Table 6. Continued from page 4. References Continued from page 5. Primary 7. Kearon C. Hirsh J. Management of anticoagulation before and after elective surgery. New England Journal of Medicine. 336(21):1506-11, 1997. Anticoagulant Anticoagulation Reversal Anticoagulant Half-Life Excretion Therapeutic Anticoagulation Dose 8. Hanley JP. Warfarin reversal. Journal of Clinical Pathology. 57(11):1132-9, 2004 Nov. Action Monitoring Agents Mode 9. Holland L. Warkentin TE. Refaai M. Crowther MA. Johnston MA. Sarode R. Suboptimal effect of a three-factor prothrombin complex concen- trate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose. Transfusion. 49(6):1171-7, 2009 Pediatrics Adults 10. Bauer KA. New anticoagulants. Hematology Am Soc Hematol Educ Program. 2006:450-6. Xa-Inhibitors 11. O'Connell NM. Perry DJ. Hodgson AJ. O'Shaughnessy DF. Laffan MA. Smith OP. Recombinant FVIIa in the management of uncontrolled hemorrhage. Transfusion. 43(12):1711-6,2003. Winter 2011 Fondaparinux: 17-21 Renal Anti-thrombin 0.15 mg/kg, daily, SC <50 kg: 5 mg, SC, Typically no rFVIIa 12. O'Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM. Thromboembolic adverse events after use of recombinant human coagulation factor (Arixtra) hours mediated inhibi- daily monitoring (NovoSeven) VIIa. JAMA. 2006 Jan 18;295(3):293-8. tion of factor Xa 50-100 kg: 7.5 mg, required SC, daily Anti-factor Xa 13. Riess HB. Meier-Hellmann A. Motsch J. Elias M. Kursten FW. Dempfle CE. Prothrombin complex concentrate (Octaplex) in patients requiring >100 kg: 10 mg daily (Calibrated with immediate reversal of oral anticoagulation. [Clinical Trial. Journal Article. Multicenter Study. Research Support, Non-U.S. Gov't] Thrombosis Arixtra curve) Research. 121(1):9-16, 2007. Reversal of Anticoagulation 14. van Ryn J. Stangier J. haertter S. Liesenfeld KH. Feuring M. Clemens A. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: Rivaroxaban: 5.7 to 9 Renal Direct Xa Not available 10 mg (prophylaxis No monitoring rFVIIa (Novo interpretation of coagulation assays and reversal of anticoagulant activity. Thrombosis and Haemostasis. 2010 Jun; 103(6):1116-27. Anne Greist, MD (Xarelto) hours inhibition only), PO, daily required Seven), aPCC Direct March is Hemophilia Awareness Month Patients who receive anticoagulation may require reversal appreciating the risk of acute thrombosis if anti- Bivalirudin: 25 Enzymatic Direct inhibition Loading dose: PCI APTT, TCT, ACT Desmopressin of their treatment. This typically occurs for two main coagulation is reversed. (Angiomax) minutes cleavage of thrombin 0.25 mg/kg, IV Loading dose: Acetate; see how the IHTC is helping patients reasons: there is a bleeding complication or the patient 0.75 mg/kg, IV Cryoprecipitate; It is important to note the time the last dose of the anti- Maintenance, CI: Maintenance, CI: Antifibrinolytics: needs to undergo surgery or other invasive procedure. The IHTC has created the "Thrive" website, www.seehowithrive.org, and it features 0.07±0.16 1.75 mg/kg/hr, IV Amicar (EACA); The approach to reversal of anticoagulation depends upon coagulant was given to appropriately select the reversal mg/kg/hour hemophilia facts and a series of videos highlighting the stories of people in Indiana who Tranexamic acid the circumstances that require cessation of treatment, and agent for the situation. Consultation with a hematologist Unstable angina live with hemophilia. The videos and website were created to emphasize that with care Load: 0.1 mg/kg whether the situation is emergent or elective. may be necessary for dosing and follow-up recommenda- Maintenance: and treatment, those affected with hemophilia are living productive, normal lives. tions. Agents utilized for the reversal of anticoagulation 0.25 mg/kg/hr Hemophilia is one of the most expensive chronic medical conditions largely due to the General Considerations: have the potential to precipitate a thrombosis; for example, Argatroban 40-50 Biliary, Liver Direct inhibition Loading dose: Loading dose: None APTT Desmopressin cost of required therapy to treat or prevent bleeding episodes. People with bleeding disorders require expert medical Bleeding complications that arise while on anticoagulation protamine sulfate, used to reverse heparin, has an anticoagu- minutes of thrombin 65-250 mg/kg, IV Acetate; are classified as either major or minor. Major bleeding is Maintenance, CI: care from dedicated experts who have extensive experience and a wide range of available services to address the many lant property if an excessive dose is administered. Newer Cryoprecipitate; bleeding that carries a risk of death or long-term morbidity, anticoagulants may not have a specific antidote. CI:0.5- 0.5-2.0 mg/kg/hr, Antifibrinolytics: aspects of life that are impacted by hemophilia; these include individually tailored medical needs, physical and social Amicar (EACA); functioning, and the impact on their family, work, and school. such as intracranial or intraocular bleeding; need for transfu- Tranexamic acid sion; or bleeding from a non-compressible vessel. Bleeding Warfarin: As Indiana’s only federally recognized hemophilia treatment center, the IHTC offers lifelong, comprehensive, patient- that has the potential to result in loss of life, organ, limb Lepirudin 80 Renal Direct inhibition Loading dose: Loading dose: APTT, Desmopressin Warfarin is the most common anticoagulant in use and acts (Recombinant minutes of thrombin Not recommended 0.4 mg/kg Ecarin clotting Acetate; centered, multidisciplinary healthcare that goes beyond what we often consider as event or disease based interventions. or digits, should be considered an emergency that requires by inhibiting the terminal gamma carboxylation step in the Hirudin, time, Cryoprecipitate; The IHTC’s multidisciplinary team includes hematologists, nurses, physical therapists, social workers, dental hygienists, reversal of anticoagulation. All other bleeding events are production of coagulation factors II, VII, IX and X. Patients Refludan) Maintenance, CI: Maintenance, CI: Chromogenic Antifibrinolytics: dietician, career counselor, and an integrated onsite pharmacy – all of these are focused on serving the patient, and 0.1 mg/kg/hr 0.15 mg/kg/hr, IV classified as minor and include bruising, oozing from are anticoagulated to a target INR of 2.0-3.0, although the Lepirudin assay Amicar (EACA); supporting and educating the patient’s family. The IHTC also provides medical education to assist care providers in caring injection sites, injuries, surgical sites, gingival bleeding, target is higher (2.5-3.5) for patients with mechanical heart Tranexamic acid for the bleeding disorder community throughout the state. Educational efforts include on-line learning modules through epistaxis that is easily controlled with local measures, and valves. For ophthalmic surgery, other than cataracts, and Dabigatran 12-17 hrs Biliary, renal Direct inhibition Not available 150 mg, PO, BID APTT, rFVIIa our PartnersPRN.org website, local grand rounds and medical in-services as requested, and distribution of IHTC developed menorrhagia not requiring transfusion. It is often possible procedures such as lumbar puncture or endoscopy, warfarin of thrombin Ecarin clotting (NovoSeven), educational materials. The IHTC is Indiana’s center of excellence for bleeding disorders. time, aPCC to manage minor bleeding by holding one or two doses of should be held for three days preoperatively. Otherwise, the TCT anticoagulant therapy with provision of supportive care. To learn more about Hemophilia Awareness Month and how the IHTC helps our patients thrive, visit Continued on page 2 Xa-Inhibitors http://www.seehowithrive.org. For more information about the IHTC, visit www.ihtc.org. For patients who are in need of emergency surgery, the Idraparinux 5-6 days Renal Anti-thrombin Not available 2.5 mg/week, SC No monitoring Avidin (NOT risk of bleeding due to the use of anticoagulants must be March is Hemophilia Awareness Month (Pending FDA mediated required available in US)*; weighed against the risk of immediate thrombosis if reversal March is designated approval) inhibition of rFVIIa is performed. There are some procedures that may be per- factor Xa (NovoSeven) Hemophilia Awareness formed without reversal of anticoagulation. These include Month, dedicated to Apixaban 12 Biliary, Renal Direct Xa Not available 5-10 mg, PO, BID No monitoring rFVIIa placement of peripherally inserted central catheter (PIC) increasing awareness (Pending FDA inhibition required (NovoSeven) lines, or tympanostomy tubes, removal of chest tubes, and approval) about bleeding disorders, 8402 Harcourt Road, Suite 500 cardiac catheterization. Minor dental procedures, minor Indianapolis, IN 46260 inspiring advancements in References Continued on back page. dermatological procedures, cataract surgery, and endometrial diagnosis and treatment, ablation are also examples of procedures where reversal of 1. Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). and dispelling common American College of Chest Physician. Chest. 2008 Jun; 133(6 Suppl):67S-968S. anticoagulation may not be necessary. misconceptions. To 2. Monagle P, Chan AKC, deVeber G, Massicotte P. Andrew’s Pediatric Thromboembolism and Stroke; Third edition advance these objectives in our state, the Indiana 3. Crowther MA, Warkentin TE. Bleeding risk and the management of bleeding complications in patients