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Pharmacology > Coagulation Systems > Flashcards

Coagulation Systems Flashcards

1
Q

What is heparin’s mechanism of action? Does it cross the Placenta?

A

Binds to antithrombin III and activates it.

It does not cross the placenta (mostly b/c its charged).

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2
Q

What is antithrombin III (AT III)?

A

A natural anticoagulant. It inactivates thrombin (factor IIa) as well as factors IX, X, XI, XII

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3
Q

If a patient does not respond to heparin, what should you consider doing?

A

Consider giving them FFP to replenish AT III.

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4
Q

What is used to evaluate heparin activity?

A

ACT (activated coagulation time) - mix blood with activation substance and measure how long it takes to clot. ACT is measured 3 min after heparin is given and compared to baseline ACT. Usually want ACT = 2x baseline for vascular procedures.

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5
Q

What is used to prevent DVT/PE/acute MIs?

A

heparin or lovenox

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6
Q

What are Streptokinase and Alteplase used for? What is their mechanism of action?

A

They are thrombolytic drugs. They are tissue plasminogen activators.

activate plasminogen-> plasmin (destroys clots)

Indications: acute coronary syndrome, stroke

Can be be given into a clogged vascular access device (dyalisis, PICC)

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7
Q

What is the mechanism of aspirin and its effects on coagulation?

A

Antiplatelet drug. NSAID (COX-1 and COX-2 inhibitor).

Irreversible prevention of platelet aggregation

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8
Q

What is aspirin commonly prescribed for?

A

prevent of stroke, MI, occlusion of coronary stents

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9
Q

What is the mechanism of Clopidogrel (Plavix) and its effects on coagulation?

A

irreverible inhibition of platelet activation and aggregation

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10
Q

What is the mechanism of Amicar (E-aminocaproic acid) and Tranexamic acid and their effects on coagulation?

A

they are antifibrinolytic drugs - they protect the clot.

prevent plasminogen->plasmin AND inactivate plasmin

plasmin degrades fibrin (fibrin cross-links stabilize platelets)

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11
Q

What is recombinant factor VIIa?

A

Directly activates Factor X and initiates thrombin burst without requiring Factors VIII or IX.

Requires presence of factors V,X,II, fibrinogen, and at least some platelets

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12
Q

What is DDAVP?

A

causes release of factor VIII, vWF, and t-PA

used in vWD, mild hemophilia, uremia, ASA/NSAIDS/dextran/plavix

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13
Q

What are the side effects of heparin?

A

Hemorrhage and hematoma formation
Thrombocytopenia (low platelet level in blood) - this includes mild thrombocytopenia and HITT
Allergic reaction (its derived from animal tissue)

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14
Q

What is HITT?

A

Heparin Induced Thrombocytopenia and Thrombosis

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15
Q

What is used to reverse heparin?

A

Protamine - derived from salmon sperm

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16
Q

In the absence of heparin, protamine has what effect?

A

anticoagulant effect

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17
Q

What are the side effects of heparin?

A

hTN, pulmonary HTN, allergic rxn

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18
Q

What drug is characterized by the following:

Strong base
Combines w/ negatively charged heparin to form a complex
Derived from salmon sperm

A

Protamine

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19
Q

What 4 factors are part of the extrinsic pathway?

A

Factors II, V, VII, X

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20
Q

What are the 4 vitamin K dependent factors?

A

Factors II, VII, IX, X

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21
Q

Factor IIa is also known as what?

A

thrombin

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22
Q

Hemophilia A is characterized by what factor deficiency?

A

VIII

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23
Q

Clotting factors are all inactive pro-enzymes that, with the exception of one factor, are all synthesized where? Which factor is the exception?

A

All synthesized in the liver except fact VIII

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24
Q

What is vWF deficiency characterized by?

A

poor platelet adhesion AND clinical hemophilia

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25
Q

What are the 3 Phases of Coagulation?

A

Activation
Amplification
Propogation

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26
Q

Describe the 3 steps involved with the Activation Phase of Coagulation.

A

Injury->Tissue Factor-> activates VII, X, V, II (thrombin)

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27
Q

Describe the 3 steps involved with the Amplification Phase of Coagulation.

A

Amplification (“thrombin burst”)

Platelets activated; Thrombin activates V, VIII, IX; platelets bind to collagen

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28
Q

Describe the Propagation Phase of Coagulation.

A

Propagation: fibrin cross-links stabilize the platelets

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29
Q

Heparin is given as DVT prophylaxis in what group of people most commonly? what is the typical dose?

A

Hospitalized pts, esp surgical pts (esp hip replacements)

DVT Prophylaxis= 5,000units SQ q8-12h (7,500 for very obese)

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30
Q

What is the heparin dose for treatment of DVT/PE?

What PTT are you aiming for?

A

80 units/kg bolus + infusion at 18 units/kg/hr

PTT: titrate to 1.5-2.5x normal, q6hr

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31
Q

What is Enoxaparin?

A

Also called Lovenox. It is a LMWH (low molecular weight heparin)

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32
Q

True or False. Lovenox has more protein binding when compared with unfractionated heparin?

A

False. Lovenox has less protein binding

33
Q

T or F. Lovenox has no effect on PT/PTT.

A

TRUE

34
Q

What are the routes of administration for heparin? Do any have associated risks?

A

IV or SC. IM carries risk of hematoma

35
Q

What are the pharmacokinetics of Heparin (unfractionated)?

A

Non-linear dose-response relationship, partially du to extensive protein binding.

Elimination half-life changes based on dose (usually 1-2 hrs)

36
Q

Which has more predictable pharmacokinetics, Heparin or Enoxaparin?

A

Enoxaparin (Lovenox) does. More consistent and predictable pharmacokinetics. Less protein binding than Heparin.

Heparin: Non-linear dose-response relationship, partially due to extensive protein binding. Elimination half-life changes based on dose (usually 1-2 hrs)

37
Q

Which has a longer elimination half-life, Heparin or Lovenox.

A

Lovenox = 4-5 hrs

Heparin = 1-2 hrs usually

38
Q

How long must a surgery be delayed after the last dose of Lovenox?

A

12 hrs

39
Q

How often are Heparin and Lovenox dosed?

A

Lovenox = once daily

Heparin = q8-12hrs

40
Q

T or F. Protamine is more effective reversing Lovenox than Heparin?

A

False. Lovenox only gets partial reversal with Protamine.

neutralizes ~ 65% of anti-Xa activity

41
Q

What is the dose of Protamine for Heparin reversal?

A

1mg Protamine for every 100 units of heparin believed to be in circulation.

42
Q

What is the difference b/n mild thrombocytopenia and HITT? What % of pts are effected by each as a side effect of heparin?

A

Mild: < 100,000 platelets - (30-40% of pts) -
DRUG-INDUCED platelet aggregation - can happen even w/trivial exposure to heparin

HITT: (0.5-6% of pts) -
IMMUNE-MEDIATED formation of ANTIPLATELET ANTIBODIES

43
Q

T or F. Warfarin (Coumadin) has no effect on platelet activity.

A

True

44
Q

What is the mechanism of action of Warfarin?

A

inhibits vit K epoxide reductase -> deficiency of vit K-dependent coagulation factors (II,VII,IX,X)

45
Q

What is the time of Warfarin’s onset of action, peak effect, and duration?

A 
onset = 8-12 hrs
peak  = 36-72 hrs
duration = 2-5 days after stopping therapy
46
Q

Which of the following cross the placenta and should not be used during pregnancy?

a. Heparin
b. Enoxaparin
c. Warfarin

A

c

47
Q

What would happen if a pregnant woman took Coumadin?

A

It crosses the placenta, so it would cause CNS damage, bleeding and developmental defects

48
Q

T or F. The effects of Warfarin can be measured with PT/INR?

A

true

49
Q

What effects the dose response of Coumadin?

A

changes in intake and absorption of dietary vit K

50
Q

What is the target INR for a pt on Coumadin?

A

Target INR = 2.0-3.0

51
Q

What can be given in an emergency situation to a pt that is on Coumadin?

A

1mg vit k and/or FFP (up to 15 mL/kg)

can also use recombinant FVIIa or prothrombin complex concentrate

52
Q

Although Lovenox is safe to use during pregnancy, there are still some risks. Name 2.

A

spontaneous hematoma formation (esp w/neuroaxial blocks)

some risk of HITT

53
Q

What are the indications for use for Warfarin?

A

prevent and treat DVT/PE

thrombus associated with a-fib

prosthetic heart valves

54
Q

What is the most common side effect of Warfarin?

A

bleeding (esp intracranial hemorrhage)

55
Q

T or F. Regarding drug interactions with Warfarin, few drugs can affect absorption, metabolism, protein binding, and vit K levels.

A

False. many drugs affect these things

56
Q

T or F. ACT is used to measure Heparin levels.

A

False. It is used to measure heparin activity…it is hard to measure heparin levels

57
Q

T or F. PTT reflects heparin activity and PT reflects Warfarin effects.

A

True

58
Q

What is a typical heparin IV bolus and what is the typical ACT goal for vascular surgeries?

A

Bolus = 5,000 units

ACT = 2x baseline

59
Q

What is the acceptable ACT (in seconds) and what is a typical heparin bolus dose for CPB?

A

Acceptable ACT = at least 300-480 seconds

Bolus = 300-350 units/kg = 20,000-30,000 units IV

60
Q

When should Clopidigrel (Plavix) be stopped for elective surgery?

A

7 days prior to surgery

61
Q

T or F. You should try to avoid regional anesthesia in pts on Plavix?

A

True

62
Q

In an emergent case, what would you give to a pt on Clopidogrel (Plavix) to restore hemostasis?

A

consider platelet transfusion

63
Q

What drug is characterized by the following:

Mimics the active binding site of heparin - when bound to AT III it inhibits Factor Xa but not thrombin

A

Fondaparinux (Arixtra)

64
Q

T or F. Fondaparinux (Arixtra) has a high risk for HITT?

A

False. Fondaparinux (Arixtra) has a low risk for HITT

65
Q

Argatroban, Dabigatran (Pradaxa), and Bivalirudin (Angiomax) are what type of anticoagulant drugs?

A

Direct Thrombin Inhibitors

Highly Specific thrombin inhibitors - suppress platelet function

66
Q

What 3 drugs are characterized by the following:

Can be used as an alternative to heparin in pts w/ HITT - Can be used for CPB and ECMO - Used in tx of acute coronary syndrome

A

Argatroban, Dabigatran (Pradaxa), and Bivalirudin (Angiomax)

67
Q

Which if the following can be used to titrate the dose of Argatroban, Dabigatran (Pradaxa), and Bivalirudin (Angiomax)?

a. PT
b. PTT
c. ACT
d. none of the above

A

b. PTT

68
Q

Describe the steps of fibrinolysis.

A

Plasminogen -> plasmin -> degrades fibrin

69
Q

What are the contraindications for Tranexamic acid?

A

Antifibrinoytics are contraindicated in pts w/pro-thombic conditions (Hx DVT/PE, MI, CABG, coronary stents, CVA)

also in pts w/ Hx of seizure or known retinal microcirculatory problems

70
Q

T or F. Recombinant Factor VIIa has become the hemostatic agent of choice for pts w/ hemophilia A or B.

A

False. It has become the hemostatic agent of last resort.

71
Q

When is Recombinant Factor VIIa typically used?

A

trauma, hepatic failure, GI bleed, OB hemorrhage, ICH, transplantation

72
Q

T or F. Recombinant Factor VIIa can be used to reverse Warfarin.

A

True

73
Q

What are complications associated with Recombinant Factor VIIa?

A

Thrombotic complications - stroke, MI, PE, clotted devices (LVAD)

74
Q

Recombinant Factor VIIa must be used with caution in high risk pts. List 3 things that would be considered high risk.

A

CAD, cerebrovascular disease, and DIC

75
Q

When is Desmopressin (DDAVP) used?

A

used in vWD, mild hemophilia, uremia, ASA/NSAIDS/dextran/plavix

76
Q

T or F. DDAVP works at the V2 recceptors only, causing vasoconstriction and anti-diuresis.

A

False. no vasoconstriction - only anti-diuresis

77
Q

What is the cost of Recombinant Factor VIIa and what is the hemophilia dose?

A

$1/mcg and hemophilia dose = 90mcg/kg

78
Q

What is the half-life of Recombinant Factor VIIa?

A

half-life = 2hrs

Pharmacology (22 decks)

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