BackgroundSuitable procedures for transport of blood samples from general practitioners to hospital laboratories are requested. Here we explore routine testing on samples stored and transported as whole blood in lithium-heparin or serum tubes.MethodsBlood samples were collected from 106 hospitalized patients, and analyzed on Architect c8000 or Advia Centaur XP for 35 analytes at base line, and after storage and transport of whole blood in lithium-heparin or serum tubes at 21 ± 1°C for 10 h. Bias and imprecision (representing variation from analysis and storage) were calculated from values at baseline and after storage, and differences tested by paired t-tests. Results were compared to goals set by the laboratory.ResultsWe observed no statistically significant bias and results within the goal for imprecision between baseline samples and 10-h samples for albumin, alkaline phosphatase, antitrypsin, bilirubin, creatinine, free triiodothyronine, γ-glutamyl transferase, haptoglobin, immunoglobulin G, lactate dehydrogenase, prostate specific antigen, total carbon dioxide, and urea. Alanine aminotransferase, amylase, C-reactive protein, calcium, cholesterol, creatine kinase, ferritin, free thyroxine, immunoglobulin A, immunoglobulin M, orosomucoid, sodium, transferrin, and triglycerides met goals for imprecision, though they showed a minor, but statistically significant bias in results after storage. Cobalamin, folate, HDL-cholesterol, iron, phosphate, potassium, thyroid stimulating hormone and urate warranted concern, but only folate and phosphate showed deviations of clinical importance.ConclusionsWe conclude that whole blood in lithium-heparin or serum tubes stored for 10 h at 21 ± 1°C, may be used for routine analysis without restrictions for all investigated analytes but folate and phosphate.

No abstract

No abstract

Idarucizumab, an antidote specific for dabigatran, became available recently. Dabigatran is not associated with increased risk of hepatotoxicity in comparison with warfarin, but it is seen as a rare side-effect. Cases of cholestatic liver injury due to dabigatran have not been reported previously. We present a case of severe gastro-intestinal bleeding with underlying dabigatran intoxication in a patient with renal failure and the effect of reversal of dabigatran using idaruzicumab on coagulation assays. International normalized ratio (INR) and activated partial thromboplastin time (APTT) results were elevated in a setting of sepsis, possibly due to liver failure. INR and APTT can be elevated if sepsis is complicated by disseminated intravascular coagulation (DIC) or liver failure, making it challenging to determine dabigatrans contribution to their prolongation. A rebound effect after administration of idarucizumab and slow elimination of dabigatran due to reduced kidney function could be detected using the Hemoclot diluted thrombin time (dTT) in this situation, in contrast to with non-dilutional assays. Before admission, cholestatic liver injury started shortly after initiation of dabigatran etexilate therapy. As no other cause was found, this liver injury was likely to be drug-induced. Bleeding cessated promptly after administration of idarucizumab in dabigatran intoxication. In conclusion, the anticoagulant effect of dabigatran can be measured by Hemoclot dTT in sepsis and cholestatic liver injury was seen as a possible rare side-effect of dabigatran treatment.

Analogues of vitamin D₃ have recently been introduced for the topical treatment of psoriasis. Their therapeutic effects are thought to be mediated by interaction with the vitamin D₃ receptor (VDR) in epidermal keratinocytes (KCs). The purpose of the present study was to investigate the trans-acting activity of the endogenous VDR in human KCs transfected with a vitamin D response element (VDRE) in response to 1,25-dihydroxÝvitamin D₃ [1,25(OH)₂D₃] and the synthetic vitamin D₃ analogues GS 1500, EB 1213, MC 903 (calcipotriol) and KH 1060. Cultured KCs obtained from normal human adults were transfected with a VDRE consisting of a direct repeat (DR) of 2 hexanucleotides separated by 3 nucleotides (AGGTCAaggAGGTCA) cloned as a triple copy into the chloramphenicol acetyltransferase (CAT) reporter plasmid pBLCAT2. This DR3 response element is preferentially activated by heterodimers of the VDR and the retinoid X receptor. Twenty-four hours after transfec-tion, 1,25(OH)₂D₃, vitamin D₃ analogues or 9-cis-retinoic acid (9-cis-RA) were added, and, after an additional 24 h, cells were harvested and assayed for CAT activity. 1,25(OH)₂D₃ dose-dependently induced CAT activity in VDRE-transfected KCs and co-transfection with exogenous human VDR enhanced the response to 1,25(OH)₂D₃. Induction of CAT activity by 1,2 5 (OH) ₂D₃ was enhanced in the presence of the endogenous ligand for retinoid X receptor, 9-cis-RA. The synthetic vitamin D₃ analogues dose-dependently stimulated CAT activity. Compared to 1,25(OH)₂D₃, KCs were less sensitive to stimulation with MC 903, equally sensitive to EB 1213 and more sensitive to GS 1500 and KH 1060. In conclusion, the endogenous VDR in KCs is responsive to 1,25(OH)₂D₃ and its synthetic analogues in stimulating gene transcription. To the extent that the biological actions of vitamin D₃ are dependent on its ability to induce gene transcription through the endogenous VDR, this transfection model may be used in the screening of novel vitamin D₃ analogues for biological activity.