Macroprolactin: From laboratory to clinical practice.

Prolactin measurement is very common in standard clinical practice. It is indicated not only in the study of pituitary adenomas, but also when there are problems with fertility, decreased libido, or menstrual disorders, among other problems. Inadequate interpretation of prolactin levels without contextualizing the laboratory results with the clinical, pharmacological, and gynecological/urological history of patients leads to erroneous diagnoses and, thus, to poorly based studies and treatments. Macroprolactinemia, defined as hyperprolactinemia due to excess macroprolactin (an isoform of a greater molecular weight than prolactin but with less biological activity), is one of the main causes of such erroneous diagnoses, resulting in poor patient management when not recognized. There is no unanimous agreement as to when macroprolactin screening is required in patients with hyperprolactinemia. At some institutions, macroprolactin testing by polyethylene glycol (PEG) precipitation is routinely performed in all patients with hyperprolactinemia, while others use a clinically based approach. There is also no consensus on how to express the results of prolactin/macroprolactin levels after PEG, which in some cases may lead to an erroneous interpretation of the results. The objectives of this study were: 1. To establish the strategy for macroprolactin screening by serum precipitation with PEG in patients with hyperprolactinemia: universal screening versus a strategy guided by the alert generated by the clinician based on the absence or presence of clinical symptoms or by the laboratory when hyperprolactinemia is detected. 2. To create a consensus document that standardizes the reporting of prolactin results after precipitation with PEG to minimize errors in the interpretation of the results, in line with international standards.

Macroprolactin: From laboratory to clinical practice. / Macroprolactina: del laboratorio a la práctica clínica. Recomendaciones del grupo de trabajo de laboratorio de la SEEN y de la comisión de hormonas de la SEQCML sobre la medición e informe del resultado de la macroprolactina.

Prolactin measurement is very common in standard clinical practice. It is indicated not only in the study of pituitary adenomas, but also when there are problems with fertility, decreased libido, or menstrual disorders, among other problems. Inadequate interpretation of prolactin levels without contextualizing the laboratory results with the clinical, pharmacological, and gynecological/urological history of patients leads to erroneous diagnoses and, thus, to poorly based studies and treatments. Macroprolactinemia, defined as hyperprolactinemia due to excess macroprolactin (an isoform of a greater molecular weight than prolactin but with less biological activity), is one of the main causes of such erroneous diagnoses, resulting in poor patient management when not recognized. There is no unanimous agreement as to when macroprolactin screening is required in patients with hyperprolactinemia. At some institutions, macroprolactin testing by polyethylene glycol (PEG) precipitation is routinely performed in all patients with hyperprolactinemia, while others use a clinically based approach. There is also no consensus on how to express the results of prolactin/macroprolactin levels after PEG, which in some cases may lead to an erroneous interpretation of the results. The objectives of this study were: 1. To establish the strategy for macroprolactin screening by serum precipitation with PEG in patients with hyperprolactinemia: universal screening versus a strategy guided by the alert generated by the clinician based on the absence or presence of clinical symptoms or by the laboratory when hyperprolactinemia is detected. 2. To create a consensus document that standardizes the reporting of prolactin results after precipitation with PEG to minimize errors in the interpretation of the results, in line with international standards.

Impact of a Novel Strategy for Critical Values Communication for the Management of Patients Treated with Clozapine.

INTRODUCTION: Clozapine is an antipsychotic drug used to treat resistant schizophrenia and other disorders. Based on the actual Spanish legislation, patients treated with clozapine must undergo periodical haematological examinations and treatment should be reviewed when the haemogram shows either a leukocyte count of ≤ 3500/mm3 or neutrophil count < 2000/mm3. An automatic notification system has been developed to optimize patient management and it's utility was assessed following the implementation of the new system. MATERIAL AND METHODS: When clozapine (CLO) laboratory test request was made, a reflex complete blood count test was also done. An automatic e-mail was sent by the laboratory information system to the physician when a CLO was ordered and low leukocyte or neutrophil counts were detected, or when a patient with an ordered CLO test did not attend the laboratory for blood drawing. RESULTS: For patients with haemogram alterations, the time to take clinical action was significantly decreased from 23 to 7 days (p = 0.02). Moreover, the adherence to Spanish Agency of Drugs and Sanitary Devices recommendations significantly increased from 45% to 76% (p = 0.02). For not attending patients, the days out of control decreased from 29 to 12 days, although it was not statistically significant (p = 0.06). CONCLUSIONS: This strategy has allowed the compliance of legal requirements, the improvement of patient safety, and the optimisation of clinical and laboratory procedures.

Description of interference in the measurement of troponin T by a high-sensitivity method.

INTRODUCTION: Measurement of high-sensitivity troponin T (hs-TnT) has become an essential step in the diagnosis of acute myocardial infarction. This high-sensitivity method allows quantifying the concentration of troponin T in blood of healthy subjects with a lower inaccuracy compared to previous reagent generations. However, the presence of certain compounds in the sample may interfere with the result. We present a patient who had repeatedly high concentrations of hs-TnT in the serum sample that did not agreed with the signs and symptoms. In addition, ultrasensitive troponin I concentration was undetectable. MATERIALS AND METHODS: To investigate the presence of an interfering compound, different analysis were carried out. In order to discard macro complexes in the sample, the serum was precipitated with polyethylene glycol. In addition, the serum was incubated with Scantibodies Heterophilic Blocking Tube, which can block heterophilic antibodies. Finally, a size exclusion chromatography of the sample was performed by the manufacturer. WHAT HAPPENED: The interfering substance was allocated into fractions with proteins of 150kDa, corresponding to high molecular weight proteins like immunoglobulin G (IgG). This compound was responsible for the falsely elevated hs-TnT results and it affected only the high-sensitivity methods. MAIN LESSON: The detected interfering compound was probably an IgG. This type of interference must be kept in mind in front of discordant results, even if they are extremely rare. Therefore, interdisciplinary cooperation between clinicians, laboratory and manufacturer is essential.

Estudio de correlación entre la concentración de antígeno de superficie y la carga viral del virus de la hepatitis B en una población negativa para el antígeno e / Correlation between hepatitis B surface antigen serum levels and viral load in an hepatitis B e antigen negative population

Introducción. La posible falta de correlación entre la concentración de HbsAg del virus de la hepatitis B y la carga viral observada en nuestro hospital, y la gran controversia existente en torno a este aspecto, ha motivado el presente estudio. Adicionalmente, se realizan estudios de eficiencia diagnóstica de la cuantificación de HbsAg para verificar la utilidad real de la introducción de esta determinación en nuestro laboratorio. Métodos. Se han usado 150 muestras de portadores crónicos del virus. Los individuos HbeAg negativos se dividen en 4 grupos: (HbsAg < 1.000 UI/mL [subgrupo 1], HbsAg > 1.000 UI/mL [subgrupo 2], DNA < 2.000 UI/mL [subgrupo 3], DNA > 2.000 UI/mL [subgrupo 4]). Tanto la cuantificación de HbsAg como la determinación cualitativa de HbeAg se han realizado mediante inmunoanálisis quimioluminiscente en el analizador Architect® i2000SR (Abbott Laboratories, Sligo, Irlanda). La carga viral se ha cuantificado mediante PCR a tiempo real (RT-PCR) (Cobas Ampliprep/Cobas TaqMan® de Roche Diagnostics) (Manheim, Alemania). Los estudios de correlación se han realizado mediante la prueba de Spearman utilizando el programa estadístico MedCalc®. Resultados. Los coeficientes de correlación obtenidos han sido: grupo total HbeAg negativo (r=0,322; p=0,0002); subgrupo 1 (r=0,501; p=0,0001); subgrupo 2 (r=-0,105; p=0,362); subgrupo 3 (r=0,275; p=0,0052); subgrupo 4 (r=0,299; p=0,092). Conclusión. Se ha observado una modesta pero significante correlación entre las concentraciones séricas de HbsAg y los valores de DNA-VHB en individuos HbeAg negativos (AU)

Background. Possible lack of correlation observed among serum hepatitis B surface antigen (HbsAg) concentration results and viral load in our hospital, and the great controversy surrounding this aspect in the literature, has motivated this study. Additionally, diagnostic efficiency analysis of quantitative HbsAg measurement are done in order to verify the real usefulness of the introduction of this test in our laboratory. Methods. 150 hepatitis B chronic carriers samples have been used. Negative HbeAg individuals were divided in four groups (HbsAg < 1,000 UI/mL [subgroup 1], HbsAg > 1,000 UI/mL [subgroup 2], DNA < 2,000 UI/mL [subgroup 3], DNA > 2,000 UI/mL [subgroup 4]). Both quantitative HbsAg and qualitative HbeAg have been performed by a chemiluminiscent immunoassay from Architect® i2000SR analyzer (Abbott Laboratories, Sligo, Ireland). Viral load has been quantified by real time polymerase chain reaction (RT-PCR) (Cobas Ampliprep/Cobas TaqMan® from Roche Diagnostics) (Manheim, Germany). Correlation studies have been performed by the Spearman test. Statistical analysis have been performed using MedCalc® software. Results. Correlation coeficients obtained in this study have been: Total negative HbeAg group (r=0.322; p=.0002); subgroup 1 (r=0.501; p=.0001); subgroup 2 (r=-0.105; p=.362); subgroup 3 (r=0.275; p=.0052); subgroup 4 (r=0.299; p=.092). Conclusion. Modest but significant correlation between HbsAg levels and VHB-DNA values in negative HbeAg individuals has been observed (AU)

Haptoglobin genotype is associated with increased endothelial dysfunction serum markers in type 1 diabetes.

BACKGROUND: To evaluate the genotype-driven effect of haptoglobin (Hp) in patients with type 1 diabetes without clinical cardiovascular (CV) disease, considering endothelial dysfunction (ED) and arterial stiffness (AS). MATERIAL AND METHODS: About 137 patients with type 1 diabetes (duration ≥ 5 years) and 68 age- and sex-matched controls were evaluated for the following: (i) smoking, alcohol intake, BMI, blood pressure, fasting plasma glucose, HbA1c and lipid profile; (ii) microvascular complications; (iii) serum markers of ED (ICAM-1, VCAM-1 and E-selectin); (iv) AS, assessed as aortic pulse wave velocity (aPWV); and (v) Hp genotype. RESULTS: The prevalence of the 1/1, 2/1 and 2/2 Hp genotypes was 28.5%, 46.7% and 24.8% in patients with type 1 diabetes and 20.9%, 38.8% and 40.3% in controls, respectively. No differences were found in classical CV risk factors between patients homozygous for allele 2 and the remaining genotypes, both in patients with type 1 diabetes and controls. Patients with type 1 diabetes carrying the Hp2/2 genotype had higher concentrations of ICAM-1 (65.1 (56.7-76.0) ng/mL vs. 59.0 (51.7-69.3) ng/mL; P = 0.033) and sVCAM-1 (1133.1 (884.6-1458.6) ng/mL vs. 956.4 (738.5-1206.1) ng/mL; P = 0.040) than those without it. The Hp2/2 genotype remained independently associated with ED after adjusting for CV risk factors (P = 0.038). No significant differences were found for aPWV between Hp genotypes. CONCLUSIONS: Endothelial dysfunction may be influenced by Hp2/2 genotype in patients with type 1 diabetes with independence of classical CV risk factors.