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Flashcards in Anticoagulants Deck (86)
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1
Q

The three basic mechanisms of hemostasis are

A

Vasoconstriction, platelets, and clotting factors

2
Q

Basic steps in hemostasis

A

1) Vasoconstriction
2) Formation of platelet plug
3) Activation of clotting cascade
4) Formation of fibrin blood clot
5) Clot retraction and dissolution

3
Q

Primary hemostasis

A

Occurs immediately

Results in platelet plug

Exposed subendothelial collagen attracts platelets which start to adhere to each other

4
Q

Factors involved in primary hemostais (also causes local vasoconstriction)

A

vWF
CF VIII
ADP

5
Q

Adhered platelets release ________ and use _____ and _____ as a connecting agent

A

TXA2

Fibrinogen and vWF

6
Q

Platelet degranulation agents

A

5-HT, Histamine- vasoconstrictors

Thromboxane- vasoconstriction/degranulation

ADP- promotes adherence and degranulation

CF Va, VIIIa, IXa

Platelet factor 4 (heparin neutralizing factor)

7
Q

Secondary hemostasis takes place over what kind of time frame?

A

Minutes to hours

8
Q

What is the end product of the coag cascade in secondary hemostasis?

A

FIBRIN

This forms the meshwork of protein that helps to stabilize the platelet plug and trap other cells

9
Q

Basic intrinsic pathway (PTT)

A

Factor XIIa–> Xa–>Prothrombin–> Thrombin

Fibrinogen–> Fibrin

10
Q

Basic extrinsic pathway (PT)

A

Tissue factor and Factor VIIa–> Xa–>
Prothrombin–> Thrombin
Fibrinogen–> Fibrin

11
Q

Natural anticoagulants

A
PCI2
Antithrombin III
Heparin
Protein C
Protein S
12
Q

After a clot forms and stabilizes, it then

A

Retracts

13
Q

How does clot retraction work?

A

Platelets trapped in the fibrin mess contain actinomyosin-like contractile proteins, which squeeze out protein-free serum. This mostly takes place within the first hour.

14
Q

Describe the fibrinolytic system

A

Mediated by plasmin,which becomes activated by coagulation and inflammation substances

Plasmin splits fibrin and fibrinogen into fibrin degradation products

15
Q

Antiplatelet aggregation agents

5 oral

3 IV

A

Oral agents- aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor

IV- abciximab, eptifibatide, tirofiban

16
Q

What does aspirin inhibit? What type of inhibition is it?

A

COX inhibitor

Irreversible! Remember platelets are around for about 10 days.

17
Q

Aspirin is indicated for

A

Prevention of recurrent ischemic events, such as stroke, MI, and symptomatic PVD

18
Q

ASA dose

A

81-325mg qday

19
Q

ASA precautions

A

Children (Reye’s syndrome)
Pregnancy
CV- blocks ACE, BB, and diuretic effects d/t prostaglandin inhibition
Asthmatics- results in increased leukotriene production
Increased bleeding with other anticoags

20
Q

Treatment for over anti-coagulation with ASA?

A

Platelet transfusion, otherwise you gotta wait a long time

21
Q

How does ticlopidine (ticlid) work?

A

Blocks APD receptor on platelets and inhibits fibrinogen binding

22
Q

When is ticlopidine used?

A

Same indications as ASA, usually used for ASA intolerance

23
Q

Ticlopidine is bad news bears because…

A

It causes extreme neutropenia, thrombotic thrombocytopenic purpura, GI upset (really..?), and its also teratogenic

24
Q

Clopidogrel (Plavix) works by

A

Irreversibly blocking ADP receptor on platelet and inhibits fibrinogen binding

Used for same stuff as ASA, usually as dual therapy with ASA (more effective, also more bleeding)

25
Q

Clopidogrel dosing

A

Loading dose of 300mg or 600mg

Daily dose of 75mg

26
Q

Clopidogrel precautions

A

Metabolized by CYP2C19, may need increased dosing due to genetic variation

Inhibits CYP450

Severe renal/hepatic disease, reduce dose

27
Q

For alllllll of these drugs using more than one will…

A

Increase your risk of bleeding

28
Q

Clopidogrel pts most at risk of bleeding?

A

Elderly, underweight, previous TIA/stroke

29
Q

Bleeding treatment on clopidogrel

A

Stop drug

GIve platelets

30
Q

Prasugrel (Effient) what is it? When might a pt be on it?

A

New thienopyridine, better risk reduction than clopidogrel, but also causes more fatal bleeding events

Often used in clopidogrel non-responders

31
Q

Prasugrel dosing and precautions

A

10mg qday

Active bleeding

Previous stroke/tia, underweight, >75- consider 5mg qday

Risk of bleeding during CV surg is 4x greater than clopidogrel. Don’t use pre-cath.

32
Q

Ticagrelor (Brilinta) works by ______? How does it compare to clopidogrel?

A

Blocks ADP receptors by allosteric antagonism

Better than clopidogrel for mortality reduction post MI/stroke, but also more bleeding and much higher rate of fatal ICH

33
Q

Ticagrelor uses and dosing

A

Prevention of recurrent ischemic events after stroke, ACS, and post PCI

180mg once, 90mg bid thereafter

Always as dual therapy with ASA unless contraindicated

34
Q

Ticagrelor precautions

A

ASA more than 100mg aday

Hepatic dysfunction

Hold for >5 days pre-surg

BID dosing

Contraindications- active bleeding, ICH history

35
Q

How do GPIIb/IIIa inhibitors work? Uses? 3 drugs-

A

Block GPIIb/IIIa receptor, which prevents fibrinogen binding

Used for ACS and PCI

Abciximab (ReoPro), Eptifibatide (Integrilin), Tirofiban (Agrastat)

36
Q

Abciximab (ReoPro) is used for _______? When used with heparin what’s the aPTT goal? Downsides?

A

Used in ACS with planned PCI

aPPT goal of 60-85 sec

Most expensive in its class and most prolonged effects

37
Q

Eptifibatide uses and dosing considerations

A

Used for ACS and PCI

Dosing based on serum creatinine
<2.0 mg/dl- 2.0 mcg/kg/min for up to 72 hours
2.0-4.0 mg/dl- 1.0mcg/kg/min for up to 72 hours

38
Q

GPIIb/IIIa inhibitors- How do you treat bleeding?

A

Abciximab (ReoPro)- reverse with platelets

Eptifibatide (Integrilin) and Tirofiban- turn it off and wait

39
Q

Temporary interruption of anti-platelet therapy should take place _______ prior to surgery

A

7-10 days

40
Q

Anti-platelet therapy should resume ________ post-op as long as hemostasis is achieved

A

within 24 hours or next AM

41
Q

For pts at high risk of CV events, when should ASA/Clopidogrel be stopped?

A

ASA should NOT be discontinued

Clopidogrel should be stopped at least 5 days prior to surg

42
Q

How does heparin work and what is it used for?

A

Activates antithrombin III–> increases inhibition of thrombin IIa and Factor Xa 1000 fold

Used for DVT prophylaxis/treatment, PE treatment, ACS, when warfarin is started or contraindicated

43
Q

Heparin dosing for DVT prophylaxis

A

5000 units SubQ q8hrs (q12hr dosing sometimes…for NeuroSurg, ESRD)

44
Q

IV infusion heparin dosing

A

Weight-based bolus
Weight-based infusion

Protocol adjusted by aPTT or anti-Xa values (q6hrs until stable, then qday)

45
Q

Drawbacks of heparin

A

Variable effect, frequent titration

DOES NOT inhibit clot-bound thrombin

46
Q

Heparin reversal agent

A

Protamin 1mg/100u of heparin

47
Q

Incidence of HIT

A

1% @ 7 days

3% @ 14 days

48
Q

HIT type I

A

Non-immune mediated, BENIGN

Mild drop in platelets, <4 days, not progressive nor associated with thrombosis

49
Q

HIT type II

A

Immune mediated, more typical onset and MORE BAD

Always follows heparin exposure (check history)
Reduction in platelets to <150,000 OR 50% reduction from PRE-HEPARIN exposure

Typically 7-14 after initial exposure, but may be much shorter if pt was exposed in the past

50
Q

Thrombocytopenia occurs what percent of the time with heparin therapy? More common in UF or LMWH?

A

about 2-5

More common in UF heparin

51
Q

Typical pt/platelet count/onset time for thrombocytopenia

A

Surg>med>OB

38,000-60,000

Typical onset (66%)- exposure of 5-14 days
Delayed (3-5%)- exposure of 2-6 weeks
Rapid (25-30%) hours-days (usually has history of heparin exposure and circulating antibodies from previous 100 days)

52
Q

HITT (HIT with thromboembolism)

% of cases

Venous vs Arterial

Mortality rate and amputation rate

A

10-25% of cases

Venous (4x more common)- DVT, PE, venous limb gangrene, dural sinus thrombosis

Arterial- CVA, limb ischemia, skin necrosis, MI, gut ischemia, adrenal/renal/spinal artery infarcts

25-30% mortality, 25% amputation rate

53
Q

HIT lab tests

A

ELISA

  • measures titer of IgG to heparin-PF4 complex
  • simple and readily available
  • 90% sensitive, 80% specific

SRA

  • detects platelet activation
  • labor intensive, usually a send-out lab
54
Q

Management of HIT

A

Stop all pro-thrombocytopenic drugs

STOP heparin (FOREVER) and START non-heparin anti-coag (usually Argatroban)

Check history for heparin exposure

Remove all sources of heparin (flushes, coated devices, sq DVT prophylaxis)

55
Q

LMWH (Enoxaparin) MOA and uses

A

~5,000 daltons in size

Binds antithrombin III and inhibits factor Xa

Used for DVT prophylaxis, ACS, and VTE treatment

56
Q

How can the effects of LMWH be checked?

A

Anti-Xa levels, but this is not routinely done

57
Q

In what pt population on LMWH therapy would you want to monitor anti-Xa levels

A

Pregnant women

58
Q

Precautions with LMWH

A

Use weight based dosing for obese pts

Not recommended in severe renal insufficiency, decrease dose by 50% if no alternative

Contraindicated in spine surg and patients with epidural catheters

59
Q

Can protamine reverse LMWH?

A

Yes, but only ~60% reversal

60
Q

How does Fondaparinux (Arixtra) work? What is it used for?

A

It is a synthetic factor Xa inhibitor. Binds with anti-thrombin III to potentiate Xa inhibition (300x). No effect on IIa (thrombin).

Used in ACS, PE/DVT prophylaxis, DVT treatment

61
Q

Fondaparinux dosing, contraindications, reversal

A

7.5mg subq qday for prophylaxis, 10mg for VTE or wt >100kg

Contraindicated for CrCl< 30 ml/min, spinal puncture/anesthesia

No known reversal, FFP ineffective. Discontinue drug and provide supportive care.

62
Q

Direct thrombin (IIa) inhibitors

A

Hirudin, lepirudin, desirudin, hirulog, argatroban (reversible), bivalirudin

Used in HIT (argatroban, lepirudin)
PCI (Bivalirudin)

63
Q

Toxicities, interactions, and bleeding treatment for direct thrombin inhibitors

A

Bleeding
Lepirudin and Desirudin can only be used once on a patient d/t anaphylaxis risk

Increased bleeding with other anti-coagulants

Stop infusion, may respond to factor VII, FFP, and cryoprecipitate

64
Q

What does warfarin interfere with?

A

Production of vitamin K dependent clotting factors (II, VII, IX, X) and carboxylation of natural anticoagulants protein C and protein S

65
Q

What is warfarin used for?

A

DVT, a-fib, mechanical heart valve thrombosis prevention

Long-term VTE treatment

66
Q

The INR goal for most warfarin indications is

A
  1. 0-3.0

2. 5-3.0 in high risk pts

67
Q

For uncomplicated DVT/PE what is the normal duration of warfarin therapy?

A

3 months

68
Q

When transitioning to warfarin, how long should heparin or LMWH overlap for?

A

1-2 days

69
Q

What genetic variants can require changes in warfarin dosing?

A

Variations in CYP2C9 can decrease warfarin metabolism

Variations in vitamin k expoxide reductase can require dose reductions

70
Q

Warfarin toxicities

A

Bleeding, birth defects, cutaneous necrosis

71
Q

Warfarin interactions

A
Increased effect-
Amiodarone
CImetidine
Acetaminophen
Phenylbutazone
Decreased effect-
Sucralfate
Cholestyramine
Spironolactone
Barbiturates
Vitamin k containing foods
72
Q

Warfarin reversal

A

Vitamin K, IV or PO

FFP

73
Q

In terms of surgery, when should warfarin be stopped and restarted?

A

5 days prior to OR

Restarted 12-24 hours post-op if normal hemostasis has been achieved

High risk patients can be bridged with heparin up to 4-6hrs pre-op

74
Q

What does dabigatran (pradaxa) inhibit? What is it used for?

A

It is a direct thrombin inhibitor (IIa)

Stroke prevention in non-valvular a-fib and VTE prophylaxis after total knee/hip replacement

110mg bid for high bleeding risk or renal impairment , otherwise 150mg bid

75
Q

How does dabigatran to warfarin?

A

150mg dose is superior for reduction of stroke and systemic embolism with no difference in bleeding.

110mg dose in noninferior for prevention and has a 20% reduction in bleeding risk

76
Q

All of the new oral anticoagulants (dabigatran, rivaroxaban, and apixaban) have what disadvantages?

A

High cost (bid dosing for apixaban), no antidote, no assay for monitoring, and no long term data.

77
Q

Rivaroxaban (Xarelto) MOA, uses, and dosing

A

Direct factor Xa inhibitor

Used for stroke and systemic embolism prevention in a-fib

20mg qday

78
Q

How does rivaroxaban compare to warfarin?

A

noninferior, similar bleeding risk, but decreased risk of ICH and fatal bleeding

79
Q

Advantages of dabigatran

A

No routine monitoring needed
Less influenced by diet and other drugs
Rapid time to peak action (1 hr)
Short half like (12-14 hrs) in pts with normal renal function

80
Q

Apixaban (Eliquis) MOA, uses, dosing

A

Direct Xa inhibitor

Used for stroke and systemic embolism prevention in a-fib

5mg bid

81
Q

How does apixaban compare to other anti-coags

A

Clear benefit over ASA for patients unable to take warfarin

Superior to warfarin for prevention and reduced risk of bleeding, in particular lower rates of ICH and mortality

82
Q

Fibrinolytic drugs and how they work

A

Streptokinase, Urokinase, t-PA, Tenecteplace (TNK-ase)

Plasminogen activators convert plasminogen to plasmin–> plasmin causes fibrinolysis

83
Q

Uses for fibrinolytics

A

Acute ST-elevation MI

Acute ischemic stroke (within 6 hours of symptom onset) t-PA only

Urokinase only for PE or central line de-clotting

84
Q

tPA dosing vs TNKase dosing

A

tPA 10 units over 2 min, repeat in 30 minutes

TNKase 30-50mg given as a one time bolus over 5 seconds

85
Q

Absolute contraindications for fibrinolytics

A

Previous hemorrhagic stroke
Ischemic stroke in last 3 months or acute within last 3 hours
Known intracranial neoplasm
Active internal bleeding, excluding menses
Suspected aortic dissection
SIgnificant closed head or facial trauma within 3 months

86
Q

Relative contraindications for fibrinolytics

A

BP > 180/110, treating it is ok in terms of removing this contraindication

Severe chronic HTN

INR>2.5, use of other anticoagulants

Known bleeding disorder

Non-compressible vascular puncture

Recent trauma within 2-4 weeks (traumatic CPR)

Major surg <3 weeks

Recent internal bleeding or PUD (2-4 weeks)

Pregnancy

For streptokinase allergy or prior exposure (5 days to 2 years)