Search

Wilson disease (WD) is a rare genetic disorder characterized by copper overload, primarily affecting the liver and brain, and the organ damage is believed to be caused by non-ceruloplasmin-bound copper (NCC). Accurate and early diagnosis is important for prognosis. Recently, a method for the measurement of NCC, exchangeable serum copper (CuEXC), was developed and shown to be a promising marker of WD, especially as the fraction of total copper, relative exchangeable copper (REC). This study aimed to validate the CuEXC extraction method and establish reference intervals for CuEXC and REC, as well as to examine short- and long-term stability of CuEXC in serum samples. The adult reference interval for CuEXC was 0.61-1.62 µmol/L and for REC 3.0-9.7 % based on 120 blood donors. Based on 88 children, the reference intervals for CuEXC was 0.45-1.16 µmol/L. The intervals for REC were 1.8-5.8 % for children <10 years and 2.3-8.5 % for children ≥10 years. Regarding stability, CuEXC increased following a logarithmic scale in uncentrifuged serum and exceeded the permissible difference of 10 % after 4 h. With long-term freezing at -20 °C, CuEXC was stable for 1.7 months. In conclusion, reference intervals for CuEXC and REC were established and confirmed to be substantially lower in children. Accurate reference intervals are important to ensure timely diagnosis of WD. Finally, our findings on stability have important implications and highlight the need for standardization of the pre-analytical handling of CuEXC samples in order to obtain comparable results within and between laboratories both for clinical and research use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The ability to achieve hemostasis after spontaneous subarachnoid hemorrhage (SAH) plays a pivotal role in outcome. Changes in coagulation in the early hours after SAH have been only sparsely investigated., Objective: To investigate changes in coagulation after SAH and illuminate underlying mechanisms., Methods: We enrolled 46 patients with spontaneous aneurysmal SAH. Blood samples were collected at admission and 24 hours after symptom onset. Thromboelastometry (ROTEM) was performed using the standard assays EXTEM, INTEM, and FIBTEM. Platelet maximum clot elasticity was calculated based on ROTEM results. Thrombin generation, levels of thrombin-antithrombin complex, fibrinogen, and coagulation factor XIII were measured. All data were compared with a gender-matched healthy control group., Results: At admission (median, 3 hours 39 minutes from symptom onset), maximum clot firmness (EXTEM, P < 0.0001; INTEM, P = 0.08; FIBTEM, P < 0.0001) and platelet maximum clot elasticity (P < 0.0001) were higher in patients with SAH than in healthy controls. Thrombin generation showed higher, although nonsignificant, endogenous thrombin potential in patients with SAH than in healthy controls (P = 0.06), and thrombin-antithrombin complex levels were above the reference interval. Median fibrinogen and coagulation factor XIII levels were both within the reference parameters and remained increased 24 hours after symptom onset, whereas endogenous thrombin potential (P = 0.01) and thrombin-antithrombin complex levels decreased (P < 0.0001)., Conclusions: Patients with SAH were in a hypercoagulable state at admission and remained so 24 hours after SAH. Increased clot firmness could be caused by increased platelet function, because platelet maximum clot elasticity was increased despite normal fibrinogen and coagulation factor XIII levels., (Copyright © 2019 Elsevier Inc. All rights reserved.)