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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
Q

How does antithrombin decrease coagulation?

A
  • Neutralizes procoagulant serine proteases (thromgin, Xa, IXa)
  • Reaction is accelerated by heparin
26
Q

How does the Protein C system decrease coagulation?

A
  • Activated by thrombin binding to thrombomodulin

- Activated protein C complex (APC) forms a complex with protein S to inactivate factors Va and VIIIa

27
Q

How does factor Xa decrease coagulation?

A

Activates tissue factor pathway inhibitor (TFPI) to block initial activation of factor VII

28
Q

What are 5 common tests of hemostatic function that come as part of a DIC panel?

A
  • Platelet count
  • Prothrombin time (PT/INR)
  • aPTT
  • Fibrinogen
  • D-dimer
29
Q

What are tests of hemostatic function used for?

A

Diagnostic purposes or to monitor anticoagulant therapy

30
Q

What do the results of the platelet count test mean?

A

Too low - thrombocytopenia; bone marrow malfunction, nutritional deficiencies

Too high - thrombocytosis

31
Q

How long does it take for Plasma + thromboplastin + Ca to clot?

A

11-14 seconds

32
Q

What does the prothrombin time (PT/INR) test measure?

A

Plasma + thormboplastin + calcium

33
Q

What does the aPTT test measure?

A

Plasma + phospholipid (no TF) + activaitng agent

34
Q

How long does it take Plasma + phospholipid (no TF) + activaitng agent to clot?

A

25-40 seconds

35
Q

What is the range for fibrinogen?

A

200-400 mg/dL

36
Q

Warfarin acts by inhibiting the synthesis of what?

A

Clotting factors 2, 7, 9, and X

37
Q

What are 5 drugs/drug classes/conditions that decrease Warfarin’s anticoagulant effects?

A
  • Cholestyramine
  • Barbiturates, carbamazepine, rifampin
  • Nephrotic syndrome/hypoporteinemia
  • Vitamin K
  • Pregnancy
38
Q

How does cholestyramine diminish warfarin’s anticoagulant effect?

A

Inhibits warfarin absorption in the GI tract

39
Q

How do barbiturates, carbamazepine, rifampin diminish warfarin’s anticoagulant effect?

A

Accelerates warfarin metabolism by inducing P450 enzymes

40
Q

How does nephrotic syndrome/hypoproteinemia diminish warfarin’s anticoagulant effect?

A

Increases V and decreased t1/2

41
Q

How does vitamin K diminish warfarin’s anticoagulant effect?

A

Bypasses warfarin-induced epoxidise reductase inhibition

42
Q

How does pregnancy diminish warfarin’s anticoagulant effect?

A
  • SHOULD NOT BE ON WARFARIN IF PREGNANT

- Increased levels of clotting factors

43
Q

What are 4 drugs/drug classes that enhance warfarin’s anticoagulant effect?

A
  • Chloral Hydrate
  • Chloramphenicol, SSRI’s amiodarone
  • Broad-spectrum antibiotics
  • Anabolic steroids (e.g. testosterone)
44
Q

How does choral hydrate enhance warfarin’s anticoagulant effect?

A

Displaces warfarin from plasma albumin

45
Q

How does chloramphenicole, SSRI’s amiodarone enhance warfarin’s anticoagulant effect?

A

Decreases warfarin metabolized by inhibiting P450

46
Q

How do broad-spectrum antibiotics enhance warfarin’s anticoagulant effect?

A

Reduce availability of vitamin K in the GI tract

47
Q

How do anabolic steroids enhance warfarin’s anticoagulant effect?

A

Inhibits synthesis and increases degradation of clotting factors

48
Q

Vitamin K is involved in the post-translational modification of what?

A
  • Prothrombin

- Factors 7, 9, X

49
Q

What are the 3 uses for Vitamin K?

A
  • 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
Q

What is the major enzyme responsible for converting the S-enantiomer warfarin to its inactive metabolites?

A

CYP2C9

51
Q

What does protamine sulfate do and how does it work?

A
  • Antagonizes heparin

- Binds tightly to heparin to neutralize the anticoagulant action

52
Q

Place the indirect factor Xa inhibitors in order of highest to lowest risk of causing HIT

A

Unfractionated heparin > heparin > LMWH > fondaparinux

PHRM 844 (9 decks)

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