generally do not require lab monitoring but if they are monitored, then the anti-Xa assay is used (NOT the APTT). ▲ Half-life is 3-6 hours. LMWHs are renally cleared therefore the half-life will be prolonged in patients with renal failure. ▲ Elective reversal. • Discontinue LMWH 12-24 hours prior to planned procedure depending on the dose of the LMWH, the specific procedure and renal function ▲ Urgent reversal. • There is no antidote • Protamine may reverse the antithrombin (IIa) activity of LMWH but will not reverse the anti-Xa activity. Furthermore, protamine would only affect the intravascular LMWH, not the subcutaneous depot 193. Anticoagulant Drugs Fibrinogen Common V II X VIII IX XI VII XII Pathway Fibrin Clot Intrinsic Pathway Extrinsic Pathway Fibrinogen Common V II X VIII IX XI VII XII Pathway Fibrin Clot Intrinsic Pathway Extrinsic Pathway ! Consider measuring anti-Xa levels in the following populations: • CrCl < 30 mL / minute • Weight < 40kg • Weight > 100kg • Pregnancy A T T E N T I O N 20 21 3. ANTICOAGULANT DRUGS Fondaparinux ▲ Fondaparinux is the synthetically produced five saccharide units (pentasaccharide) that combine with antithrombin. ▲ Fondaparinux is an “indirect” anticoagulant. It exerts its anticoagulant effect by combining with antithrombin. The fondaparinuxantithrombin complex inhibits only coagulation factor Xa. ▲ It is administered subcutaneously (SC). ▲ Fondaparinux generally does not require lab monitoring, but if it is monitored, the anti-Xa assay is used (NOT the APTT). ▲ Half-life is 17-21 hours. It is renally cleared so the half-life will be prolonged in patients with renal failure. ▲ Elective reversal. • For most procedures, stop prophylactic fondaparinux 24 hours before and therapeutic fondaparinux 1-2 days before if renal function is normal ▲ Urgent reversal. • There is no antidote • Protamine has no effect • There is no evidence to support the use of tranexamic acid, PCCs, FEIBA or recombinant activated VIIa Warfarin ▲ Warfarin is an oral Vitamin K antagonist. ▲ Clotting factors II, VII, IX and X as well as natural anticoagulant proteins, Protein C and Protein S, require the action of Vitamin K to become activated so that they may participate in coagulation. By inhibiting Vitamin K, warfarin prevents the activation of these factors. ▲ It is monitored using the PT which is converted to an INR. ▲ Individual doses vary and the dose is adjusted to prolong the INR into a therapeutic range. • Target INR = 2.5 (range = 2.0-3.0) for most indications requiring therapeutic anticoagulation • Target INR = 3.0 (range = 2.5-3.5) for therapeutic anticoagulation for mechanical mitral valves ▲ Patient INR can be measured by sending a citrated plasma sample to the lab (blue top tube) or using a drop of whole blood from a finger-prick using point-of-care devices. ▲ Half-life is 36-42 hours. 3. Anticoagulant Drugs 21 Fibrinogen Common V II X VIII IX XI VII XII Pathway Fibrin Clot Intrinsic Pathway Extrinsic Pathway Fibrinogen Common V II X VIII IX XI VII XII Pathway Fibrin Clot Intrinsic Pathway Extrinsic Pathway ▲ DTIs include intravenously administered drugs like argatroban, bivalirudin and lepirudin which are used primarily in the treatment of Heparin-Induced Thrombocytopenia (HIT). DTIs also include the oral drug dabigatran which is used for the prevention of stroke related to non-valvular atrial fibrillation and in the prophylaxis and treatment of venous thromboembolism. ▲ Dabigatran does not require routine monitoring. Since the drug inhibits thrombin, APTT, TT and PT may be variably affected. ▲ Half-life of dabigatran is 15 hours (12-18 hours). • Renally cleared so half-life will be prolonged in patients with renal failure • Note: Dabigatran is contraindicated in patients with CrCl < 30 mL / minute 22 3. ANTICOAGULANT DRUGS Warfarin (continued) ▲ Elective reversal. • Stop warfarin 5 days before major invasive procedure • Note: bridging therapy may be considered for selected patients at high risk for thrombosis ▲ Urgent reversal. • Antidotes: – Vitamin K ◆ IV vitamin K acts more quickly than the oral route (6-12 hours vs. 18-24 hours) ◆ Vitamin K works quickly because it activates factors