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Anticoagulant therapy. Background Cost Benefit Complication. External(F7)15s Internal(F12)1 to6minute Result> prothrombin activator prothrombin (F2)>thrombin>fibrinogen(F1)>fibrin. Clot formation: fibers+platlet+red cell+plasma - PowerPoint PPT Presentation
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Anticoagulant therapy
Background Cost
Benefit Complication
External(F7)15s Internal(F12)1 to6minute Result>prothrombin activator
prothrombin(F2)>thrombin>fibrinogen(F1)>fibrin
Clot formation: fibers+platlet+red cell+plasma
Restrictive clot formation:antithrombin3+thrombin(12_20minute)
Clot retraction:30to60minute
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 ?
Heparin(UFH) release from mast cell basophile around capillary and concentration lung and liver
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
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 act250-350seconds but with GP2b/3a inhibitor 40-70iu/kg target ACT 200to 250sec
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 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
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
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
Threatment HITT
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) 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.
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 · 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 · Stop drug, give 5 mg K PO or 2-5 SQ· Consider 10 mL/kg FFP or 25 U/kg PCCs (p. 36)
Major bleeding 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 · 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)
INR 5-8 · Stop drug, give 5-10 mg K SQ or IV, repeat· Give 15 mL/kg FFP or 25-50 U/kg PCCs (p. 36)
INR >8 · Stop drug, give10 mg K SQ or IV, repeat 6h· Give 15 mL/kg FFP or 25-50 U/kg PCCs (p. 36)
Managing warfarin overdose
Pitfall in anticoagulant
therapy
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