Evaluation of the in vitro stability of direct oral anticoagulants in blood samples under different storage conditions.

In this study, we evaluated the in vitro stability of direct oral anticoagulants (DOACs) in blood samples of 57 patients under different storage conditions using functional coagulation assays. We determined the analyte concentrations (1) immediately after blood collection (baseline); (2) after storage of citrated whole blood (agitated) at room temperature and citrated plasma at room temperature and at 4 °C for 4, 8, and 24 h, respectively; and (3) after storage of citrated plasma at -20 °C for 30, 60, and 90 days. According to the concept of acceptable change limits (ACL), analytes were considered stable if the mean relative analyte recovery at a given time was >78%. The mean baseline values (range) of dabigatran, rivaroxaban, apixaban, and edoxaban were 115 ng/mL (62-217), 129 ng/mL (31-215), 156 ng/mL (49-362), and 101 ng/mL (33-283), respectively. After applying the analyte stability limit, all four DOACs were stable for 24 h at room temperature and at 4 °C. The mean recovery after 24 h was 102-111% for dabigatran, 88-97% for rivaroxaban, 95-98% for apixaban, and 90-96% for edoxaban. When plasma samples were stored at -20 °C, the mean percentage deviation after 90 days for all four DOACs was ≤10%, even after three freeze-thaw cycles. Thus, for the correct determination of DOAC plasma concentrations, blood samples do not have to be analyzed immediately and can be stored at room temperature for up to 24 h before analysis. In clinical practice, blood sample transport and storage for DOAC measurements appear to be unproblematic.

Evaluation of sex-specific cut-off values of high-sensitivity cardiac troponin I and T assays in an emergency department setting - Results from the Linz Troponin (LITROP) study.

BACKGROUND: The aim of the present analysis was to evaluate sex-specific cut-off values of a high-sensitivity cardiac troponin T (hs-cTnT) assay and a high-sensitivity cardiac troponin I (hs-cTnI) assay in an emergency department setting. METHODS: We retrospectively studied 1945 male and 1643 female emergency department patients in whom we had measured both Roche hs-cTnT and Abbott hs-cTnI routinely upon every troponin measurement request. We performed reclassification analyses of sex-specific thresholds versus sex-neutral thresholds of both assays. In addition, we performed sensitivity analyses to find those sex-specific cut-off values for the Roche hs-cTnT and the Abbott hs-cTnI assays with the lowest possible rate of discordant classifications by both assays. RESULTS: Compared with the classification by the sex-neutral thresholds (i.e., 14 ng/L for hs-cTnT and 26 ng/L for hs-cTnI), using sex-specific thresholds (i.e., 16 ng/L in males and 9 ng/L in females for hs-cTnT; and in 34 ng/L males and 16 ng/L in females for hs-cTnI) resulted in a total reclassification rate of 4% for hs-cTnT and 3% for hs-cTnI in male individuals, and of 11% and 6%, respectively, in female individuals. In our cohort, the sex-specific hs-cTnT cut-off values currently in use (i.e., 16 ng/L in males and 9 ng/L in females) were best matched to a hs-cTnI cut-off value of 11 ng/L in male and 5 ng/L in female individuals. Conversely, the sex-specific hs-cTnI cut-off values currently in use (i.e., 34 ng/L in males and 16 ng/L in females) were best matched to a hs-cTnT cut-off value of 49 ng/L in male and 24 ng/L in female individuals. These "harmonised" cut-off values reduced discordant classifications between both assays by 43-68% compared to using cut-off values currently in use. CONCLUSION: Especially in women, reclassification rates were high, when using sex specific versus sex-neutral thresholds. Best matching cut-off values for hs-cTnT and hs-cTnI were markedly different to those currently in use. These "harmonised" cut-off values minimised discordant classifications between both assays.

The role of telomeres and vitamin D in cellular aging and age-related diseases.

Aging is a complex biological process characterized by a progressive decline of organ functions leading to an increased risk of age-associated diseases and death. Decades of intensive research have identified a range of molecular and biochemical pathways contributing to aging. However, many aspects regarding the regulation and interplay of these pathways are insufficiently understood. Telomere dysfunction and genomic instability appear to be of critical importance for aging at a cellular level. For example, age-related diseases and premature aging syndromes are frequently associated with telomere shortening. Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. Here we review existing knowledge about the link between telomere biology and cellular aging with a focus on the role of vitamin D. We searched the literature up to November 2014 for human studies, animal models and in vitro experiments that addressed this topic.

Influence of centrifuge brake on residual platelet count and routine coagulation tests in citrated plasma.

Sample centrifugation is an essential step in the coagulation laboratory, as clotting tests are typically performed on citrated platelet (PLT) poor plasma (PPP). Nevertheless, no clear indication has been provided as to whether centrifugation of specimens should be performed with the centrifuge brake set to on or off. Fifty consecutive sodium citrate anticoagulated samples were collected and divided into two aliquots. The former was centrifuged as for Clinical Laboratory Standards Institute (CLSI) guidelines with the centrifuge brake set to on, whereas the latter was centrifuged again as for CLSI guidelines, but with the brake set to off. In the PPP of all samples, a PLT count was performed, followed by the analysis of activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FBG). The PLT count after samples centrifugation was substantially reduced, either with centrifuge brake set to on or off (5 ±â€Š1 versus 3 ±â€Š1 × 10/l; P = 0.009). The frequency of samples exceeding a PLT count less than 10 × 10/l was nearly double in samples centrifuged with the brake on than in those with the brake off (14 versus 8%; P < 0.01). Although no significant difference was found for APTT values, PT was slightly prolonged using the centrifuge brake set to on (mean bias 0.2 s; P < 0.001). FBG values were also significantly higher using the centrifuge brake set to on (mean bias 0.29 g/l; P < 0.001). The results of this study indicate that sample centrifugation for routine coagulation testing should be preferably performed with the centrifuge brake set to off for providing a better quality specimen.