Download Anticoagulant therapy

Background
 Cost
 Benefit
 Complication
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External(F7)15s
Internal(F12)1 to6minute
Result>prothrombin activator
prothrombin(F2)>thrombin>fibrinogen(F1)>fib
rin
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Clot formation: fibers+platlet+red
cell+plasma
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Restrictive clot
formation:antithrombin3+thrombin(12_20minute)
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Clot retraction:30to60minute
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Clot leases During 24hours TPA release
injury endothelium and activated
plasminogen>plasmin(fibrinolisin)>leases:
Fibrinogen,prothrombin,F5,F7
 Anticoagulant
drugs:
1__HEPARIN
 UFH or LMWH ?
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Heparin(UFH) release from mast cell
basophile around capillary and concentration
lung and liver
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UFH: heterogenus mixture
glycosaminoglycant with MW3000 to30,000
only one third is active anticoagulant with bind
antithrombin and increase activation 1000X for
neutralize troponin and F9,F10,F11,F12
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Half life: dependent dose 25U/kg 30min
100u/kg60min
400u/kg150min
aPTT only sensetive heparin range1.0-0.1u/ml
More than 1.ou/ml withACT(hemotec parker-itc
edison medtronic)350-375 secischemic
complication at 7days are 34%lower than thy were
ACT171-295
Heparin doses70 to 100iu/kg and target act250350seconds but with GP2b/3a inhibitor 40-70iu/kg
target ACT 200to 250sec
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Low molecular weight hepaarins(LMWH)
Manifactured from UFH withchemical or
enzymatic fragment s one third size
Binds less readily to plasma protein, more
resistant to neutralization by platelet F4(half
life4hours),less effect on platelet function
Relatively selective inactivation factor xa
Complication:
 Bleeding,predispose with increase risk
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was :age ,alcohol,aspirin, ,renal failure, serious
concurrent illness. LMWH risk more increase
in RF
Prothamine sulfat dose not comletly effective in
reverse antifactor xa activity inLMWH
 Thrombocytopenia:tow type
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Begins 4-14 days exceptions are in patient
received heparin the past three month.50% drop in
platelet count
Dose depended 15% benign and self limited
Immune form(HIT) paradoxically cause serious
arterial and venous thrombosis(HITT) mechanism
interaction antibody IgG with complex of heparin
and platelet factor4 is released on activation
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Declin inplatlet count in HIT is usually:50;000
to 60,000/mm3
Immune –mediated HIT is not heparin dose
dependent even heparin flushes
HIT no single definitive laboratory test(platlet
activation assay, serotonin release assay)
When HIT is suspected heparin discotinude
but HIT is associated with marked
hypercoagulable state with 30to 50%
thrombosis in 30 days after diagnosis
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No LMWH because strong cross reaction with
HIT
No warfari
Tow direct Thrombin inhibitors :lepirudin and
argatroban and pentasacaride
fondaparinux(binding platlet factor4)
 2-Warfarin(coumadin)
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Vitamin K antagonist Vkh2 is cofactor
forF2(prothrombin)F7,F9,F10
Mean plasma half life` 40hours metabolism is affected allelic
variant of P450,CYP2C9 homozygous for active alleles with
low warfarin dose and high bleeding complication and
polimorphism in VK epoxid reductase(VKOR)gene also
influence anticoagulant respone
Drugs:
propranolol,amiodaron,clofibrate,cimetidine……increase
warfarin levels and cholestyramine rifampin …..decreas
high VK in diet(nutritional supplement)
Loading doses of warfarin should not be used
 Because:VK dependent factors have different
half life F7 shortest initial increase INR
withsevere F& deficiency state while still
failing to provide antithrombotic effect.
 Reduction in plasma level protein C (VK
dependent anticoagulant with shortest HL)
Lead to transient paradoxical hypercoagulated
state.
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Managing warfarin overdose
No bleeding
Warfarin dosage
INR 3.5-5
Decrease, do not stop drug
INR 5-8
Decrease, consider 1 mg K PO
INR 5-8, bleeding risk high
Decrease, give 2.5-5 mg K PO or1 mg SQ
INR > 8
Stop drug, give 2.5-5 mg K PO or 2-3 mg SQ
INR > 8, bleeding risk high
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Stop drug, give 5 mg K PO or 3-5 mg SQ
Consider 10 mL/kg FFP or 25 U/kg PCCs (p. 36)
Minor bleeding
Warfarin dosage
INR 2-3.5
Decrease, look for site
INR 3.5-5
Stop drug, reinstitute at lower dose
INR 5-8
Stop drug, give 2.5 mg K PO or 1 mg SQ
INR 5-8, thrombotic risk high
Stop drug, do not give K
INR > 8
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Major bleeding
Stop drug, give 5 mg K PO or 2-5 SQ
Consider 10 mL/kg FFP or 25 U/kg PCCs (p. 36)
Warfarin dosage
INR 2-3.5
Stop drug, give 5 mg SQ K or IV, repeat as necessary, look for bleeding site
INR 3.5-5
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INR 5-8
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INR >8
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Stop drug, give 5-10 mg K SQ or IV, repeat
Consider 10-15 mL/kg FFP or 25-50 U/kg PCCs (p. 36)
Stop drug, give 5-10 mg K SQ or IV, repeat
Give 15 mL/kg FFP or 25-50 U/kg PCCs (p. 36)
Stop drug, give10 mg K SQ or IV, repeat 6h
Give 15 mL/kg FFP or 25-50 U/kg PCCs (p. 36)
Pitfall in
anticoagulant
therapy