The Interlaboratory Performance in Measurement of Dabigatran and Rivaroxaban: Results of the College of American Pathologists External Quality Assessment Program

Context.— Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios. Objective.— To evaluate the performance of DOAC-specific assays for various concentrations of dabigatran and rivaroxaban, assess the interlaboratory variability in measurement of these DOACs, and investigate the responsiveness of the routine clotting assays to various concentrations of these oral anticoagulants. Design.— College of American Pathologists proficiency testing survey data from 2013 to 2016 were summarized and analyzed. Results.— For dabigatran, the interlaboratory coefficient of variation (CV) of ecarin chromogenic assay was broad (ranging from 7.5% to 29.1%, 6.3% to 15.5%, and 6.8% to 9.0% for 100-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The CV for diluted thrombin time for dabigatran was better overall (ranging from 11.6% to 17.2%, 9.3% to 12.3, and 7.1% to 11.2% for 100 ng/mL, 200 ng/mL, and 400 ng/mL, respectively). The rivaroxaban-calibrated anti-Xa assay CVs also showed variability (ranging from 11.5% to 22.2%, 7.2% to 10.9%, and 6.4% to 8.1% for 50-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed variable dose and reagent-dependent responsiveness to DOACs: PT was more responsive to rivaroxaban and aPTT to dabigatran. The undiluted thrombin time showed maximum prolongation across all 3 dabigatran concentrations, making it too sensitive for drug-level monitoring, but supporting its use as a qualitative screening assay. Conclusions.— DOAC-specific assays performed reasonably well. While PT and aPTT cannot be used safely to determine DOAC degree of anticoagulation, a normal thrombin time excludes the presence of dabigatran.

Drug level monitoring in palliative patients

Palliative medicine is always patient centred and promotes the principle that no unnecessary investigations are performed. The case is reported of a patient with suspected carbamazepine toxicity presenting as progression of symptoms of primary brain tumour. A comparison is made of the symptoms and signs of toxicity versus tumour, and an aid for deciding when to perform therapeutic drug level monitoring for some common drugs.

Teicoplanin Therapeutic Drug Monitoring and Treatment Outcomes in Children With Gram-Positive Infections

This is a retrospective audit of teicoplanin dosing, drug-level monitoring, and outcomes in 29 children who received 31 courses of teicoplanin. Our study of noncritically ill children showed that the majority (35/43, 81%) of trough concentrations were within the therapeutic range (10-30 mg/L) contrasting previous studies in children. Overall, 21 of the 24 (88%) children with Gram-positive infections achieved cure.

Dramatic Deep and Durable Remission of Acute Fulminant Ulcerative Colitis Achieved with Cyclosporine in a Patient Who Failed the Induction Intravenous Phase of Cyclosporine

Medical rescue therapy for patients with severe steroid-refractory ulcerative colitis (UC) consists of intravenous (IV) cyclosporine or infliximab and remains limited. Cyclosporine is used by fewer medical facilities due to comfort and need for close drug level monitoring, despite evidence that it can have dramatic benefits. In many tertiary centers it is accepted that after 3–7 days of treatment with IV cyclosporine without response, a patient will not respond to the therapy, and other modalities, namely surgery, should be considered. We present the case of a 36-year-old man with acute severe UC refractory to steroids and multiple biologics, who “failed” IV cyclosporine for 2 weeks, much longer than the usually accepted induction phase, and achieved remission with continuation of oral cyclosporine. This case demonstrates the possibility that continued therapy with cyclosporine for a longer duration than the currently accepted timeline can lead to remission and avoidance of colectomy in properly selected and monitored patients.

Cure of limb-threatening XDR Pseudomonas aeruginosa infection: combining genome sequencing, therapeutic drug level monitoring, and surgical debridement

We describe a case of limb-threatening osteomyelitis and metalware infection with carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa successfully cured with aggressive surgical debridement and combined intravenous fosfomycin and colistin. Real-time therapeutic drug monitoring was used to maximize probability of efficacy and minimize potential for toxicity.