Joint EFLM-COLABIOCLI Recommendation for venous blood sampling

This document provides a joint recommendation for venous blood sampling of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE) and Latin American Working Group for Preanalytical Phase (WG-PRE-LATAM) of the Latin America Confederation of Clinical Biochemistry (COLABIOCLI). It offers guidance on the requirements for ensuring that blood collection is a safe and patient-centered procedure and provides practical guidance on how to successfully overcome potential barriers and obstacles to its widespread implementation. The target audience for this recommendation are healthcare staff members directly involved in blood collection. This recommendation applies to the use of a closed blood collection system and does not provide guidance for the blood collection with an open needle and syringe and catheter collections. Moreover, this document neither addresses patient consent, test ordering, sample handling and transport nor collection from children and unconscious patients. The recommended procedure is based on the best available evidence. Each step was graded using a system that scores the quality of the evidence and the strength of the recommendation. The process of grading was done at several face-to-face meetings involving the same mixture of stakeholders stated previously. The main parts of this recommendation are: 1) Pre-sampling procedures, 2) Sampling procedure, 3) Post-sampling procedures and 4) Implementation. A first draft of the recommendation was circulated to EFLM members for public consultation. WG-PRE-LATAM was also invited to comment the document. A revised version has been sent for voting on to all EFLM and COLABIOCLI members and has been officially endorsed by 33/40 EFLM and 21/21 COLABIOCLI members. We encourage professionals throughout Europe and Latin America to adopt and implement this recommendation to improve the quality of blood collection practices and increase patient and workers safety.

Patient's knowledge and awareness about the effect of the over-the-counter (OTC) drugs and dietary supplements on laboratory test results: a survey in 18 European countries.

Background Nowadays over-the-counter (OTC) drugs and dietary supplements are widely used. Their use can have a significant impact on the validity of laboratory results. The aim of this multicenter European study was to determine the frequency of consumption of various dietary products and OTC drugs among patients and explore their level of knowledge and awareness about the potential impact of various products on laboratory test results. Methods Eighteen European countries participated in this study. The survey was carried out anonymously on a subsequent series of outpatients (n=200) in each participating country. Included were patients who were referred to the laboratory for blood sampling and who voluntarily agreed to participate in the study. The survey included questions about the frequency of consumption of various products, awareness of the importance of informing physicians and laboratory staff about it and information about influence of preanalytical factors in general on laboratory test results. Results In total, 68% of patients were regularly taking at least one OTC drug or dietary supplement. The frequency of patients consuming at least one OTC drug or dietary supplement differed between countries (p=0.001). Vitamins (38%), minerals (34%), cranberry juice (20%), acetylsalicylic acid (ASA) (17%) and omega fatty acids (17%) were the most commonly used in our study. Conclusions The use of various OTC drugs and dietary supplements is highly prevalent in Europe and patients are often not willing to disclose this information to the laboratory staff and ordering physician. The education of both patients and healthcare staff is needed.

Order of blood draw: Opinion Paper by the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE).

It has been well reported over recent years that most errors within the total testing process occur in the pre-analytical phase (46%-68.2%), an area that is usually outside of the direct control of the laboratory and which includes sample collection (phlebotomy). National and international (WHO, CLSI) guidelines recommend that the order of draw of blood during phlebotomy should be blood culture/sterile tubes, then plain tubes/gel tubes, then tubes containing additives. This prevents contamination of sample tubes with additives from previous tubes that could cause erroneous results. There have been a number of studies recently looking at whether order of draw remains a problem with modern phlebotomy techniques and materials, or it is an outdated practice followed simply because of historical reasons. In the following article, the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase (EFLM WG-PRE) provides an overview and summary of the literature with regards to order of draw in venous blood collection. Given the evidence presented in this article, the EFLM WG-PRE herein concludes that a significant frequency of sample contamination does occur if order of draw is not followed during blood collection and when performing venipuncture under less than ideal circumstances, thus putting patient safety at risk. Moreover, given that order of draw is not difficult to follow and knowing that ideal phlebotomy conditions and protocols are not always followed or possible, EFLM WG-PRE supports the continued recommendation of ensuring a correct order of draw for venous blood collection.

Patient identification and tube labelling - a call for harmonisation.

Venous blood sampling (phlebotomy) is the most common invasive procedure performed in patient care. Guidelines on the correct practice of phlebotomy are available, including the H3-A6 guideline issued by the Clinical Laboratory Standards Institute (CLSI). As the quality of practices and procedures related to venous blood sample collection in European countries was unknown, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase conducted an observational study in 12 European countries. The study demonstrated that the level of compliance of phlebotomy procedures with the CLSI H3-A6 guideline was unacceptably low, and that patient identification and tube labelling are amongst the most critical steps in need of immediate attention and improvement. The process of patient identification and tube labelling is an essential safety barrier to prevent patient identity mix-up. Therefore, the EFLM Working Group aims to encourage and support worldwide harmonisation of patient identification and tube labelling procedures in order to reduce the risk of preanalytical errors and improve patient safety. With this Position paper we wish to raise awareness and provide recommendations for proper patient and sample identification procedures.

Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: An observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE).

BACKGROUND: An observational study was conducted in 12 European countries by the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase (EFLM WG-PRE) to assess the level of compliance with the CLSI H3-A6 guidelines. METHODS: A structured checklist including 29 items was created to assess the compliance of European phlebotomy procedures with the CLSI H3-A6 guideline. A risk occurrence chart of individual phlebotomy steps was created from the observed error frequency and severity of harm of each guideline key issue. The severity of errors occurring during phlebotomy was graded using the risk occurrence chart. RESULTS: Twelve European countries participated with a median of 33 (18-36) audits per country, and a total of 336 audits. The median error rate for the total phlebotomy procedure was 26.9 % (10.6-43.8), indicating a low overall compliance with the recommended CLSI guideline. Patient identification and test tube labelling were identified as the key guideline issues with the highest combination of probability and potential risk of harm. Administrative staff did not adhere to patient identification procedures during phlebotomy, whereas physicians did not adhere to test tube labelling policy. CONCLUSIONS: The level of compliance of phlebotomy procedures with the CLSI H3-A6 guidelines in 12 European countries was found to be unacceptably low. The most critical steps in need of immediate attention in the investigated countries are patient identification and tube labelling.

Point accuracy and reliability of an interstitial continuous glucose-monitoring device in critically ill patients: a prospective study.

INTRODUCTION: There is a need for continuous glucose monitoring in critically ill patients. The objective of this trial was to determine the point accuracy and reliability of a device designed for continuous monitoring of interstitial glucose levels in intensive care unit patients. METHODS: We evaluated point accuracy by comparing device readings with glucose measurements in arterial blood by using blood gas analyzers. Analytical and clinical accuracy was expressed in Bland-Altman plots, glucose prediction errors, and Clarke error grids. We used a linear mixed model to determine which factors affect the point accuracy. In addition, we determined the reliability, including duration of device start-up and calibration, skips in data acquisition, and premature disconnections of sensors. RESULTS: We included 50 patients in whom we used 105 sensors. Five patients from whom we could not collect the predefined minimum number of four consecutive comparative blood draws were excluded from the point accuracy analysis. Therefore, we had 929 comparative samples from 100 sensors in 45 patients (11 (7 to 28) samples per patient) during 4,639 hours (46 (27 to 134) hours per patient and 46 (21 to 69) hours per sensor) for the accuracy analysis. Point accuracy did not meet the International Organization for Standardization (ISO) 14971 standard for insulin dosing accuracy but did improve with increasing numbers of calibrations and was better in patients who did not have a history of diabetes. Out of 105 sensors, 60 were removed prematurely for a variety of reasons. The device start-up time was 49 (43 to 58) minutes. The number of skips in data acquisition was low, resulting in availability of real-time data during 95% (89% to 98%) of the connection time per sensor. CONCLUSIONS: The point accuracy of a device designed for continuous real-time monitoring of interstitial glucose levels was relatively low in critically ill patients. The device had few downtimes, but one third of the sensors were removed prematurely because of unresolved sensor- or device-related problems. TRIAL REGISTRATION: Netherlands Trial Registry number: NTR3827 . Registered 30 January 2013.

Hepcidin and hemoglobin content parameters in the diagnosis of iron deficiency in rheumatoid arthritis patients with anemia.

OBJECTIVE: To explore the utility of the novel iron indices hepcidin, reticulocyte hemoglobin content (Ret-Hgb), and erythrocyte (red blood cell) hemoglobin content (RBC-Hgb) for detection of iron deficiency in rheumatoid arthritis (RA) patients with anemia and active inflammation and to compare these indices with conventional parameters of iron deficiency. METHODS: Blood samples from 106 outpatients with RA were analyzed in a cross-sectional exploratory study. Forty patients were classified as having either iron deficiency anemia (IDA), anemia of chronic disease (ACD), their combination (IDA/ACD), or "other anemia" based on biochemical parameters for inflammation and iron deficiency. The ability of serum and urine hepcidin, Ret-Hgb, and RBC-Hgb measurement to discriminate among these states was evaluated. RESULTS: Hepcidin content in serum from patients in the IDA group as well as that from patients in the combined IDA/ACD group differed significantly from that in serum from patients in the ACD group. This difference was also observed with hepcidin in urine, Ret-Hgb, and RBC-Hgb, although with less significance. The area under the receiver operating characteristic curve for serum hepcidin was 0.88 for the comparison of IDA/ACD patients with ACD patients and 0.92 for the comparison of the combined IDA group and IDA/ACD group to all other patients with anemia. Hepcidin at <2.4 nmoles/liter had a sensitivity of 89% and a specificity of 88% to distinguish IDA/ACD from ACD. Both Ret-Hgb and RBC-Hgb measurements also allowed differentiation between these latter groups, with a sensitivity of 67% and 89%, respectively, and a specificity of 100% and 75%, respectively. CONCLUSION: Serum hepcidin and, to a lesser extent, urine hepcidin, Ret-Hgb, and RBC-Hgb, are potential useful indicators for detecting iron deficiency in RA patients with anemia and active inflammation.

Introduction of a Standardized Approach of Electronic Urinary pH Monitoring to Assist Alkalization Therapy: A Uric Acid Urolithiasis Patient's Perspective.

Introduction: This study evaluates the introduction of an electronic pH meter to measure the urinary pH in patients with uric acid (UA) urolithiasis and assess patient's perspective. Materials and Methods: Patients known with UA urolithiasis were included in this single-center, nonrandomized, prospective feasibility study, IDEAL stage 2a. Their experience with urolithiasis and satisfaction with the method of urinary pH monitoring before inclusion was evaluated. All patients received an electronic pH meter and standardized instructions. After a period of 6-12 weeks their experience and satisfaction with this pH meter and new regimen was assessed. Patient satisfaction was scored on a Likert scale 1-5. Results: Eighteen patients were included. Median age was 63 years and median body mass index was 30 kg/m2. The cohort consisted of 67% men and 33% women. In their medical history, 55% had unilateral stones, whereas 45% had bilateral stones. The median estimated glomerular filtration rate was 58 mL/minute/1.73 m2. Eighty-nine percent took medication to alkalize their urine, median 3.5 years. Fifteen patients used paper reagent strips and three used an electronic pH meter to assess urinary pH before this study. Satisfaction with the method of urinary pH measurement at inclusion was reasonable (median score 3; interquartile range [IQR] 1-4). Satisfaction with the new electronic pH meter was good (median score 4; IQR 3-5), as was the overall satisfaction (median score 4; IQR 3-5). The new electronic pH meter was slightly easier to use (median 3.5; IQR 1.75-5), as easy in maintenance (median 3; IQR 2-4), and significantly easier to read (median 5; IQR 4-5). The new electronic pH meter was better (median score 4; IQR 2.75-5) than their previous method. Conclusion: The introduction of a standardized approach of urinary pH monitoring for UA urolithiasis patients with an electronic pH meter leads to an easier interpretable outcome and higher patient satisfaction.

Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy.

Thrombocytopenia develops early in malaria, but the underlying mechanisms remain incompletely understood. We studied the aetiology of malaria-associated thrombocytopenia in volunteers experimentally infected with Plasmodium falciparum malaria, in Indonesian malaria patients and in ex vivo studies. In experimental human malaria, the decrease in platelet counts was associated with a concurrent rise in young platelets (immature platelet fraction) and thrombopoietin. D-dimer concentrations were moderately elevated without a prolongation in the activated partial thromboplastin time or decrease in fibrinogen. There was no increase in expression of the platelet surface markers CD62P, PAC-1 and CD63 and in plasma concentrations of the platelet factors P-selectin, CXCR4, CXCL7, RANTES and CD40L. In contrast, concentrations of soluble glycoprotein-1b (sGP1b), the external domain of the platelet receptor for von Willebrand factor (VWF), increased early. Indonesian malaria patients also had elevated concentrations of sGP1b, which correlated with VWF concentrations. Finally, incubation of platelets with parasitized erythrocytes in vitro failed to induce platelet aggregation or activation. We concluded that neither compromised platelet production nor platelet activation or consumptive coagulopathy were responsible for the early thrombocytopenia in malaria. We hypothesize that the increase in sGP1b concentrations results from VWF-mediated GP1b shedding; a process that may prevent excessive adhesion of platelets and parasitized erythrocytes.

Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disorders.

BACKGROUND: Hepcidin is an iron-regulatory peptide hormone that consists of 3 isoforms: bioactive hepcidin-25, and inactive hepcidin-22 and hepcidin-20. Hepcidin is instrumental in the diagnosis and monitoring of iron metabolism disorders, but reliable methods for its quantification in serum are sparse, as is knowledge of their relative analytical strengths and clinical utility. METHODS: We developed a competitive (c)-ELISA and an immunocapture TOF mass-spectrometry (IC-TOF-MS) assay. Exploiting these 2 methods and our previously described weak cation exchange (WCX)-TOF-MS assay, we measured serum hepcidin concentrations in 186 patients with various disorders of iron metabolism and in 23 healthy controls. RESULTS: We found that (a) the relative differences in median hepcidin concentrations in various diseases to be similar, although the absolute concentrations measured with c-ELISA and WCX-TOF-MS differed; (b) hepcidin isoforms contributed to differences in hepcidin concentrations between methods, which were most prominent in patients with chronic kidney disease; and (c) hepcidin concentrations measured by both the c-ELISA and IC-TOF-MS correlated with ferritin concentrations <60 µg/L, and were suitable for distinguishing between iron deficiency anemia (IDA) and the combination of IDA and anemia of chronic disease. CONCLUSIONS: c-ELISA is the method of choice for the large-scale quantification of serum hepcidin concentrations, because of its low limit of detection, low cost, and high-throughput. Because of its specificity for bioactive hepcidin-25, WCX-TOF-MS can be regarded as a valuable special-purpose assay for disorders with variable concentrations of hepcidin isoforms, such as chronic kidney disease.

Mild increases in serum hepcidin and interleukin-6 concentrations impair iron incorporation in haemoglobin during an experimental human malaria infection.

The correct selection of individuals who will benefit from iron supplements in malaria-endemic regions requires improved insight in the effects of malaria on host iron homeostasis and innovative biomarkers. We assessed sequential changes in serum hepcidin and in traditional biochemical iron status indicators during an experimental Plasmodium falciparum malaria infection with five adult volunteers. The haemoglobin content of reticulocytes (Ret-H(e)) and of mature red blood cells (RBC-H(e)) represented iron incorporation into haemoglobin. Low-density parasitaemia and its treatment induced a mild increase in interleukin (IL)-6 and serum hepcidin concentrations. Despite this only mild increase, a marked hypoferraemia with a strong increase in serum ferritin concentrations developed, which was associated with a sharp fall in Ret-H(e), while RBC-H(e) remained unchanged. The ratio of soluble transferrin receptor (sTfR) to log ferritin concentrations decreased to an average nadir of 63% of the baseline value. We concluded that even mild increases in serum hepcidin and IL-6 concentrations result in a disturbed host iron homeostasis. Serum hepcidin, Ret-H(e) and Delta-H(e) (Ret-H(e) minus RBC-H(e)) are promising biomarkers to select those individuals who will benefit from iron supplements in malaria endemic regions, while the sTfR/log ferritin ratio should be used with caution to assess iron status during malaria.

Flushing of an intravenous catheter: a cause for unreliable laboratory results.

INTRODUCTION: Phlebotomy is an error-prone process in which mistakes are difficult to reveal. This case report describes the effect on laboratory results originating from a blood sample collected in close proximity to an intravenous catheter. MATERIALS AND METHODS: A 69-year-old male patient was referred to the Emergency department where pneumonia was suspected. Phlebotomy was performed to collect blood samples to assess electrolytes, renal function, liver function, infection and haematological parameters. RESULTS: The laboratory analysis showed reduced potassium and calcium concentrations. To prevent life-threatening cardiac failure the clinician decided to correct those electrolytes. Remarkably, the electrocardiogram showed no abnormalities corresponding to hypokalaemia and hypocalcaemia. This observation, in combination with an overall increase in laboratory parameters with the exception of sodium and chloride, led to the suspicion of a preanalytical error. Retrospectively, an intravenous catheter was inserted in close proximity of the puncture place but no continuous infusion was started prior to phlebotomy. However, the intravenous catheter was flushed with sodium chloride. Since potential other causes were excluded, the flushing of the intravenous catheter with sodium chloride prior to phlebotomy was the most probable cause for the deviating laboratory results and subsequently for the unnecessary potassium and calcium suppletion. CONCLUSION: This case underlines the importance of caution in the interpretation of laboratory results obtained from specimens that are collected in the proximity of an intravenous catheter, even in the absence of continuous infusion.

[Joint EFLM-COLABIOCLI recommendation for venous blood sampling]. / Recommandations communes EFLM-COLABIOCLI relatives au prélèvement sanguin veineux.

This document provides a joint recommendation for venous blood sampling of the European federation of clinical chemistry and laboratory medicine (EFLM) Working Group for preanalytical phase (WG-PRE) and Latin American working group for preanalytical phase (WG-PRE-LATAM) of the Latin America confederation of clinical biochemistry (COLABIOCLI). It offers guidance on the requirements for ensuring that blood collection is a safe and patient-centered procedure and provides practical guidance on how to successfully overcome potential barriers and obstacles to its widespread implementation. The target audience for this recommendation are healthcare staff members directly involved in blood collection. This recommendation applies to the use of a closed blood collection system and does not provide guidance for the blood collection with an open needle and syringe and catheter collections. Moreover, this document neither addresses patient consent, test ordering, sample handling and transport nor collection from children and unconscious patients. The recommended procedure is based on the best available evidence. Each step was graded using a system that scores the quality of the evidence and the strength of the recommendation. The process of grading was done at several face-to-face meetings involving the same mixture of stakeholders stated previously. The main parts of this recommendation are: 1) Pre-sampling procedures, 2) Sampling procedure, 3) Post-sampling procedures and 4) Implementation. A first draft of the recommendation was circulated to EFLM members for public consultation. WG-PRE-LATAM was also invited to comment the document. A revised version has been sent for voting on to all EFLM and COLABIOCLI members and has been officially endorsed by 33/40 EFLM and 21/21 COLABIOCLI members. We encourage professionals throughout Europe and Latin America to adopt and implement this recommendation to improve the quality of blood collection practices and increase patient and workers safety.

Blood Glucose Determination: Effect of Tube Additives.

The measurement of fasting plasma glucose may be biased by a time-dependent decrease of glucose in blood tubes, mainly attributable to blood cell metabolism when glycolysis is not rapidly inhibited or blood cells cannot be rapidly separated from plasma. Although glycolysis inhibitors such as sodium fluoride (NaF) in combination with potassium oxalate (KOx) are currently used for overcoming this drawback, their efficacy for stabilizing blood glucose is seemingly limited, and probably lower than that of newer additives such as the citrate buffer. Therefore, we performed a critical analysis of the current scientific literature aimed to generate evidence-based information about the advantages of using citrate buffer in blood tubes compared to the more conventional NaF additive. The results of our systematic overview of the literature show that citrate blood tubes represent a considerable step forward in achieving more accurate and reliable plasma glucose measurements, thereby limiting the risk of underdiagnosing diabetes due to spurious decrease of glucose concentration in uncentrifuged blood specimens, ensuring higher stability of glucose levels over time, while simultaneously producing less hemolysis compared to NaF blood tubes. Therefore, we suggest that the use of this new mixture should be encouraged for achieving a higher degree of accuracy and standardization of plasma glucose measurements.

The role of European Federation of Clinical Chemistry and Laboratory Medicine Working Group for Preanalytical Phase in standardization and harmonization of the preanalytical phase in Europe.

Patient safety is a leading challenge in healthcare and from the laboratory perspective it is now well established that preanalytical errors are the major contributor to the overall rate of diagnostic and therapeutic errors. To address this, the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for Preanalytical Phase (EFLM WG-PRE) was established to lead in standardization and harmonization of preanalytical policies and practices at a European level. One of the key activities of the WG-PRE is the organization of the biennial EFLM-BD conference on the preanalytical phase to provide a forum for National Societies (NS) to discuss their issues. Since 2012, a year after the first Preanalytical phase conference, there has been a rapid growth in the number of NS with a working group engaged in preanalytical phase activities and there are now at least 19 countries that have one. As a result of discussions with NS at the third conference held in March 2015 five key areas were identified as requiring harmonisation. These were test ordering, sample transport and storage, patient preparation, sampling procedures and management of unsuitable specimens. The article below summarises the work that has and will be done in these areas. The goal of this initiative is to ensure the EFLM WG-PRE produces work that meets the needs of the European laboratory medicine community. Progress made in the identified areas will be updated at the next preanalytical phase conference and show that we have produced guidance that has enhanced standardisation in the preanalytical phase and improved patient safety throughout Europe.

Accuracy and limitations of continuous glucose monitoring using spectroscopy in critically ill patients.

BACKGROUND: OptiScanner devices, continuous glucose monitoring devices that perform automated blood draws via a central venous catheter and create plasma through centrifugation, measure plasma glucose levels through mid-infrared spectroscopy at the bedside. The objective of this study was to determine accuracy and practicality of the devices in critically ill patients attempting glycemic control. METHODS: The plasma glucose level was measured by the devices and in comparative plasma samples using Yellow Springs Instrument (YSI) plasma analyzers. After adding several previously unrecognized interferences in the interference library, we reanalyzed the mid-infrared signals and compared the resulting plasma glucose level with the reference value. Results are presented in Clarke error grids, glucose prediction errors and Bland-Altman plots and expressed as correlation coefficients. RESULTS: We analyzed 463 comparative samples from 71 patients (median 6 (4 to 9) samples per patient). After calibrating the system, a Clarke error grid showed 100% of the values in zones A or B. The glucose predictor error demonstrated that 86% of the glucose values < 75 mg/dL were within ± 15 mg/dL of the YSI results and 95% ≥ 75 mg/dL were within 20% of the comparative YSI results. Bland-Altman plot showed a bias of -0.6 with limit of agreement of -24.6 to 23.3. The Pearson correlation coefficient was 0.93 and R2 was 0.87. In one third of the patients the devices had to be disconnected prematurely (that is before planned disconnection) because of repeated occlusion alarms suggesting blood draw errors. CONCLUSION: The devices needed calibration for several previously unrecognized interferences. Thereafter, accuracy of the device to measure plasma glucose levels in 'our cohort' of critically ill patients improved, but external validation is highly recommended. The automated blood draw system of the devices needs further improvement to make this device of value for clinical use (trial registration (Netherlands Trial Register): NTR2864).