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![Initial Parenteral Anticoagulant Therapy in Patients With Definite
NSTE-ACS
Recommendations COR LOE
In patients with NSTE-ACS, anticoagulation, in addition to
antiplatelet therapy, is recommended for all patients
irrespective of initial treatment strategy. Treatment options
include:
• Enoxaparin: 1 mg/kg subcutaneous (SC) every 12 hours
(reduce dose to 1 mg/kg SC once daily in patients with
creatinine clearance [CrCl] <30 mL/min), continued for
the duration of hospitalization or until PCI is performed.
An initial intravenous loading dose is 30 mg.
I A](https://image.slidesharecdn.com/drugsinfluencingcoagulation-230831091443-7e61ff22/75/Drugs-influencing-coagulation-pptx-24-2048.jpg)
Uploaded byAhmed El Kacer
Drugs influencing coagulation .pptx
This document discusses various classes of drugs that influence coagulation, including anticoagulants, antiplatelet drugs, and thrombolytic drugs. It describes several classes of anticoagulants such as heparins, warfarin, direct thrombin inhibitors, and direct factor Xa inhibitors. It provides details on specific drugs within each class, their mechanisms of action, dosing, monitoring, indications, and drug interactions. The focus is on drugs used for venous thromboembolism and non-valvular atrial fibrillation.
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Drugs influencing coagulation .pptx
- 1. Drugs influencing coagulation AHMEDFOUAD Cardiology resident
- 2. Classes of Drugs •Prevent coagulation • Dissolve clots • Prevent bleeding and hemorrhage - Hemostatic • Overcome clotting deficiencies (replacement therapies)
- 3. Classes of Drugs •Prevent coagulation • Dissolve clots • Prevent bleeding and hemorrhage - Hemostatic • Overcome clotting deficiencies (replacement therapies)
- 4. Haemostasis Arrest of bloodloss from damaged blood vessels
- 5. Blood Clotting • VascularPhase • Platelet Phase • Coagulation Phase • Fibrinolytic Phase
- 6. Vascular Phase Vasoconstriction Exposure to tissues activate Tissue factor and initiate coagulation Tissue Factor
- 7. Coagulation Phase Twomajor pathways Intrinsic pathway Extrinsic pathway Both converge at a common point 13 soluble factors are involved in clotting Normally inactive and sequentially activated
- 8. Blood Vessel Injury IXIXa XI XIa X Xa XII XIIa Tissue Injury Tissue Factor VIIa VII X Prothrombin Thrombin Fibrinogen Fribrin monomer Intrinsic Pathway Extrinsic Pathway
- 9. Intrinsic Pathway Activatedpartial thromboplastin test (aPTT) Extrinsic Pathway Prothrombin test (PT/INR)
- 10. Vitamin K Synthesis of Functional Coagulation Factors VII IX X II VitaminK-Dependent Clotting Factors
- 11.
- 12. Thrombosis Pathological formation ofhaemostatic plug within the vasculature in the absence of bleeding
- 13. Arterial • White • Plateletand WBC • With atheroscerosis • Causes ischemia Venous • Red • White head and red tail • Embolus
- 14. Drugs effect ; •fibrin formation • Platelet function • Fibrinolysis Drugs influencing coagulation Anticoagulants • Antiplatelet drugs • Thrombolytic drugs
- 15. Drugs influencing coagulation •Anticoagulants • Antiplatelet drugs • Thrombolytic drugs
- 16. Anticoagulants • Antithrombin activators •Direct thrombin inhibitors • Direct Factor Xa inhibitors • Drugs that oppose action of Vitamin K
- 17. Anticoagulants • Antithrombin activators –Heparin / LMWH – Synthetic pentasaccharide analogues • Direct thrombin inhibitors • Direct Factor Xa inhibitors • Drugs that oppose action of Vitamin K
- 18.
- 19. Blood Vessel Injury IXIXa XI XIa X Xa XII XIIa Tissue Injury Tissue Factor Thromboplastin VIIa VII X Prothrombin Thrombin Fibrinogen Fribrin monomer Intrinsic Pathway Extrinsic Pathway Factors affected By Heparin
- 20. Heparin • Given s.c.or i.v. • Binds to plasma proteins, endothelial cells & macrophages • Elimination – Depolymerisation in endothelial cells & macrophages (rapid, saturable) – Renal (slow, non-saturable) and RES
- 21. Heparin: variable anticoagulanteffect • Variable protein binding • Clearance varies with chain length • Therefore, anticoagulant response monitored by activated partial thromboplastin time (APTT) • Target 1.5 – 2.5 times control
- 23. Heparin: clinical uses •Venous thrombosis ± embolism • Acute coronary syndromes • Arterial thrombosis • Extracorporeal devices (e.g. haemodialysis)
- 24. Initial Parenteral AnticoagulantTherapy in Patients With Definite NSTE-ACS Recommendations COR LOE In patients with NSTE-ACS, anticoagulation, in addition to antiplatelet therapy, is recommended for all patients irrespective of initial treatment strategy. Treatment options include: • Enoxaparin: 1 mg/kg subcutaneous (SC) every 12 hours (reduce dose to 1 mg/kg SC once daily in patients with creatinine clearance [CrCl] <30 mL/min), continued for the duration of hospitalization or until PCI is performed. An initial intravenous loading dose is 30 mg. I A
- 25. Initial Parenteral AnticoagulantTherapy in Patients With Definite NSTE-ACS (cont’d) Recommendations COR LOE (cont’d) • Bivalirudin: 0.10 mg/kg loading dose followed by 0.25 mg/kg per hour (only in patients managed with an early invasive strategy), continued until diagnostic angiography or PCI, with only provisional use of GP IIb/IIIa inhibitor, provided the patient is also treated with DAPT. • Fondaparinux: 2.5 mg SC daily, continued for the duration of hospitalization or until PCI is performed. I B B
- 26. Initial Parenteral AnticoagulantTherapy in Patients With Definite NSTE-ACS (cont’d) Recommendations COR LOE (cont’d) • If PCI is performed while the patient is on fondaparinux, an additional anticoagulant with anti-IIa activity (either UFH or bivalirudin) should be administered because of the risk of catheter thrombosis. • UFH IV: initial loading dose of 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg per hour (maximum 1,000 IU/h) adjusted per activated partial thromboplastin time to maintain therapeutic anticoagulation according to the specific hospital protocol, continued for 48 hours or until PCI is performed. I B B In patients with NSTE-ACS (i.e., without ST elevation, true posterior MI, or left bundle-branch block not known to be old), intravenous fibrinolytic therapy should not be used. III: Harm A
- 27. Heparin: adverse effects •Bleeding • Heparin-induced thrombocytopenia (HIT) – Immune-mediated • Osteoporosis
- 29. Type I ◦Rapid onset: 2-5 d ◦ Characterized by mild decrease in platelet count without thrombosis or immune response Type II ◦ Considerably more severe ◦ Occurs after more than 5 d administration (avg 9 d) ◦ Immune mediated ◦ Antibody binding between heparin-platelet complex ◦ Causes platelet activation, complement activation, white clot ◦ High morbidity Incidence thrombosis 20% Mortality after thrombosis 40%
- 31.
- 32. LMWHs • Dalteparin • Enoxaparin •Tinzaparin
- 38. Synthetic pentasaccharide analogues Bioavailability(s.c.)elimination half life (h) LMWH 80-90% renal 4 Fondaparinux 100% renal 17 Idraparinux 100% renal 80
- 39. Acts byantithrombin III inhibition of Xa. Administered SQ or IV q day. Rapidly and completely absorbed; peak steady state 3 hr; 94% bound to ATIII. Eliminated unchanged in urine in 72 hr with normal renal function. DC before surgery 2 days, longer with renal disease
- 41. Anticoagulants • Antithrombin activators •Direct thrombin inhibitors • Direct Factor Xa inhibitors • Drugs that oppose action of Vitamin K
- 42. Direct thrombin inhibitors •Recombinant hirudins • Bivalirudin • Ximelagatran / Melagatran • Dabigatran
- 43. Recombinant hirudins • Giveni.v. , s.c. • Elimination renal • Half life 1-2 h
- 44. Bivalirudin • Given i.v. •Elimination renal & hepatic • Half life 25 min
- 45. Ximelagatran • Promising oraldirect thrombin inhibitor • Converted to the active form melagatran in vivo • No dosing problems • No monitoring needed. • Recent atrial fibrillation study showed it to possibly be superior to warfarin.
- 46. Dabigatran • Given orally •Elimination renal • Half life 12 h • Substrate for P-glycoprotein in kidney, GIT
- 47. Anticoagulants • Antithrombin activators •Direct thrombin inhibitors • Direct Factor Xa inhibitors • Drugs that oppose action of Vitamin K
- 48. Apixaban • Direct FactorXa inhibitor • Oral bioavailability 60% • Half life 12 h • Elimination hepatic > renal
- 49. Rivaroxaban • Direct FactorXa inhibitor • Oral bioavailability 80% • Half life 7-11 h • Elimination renal > hepatic
- 50. Anticoagulants • Antithrombin activators •Direct thrombin inhibitors • Direct Factor Xa inhibitors • Drugs that oppose action of Vitamin K
- 51. Warfarin Reduces the post-translational carboxylationof glutamate residues of factors II, VII, IX, X
- 52. Warfarin Synthesis of Non Functional Coagulation Factors Antagonism of VitaminK Warfarin Mechanism of Action Vitamin K VII IX X II
- 53. Blood Vessel Injury IXIXa XI XIa X Xa XII XIIa Tissue Injury Tissue Factor Thromboplastin VIIa VII X Prothrombin Thrombin Fibrinogen Fribrin monomer Intrinsic Pathway Extrinsic Pathway Vit. K dependent Factors Affected by Oral Anticoagulants
- 54. Warfarin • Anticoagulant effectseen after 2-3 days • Monitored by international normalized ratio (INR) • Well absorbed form GIT • Highly protein bound • Metabolised by CYP-450
- 62. Drug interaction- withWarfarin Drugs that Increase Warfarin Activity Decrease binding to Albumin Inhibit hepatic metaboli; Decrease synthesis of Clotting Factors NSAID, Cimetidine, antifungals Antibiotics (oral) Category Mechanism Representative Drugs
- 63. Drug interaction withWarfarin cont: Drugs that promote bleeding Inhibition of platelets NSAID, Aspirin Inhibition of clotting heparin Factors Drugs that decrease Warfarin activity Induction of metabolizing Barbiturates Enzymes Griseofulvin Promote clotting factor Vitamin K Synthesis Reduced absorption cholestyramine colestipol
- 64. Warfarin: adverse effects •Bleeding • Rashes • Alopecia • Teratogenicity
- 65. Available Direct ActingOral Anticoagulants (DOACs) • Dabigatran • Rivaroxaban • Apixaban • Edoxaban
- 67. DOAC Mechanism ofAction Inhibits Factor Xa Rivaroxaban Apixaban Edoxaban Direct Thrombin Inhibitor Dabigatran
- 68. DOAC Indications andDosing NVAF DVT PE Rivaroxaban Apixaban 20 mg once daily with evening meal 5mg twice daily Rivaroxaban Apixaban 15 mg twice daily x 21 days 10 mg twice daily x 7 days 20 mg once daily with evening meal 5 mg twice daily
- 69. DOAC Indications andDosing NVAF DVT PE Dabigatran Edoxaban 150 mg twice daily 60 mg daily Dabigatran Edoxaban LMWH lead in x 5-10 days LMWH lead in x 5-10 days 150 mg twice daily 60 mg daily
- 70. DOAC Renal Dosing Rivaroxaban NVAF CrCl15-50 mL/min 15 mg once daily CrCl < 15 mL/min Use warfarin DVT/PE CrCl < 30 mL/min Use warfarin 2.5 mg Apixaban twice daily** NVAF Must meet 2 of the following Age 80 years or older Actual body weight 60 kg or less Serum Creatinine 1.5 mg/dL or greater **No dose reduction in DVT/PE patients. However, patients with SCr > 2.5 or CrCl < 25 mL/min not studied
- 71. DOAC Renal Dosing Dabigatran NVAF CrCl15-30 mL/min 75mg bid CrCl < 15 mL/min Use warfarin DVT/PE CrCl < 30 mL/min Use warfarin Edoxaban NVAF CrCl >95 mL/min DO NOT USE CrCl 15-50 mL/min 30mg daily CrCl < 15mL/min Use warfarin DVT/PE CrCl 15-50 mL/min 30mg daily CrCl < 15mL/min Use warfarin
- 72. DOAC Hepatic Dosing Child-Pugh Class Rivaroxaban Apixaban A No Adjustment No Adjustment B Use warfarin Use with caution- limited clinical experience C Use warfarin Use warfarin Child- Pugh Score calculator can be found at PresNet Anticoagulation Oral Anticoagulants Rivaroxaban (Xarelto) Child-Pugh Classification Score
- 73. DOAC Hepatic Dosing Child-Pugh Class Dabigatran Edoxaban A No Adjustment No Adjustment B No Adjustment Use Warfarin C Use warfarin Use warfarin Child- Pugh Score calculator can be found at PresNet Anticoagulation Oral Anticoagulants Rivaroxaban (Xarelto) Child-Pugh Classification Score
- 74. Focus on VenousThromboembolism and Non-valvular Atrial Fibrillation
- 75. DOAC Selection • DVTof leg or PE with active cancer • Pregnant • DVT of leg or PE without active cancer
- 76. Anticoagulant Selection • Valvularatrial fibrillation • Valve replacement • Myocardial infarction requiring dual antiplatelet therapy • Breast feeding
- 77. Anticoagulant Selection Does patienthave CrCl < 30, mechanical heart valve, moderate to severe hepatic impairment (Child- Pugh B or C), significant drug-drug interactions6? Will the patient have trouble paying for a DOAC? Yes Yes No No • Valvular atrial fibrillation • Valve replacement • Myocardial infarction requiring dual antiplatelet therapy • Pregnant or breast feeding • Non-valvular atrial fibrillation • Secondary VTE prevention • VTE prophylaxis following knee/hip replacement surgery
- 78. Anticoagulant Selection Does patienthave CrCl < 30, mechanical heart valve, moderate to severe hepatic impairment (Child- Pugh B or C), significant drug-drug interactions6? Yes Patient Characteristics Favoring DOAC • Highly like to be adherent with DOAC therapy and follow up plan • Reliable to notify health care provider about changes to health and pertinent medical issues • Confirmed ability to obtain DOAC on a longitudinal basis from a financial, insurance coverage and retail availability standpoint • Unstable diet or malnutrition • Frequent illness or health status changes • Frequent medicine changes or need for medications that interact with warfarin but not with DOAC • Frequent medical procedures with bleeding risk No Patient/ Family Preference
- 79. Blann, A. Det al. BMJ 2003;326:153-156
- 81. Enoxaparin TO/FROM DOAC Stopold medication and start new medication when the next dose is due Abo-Salem J Thromb Thrombolysis (2014)
- 82. DOAC TO DOAC StopDOAC 1 and start DOAC 2 when the next dose is due Abo-Salem J Thromb Thrombolysis (2014)
- 83. DOAC to Warfarin/Warfarinto DOAC Abo-Salem J Thromb Thrombolysis (2014)
- 84. Warfarin to DOAC •Discontinue warfarin • Begin rivaroxaban when INR below 3.0 • Begin dabigatran or apixaban when INR below 2.0
- 85. DOAC to warfarin •Need overlap therapy until INR equal or above 2.0 1. DOAC • May interfere with INR reading • Must use DOAC trough for INR draw • Make clear to the patient that they MUST go in for an INR draw right before next DOAC dose is due. OR 2. LMWH • Transition like normal LMWH bridge per PMG policy. • Start LMWH when next DOAC dose due.
- 86. Anticoagulant Transitions • Warfarinto DOAC, DOAC to Warfarin ** INR < 3.0 for Rivaroxaban
- 87. Summary of antithrombotic