1. DiaPharma Factor X Chromogenic Factor X kit for monitoring oral anticoagulation therapy in patients with falsely elevated INRs

2. Monitoring Warfarin Therapy is a Balancing Act!

3. Warfarin Monitoring in Patients with Inhibitors INRs can be falsely elevated in patients with lupus anticoagulant (LA), or patients being bridged from warfarin to direct thrombin inhibitors (DTIs) like Argatroban. Results in overestimation of anticoagulation

4. Warfarin Monitoring in Patients with LA LA patients can produce antibodies that interfere with the phospholipids-dependent clotting reactions that are part of most PT assays. Antiphospholipid antibodies have been shown to artificially prolong the clotting times of PT tests, making the PT/INR unreliable for monitoring anticoagulation 1.

5. Warfarin Monitoring in Patients with LA “To prevent supratherapeutic or subtherapeutic anticoagulation, these patients must be individually monitored with a test that is insensitive to lupus anticoagulants.” 2 Studies have shown that patients who have a LA which interferes with the PT can be effectively monitored by the Factor X assay. 3

6. Chromogenic Factor X Assay The factor X reaction does not require a phospholipid membrane surface, and therefore the chromogenic Factor X assay is a useful tool in the management of patients with LA who are receiving warfarin therapy.

7. Chromogenic Factor X Assay Use of the chromogenic factor X activity assay can avoid overtreatment and undertreatment with warfarin patients with lupus anticoagulant. 4 – Independent measure of warfarin effect

8. Chromogenic Factor X Assay The chromogenic Factor X assay can also be used when monitoring patients on direct thrombin inhibitors (DTIs) being bridged to warfarin. Argatroban elevates the PT in patients receiving warfarin therapy, so the accurate INR is not known in argatroban patients transitioning to warfarin therapy. 5

9. Chromogenic Factor X Assay Monitoring with a chromogenic factor X assay does not require interruptions in argatroban therapy and is not affected by argatroban dosage. 5 The chromogenic factor X assay is an effective way to monitor anticoagulation level when converting patients from argatroban to warfarin.

10. DiaPharma Factor X Measurement Principle RVV 1. FX FXa Ca 2+ FXa 2. FXa substrate peptide + pNA Stage 1: Factor X is activated in the presence of calcium and the activator Russell’s Viper Venom (RVV) to FXa. Stage 2: The generated FXa hydrolyses the chromogenic substrate and liberates the chromophore, pNA. – The color is then read with a spectrophotometer at 405 nm. The intensity of the color is proportional to the FX activity in the sample. Factor X testing may be performed in a microtiter plate, or on automated analyzers.

11. DiaPharma Factor X The DiaPharma Factor X kit is readily available, easy to use, and not affected by inhibitors like LA or DTIs Accurate determination of level of anticoagulation Eliminates issues of varying sensitivities of different thromboplastins

12. DiaPharma Factor X Valuable tool for monitoring oral anticoagulation in patients with prolonged pro-times, such as those with lupus anticoagulants and patients being bridged from thrombin inhibitors like hirudin or argatroban Solution to dealing with unstable INRs in warfarin patients with lupus inhibitors Assay can be brought onto automated coagulation analyzers Also useful for detecting congenital Factor X Deficiencies

13. References 1. Trask, AS, Gosselin, RC, Diaz, JA, Dager, WE. Warfarin Initiation and Monitoring with Clotting Factors II, VII, and X. The Annals of Pharmacotherapy February 2004, 38: 251-256. 2. Moll, S. and Ortel, T. Monitoring Warfarin Therapy in patients with Lupus Anticoagulants; Annals of Internal Medicine August 1, 1997, 127(3) 3. Sanfelippo MJ, Sennet, J, McMahon, EJ. Falsely Elevated INRs in Warfarin-Treated Patients with the Lupus Anticoagulant. Wisconsin Medical Journal, June 2000: 62 – 64, 43.

14. References 4. Rosborough, TK, Shepherd, MF. Unreliability of International Normalized Ratio for Monitoring Warfarin Therapy in Patients with Lupus Anticoagulant. Pharmacotherapy 2004, 24 (7): 838- 842. 5. Arpino, PA, Demirjian, Z, Van Cott, EM. Use of the Chromogenic Factor X Assay to Predict the International Normalized Ratio in Patients Transitioning from Argatroban to Warfarin. Pharmacotherapy 2005, 25 (2): 157-164.

15. Also Available: Coamatic Heparin – For measuring anti-Xa activity of LMW and UF heparin Anti-IIa and Anti-Xa reagents – To measure the activity of new anticoagulant drugs

16. Contact us today to learn more! Customer Service: (800) 526-5224 Technical Support: (800) 447-3846 E-mail: info@diapharma.cominfo@diapharma.com Web: www.diapharma.comwww.diapharma.com