and does not require synthesis of new factors – Prothrombin complex concentrates (PCCs) (Octaplex, Beriplex) ◆ PCCs contain vitamin K dependent clotting factors (II, VII, IX, X, Protein C and S) and a small amount of heparin ◆ Contraindicated in patients with heparin-induced thrombocytopenia • For emergent reversal of warfarin (reversal within 6 hours), give vitamin K 5-10mg IV and PCCs. At present, a PCC dose of 1000 IU is recommended for INR 1.5-3.0 • If urgent reversal is not required, vitamin K alone may be administered Direct Thrombin Inhibitors (DTIs) ▲ DTIs are synthetically derived and directly inhibit thrombin (Factor IIa). They are called “direct” because unlike heparin, LMWH and fondaparinux, they do not require antithrombin to inhibit their target. 3. Anticoagulant Drugs 23 ! Vitamin K should not be administered subcutaneously. A T T E N T I O N A T T E N T I O N ! Dabigatran is contraindicated in patients with CrCl < 30 mL / minute. Fibrinogen Common V II X VIII IX XI VII XII Pathway Fibrin Clot Intrinsic Pathway Extrinsic Pathway 24 3. ANTICOAGULANT DRUGS Direct Thrombin Inhibitors (continued) ▲ Elective reversal of dabigatran is based on its half-life of 15 hours (12-18 hours). • If CrCl is > 50 mL / minute, stop dabigatran 1-2 days prior to procedures that are not associated with a high risk of bleeding • If CrCl is 30-50mL / minute, stop dabigatran 2-4 days prior to the procedure depending on the risk of blood loss and consider obtaining an APTT prior to the procedure ▲ Urgent reversal of dabigatran. • Antidote: none • Activated charcoal if ingested within 2 hours • Hydration to correct pre-renal dysfunction • Hemodialysis may remove 60% of drug after two hour run • There is no definitive evidence to support the use of tranexamic acid, PCCs, FEIBA or recombinant factor VIIa • Consult an expert in hematology or transfusion medicine Direct Xa inhibitors ▲ Direct factor Xa inhibitors are synthetically derived and directly inhibit Factor Xa. They are called “direct” because unlike heparin, LMWH and fondaparinux, they do not require antithrombin to inhibit their target. ▲ Direct Xa inhibitors include apixaban and rivaroxaban which are used for the prevention of stroke related to non-valvular atrial fibrillation and in the prophylaxis and / or treatment of venous thromboembolism. Other factor Xa inhibitors are under development. ▲ Apixaban and rivaroxaban do not require routine monitoring. Since the drug inhibits factor Xa, PT and APTT may be variably affected. These drugs can also be monitored using the anti-Xa assay. ▲ Half-life: apixaban 7-8 hours; rivaroxaban is 11-13 hours. • Partially renally cleared so half-life will be prolonged in patients with renal failure ▲ Elective reversal. • Stop apixaban and rivaroxaban 1-2 days prior to the procedure depending on the risk of blood loss and renal function ▲ Urgent reversal. • Antidote: none • Hemodialysis is not effective • There is no definitive evidence to support the use of tranexamic acid, PCCs, FEIBA or recombinant factor VIIa • Consult an expert in hematology or transfusion medicine 3. Anticoagulant Drugs 25 ! Apixaban and rivaroxaban are contraindicated in patients with CrCl < 30 mL / minute. A T T E N T I O N Fibrinogen Common V II X VIII IX XI VII XII Pathway Fibrin Clot Intrinsic Pathway Extrinsic Pathway 26 4. EVALUATING ABNORMAL COAGULATION TESTS Karen Moffat Prolonged PT / INR with normal APTT If the PT / INR is prolonged but the APTT is not, the probable cause is related to Factor VII (FVII). What is the differential diagnosis? ▲ Congenital deficiency of FVII. ▲ Acquired deficiency of FVII. • Early warfarin therapy or early vitamin K deficiency (FVII has the shortest half-life of the vitamin K dependent factors so FVII levels will be lower than the other Vitamin K dependent factors (IX, X and II) early on in the course of warfarin therapy or Vitamin K deficiency) • Early liver disease ▲ Specific inhibitors to FVII can occur but are exceptionally rare. To distinguish between factor deficiency and inhibitor ▲ Perform a 50:50 mix: This test is performed by combining 1 part patient plasma with 1 part normal plasma. A PT is performed on