Considerations in using anticoagulant therapy in special patient populations.

PURPOSE: The role of genetic polymorphisms and genetic testing in guiding warfarin dosing is discussed, as are the selection and monitoring of anticoagulant therapy for obese patients, patients with severe renal impairment, and patients with heparin-induced thrombocytopenia (HIT); case studies are used to illustrate each topic.
SUMMARY: Genetic polymorphisms influence metabolism of and sensitivity to warfarin. People with certain ethnic backgrounds have a greater likelihood of having genetic polymorphisms that reduce warfarin dosing requirements and increase the risk of bleeding. Genetic testing has the potential to improve patient safety; however, its cost is high, and genetic polymorphisms account for only part of interindividual variation in dosing requirements. For obese patients, dose capping of low molecular weight heparin is not warranted, and twice-daily enoxaparin is preferred over once-daily dosing. Anti-Xa monitoring is perhaps not necessary for patients weighing less than 190 kg (418 lb), but it may be useful to adjust dosing in heavier patients. In patients with severe renal impairment, bleeding during anticoagulant therapy may be attributed to the uremic state, excessive doses, or both. Dosage reduction and anti-Xa monitoring are recommended for patients with severe renal impairment. Treatment of patients with HIT should include discontinuation of heparin, temporary interruption of warfarin therapy, and initiation of a direct thrombin inhibitor.
CONCLUSION: Safe and effective use of anticoagulant therapy may require consideration of genetics, obesity, renal impairment, or the potential for HIT; selecting anticoagulant therapy on the basis of these considerations can present a challenge.