Transplant patient classification and tacrolimus assays: more evidence of the need for assay standardization.

BACKGROUND: A global tacrolimus proficiency study recently showed clinically significant variability between laboratories, the inability of a common calibrator to harmonize methods, and differences in patient classification depending on the test method. The authors evaluated (1) the effect of a change in methodology on patient classification based on tacrolimus blood concentration and (2) the ability of 2 methods to position the concentration in a given specimen within the correct range. METHODS: A total of 839 consecutive samples were analyzed at The Rogosin Institute and New York Presbyterian Hospital for routine tacrolimus monitoring over 30 days. Concordance analysis between the methods was performed covering dosage target ranges of 8-10, 6-8, 4-6 ng/mL currently used at our center. Six Sigma Metrics were applied to statistically evaluate the discordance rate. RESULTS: Deming regression comparing liquid chromatography-tandem mass spectrometry and immunoassay yielded y = 0.927x - 0.24; 95% confidence interval, 0.903-0.951; R = 0.875; n = 839. There were 310 pairs (37%) discordant by 1, 21 (2.5%) discordant by 2, and 4 (0.5%) discordant by 3 therapeutic ranges. Surprisingly, 40% of patient samples were discordant when therapeutic ranges were 2 ng/mL wide. This discordant rate is equivalent to 1.7 Sigma and falls far below the minimum acceptable threshold of 3 Sigma. CONCLUSIONS: Both methods are capable of measuring tacrolimus in the clinically relevant range between 1 and 10 ng/mL, yet 40% of the samples were discordant with an unacceptable Sigma level. Standardization of tacrolimus assays will mitigate this issue.

Pharmacogenomics and the future of toxicology testing.

Pharmacogenomics is a useful tool in clinical toxicology for characterizing many gene polymorphisms associated with different pharmacokinetics or pharmacodynamics of exogenously administered drugs. These genetic variants may determine ranges of variation in such fundamental aspects as drug-metabolizing enzymes, drug transporters, drug receptors, or targets of drug action. Toxicologically significant drugs for which the FDA has required the manufacturer to identify relevant pharmacogenomics markers on the label include carisoprodol, citalopram, codeine, and risperidone. For personalized medicine, combining pharmacogenomics testing with therapeutic drug monitoring may allow the identification of individuals who need lower or higher doses, or even a different drug.

An assay to monitor bivalirudin levels on cardiopulmonary bypass.

Anticoagulation therapy for cardiopulmonary bypass in patients with recently diagnosed heparin-induced thrombocytopenia can be particularly challenging. Although heparin is the standard of care, in these situations anticoagulation is achieved with alternative agents such as direct thrombin inhibitors. Therapeutic concentrations are difficult to assess with direct thrombin inhibitors, and their use is riddled with bleeding and thrombotic complications. We report the successful use of a specific chromogenic antifactor IIa assay in a patient with heparin-induced thrombocytopenia who received anticoagulation therapy with bivalirudin during cardiopulmonary bypass for coronary artery bypass graft surgery.