44 research outputs found
Protocolled Redefinition of the Therapeutic Range for Unfractionated Heparin: Lost in Translation?
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Monitoring direct thrombin inhibitors with routine and dedicated coagulation assays : which assay is helpful?
The use of direct thrombin inhibitors (DTIs) for prophylactic or therapeutic anticoagulation is increasing because of the predictable bioavailability and short half-life of these DTIs. However, in certain situations, indication of the concentration is warranted. We investigated the effects of 3 DTIs (lepirudin, argatroban, and bivalirudin) in 6 pooled plasma specimens on routine coagulation assays (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]) and dedicated DTI assays (Hemoclot, HemosIL, the ecarin clotting time, and a chromogenic ecarin clotting time) on 2 coagulation analyzers. We found routine tests to be nondiscriminative between concentrations of different DTIs in the aPTT. Moreover, for PT and TT, the responses for different DTIs differed. This was similar for ecarin clotting assays. The Hemoclot and HemosIL assays showed identical linear increases for all 3 DTIs. We conclude that dedicated calibrated assays based on a diluted TT (Hemoclot and HemosIL) appear to be the most suitable for monitoring purposes
Novel urinary biomarkers ADXBLADDER and bladder EpiCheck for diagnostics of bladder cancer: A review
Non-muscle-invasive bladder cancer (NMIBC) is accompanied with high incidence and recurrence rates. The extensive need for cystoscopic follow up causes substantial patient discomfort and leads to a high economic burden. Cytology of exfoliated tumor cells in urine is not able to safely reduce or replace the amount of cystoscopies. Here, we give a short overview of established urinary biomarkers and review 2 novel urinary biomarkers, ADXBLADDER and Bladder EpiCheck, for their clinical utility in NMIBC. A Pubmed literature search was performed on the subject of urinary biomarkers for NMIBC. The performance of urinary cytology and established biomarkers Nuclear matrix proteins (NMP22), BTA, UroVysion, and ImmunoCyt was evaluated. The performance of novel biomarkers ADXBLADDER and Bladder EpiCheck was critically reviewed. Based on available clinical studies, established urinary biomarkers have no clear role in the diagnosis or follow-up of NMIBC. Three available prospective studies of ADXBLADDER (2 studying initial diagnosis and 1 follow-up study) reported overall sensitivity (45%ā73%) and negative predictive values (NPV) (74%ā100%) superior to cytology, with reasonable specificity (70%ā73%). Four follow-up Bladder EpiCheck studies reported overall sensitivity (62%ā90%) and NPV (79%ā97%) superior to cytology, with a high specificity (82%ā88%). For detection of high grade recurrences, sensitivity, and NPV of both novel biomarkers were even higher, with a sensitivity and NPV of 76% to 88% and 99% respectively for ADXBLADDER and 79% to 95% and 99% respectively for Bladder EpiCheck ā Novel urinary biomarkers ADXBLADDER and Bladder EpiCheck have better sensitivity and NPV, but worse specificity than cytology in the follow-up of NMIBC. In the future, these biomarkers might reduce the amount of follow-up cystoscopies, for instance via an intermittent follow-up scheme alternating between cystoscopy and biomarker testing. The main biomarker objective should be to rule out high grade tumor recurrence without the need for any invasive procedures. Nevertheless, the clinical implementation of these biomarkers in the follow up of NMIBC has to be further investigated in prospective randomized trials for low as well as high grade tumors
Heterophilic antibodies leading to falsely positive D-dimer concentration in an adolescent
BACKGROUND: We present the case of a 15-year-old adolescent with suspected pulmonary embolism and repeatedly elevated D-dimer levels. KEY CLINICAL QUESTION: We aim to determine the cause for elevated D-dimer levels in a patient without venous thromboembolism. CLINICAL APPROACH: When the D-dimer measurement was repeated with different assays, D-dimer levels were within the normal reference interval. Dilution series with assay diluent or low-affinity antibody blocking reagents either did not or only partially decreased the D-dimer value using the original reagent kit. CONCLUSION: Analyses suggested the presence of interfering heterophilic antibodies in patient plasma, a known phenomenon with immunoturbidimetric D-dimer assays, which is rarely described. Prior to drawing this conclusion, the patient underwent extensive diagnostic testing, which led to uncertainty and discomfort for the health care providers, the patient, and their family
Protocolled Redefinition of the Therapeutic Range for Unfractionated Heparin: Lost in Translation?
Successful co-administration of dabigatran etexilate and protease inhibitors ritonavir/lopinavir in a patient with atrial fibrillation
Troponin I concentrations in heparinized plasma and serum differ when measured with the Advia Centaur TnIāUltra assay
A value proposition for trough level-based anti-TNFĪ± drug dosing
\u3cp\u3eTreatment of inflammatory bowel diseases and rheumatic disorders with anti-tumor necrosis factor alpha (TNFĪ±) drugs is expensive, while a significant proportion of patients does not show adequate clinical response. Therapeutic drug monitoring (TDM) enables patient-specific anti-TNFĪ± therapy. The role of laboratory tests in clinical care has recently been described in a value proposition framework. It describes care processes, stakeholders, costs, risks, benefits and patient outcomes based on the use of a laboratory test in a clinical care pathway. We have applied this concept to the use of TDM for anti-TNFĪ± drugs, describing evidence that supports the intervention and its cost effectiveness, steps that need to be adjusted in the care pathway, possible treatment algorithms and measures to assess adoption of this framework into clinical practice. For effective TDM, an assay for measurement of drug levels together with appropriate target ranges and an anti-drug-antibody assay have to be implemented. Also, instead of only reporting the drug concentration, laboratorians, pharmacists and clinicians should deliver added value by introducing a TDM-based treatment algorithm into clinical practice. Thus, to maximize effectiveness of TDM of anti-TNFĪ± therapy in routine care, adjustment of current care pathways and cooperation of many stakeholders are needed.\u3c/p\u3