Moving average quality control of routine chemistry and hematology parameters: a toolbox for implementation

Objectives: Moving average quality control (MA QC) is a patient-based real-time quality control system. Advantages compared to conventional periodic internal quality control (IQC) include absence of commutability problems and continuous monitoring of performance. We implemented MA QC for multiple routine hematology and chemistry parameters. We describe the evaluation process and provide practical tools to aid MA QC implementation. Methods: Nine parameters (serum sodium, calcium, bicarbonate and free thyroxine, hemoglobin [Hb], mean corpuscular volume, mean corpuscular hemoglobin concentration [MCHC], reticulocyte count and erythrocyte sedimentation rate [ESR]) were chosen for initial consideration. Using data extractions from the laboratory information system (LIS; General Laboratory Information Management System), evaluation of usefulness and optimization of MA QC settings was performed using bias detection curves. After this, MA QC settings were incorporated in our LIS for further evaluation and implementation in routine care. Results: Three out of nine parameters (Hb, ESR, and sodium) were excluded from MA QC implementation due to high variation and technical issues in the LIS. For the six remaining parameters, MA QC showed added value to IQC and was therefore implemented in the LIS. For three parameters a direct MA alarm work-up method was set up, including newly developed built-in features in the LIS. For the other parameters, we identified MA utilization beyond real-time monitoring. Conclusions: Implementation of MA QC has added value for our laboratory setting. Additional utilization beyond real-time QC monitoring was identified. We find MA QC especially useful for trend monitoring, detection of small shifts after maintenance and inter-analyzer comparisons.Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL

Moving average quality control of routine chemistry and hematology parameters: a toolbox for implementation

ObjectivesMoving average quality control (MA QC) is a patient-based real-time quality control system. Advantages compared to conventional periodic internal quality control (IQC) include absence of commutability problems and continuous monitoring of performance. We implemented MA QC for multiple routine hematology and chemistry parameters. We describe the evaluation process and provide practical tools to aid MA QC implementation.MethodsNine parameters (serum sodium, calcium, bicarbonate and free thyroxine, hemoglobin [Hb], mean corpuscular volume, mean corpuscular hemoglobin concentration [MCHC], reticulocyte count and erythrocyte sedimentation rate [ESR]) were chosen for initial consideration. Using data extractions from the laboratory information system (LIS; General Laboratory Information Management System), evaluation of usefulness and optimization of MA QC settings was performed using bias detection curves. After this, MA QC settings were incorporated in our LIS for further evaluation and implementation in routine care.ResultsThree out of nine parameters (Hb, ESR, and sodium) were excluded from MA QC implementation due to high variation and technical issues in the LIS. For the six remaining parameters, MA QC showed added value to IQC and was therefore implemented in the LIS. For three parameters a direct MA alarm work-up method was set up, including newly developed built-in features in the LIS. For the other parameters, we identified MA utilization beyond real-time monitoring.ConclusionsImplementation of MA QC has added value for our laboratory setting. Additional utilization beyond real-time QC monitoring was identified. We find MA QC especially useful for trend monitoring, detection of small shifts after maintenance and inter-analyzer comparisons.Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL

Letter regarding Zhao et al. entitled "DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia"

Personalised Therapeutic

Individualized dosing of fluoropyrimidine-based chemotherapy to prevent severe fluoropyrimidine-related toxicity: what are the options?

Fluoropyrimidines are widely used in the treatment of several types of solid tumors. Although most often well tolerated, severe toxicity is encountered in similar to 20-30% of the patients. Individualized dosing for these patients can reduce the incidence of severe fluoropyrimidine-related toxicity. However, no consensus has been achieved on which dosing strategy is preferred. The most established strategy for individualized dosing of fluoropyrimidines is upfront genotyping of the DPYD gene. Prospective research has shown that DPYD-guided dose-individualization significantly reduces the incidence of severe toxicity and can be easily applied in routine daily practice. Furthermore, the measurement of the dihydropyrimidine dehydrogenase (DPD) enzyme activity has shown to accurately detect patients with a DPD deficiency. Yet, because this assay is time-consuming and expensive, it is not widely implemented in routine clinical care. Other methods include the measurement of pretreatment endogenous serum uracil concentrations, the uracil/dihydrouracil-ratio, and the 5-fluorouracil (5-FU) degradation rate. These methods have shown mixed results. Next to these methods to detect DPD deficiency, pharmacokinetically guided follow-up of 5-FU could potentially be used as an addition to dosing strategies to further improve the safety of fluoropyrimidines. Furthermore, baseline characteristics, such as sex, age, body composition, and renal function have shown to have a relationship with the development of severe toxicity. Therefore, these baseline characteristics should be considered as a dose-individualization strategy. We present an overview of the current dose-individualization strategies and provide perspectives for a future multiparametric approach

DPYD genotype-guided dose individualisation of fluoropyrimidine therapy: who and how? reply

Personalised Therapeutic

Acute haemolytic transfusion reaction after transfusion of fresh frozen plasma in a neonate-Preventable by using solvent/detergent-treated pooled plasma?

Background Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent-treated plasma has become the standard product in the adult population since several years, but for neonatal use, FFP remains the product of preference. Description A preterm neonate developed lung bleeding at day 8 postpartum, for which intubation and mechanical ventilation was required and transfusions with packed red blood cells and plasma, in the form of FFP, were given. Five hours after transfusion, a red discoloration of the urine occurred. An acute haemolytic transfusion was suspected, confirmed by laboratory investigations (fast decrease in haemoglobin, increased free haemoglobin, decreased haptoglobin, increased lactate dehydrogenase and a positive direct antiglobulin test [IgG 2+]). Additional research showed that the FFP product contained nonspecific auto-antibodies that reacted with the transfused erythrocytes, most test erythrocytes and the donor's own erythrocytes. Conclusion A neonate experienced an acute haemolytic reaction, most probably caused by administrating a FFP product containing auto-antibodies. If transfused with solvent/detergent-treated plasma, such antibodies would have been diluted or captured. This case adds a new argument to the discussion on expanding the use of solvent/detergent-treated plasma to the paediatric population.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Acute haemolytic transfusion reaction after transfusion of fresh frozen plasma in a neonate-Preventable by using solvent/detergent-treated pooled plasma?

Background Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent-treated plasma has become the standard product in the adult population since several years, but for neonatal use, FFP remains the product of preference. Description A preterm neonate developed lung bleeding at day 8 postpartum, for which intubation and mechanical ventilation was required and transfusions with packed red blood cells and plasma, in the form of FFP, were given. Five hours after transfusion, a red discoloration of the urine occurred. An acute haemolytic transfusion was suspected, confirmed by laboratory investigations (fast decrease in haemoglobin, increased free haemoglobin, decreased haptoglobin, increased lactate dehydrogenase and a positive direct antiglobulin test [IgG 2+]). Additional research showed that the FFP product contained nonspecific auto-antibodies that reacted with the transfused erythrocytes, most test erythrocytes and the donor's own erythrocytes. Conclusion A neonate experienced an acute haemolytic reaction, most probably caused by administrating a FFP product containing auto-antibodies. If transfused with solvent/detergent-treated plasma, such antibodies would have been diluted or captured. This case adds a new argument to the discussion on expanding the use of solvent/detergent-treated plasma to the paediatric population

Dihydropyrimidine Dehydrogenase Phenotyping Using Pretreatment Uracil: A Note of Caution Based on a Large Prospective Clinical Study

In clinical practice, 25-30% of the patients treated with fluoropyrimidines experience severe fluoropyrimidine-related toxicity. Extensively clinically validated DPYD genotyping tests are available to identify patients at risk of severe toxicity due to decreased activity of dihydropyrimidine dehydrogenase (DPD), the rate limiting enzyme in fluoropyrimidine metabolism. In April 2020, the European Medicines Agency recommended that, as an alternative for DPYD genotype-based testing for DPD deficiency, also phenotype testing based on pretreatment plasma uracil levels is a suitable method to identify patients with DPD deficiency. Although the evidence for genotype-directed dosing of fluoropyrimidines is substantial, the level of evidence supporting plasma uracil levels to predict DPD activity in clinical practice is limited. Notwithstanding this, uracil-based phenotyping is now used in clinical practice in various countries in Europe. We aimed to determine the value of pretreatment uracil levels in predicting DPD deficiency and severe treatment-related toxicity. To this end, we determined pretreatment uracil levels in 955 patients with cancer, and assessed the correlation with DPD activity in peripheral blood mononuclear cells (PBMCs) and fluoropyrimidine-related severe toxicity. We identified substantial issues concerning the use of pretreatment uracil in clinical practice, including large between-center study differences in measured pretreatment uracil levels, most likely as a result of pre-analytical factors. Importantly, we were not able to correlate pretreatment uracil levels with DPD activity nor were uracil levels predictive of severe treatment-related toxicity. We urge that robust clinical validation should first be performed before pretreatment plasma uracil levels are used in clinical practice as part of a dosing strategy for fluoropyrimidines.Personalised Therapeutic