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R9 > Chapter 39 - Anticoagulants > Flashcards

Chapter 39 - Anticoagulants Flashcards

1
Q

Arterial thrombi vs venous thrombi

A

Arterial = rich in platelets because of high shear Venous = low shear - few platelet mostly fibrin and trapped RBC

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2
Q

Antithrombotic drugs classes

A

1) Antiplatelet 2) anticoagulant 3) thrombolytic

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3
Q

Heparin molecule

A

1) Sulfated polysaccharide 2) isolated from mammalian tissue rich in mast cells 3) commercially derived from porcine intestinal mucosa 4) polymer of alternating D-glucoronic acid and N-acetyl-D-glucosamine residues

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4
Q

Effect of heparin

A

1) activate antithrombin 2) antithrombin inhibits thrombin and Factor 10a 3) heparin causes release of TFPI = factor Xa dependent inhibitor of factor 8a

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5
Q

Antithrombin key points

A

1) serine protease inhibitor 2) made from liver 3) concentration 2.6 +/- 0.4 mcM 4) suicide substrate for target enzyme

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6
Q

Steps of heparin to activate antithrombin

A

1) pentasaccharide on heparin binds antithrombin 2) conformational change to antithrombin 3) enhances rate of antithrombin to inhibit factor Xa 4) heparin act as template to bind thrombin as well bringing the two together 5) form thrombin-antithrombin complex

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7
Q

Heparin, LMWH and fondaparinox activity ratio for anti factor Xa and IIa

A

heparin 1:1 LMWH 2:1 to 4:1 fondaparinox only Xa inhibition

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8
Q

Molecular weight of heparin

A

15000 (range 5000-30000)

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9
Q

Size of heparin needed to bridge thrombin and antithrombin

A

5400 Da

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10
Q

Half life phenomenon of heparin

A

low dose binds endothelium - short half life higher doses - saturate endothelium - longer half life range from 30-60 minutes

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11
Q

Clearance of heparin

A

1) binds to macrophages 2) internalizes and depolymerizes the long heparin chain 3) shorter chain secreted back to circulation

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12
Q

Heparin binding proteins in circulation

A

The more there are, the lower activity of heparin (less available to bind antithrombin) Acute phase reactants multimers of vWF during platelet activation PF4

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13
Q

Heparin rebound

A

Slow release of protein-bound heparin back into circulation after heparin reverse

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14
Q

Therapeutic heparin level define

A

2-3x prolongation of aPTT

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15
Q

Key points about heparin resistant patients based on aPTT

A

need to check anti-factor Xa level Possible that high protein binding heparin reduces aPTT but does not affect factor Xa level

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16
Q

Heparin titration bolus and maintenance regimens

A

1) IV 70 U/kg then infusion 12-15 U/kg/hr if ACS 2) IV 80 U/kg then infusion 18 U/kg/hr if VTE

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17
Q

Pharmacokinetic and biophysical limitations of heparin

A

TABLE 39.1

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18
Q

Protamine sulfate origin

A

Salmon sperm binds heparin then clears it

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19
Q

HIT features

A

TABLE 39.2

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20
Q

HIT test

A

1) ELISA against antibodies against heparin-PF4 2) serotonin release assay - platelet with labelled serotonin exposed to serum in absence or presence of heparin

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21
Q

Risk of osteoporosis with long term heparin therapy

A

30% 2-3% have vertebral fracture

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22
Q

Perioperative heparin management

A

1) stop 2 hours before surgery if prophylaxis 2) stop full dose IV heparin 4-6 hours before 3) low dose heparin restart 12-24 hours after surgery

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23
Q

Advantages of LMWH over heparin

A

TABLE 39.4

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24
Q

LMWH MOA

A

1) activate antithrombin 2) half too short to bridge thrombin

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25
Q

half life of LMWH

A

4-6 hours

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26
Q

clearance of LMWH

A

kidney

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27
Q

LMWH binding in plasma

A

90% bioavailable after sc doesn’t bind protein as much

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28
Q

monitoring effect of LMWH

A

only anti-factor Xa level little effect on aPTT

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29
Q

VTE treatment dose of LMWH

A

150-200 U/kg daily or 100 U/kg BID

30
Q

protamine on LMWH

A

only partial effect on anti-Xa completely block anti-factor IIa activity

31
Q

LMWH on HIT

A

less likely to bind PF4 but still can

32
Q

LMWH perioperative holding

A

prophylaxis 12 hours before surgery treatment dose 24 hour before surgery restart 12-24 hr postop start with half dose

33
Q

Comparison of heparin, LMWH and fondaparinux

A

TABLE 39.5

34
Q

Bioavailability of fondaparinux after sc injection

A

100%

35
Q

half life of fondaparinux

A

17 hours

36
Q

Clearance of fondaparinux

A

renal only

37
Q

Dose of fondaparinux for VTE

A

2.5 mg prophylaxis 5-10 mg treatment

38
Q

Risk of fondaparinux in PCI

A

catheter thrombosis need to give heparin as well

39
Q

fondaparinux with HIT

A

unlikely

40
Q

Reversal of fondaparinux

A

Recombinant activated factor 7

41
Q

Preoperative fondaparinux

A

36 hours before surgery

42
Q

Comparison of direct thrombin inhibitors

A

TABLE 39.6

43
Q

Hirudins

A

Lepirudin and desirudin Act on active site and exosite 1 of thrombin

44
Q

Dose of desirudin

A

15 mg BID

45
Q

Monitoring of lepirudin

A

aPTT to maintain 1.5-2.5 of control ecarin clotting time also usable

46
Q

Argatroban

A

Acts on the active site of thrombin

47
Q

Clearance of argatroban

A

liver

48
Q

Monitoring argatroban

A

aPTT 1.5-3x baseline but less than 100 seconds INR also elevated

49
Q

Bivalirudin

A

divalent thrombin inhibitor

50
Q

Monitor bivalirudin

A

ACT

51
Q

Vitamin K cycle and inhibition by warfarin

A

FIGURE 39.2

52
Q

Factor X half life

A

24 hr

53
Q

Prothrombin half life

A

72 hours

54
Q

Warfarin pharmacology key points

A

1) 90 min to peak concentration 2) half life 36-42 hours 3) 97% bound to albumin 4) free is biologically active 5) S-isomer (more active) metabolized by CYP2C9

55
Q

Monitoring of warfarin effect

A

Prothrombin time converted to INR

56
Q

Treatment for supratherapeutic INR

A

4.5-9 asymptomatic = withhold warfarin until therapeutic again INR > 9 = vitamin K 2-5 mg bleeding = prothrombin complex concentrate and vitamin K

57
Q

Prothrombin complex concentrate types

A

3 factor or 4 factor 4 adds factor 7 to 7, 9 and 10

58
Q

Warfarin necrosis skin biopsies

A

thrombi in microvasculature

59
Q

Warfarin in fetus

A

1) crosses placenta 2) embryopathy, nasal hypoplasia, stippled epiphyses 3) avoid in 1st and 3rd trimester 4) does not pass to breast milk

60
Q

DOAC comparisons

A

TABLE 39.7

61
Q

DOAC uses in afib

A

all except 1) mechanical heart valve 2) severe rheumatic valvular disease

62
Q

DOAC use in VTE

A

all except active cancer

63
Q

Dosing of DOAC in AFIB

A

Dabigatran 150 mg BID (renal adjust 75 mg if < 30) Rivaroxaban 20 mg daily (renal 15 mg < 49) Apixaban 5 mg BID (2.5 renal) Edoxaban 60 mg daily (30 if < 50 gfr)

64
Q

Dosing of DOAC in VTE

A

Dabigatran 150 mg BID Rivaroxaban 15 mg BID x 21 days then 20 daily Apixaban 10 mg BID x 7 days then 5 mg BID Edoxaban 60 mg daily (30 if gfr <50)

65
Q

Reasons to reduce DOAC doses

A

Renal failure weight < 60 kg age > 80 also receiving P-glycoprotein inhibitors (amiodarone, verapamil)

66
Q

Monitoring DOAC effects

A

prothrombin time for Xa inhibitors aPTT for dabigatran

67
Q

Side effects of oral anticoagulation

A

Warfarin - intracranial bleed (factor 7 reduction) DOAC - GI bleed (active drug stuck there) Dabigatran - dyspepsia 10%

68
Q

Flow diagram for bleeding in DOAC treatment

A

FIGURE 39.3

69
Q

Reversal for DOAC

A

Idarucizumab 5g IV for dabigatran - bind 1:1 renal clear Andexanet alfa and ciraparantag - Xa inhibitor not yet approved IV PCC 25-50 U/kg

70
Q

DOAC in pregnancy

A

not to be used also cannot use if breastfeeding

71
Q

DOAC in mechanical heart valves

A

cause more stroke and bleeding cannot be used

R9 (200 decks)

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