Antithrombotics Flashcards

1
Q

What is the action of anticoagulants?

A

Prevents clot formation & extension (doesn’t help against pre-existing clots)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the action of fibrinolytics?

A

Breaks up existing clots

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the action of antiplatelets?

A

Interferes with platelet activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 2 types of thrombi?

A

White thrombus

Red thrombus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q
Describe the makeup of white thrombi and where they form.
Which medication class would be most effective?
A
  • Platelet rich
  • Forms in the arteries i.e. coronary artery clot
  • Antiplatelets: good for s/p M.I for 2nd prevention
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q
Describe the makeup of red thrombi and where they form.
Which medication class would be most effective?
A
  • Fibrin and RBC-rich
  • Forms in the veins i.e. DVT, P.E.
  • Anticoagulants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are some common sites for DVTs? Complication? White clot or red clot?

A
  • Iliac vein, femoral vein, popliteal vein, small saphenous vein
  • Proximal leg veins more likely to become P.E
  • Fibrin-rich red clot
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Is a P.E. thrombus likely a white or red clot?

A

Red clot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Is a CVA more likely a white or red clot?

A

White clot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Is an acute myocardial infarction mor4e likely a white or red clot?

A

White clot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the action of thromboxane A2 (TXA2)?

A
  • Vasoconstriction

- Platelet activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does vonWillebrand Factor do?

A

Links exposed collagen with platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What does fibrinogen do?

A

Forms platelet bridges –> occlusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does thrombin (Fx IIa) do?

A
  • Generates a more stable clot

- Converts fibrinogen –> fibrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which factors does thrombin (Fx IIa) activate?

A

F8

F5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the final result of the coagulation cascade?

A
  • Fibrinogen –> Fibrin

- Fibrin: seals hemostatic/ platelet plug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the 7 steps to platelet activation?

A
  1. Injury
  2. Collagen and vWF exposed
  3. Platelet adherence & activation
  4. Vasoconstrictors (i.e. TXA2) platelet recruiters (ADP), platelet activators (TXA2)
  5. Conformational change to IIb/IIIa receptor (on platelet surface)
  6. Binding of fibrinogen (crosslink platelets)
  7. Aggregation and platelet plug formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the role of Serotonin in platelet activation?
Is serotonin a target of anti-platelet therapy?
What is the risk of SSRIs and clot formation?

A
  • Key role in platelet aggregation, vasoconstriction
  • NO
  • SSRIs carry an increased bleeding risk d/t its effects on platelet aggregation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the 3 key/ target factors in anti-platelet therapy?

A
  • ADP
  • TXA2
  • GPIIb/IIIa Receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the role of ADP?

A

Platelet activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the role of an activated GPIIb/IIIa receptor?

A

When activated, binds fibrinogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the 3 pathways of the coagulation cascade?

A
  • Intrinsic pathway
  • Extrinsic pathway
  • Common pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the intrinsic pathway activated by?

A

Damaged cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the extrinsic pathway activated by?

A

Damaged vessel walls

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the common pathway? Which clotting factor does it start with?

A
  • The convergence of the intrinsic/ extrinsic pathways

- Factor XA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the 3 key steps in the Extrinsic pathway of clotting?

A
  1. Damaged endothelium/ tissue trauma produces TISSUE FACTOR
  2. Tissue factor binds to FACTOR VII –> activates
  3. Tissue Fx/ Fx VIIA complex activates Fx X –> FACTOR XA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the 5 key steps in the Intrinsic pathway of clotting?

A
  1. Damaged cells produce POLY P
  2. Poly P activates PRE-KALLIKREIN & FACTOR XII
  3. Fx XIIA activates FACTOR XI
  4. Fx XIA activates FACTORS IX & VIII
  5. Factors VIIIA & IXA complex –> ACTIVATES Fx X –> FACTOR XA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the end product of both intrinsic/ extrinsic pathways of clotting?

A

Factor XA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the 3 key steps in the common pathway of clotting?

A
  1. Factor XA converts Prothrombin (Fx II) to Thrombin (Fx IIA)
  2. Thrombin converts FIBRINOGEN TO FIBRIN (ultimate goal)
  3. Stable fibrin clot forms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are some co-factors in the common pathway of clotting?

A

Ca2+
Platelet phospholipids
Prothrombin activator

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the role of anti-thrombin?

A

Can deactivate thrombin (Fx IIA) to prevent massive clotting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What does factor II do in the clotting cascade? Where does it act?

A
  • Found in the common pathway aka Prothrombin

- Converted to thrombin (Fx IIA) by Factor XA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What does factor VII do in the clotting cascade? Where does it act?

A
  • Binds to/activated by tissue factor to form a complex that will activate Fx XA
  • End of extrinsic pathway of clotting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What does factor IX do in the clotting cascade? Where does it act?

A
  • Activated by Fx XIA to form a complex with Fx VIII

- Complex with Fx VIIIA activates Fx XA to end the intrinsic pathway of clotting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What does Factor X do in the clotting cascade? Where does it act?

A
  • Factor X is activated in both the intrinsic & extrinsic pathways of clotting
  • Starts the common pathway of clotting by converting prothrombin (Fx II) to thrombin (Fx IIA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What does Factor II do in the clotting cascade? Where does it act?

A
  • Factor II aka Prothrombin is converted to Thrombin (Factor IIA) by Fx XA –> converts fibrinogen to fibrin
  • Start of the common pathway of clotting
37
Q

What are the main 4 Factor targets of anticoagulant therapy?

A

Factors II, VII, IX and X

38
Q

Which factors does Warfarin affect?

A

Factors II, VII, IX, and X (not yet-activated factors)

39
Q

Which factors do heparin, enoxaparin (Lovenox), and fondaparinux affect?

A

Thrombin (IIA) and XA

40
Q

Prothrombin time (PT) is the measurement of the activity of which factors? Variable?

A
  • Measures activity of factors II, VII, IX, & X

- Yes, may vary from hospital to hospital

41
Q

What is an INR? Which medication is this most reflective of?

A
  • International Normalized Ratio is the same as PT but standardized worldwide
  • Key for warfarin
42
Q

Partial thromboplastin time (PTT) is the measurement of the activity of which factors?

A

Factors II, V, VII, IX, X, XI, and XII

43
Q

What are the 3 INDIRECT THROMBIN INHIBITORS?

A
  • Unfractionated heparin (Heparin/ UFH)
  • Low molecular weight heparin (LMWH): enoxaparin (Lovenox)
  • Fondaparinux (Arixtra)
44
Q

What is the MOA of an indirect thrombin inhibitor?

A
  • Normal activity of antithrombin: binds factors IIA (thrombin), IXA, XA, XIA, and XIIA to inactivate them
  • Helps bridge anti-thrombin with thrombin to increase de-activation activity
45
Q

Which 2 factors does unfractionated heparin de-activate?

A

Factors X and II (prothrombin)

46
Q

What are 2 ways in which UFH can be administered? What are the indications?

A
  • Continuous IV infusion for ACS and Warfarin bridging (acute VTE tx)
  • Subcutaneous injection: VTE prophylaxis
47
Q

Which monitoring test should be used for UFH? Goal?

A
  • aPTT

- Goal level is 2-2.5x control (baseline before heparin); approx 60-80 sec

48
Q

What are 3 adverse effects of UFH?

A
  • Bleeding
  • Heparin-Induced Thrombocytopenia (HIT) – intolerance
  • Osteoporosis (long-term)
49
Q

What is HIT? Potential complications?

A
  • An antibody-mediated adverse effect of heparin (or enoxaparin)
  • It is strongly associated with venous & arterial thrombosis
50
Q

How should you monitor a pt for HIT?

A
  • If platelets fall >50% from baseline with nadir (lowest point) > 20K
  • If the platelets start to fall on days 5-10 of Rx
  • If thrombosis occurs while on heparin (abnormal!!)
  • Must R/O other causes of thrombocytopenia e.g. drugs: other antiplatelets, many antibiotics i.e. Zosin
51
Q

What is the treatment for HIT?

A

STOP HEPARIN

Treat with an IV direct thrombin inhibitor

52
Q

Describe the process behind HIT.

A
  1. Heparin and Platelet Fx IV form a complex
  2. Complex is seen as foreign, immune complex with IgG forms
  3. Immune complex attaches to resting platelet on Fc receptor
  4. Platelet activation –> thrombus formation –> decreased platelet count –> + feedback loop
53
Q

What is the MC Low molecular weight Heparin?

A

Enoxaparin (Lovenox)

54
Q

Which factors does enoxaparin inhibit?

A

Factors X and II (prothrombin), mostly Fx X

55
Q

How is enoxaparin administered? Indications?

A

Subcutaneous injection for:

  • ACS
  • Warfarin bridging (acute VTE Rx)
  • VTE prophylaxis
56
Q

How would you monitor enoxaparin?

A
  • Not routinely monitored

- Could use Anti-XA level

57
Q

What are 2 adverse effects of enoxaparin?

A

-Bleeding
-NOT FOR PTS w/ severely reduced renal fxn: CrCl < 20mL/min
REDUCE DOSE for pts w/ CrCl 20-30 mL/min

58
Q

What are the commonalities between UFH and enoxaparin?

A

Both are used for ACE, acute VTE treatment and VTE prophylaxis

59
Q

What are some benefits of using UFH over enoxaparin?

A
  • UFH has a shorter half-life (1.5h vs. 7 hrs) – used in surgery prep
  • Enoxaparin accumulates in renal dysfunction
60
Q

What are some benefits of using enoxaparin over UFH?

A
  • Enoxparain has a more predictable dose-response curve
  • Doesn’t require routine monitoring
  • UFH therapeutic anticoagulation (ACS, VTE treatment) must be given as a continuous infusion; Lovenox would be preferred for outpatients (SQ)
61
Q

Which factor does Fondaparinux inhibit?

A

Factor XA

62
Q

How is Fondaparinux administered? Indications?

A

Subcutaneous injection for:

  • Acute VTE treatment
  • VTE prophylaxis
  • NOT FOR ACS
63
Q

How is Fondaparinux monitored?

A
  • Not routinely done!

- Anti XA level

64
Q

What are 2 adverse effects of Fondaparinux?

A
  • Bleeding

- NOT FOR PTS with renal dysfunction: CrCl <30 mL/min

65
Q

How are INDIRECT thrombin inhibitors reversed?

A
  1. D/C indirect thrombin inhibitor

2. Protamine sulfate, given by IV infusion (binds to drug, deactivates it) –> Max dose 50 mg/10 min

66
Q

What is the dose of protamine sulfate given for heparin?

A

1 mg/100 units heparin in the body

67
Q

What is the dose of protamine sulfate given for enoxaparin? How effective is this?

A

1 mg/ mg enoxaparin in the body

-Only 60% effective

68
Q

What is the dose of protamine sulfate given for fondaparinux?

A

NOT EFFECTIVE to reverse fondaparinux

69
Q

What is the MOA of UFH? LMWH? Fondaparinux?

A
  • UFH binds to antithrombin to help deactivate thrombin
  • LMWH binds to antithrombin partially affecting thrombin
  • Fondaparinux binds to antithrombin and stops thrombin from binding?
70
Q

What are 2 Oral Direct Xa inhibitors?

A
  • RivaroXABAN

- ApiXABAN

71
Q

What are the indications for Rivaroxaban?

A
  • VTE prophylaxis and treatment

- Prevention of stroke and systemic embolism in pts with nonvalvular ATRIAL FIBRILLATION

72
Q

What are the indications for Apixaban?

A
  • VTE prophylaxis after hip/knee replacement surgery

- Prevention of stroke and systemic embolism in pts with nonvalvular ATRIAL FIBRILLATION

73
Q

What is the general MOA of Direct thrombin inhibitors (DTIs)?

A

-Binds directly to thrombin, action is INDEPENDENT of antithrombin

74
Q

Name 2 IV DTIs and 1 PO DTI.

A

IV: Bivalirudin
-Argatroban

PO: Dabigatran

75
Q

What are the indications for Bivalirudin?

A
  • ACS undergoing PCI

- Anticoagulation in pts with HIT (after stopping heparin)

76
Q

What are the indications for Argatroban?

A
  • Anticoagulation in pts with HIT

- Coronary angioplasty in pts with HIT

77
Q

How are the IV DTIs administered?

A

Continuous IV infusion

78
Q

Which monitoring test should be used for the IV DTIs?

A

aPTT

79
Q

What adverse effect is expected with the IV DTIs?

A

Bleeding

80
Q

What reversal agent can be used against IV DTIs?

A

NONE: give supportive care (IV fluids) and blood products (e.g. packed RBCs)

81
Q

What is the indication for Dabigatran (PO DTI)?

A
  • -Prevention of stroke and systemic embolism in pts with nonvalvular ATRIAL FIBRILLATION
  • DVT prophylaxis and treatment
82
Q

What is a major consideration for Dabigatran?

A

ACCUMULATES IN RENAL DYSFUNCTION – may cause massive bleed

  • REDUCE dose if: CrCl 15-30 mL/min
  • DON’T USE if: CrCl <15 mL/min
83
Q

Which monitoring test should be used for Dabigatran?

A

None

84
Q

Which adverse effects are expected with Dabigatran?

A
  • Bleeding

- G.I. upset

85
Q

What reversal agent can be used against Dabigatran?

A

NONE; use dialysis

86
Q

What is the MOA of Warfarin?

A
  • Inhibits (inactive) factors II, VII, IX, X and proteins C and S (natural anticoagulants)
  • Vitamin K antagonist (precursor of activating clotting factors)
87
Q

What are the indications of Warfarin?

A
  • DVT/ PE treatment

- Prevention of stroke in pts with Afib or heart valve replacement

88
Q

What is the monitoring test used for Warfarin? How many days would it take to become therapeutic on Warfarin? How is it usually initated?

A
  • INR
  • Takes ~5 days to become therapeutic
  • Would need BRIDGE THERAPY d/t hypercoagulable state