Downloaded 285 times
More Related Content
Similar to UFH & LMWH & fondaparinux
UFH & LMWH & fondaparinux
- 1.
- 2. Non-Warfarin Anticoagulants From comparisoninto clinical practice By: Mohammed Adel B.Sc., PharmD Clinical Pharmacy Department Al-Ahrar General Hospital 2
- 3. Content •Blood hemostasis •UFH vsLMWH vs Fondaparinux •Practice guidelines recommendations about: •UFH •LMWH •Fondaparinux 3
- 4.
- 5. UFH vs LMWHvs Fondaparinux •Mechanism of action •Timing of treatment before surgery •Pharmacokinetic Parameters •Dosing frequencies 5
- 6. UFH vs LMWHvs Fondaparinux •Pregnancy •Ability to cause HIT •Use in HIT treatment •Use in Pt with Hx of HIT 6
- 7. UFH vs LMWHvs Fondaparinux •Mechanism of action: UFH: Binds to and potentiates the actions of antithrombin (AT) to inactivate factor Xa Prevent the conversion of prothrombin to thrombin 7
- 8. UFH vs LMWHvs Fondaparinux •Mechanism of action: UFH: Prevent the conversion of fibrinogen to fibrin Binds nonspecifically to various plasma proteins and endothelial cells resulting in an unpredictable dose-response relationship and low bioavailability after subcutaneous (SC) administration 8
- 9. UFH vs LMWHvs Fondaparinux •Mechanism of action: LMWH: Same as UFH but with longer and more preferential binding with factor Xa Less able to inhibit the production of thrombin and bind to plasma proteins and endothelial cells less due to their decreased size 9
- 10. UFH vs LMWHvs Fondaparinux •Mechanism of action: LMWH: More predictable anticoagulant response Less inter-patient variability Longer duration of action than heparin. 10
- 11. UFH vs LMWHvs Fondaparinux •Mechanism of action: Fondaparinux: Enhances the anti-Xa activity of AT by 300-fold AT specificity does not allow binding to other plasma proteins 11
- 12. UFH vs LMWHvs Fondaparinux •Mechanism of action: Fondaparinux: It has no direct effect on thrombin It has excellent bioavailability after SC administration and longer half-life 12
- 13. UFH vs LMWHvs Fondaparinux •Timing before surgery: Agent of treatment Half life Last dose before procedure UFH 45 mins 4 Hrs LMWH 4-7 Hrs 24 Hrs Fondaparinux 17-21 Hrs 2-4 days 13
- 14. 14 UFH vs LMWHvs Fondaparinux
- 15. Practice guidelines recommendations Primary andsecondary prevention of cardiovascular diseases Management of anticoagulants Prevention of VTE in non-surgical Pts Treatment of VTE 15
- 16. ACCF/AHA RECOMMENDATIONS 3.5. Adjunctive AntithromboticTherapy to Support Reperfusion With Primary PCI 16
- 17. ACCF/AHA RECOMMENDATIONS 4.2.2. Adjunctive AntithromboticTherapy to Support Reperfusion With Fibrinolytic Therapy 17
- 18. ACCF/AHA RECOMMENDATIONS 5.4.1. Anticoagulant Therapyto Support PCI After Fibrinolytic Therapy 18
- 19.
- 20.
- 21. ACCP RECOMMENDATION The 8thedition of the ACCP guidelines included 600 recommendations in 968 pages Very lengthy Practice non-friendly In 2012 the 9th edition provided highly focused and brief recommendations in addition to the detailed edition 21
- 22. ACCP RECOMMENDATION Management ofanticoagulants 6.1 UFH Dose Adjustment by Weight For VTE IV UFH, bolus 80 units/kg followed by 18 units/kg per h For cardiac or stroke patients bolus 70 units/kg followed by 15 units/kg per h Use of a fixed dose (bolus 5,000 units followed by 1,000 units/h). 22
- 23. ACCP RECOMMENDATION Management ofanticoagulants 6.2 Dose Management of (SC) UFH: For outpatients with VTE treated with SC UFH, we suggest weight-adjusted dosing (first dose 333 units/kg, then 250 units/kg) without monitoring rather than fixed or weight adjusted dosing with monitoring (Grade 2C) . 23
- 24. ACCP RECOMMENDATION Management ofanticoagulants 7.1 Therapeutic Dose of LMWH in Patients With Decreased Renal Function For patients receiving therapeutic LMWH who have severe renal insufficiency (CrCL, 30 mL/min), we suggest a reduction of the dose rather than using standard doses (Grade 2C) . 24
- 25. ACCP RECOMMENDATION Management ofanticoagulants 8.1 Fondaparinux Dose Management by Weight: For patients with VTE and body weight over 100 kg, we suggest that the treatment dose of Fondaparinux be increased from the usual 7.5 mg to 10 mg daily SC (Grade 2C). 25
- 26. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 2.3. Hospitalized Acutely ill Medical Patients For acutely ill hospitalized medical patients at increased risk of thrombosis, we recommend anticoagulant thromboprophylaxis with: Low molecular weight heparin LMWH Low-dose unfractionated heparin (LDUH) bid or tid Fondaparinux 26
- 27. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 2.4. For acutely ill hospitalized medical patients at low risk of thrombosis: We recommend against The use of: Pharmacologic prophylaxis Mechanical prophylaxis 27
- 28. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 2.7.1. For acutely ill hospitalized medical patients who are bleeding or at high risk for bleeding: we recommend against anticoagulant thromboprophylaxis (Grade 1B) . 28
- 29. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 2.7.2. For acutely ill hospitalized medical patients at increased risk of thrombosis who are bleeding or at high risk for major bleeding: we suggest the optimal use of mechanical thromboprophylaxis with graduated compression stockings (GCS)(Grade 2C) intermittent pneumatic compression (IPC) (Grade 2C) , rather than no mechanical thromboprophylaxis. 29
- 30. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 2.7.2. For acutely ill hospitalized medical patients at increased risk of thrombosis who are bleeding or at high risk for major bleeding: When bleeding risk decreases, and if VTE risk persists, we suggest that pharmacologic thromboprophylaxis be substituted for mechanical thromboprophylaxis (Grade 2B). 30
- 31. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 2.8. In acutely ill hospitalized medical patients who receive an initial course of thromboprophylaxis: We suggest against extending the duration of thromboprophylaxis beyond the period of patient immobilization or acute hospital stay (Grade 2B) . 31
- 32. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 3.2. In critically ill patients: We suggest against routine ultrasound screening for DVT (Grade 2C) . We suggest using LMWH or LDUH thromboprophylaxis over no prophylaxis (Grade 2C). 32
- 33. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 3.4.4. For critically ill patients who are bleeding, or are at high risk for major bleeding: We suggest mechanical thromboprophylaxis with GCS (Grade 2C) or IPC (Grade 2C) until the bleeding risk decreases, rather than no mechanical thromboprophylaxis. When bleeding risk decreases, we suggest that pharmacologic thromboprophylaxis be substituted for mechanical thromboprophylaxis (Grade 2C) . 33
- 34. ACCP RECOMMENDATION Prevention ofVTE in non-surgical Pts 4.2.2. In outpatients with solid tumors who have additional risk factors for VTE and who are at low risk of bleeding: We suggest prophylactic dose LMWH or LDUH over no prophylaxis (Grade 2B) . 34
- 35. ACCP RECOMMENDATION Treatment ofVTE 2.1 Initial Anticoagulation for Patients With Acute DVT of the Leg In patients with acute DVT of the leg treated with VKA therapy, we recommend initial treatment with parenteral anticoagulation (LMWH, Fondaparinux, IV UFH, or SC UFH) over no such initial treatment (Grade 1B). 35
- 36. ACCP RECOMMENDATION Treatment ofVTE 2.5 Choice of Initial Anticoagulant Regimen in Patients With Proximal DVT In patients with acute DVT of the leg, we suggest LMWH or Fondaparinux over IV UFH (Grade 2C) and over SC UFH (Grade 2B for LMWH; Grade 2C for Fondaparinux) . In patients with acute DVT of the leg treated with LMWH, we suggest once- over twice-daily administration(Grade 2C). 36
- 37.
Editor's Notes
- #2 The true incidence of VTE in the general population is unknown because many patients, perhaps more than 50%, have no overt symptoms or go undiagnosed. 7 An estimated 2 million people in the United States develop VTE each year, of whom 600,000 are hospitalized and 60,000 die. The estimated annual direct medical costs of managing the disease are well over $1 billion. The incidence of VTE nearly doubles in each decade of life over the age of 50 and is slightly higher in men. As the population ages, the total number of cases of DVT and PE continues to rise
- #15 however, has been used in patients with current or history of HIT due to a lack of an immune-mediated effect on platelets (ACCP [Guyatt, 2012]; Savi, 2005). Use is contraindicated in patients with thrombocytopenia associated with a positive in vitro test for antiplatelet antibodies in the presence of fondaparinux
- #17 ACT: activated clotting time
- #18 4.3.2.5. Argatroban Argatroban, a direct thrombin inhibitor, is indicated for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia, including those undergoing PCI (328). Steady state plasma concentrations are achieved in 1 to 3 hours after intravenous administration. Because of its hepatic metabolism, argatroban can be used in patients with renal insufficiency. The usual dose is 2 mcg/kg per minute by continuous intravenous infusion, adjusted to maintain the activated partial thromboplastin time at 1.5 to 3 times baseline (but not >100 s).
- #20 To avert catheter thrombosis when fondaparinux is used alone in patients undergoing PCI, an anticoagulant with anti-IIa activity is also administered (313–315). One regimen is 85 IU/kg of UFH loading dose at the time of PCI (reduced to 60 IU/kg if a GP IIb/IIIa inhibitor is used concomitantly)
- #21 To avert catheter thrombosis when fondaparinux is used alone in patients undergoing PCI, an anticoagulant with anti-IIa activity is also administered (313–315). One regimen is 85 IU/kg of UFH loading dose at the time of PCI (reduced to 60 IU/kg if a GP IIb/IIIa inhibitor is used concomitantly)
- #22 Management of anticoagulants Prevention of VTE in non-surgical Pts Treatment of VTE
- #27 previous VTE Recent surgery or trauma Active malignancy Pregnancy Estrogen use Advanced age Limited mobility, Severe obesity Known thrombophilic disorder