation

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9
Q

What are the therapeutic indications for anticoagulants?

A
  • Stroke
  • Post MI
  • Unstable angina
  • DVT
  • PE
  • Artificial surfaces
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10
Q

What do anticoagulants do?

A

Prevent excessive clotting that can lead to occlusion of blood vessels

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11
Q

What are the risks and benefits of anticoagulation

A

Risk: More bleeding
Benefit: Less VTE/CVA

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12
Q

What do seriene proteases do?

A

Cleave down-stream factors to activate them

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13
Q

What are examples of seriene proteases and the factors that they cleave

A
  • Factors 12, 11, 10, 9, 7, 2 cleave factors Va and VIIIa

- Protein C

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14
Q

What do glycoproteins do?

A

Co-factors for activation of proteases

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15
Q

What are examples of glycoproteins and what do they do?

A
  • Factors 8, 10, 3, Protein S bind to and inhibit thrombin

- Anti-thrombin III

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16
Q

What are 5 clotting factors?

A
  • Serine Proteases
  • Glycoproteins
  • Ca++
  • Transglutaminase
  • Fibrinogen/Fibrin
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17
Q

How does calcium act as a clotting factor?

A

Links certain factors to anionic lipids

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18
Q

What does transglutaminase do

A

Cross-links fibrin fibers (factor 8)

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19
Q

All clotting factors are produced in the liver except what?

A

von Willebrand Factor

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20
Q

Where is von Willebrand Factor produced?

A

endothelium, subendothelium, and megakaryocytes

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21
Q

What disease state can have unpredictable effects on coagulation?

A

Liver disease

22
Q

How is the extrinsic or tissue factor pathway activated?

A
  • Tissue factor is expressed on surface of cells outside of but near blood vessels
  • Factor 7 normally resides in blood
  • TF binding to factor 7 activates it
  • Factor 7a binds and cleaves factor X
23
Q

How does thrombin increase coagulation?

A
  • Activates factor V and VIII

- Enhances platelet activation

24
Q

How does platlet activation increase coagulation?

A

Increases activation of factor VII, factor X, and cleavage of prothrombin

25
How does antithrombin decrease coagulation?
- Neutralizes procoagulant serine proteases (thromgin, Xa, IXa) - Reaction is accelerated by heparin
26
How does the Protein C system decrease coagulation?
- Activated by thrombin binding to thrombomodulin | - Activated protein C complex (APC) forms a complex with protein S to inactivate factors Va and VIIIa
27
How does factor Xa decrease coagulation?
Activates tissue factor pathway inhibitor (TFPI) to block initial activation of factor VII
28
What are 5 common tests of hemostatic function that come as part of a DIC panel?
- Platelet count - Prothrombin time (PT/INR) - aPTT - Fibrinogen - D-dimer
29
What are tests of hemostatic function used for?
Diagnostic purposes or to monitor anticoagulant therapy
30
What do the results of the platelet count test mean?
Too low - thrombocytopenia; bone marrow malfunction, nutritional deficiencies Too high - thrombocytosis
31
How long does it take for Plasma + thromboplastin + Ca to clot?
11-14 seconds
32
What does the prothrombin time (PT/INR) test measure?
Plasma + thormboplastin + calcium
33
What does the aPTT test measure?
Plasma + phospholipid (no TF) + activaitng agent
34
How long does it take Plasma + phospholipid (no TF) + activaitng agent to clot?
25-40 seconds
35
What is the range for fibrinogen?
200-400 mg/dL
36
Warfarin acts by inhibiting the synthesis of what?
Clotting factors 2, 7, 9, and X
37
What are 5 drugs/drug classes/conditions that decrease Warfarin's anticoagulant effects?
- Cholestyramine - Barbiturates, carbamazepine, rifampin - Nephrotic syndrome/hypoporteinemia - Vitamin K - Pregnancy
38
How does cholestyramine diminish warfarin's anticoagulant effect?
Inhibits warfarin absorption in the GI tract
39
How do barbiturates, carbamazepine, rifampin diminish warfarin's anticoagulant effect?
Accelerates warfarin metabolism by inducing P450 enzymes
40
How does nephrotic syndrome/hypoproteinemia diminish warfarin's anticoagulant effect?
Increases V and decreased t1/2
41
How does vitamin K diminish warfarin's anticoagulant effect?
Bypasses warfarin-induced epoxidise reductase inhibition
42
How does pregnancy diminish warfarin's anticoagulant effect?
- SHOULD NOT BE ON WARFARIN IF PREGNANT | - Increased levels of clotting factors
43
What are 4 drugs/drug classes that enhance warfarin's anticoagulant effect?
- Chloral Hydrate - Chloramphenicol, SSRI's amiodarone - Broad-spectrum antibiotics - Anabolic steroids (e.g. testosterone)
44
How does choral hydrate enhance warfarin's anticoagulant effect?
Displaces warfarin from plasma albumin
45
How does chloramphenicole, SSRI's amiodarone enhance warfarin's anticoagulant effect?
Decreases warfarin metabolized by inhibiting P450
46
How do broad-spectrum antibiotics enhance warfarin's anticoagulant effect?
Reduce availability of vitamin K in the GI tract
47
How do anabolic steroids enhance warfarin's anticoagulant effect?
Inhibits synthesis and increases degradation of clotting factors
48
Vitamin K is involved in the post-translational modification of what?
- Prothrombin | - Factors 7, 9, X
49
What are the 3 uses for Vitamin K?
- Individuals with abnormalities of fat absorption (vitamin K deficiency) - All newborns receive an injection to prevent hemorrhagic disease - Reverse anticoagulant effect of excess warfarin
50
What is the major enzyme responsible for converting the S-enantiomer warfarin to its inactive metabolites?
CYP2C9
51
What does protamine sulfate do and how does it work?
- Antagonizes heparin | - Binds tightly to heparin to neutralize the anticoagulant action
52
Place the indirect factor Xa inhibitors in order of highest to lowest risk of causing HIT
Unfractionated heparin > heparin > LMWH > fondaparinux

PHRM 844 (9 decks)

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