The traditional choices for anticoagulation therapy are few and largely unsatisfactory: heparin, warfarin, and aspirin. Low-molecular-weight heparins are already giving surgeons more choices, and a new crop of thrombin inhibitors promises to expand the armamentarium. Broad experience in Europe shows that patient self-management is a viable option for some populations.
   "It is a recognized but unfortunate fact that anticoagulation is a vital part of cardiopulmonary bypass surgery and other procedures," said Jonathan Chen, MD, chair of pediatric cardiac surgery at Weill Cornell Medical Center in New York. "We are always trying to balance antithrombosis and bleeding."
   The ideal anticoagulant, he reminded the American College of Surgeons Clinical Congress, would be safe, easy to use, widely available, fast onset of action, limited half-life, tolerant of a wide temperature range, affordable, easy to monitor, and cost effective. So far, he said, no agent passes all of the tests.
   Heparin is the most widely used agent, Dr. Chen noted, but heparin-induced thrombocytopenia affects 2% to 3% of patients and antibodies remain in the system for about 100 days after last use.
   Warfarin is widely used, but has an extremely narrow therapeutic window. Aspirin is effective, but can induce GI bleeds.
   Thrombin inhibitors raise other issues. Lepirudan carries a risk of anaphylaxis and has no antidote. Bivalirudin has a short half life, but is affected by temperature and cannot easily be used in hypothermic procedures. Argatroban has no neutralizing agent.
   "There is a fair amount of difficulty in the way people manage anticoagulation in the OR," said Cleveland Clinic Foundation surgeon Nicholas Smedira, MD. "There are promising alternatives to heparin, but none are perfect."
   Managing warfarin is even tougher, noted Bengt Eriksson, Sahlgrenska/Östra University Hospital, Gothenburg, Sweden. Not only does warfarin have a narrow therapeutic index, it has a number of significant interactions with drugs and common foods and must be monitored frequently.
   Ximelagatran, a Factor X inhibitor, is available in Europe for short term use as a replacement for warfarin. The Food and Drug Administration turned thumbs down on the drug in 2004 because of the potential for liver damage with long-term use, Eriksson noted.
   Fondaparinux, a Factor Xa inhibitor, has been approved in the U.S. In trials against enoxaparin, a low-molecular-weight heparin, fondaparinux showed a 55% odds reduction for clotting after total knee and hip replacement. Used in hip fracture, the drug showed a 96% reduction in relative risk of thrombosis. But patients with impaired renal clearance are at higher risk for bleeding.
   Oral Factor IIa and Xa inhibitors are the next step in drug development, Eriksson said. Based on early studies, the agents offer rapid onset of activity, predictability, no need for monitoring, and a solid safety profile. "We believe these products are on the way," he said.
   Until they appear, patient self-management may offer the best alternative for warfarin therapy. A recent Mayo Clinic study found double the adverse events in usual care compared to patients who monitored their own INR levels.
   "All studies looking at patient self-testing have seen significant improvements compared to usual care," reported Hartzell Schaff, MD, chair of cardiac surgery at the Mayo Clinic. "The more time you spend in the therapeutic range, the better your outcome in terms of bleeds and thrombolytic events."
   Mayo encourages anticoagulation patients to not only monitor their own INR levels but to adjust their warfarin dosage, just as diabetics monitor serum glucose levels and adjust their insulin dosages. Self-testing and self-management are common in Europe, Dr. Schaff said, but 60% of anticoagulation clinics in the United States forbid self-testing. Only 1% of U.S. patients taking warfarin test their own INR levels.
   "The barriers to self-management are us," he explained. "Physicians are not terribly aware of this option."
   A 50-patient study at Mayo found that 100% of patients were able to self-test accurately and consistently after about one hour of training. Training was conducted on day three post surgery and continued daily during the duration of the hospital stay. Nurses and physicians proctored the self-testing and compared the values with standard lab values.
   "Five of our patients found out-of-range INR values before our own lab spotted the problem," Dr. Schaff reported. "When you realize that time within the therapeutic window is key to successful outcomes, patients' ability to monitor their own condition is a significant contributor to successful treatment."