A national survey of specimen contamination in the UK.

BACKGROUND: Specimen contamination that goes unnoticed can have many adverse consequences for patients including inappropriate investigations or treatment decisions based on erroneous results. Little is known about UK laboratory practices relating to specimen contamination; therefore, this national survey aimed to gather valuable baseline data. METHODS: An electronic survey consisting of 26 questions was designed to obtain key information relating to specimen contamination including its frequency, how it is identified by laboratories and actions taken in event of confirmed contamination. The survey was circulated to Heads of Departments of all NHS laboratories in the UK. RESULTS: Fifty-two responses (15%) were received from 353 laboratories surveyed. Recording and extracting specimen contamination data from laboratory IT systems appear to be a challenge for many laboratories. There is potentially a lack of awareness of correct order of draw for venous blood collection which is a factor known to contribute to contamination. There is wide variation in contamination rates (EDTA, citrate and drip arm), and the methods laboratories use to identify it which often rely on professional judgement. Similarly, there is little consensus among senior laboratory professionals on how best to report results on contaminated samples, and record events in risk management systems. CONCLUSIONS: There is a need for greater consensus on laboratories' approach to specimen contamination, particularly around mechanisms to identify and monitor it, and follow up actions. We make several recommendations to facilitate improvements it this area; however, there is a need to develop consensus guidelines which can aid both clinicians and laboratories.

Paediatric Anti-Müllerian Hormone measurement: Male and female reference intervals established using the automated Beckman Coulter Access AMH assay.

OBJECTIVE: Anti-Müllerian Hormone (AMH) concentration is high at birth in males, demonstrating the presence of functional testicular tissue in the prepubertal period, and acting as a useful marker in the investigation of paediatric reproductive disorders. AMH also provides a tool in the investigation of female virilization, premature ovarian failure and polycystic ovarian syndrome in childhood. Robust, assay-specific paediatric AMH reference intervals are therefore required for clinical interpretation of results. The aim of this study was to derive age-specific AMH reference intervals for males and females aged 0-18 years. DESIGN AND PATIENTS: Plasma samples were obtained from patients at Royal Manchester Children's Hospital and analysed for AMH using the automated Beckman Coulter Access AMH Assay. Patients under investigation for paediatric reproductive or endocrine disorders were excluded from the study. MEASUREMENTS: Seven hundred and 2 patient plasma samples (465 male, 237 female) were subject to AMH measurement, and results were analysed in order to derive continuous and discrete reference intervals for the paediatric age range. RESULTS: Clear discrimination between male and female AMH results was evident in the prepubertal age range, with some overlap between the genders following pubertal onset. CONCLUSIONS: We have derived age-related reference intervals for plasma AMH in the paediatric age range (0-18 years) using the automated Beckman Coulter Access AMH assay which will aid in the investigation of paediatric endocrine disorders such as disorders of sexual development.

Does lactate measurement performed on admission predict clinical outcome on the intensive care unit? A concise systematic review.

BACKGROUND: There is a need for practical, efficient and effective prognostic markers for patients admitted to the intensive care unit (ICU) with sepsis, to identify patients at highest risk and guide and monitor treatment. Although many biomarkers and scoring systems have been advocated, none have yet achieved this elusive combination. Most ICUs already use blood lactate concentrations to monitor patients but the evidence base for this application is unclear. METHODS: A systematic review of the last five years of evidence of effectiveness of lactate measurement in prediction of outcome in ICUs was performed. RESULTS: It was found that there is a lack of high-quality evidence, and no specific studies of prognostic accuracy. D- or L-Lactate concentrations measured in plasma, serum, whole blood or colonic washings were raised at admission in almost all patient groups, and were higher in patient groups who had the worst outcomes (in-hospital mortality, sequential organ failure). However, there was significant overlap in individual concentrations measured in those who died within 28 days of admission, or who developed multiple organ failure, and those who did not. For serum L-lactate concentrations, no specific cut-off value capable of predicting in-hospital mortality or sequential organ failure could be recommended. CONCLUSIONS: The evidence reviewed suggested that whole blood, plasma or serum lactate measurement could not provide specific prognostic information for individual patients. There may be a role for monitoring for normalization of serum D- or L-lactate concentrations during goal-directed therapy in the ICU but further good-quality studies are needed. Measurement of the D-lactate stereoisomer shows promise, such that further studies are warranted.

Reverse iontophoresis of urea in health and chronic kidney disease: a potential diagnostic and monitoring tool?

BACKGROUND: Patients with chronic kidney disease (CKD) need regular monitoring, usually by blood urea and creatinine measurements, needing venepuncture, frequent attendances and a healthcare professional, with significant inconvenience. Noninvasive monitoring will potentially simplify and improve monitoring. We tested the potential of transdermal reverse iontophoresis of urea in patients with CKD and healthy controls. METHODS: Using a MIC 2(®) Iontophoresis Controller, reverse iontophoresis was applied on the forearm of five healthy subjects (controls) and 18 patients with CKD for 3-5 h. Urea extracted at the cathode was measured and compared with plasma urea. RESULTS: Reverse iontophoresis at 250 µA was entirely safe for the duration. Cathodal buffer urea linearly correlated with plasma urea after 2 h (r = 0·82, P < 0·0001), to 3·5 h current application (r = 0·89, P = 0·007). The linear equations y = 0·24x + 1 and y = 0·21x + 4·63 predicted plasma urea (y) from cathodal urea after 2 and 3 h, respectively. Cathodal urea concentration in controls was significantly lower than in patients with CKD after a minimum current application of 2 h (P < 0·0001), with the separation between the two groups becoming more apparent with longer application (P = 0·003). A cathodal urea cut-off of 30 µM gave a sensitivity of 83·3% and positive predictive value of 87% CKD. During haemodialysis, the fall in cathodal urea was able to track that of blood urea. CONCLUSION: Reverse iontophoresis is safe, can potentially discriminate patients with CKD and healthy subjects and is able to track blood urea changes on dialysis. Further development of the technology for routine use can lead to an exciting opportunity for its use in diagnostics and monitoring.

Pseudohyperkalaemia associated with leukaemic cell lysis during pneumatic tube transport of blood samples.

BACKGROUND: Pseudohyperkalaemia is relatively uncommon in children, but needs to be considered in cases where extreme hyperkalaemia is associated with normal renal function. CASE: A previously well 12 year-old boy presented with new onset T cell acute lymphoblastic leukaemia associated with a high peripheral blood white cell count. Plasma biochemistry tests on a blood sample sent to the laboratory using a pneumatic tube system showed a high plasma potassium level of 16.6 mmol/l, with otherwise normal electrolytes and renal function. A 12-lead electrocardiogram was normal, with no changes suggestive of hyperkalaemia. Pseudohyperkalaemia was suspected, and further samples transported to the laboratory by foot showed normal plasma potassium levels. It was subsequently demonstrated that the pseudohyperkalemia was due to the lysis of leukaemic white cells during the transport of blood samples from the ward to the laboratory within the pneumatic tube system. CONCLUSIONS: Paediatricians caring for children with haematological malignancies need to be aware of this cause of pseudohyperkalaemia so that unnecessary treatment, including the commencement of acute dialysis, is avoided. We recommend that blood samples collected from children with high white cell count malignancies are transported to the laboratory by foot rather than in pneumatic tube systems.

Acute pancreatitis in Soweto, South Africa: relationship between trypsinogen load, trypsinogen activation, and fibrinolysis.

OBJECTIVE: It is not known why acute pancreatitis in Soweto, South Africa, pursues an aggressive course. We sought clues from circulating trypsinogen load at admission as marker of initial acinar injury, trypsinogen activation using the carboxypeptidase B activation peptide as surrogate, proteinase inhibitors, the coagulation-fibrinolysis axis, indicators of inflammation, oxidative stress markers, and antioxidant status. This article reports on the first four aspects. METHODS: The study involved 24 consecutive patients with a first attack. All of them were admitted within 24 h, and 22 were alcoholic. Urine was analyzed for anionic trypsinogen and the carboxypeptidase B activation peptide. Serum was tested for anionic and cationic trypsinogen, alpha1 proteinase inhibitor and alpha2 macroglobulin. Plasma from a subset was assayed for soluble fibrin, cross-linked fibrin degradation products (surrogates for thrombin and plasmin activity, respectively), and tissue-type plasminogen activator and inhibitor. RESULTS: Soweto controls had higher serum anionic trypsinogen (p = 0.004) and plasminogen activator:inhibitor ratio (p = 0.047) than U.K. controls. The outcome of acute pancreatitis was mild in 17 but severe in seven with three deaths, two on day 2. In mild pancreatitis, intense plasmin activity (p < 0.001) accompanied the surge in trypsinogen, especially anionic (p < 0.001), but without increased thrombin activity and in five patients without trypsinogen activation. In severe pancreatitis, further significant increments in plasmin activity and trypsinogens were accompanied by increased thrombin activity (p = 0.013) and trypsinogen activation (p = 0.046). There was no correlation between surrogates of plasmin and thrombin activity, or between either and the carboxypeptidase B activation peptide, which showed a curvilinear relationship to total serum trypsinogen. CONCLUSIONS: The aggressive nature of alcoholic acute pancreatitis in Soweto seems to reflect early profound fibrinolysis, which precedes coagulation and is initially independent of trypsin. Subclinical acinar-cell injury and a profibrinolytic diathesis in outwardly healthy Sowetans may predispose to this problem.