[Critical results reporting: the importance of local partnership agreements]. / Overdracht van sterk afwijkende laboratoriumuitslagen.

Critical results should be reported to the physician as soon as possible so that the physician can take the necessary follow-up actions. Failure or non-timely reporting of such results may lead to serious health damage or death to the patient. This article focusses on the reporting of results from the laboratory to the physician and discusses the bottlenecks and the separate (legal) responsibilities of the physician and the laboratory. Improving the process of the reporting and follow-up of critical results is a joint responsibility of the laboratory and the physician requesting the laboratory tests. This could be achieved by local partnership agreements.

The Relation Between Thyroid Function and Anemia: A Pooled Analysis of Individual Participant Data.

Context: Anemia and thyroid dysfunction often co-occur, and both increase with age. Human data on relationships between thyroid disease and anemia are scarce. Objective: To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia. Design: Individual participant data meta-analysis. Setting: Sixteen cohorts participating in the Thyroid Studies Collaboration (n = 42,162). Main Outcome Measures: Primary outcome measure was anemia (hemoglobin <130 g/L in men and <120 g/L in women). Results: Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants [overt hypothyroidism, pooled OR 1.84 (95% CI 1.35 to 2.50), subclinical hypothyroidism 1.21 (1.02 to 1.43), subclinical hyperthyroidism 1.27 (1.03 to 1.57), and overt hyperthyroidism 1.69 (1.00 to 2.87)]. Hemoglobin levels were lower in all groups compared with participants with euthyroidism. In the longitudinal analyses (n = 25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 (95% CI 0.86 to 2.20) for overt hypothyroidism, 1.18 (1.00 to 1.38) for subclinical hypothyroidism, 1.15 (0.94 to 1.42) for subclinical hyperthyroidism, and 1.47 (0.91 to 2.38) for overt hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups. Conclusion: Higher odds of having anemia were observed in participants with both hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.

[A woman with shortness of breath and butterfly shaped cell nuclei]. / Een benauwde vrouw met vlinderkernen in het bloed.

A 53-year-old woman with respiratory discomfort came to the Emergency Department. The blood smear, made because of a new thrombocytopenia, showed leukocytes with butterfly-shaped nuclei and fine cytoplasmic granulation. The diagnosis 'microgranular variant of acute promyelocytic leukemia' was made.

Thyroid hormones and erythrocyte indices in a cohort of euthyroid older subjects.

OBJECTIVES: Hypothyroidism is associated with normocytic anaemia. Indeed, a limited number of studies have shown significant associations between free thyroxin (T4) and erythrocyte indices. These studies did not include vitamin B12, folic acid, iron and renal function in the analyses. We therefore studied the association between thyroid hormones and erythrocyte indices in a population-based cohort of older euthyroid subjects, with adjustment for major confounding parameters. DESIGN: Data, including thyroid hormones and erythrocyte indices, are from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study on predictors and consequences of changes in health in the ageing population in the Netherlands. Multivariable linear regression analyses were applied to study the cross-sectional associations between free T4, thyroid stimulating hormone (TSH) and erythrocyte indices (haemoglobin content, haematocrit, mean cell volume (MCV) and erythrocyte count) in a euthyroid sub-sample. The final models were adjusted for vitamin B12, folic acid, iron levels and renal function. RESULTS: In 708 euthyroid older subjects, an increase of 5pmol/L free T4 was associated with a mean increase of 0.12mmol/L or 0.19g/dL of haemoglobin, 0.068 10(12)/L erythrocytes and 0.006L/L haematocrit (P=0.007, P=0.005, P=0.001, respectively). Free T4 was not significantly associated with MCV (P>0.05). TSH appeared not to be associated with any of the erythrocyte indices (all P>0.05). CONCLUSIONS: In a cohort of older subjects, free T4, but not TSH, was associated with erythrocyte indices, confirming the role of thyroid hormones in the regulation of erythropoiesis.

Haemoglobin A1c: Historical overview and current concepts.

Since the discovery of the relation between increased concentrations of fast haemoglobin fractions in patients with diabetes mellitus compared to concentrations in subjects without diabetes mellitus by Samuel Rahbar and co-workers in 1969, glycated haemoglobin A1c (HbA1c) has become a "gold standard" for glucose management in patients with diabetes mellitus. Recently, HbA1c has been advocated as a diagnostic marker for diabetes mellitus, which further underlines the importance of HbA1c. There are currently more than 30 methods available on the market with an analytical performance ranging from poor to state of the art. This review describes the biochemistry of HbA1c and the concepts of analytical and biological variation with respect to the measurement of HbA1c. Subsequently, aspects regarding the discovery of HbA1c are described. In addition, an overview is given on the assays methods that are currently available for the measurement of HbA1c. Finally, recommendations for the minimally required analytical performance characteristics of the current HbA1c assays are presented.

A patient with a prolonged activated partial thromboplastin time and a deep intracerebral haemorrhage.

We report on a 57-year-old woman with a pontine haemorrhage and an extremely prolonged activated partial thromboplastin time (aPTT) of more than 240 s, suggestive of a coagulation disorder. Given the location of the haemorrhage, which is associated with a high mortality rate, recombinant factor VIIa was administered, although not all necessary laboratory analyses could be performed at that time. In our case, a deficiency of factor XII was found, which is not associated with an increased bleeding risk. In an acute setting, evaluation of a prolonged aPTT may cause diagnostic and therapeutic challenges, in particular in situations where additional laboratory investigations may not be readily available.

Overweight children with type 1 diabetes have a more favourable lipid profile than overweight non-diabetic children.

In the present article, we aimed to compare the cardiometabolic risk between overweight children with and without type 1 diabetes (T1DM). Therefore, data with regard to cardiometabolic risk parameters of 44 overweight Caucasian children (3-18 years) with T1DM were matched with 44 overweight peers without T1DM for sex, ethnicity, age and standard deviation score of BMI (Z-BMI). Detailed history was taken, information regarding anthropometrics and family history were collected and blood pressure was measured. Blood samples were collected for evaluation of lipid profiles (fasting in controls, non-fasting in T1DM children), alanine aminotransferase and HbA1c (in children with T1DM). It was found that overweight children with T1DM had lower median standard deviation score of waist circumference (Z-WC) as compared to the overweight control group [median, 2.0 (interquartile range, IQR, 1.5-2.3) vs. 2.6 (IQR, 2.0-2.9), P < 0.001]. After adjustment for Z-WC, in children with T1DM, median high-density lipoprotein cholesterol levels were significantly higher and median low-density lipoprotein cholesterol lower in T1DM children, as compared to their peers without T1DM [1.40 (IQR, 1.2-1.5) vs. 1.2 (IQR, 1.0-1.3) and 2.7 (IQR, 2.5-3.2) vs. 3.0 (IQR, 2.5-3.4), respectively, all P < 0.01]. When dividing children according to glycaemic status, children with suboptimal glycaemic control had higher values of triglycerides as compared to well-controlled children [1.3 (IQR, 1.0-1.8) vs. 0.96 (IQR, 0.80-1.2), P = 0.036]. In conclusion, overweight children with T1DM have a more favourable lipid profile, as compared to non-diabetic overweight controls, in spite of a higher frequency of a positive family history of CVD, T2DM and hypertension. Still, paediatricians should give extra attention to cardiometabolic risk factors within this vulnerable group, taking into account the already high cardiometabolic risk.

Implementation of flow cytometry in the diagnostic work-up of myelodysplastic syndromes in a multicenter approach: report from the Dutch Working Party on Flow Cytometry in MDS.

Flow cytometry (FC) is recognized as an important tool in the diagnosis of myelodysplastic syndromes (MDS) especially when standard criteria fail. A working group within the Dutch Society of Cytometry aimed to implement FC in the diagnostic work-up of MDS. Hereto, guidelines for data acquisition, analysis and interpretation were formulated. Based on discussions on analyses of list mode data files and fresh MDS bone marrow samples and recent literature, the guidelines were modified. Over the years (2005-2011), the concordance between the participating centers increased indicating that the proposed guidelines contributed to a more objective, standardized FC analysis, thereby ratifying the implementation of FC in MDS.

One in five laboratories using various hemoglobin A1c methods do not meet the criteria for optimal diabetes care management.

BACKGROUND: We assessed the reference change value (RCV) of currently available hemoglobin A(1c) (HbA(1c)) laboratory assays, which is defined as the critical difference between two consecutive HbA(1c) measurements representing a significant change in health status. METHODS: We examined the individual laboratory coefficients of variation (CVs) in the Dutch/Belgian quality scheme based on 24 lyophilized samples and calculated the RCV per laboratory (n = 220) and per assay method. In addition, two pooled whole blood samples were sent to the participating laboratories. The individual laboratory results were compared to the assigned value ± an allowable total error (TE(a)) of 6%. RESULTS: At HbA(1c) values of 41.0 mmol/mol (5.9%-Diabetes Control and Complications Trial [DCCT]) and 61.8 mmol/mol (7.8%-DCCT), 99% and 98%, respectively, of the laboratories reported a value within a TE(a) limit of 6%. The analytical CV of the HbA(1c) method used in 78% of the laboratories is <2.4%. The mean RCV at an HbA(1c) value of 53 mmol/mol (7.0%-DCCT) for methods of Bio-Rad is 5.9 mmol/mol (0.59%-DCCT); for Arkray/Menarini, 4.3 mmol/mol (0.43%-DCCT); for Roche, 6.5 mmol/mol (0.65%-DCCT); for Tosoh, 3.3 mmol/mol (0.33%-DCCT); and for other methods, 6.3 mmol/mol (0.63%-DCCT). CONCLUSIONS: The analytical performance of the majority of laboratory HbA(1c) methods is within the clinical requirements. However, based on the calculated RCV, 21.8% of the laboratories using different HbA(1c) methods are not able to distinguish an HbA(1c) result of 59 mmol/mol (7.5%-DCCT) from a previous HbA(1c) result of 53 mmol/mol (7.0%-DCCT). It can be presumed that differences in HbA(1c) results of 5 mmol/mol (0.5%-DCCT) do influence treatment decisions.

[Monoclonal B-cell lymphocytosis: physiological entity or preliminary stage of chronic lymphocytic leukaemia?]. / Monoklonale B-cellymfocytose: fysiologische bevinding of voorstadium van chronische lymfatische leukemie?

The criteria for the diagnosis of chronic lymphocytic leukaemia (CLL) have recently been changed, with the absolute number of monoclonal B cells instead of the total number of lymphocytes now important. CLL is diagnosed when the number of monoclonal B cells with the characteristic CLL phenotype in peripheral blood exceeds 5 x 10(9)/l; fewer than 5 x 10(9)/l of monoclonal B cells with the characteristic CLL phenotype present in peripheral blood leads to a diagnosis of monoclonal B-cell lymphocytosis (MBL): a new diagnostic entity. The prevalence of MBL is estimated to be 3% and has a relatively mild course with a progression rate from MBL to CLL of 1-2% per year. After a single evaluation by a haematologist to exclude lymphadenopathy, organomegaly and infection as causes of the lymphocytosis, patients with MBL need only be evaluated once annually by their general practitioner for measurement of the blood lymphocyte count and referral in case of progression.

Overweight is highly prevalent in children with type 1 diabetes and associates with cardiometabolic risk.

OBJECTIVES: To determine the prevalence of traditional cardiometabolic risk factors and to assess the effect of overweight/obesity on the occurrence of these risk factors in a cohort of children with type 1 diabetes mellitus (T1DM). STUDY DESIGN: Two hundred eighty-three consecutive patients (3 to 18 years of age) attending an outpatient clinic for T1DM care were included. The prevalence of cardiometabolic risk factors, the metabolic syndrome, and high alanine aminotransferase, were assessed before and after stratification for weight status. RESULTS: Of all children (median age, 12.8 years; interquartile range, 9.9 to 16.0; median diabetes duration, 5.3 years; interquartile range, 2.9 to 8.6), 38.5% were overweight/obese (Z-body mass index > or =1.1). Overall, median HbA1c levels were 8.2% (interquartile range, 7.4 to 9.8), and HbA1c > or =7.5% was present in 73.9%. Microalbuminuria was found in 17.7%, high triglycerides (>1.7 mmol/L) in 17.3%, high LDL-cholesterol (>2.6 mmol/L) in 28.6%, low HDL-cholesterol (<1.1 mmol/L) in 21.2%, and hypertension in 13.1% of patients. In the overweight/obese children with T1DM, versus normal-weight children, a higher prevalence of hypertension (23.9% vs 5.7%), the metabolic syndrome (25.7% vs 6.3%), and alanine aminotransferase >30 IU/L (15.6% vs 4.5%) was found (all P < .05). CONCLUSIONS: Overweight/obesity and cardiometabolic risk factors were highly prevalent in a pediatric cohort with T1DM. Hypertension, the metabolic syndrome, and high alanine aminotransferase were significantly more prevalent in overweight/obese compared with normal-weight children with T1DM.

Does sampling site influence levels of free thyroxine and thyrotropin determined by a current immunoassay?

OBJECTIVES: To examine the effect of sampling site on levels of free thyroxine (fT4) and thyrotropin (TSH). DESIGN AND METHODS: fT4 and TSH were determined by a current immuno-assay in paired samples of capillary and venous blood drawn from 30 euthyroid adults. RESULTS: Mean levels of fT4 and TSH did not differ significantly between capillary and venous blood; capillary and venous levels correlated well and did not differ significantly from unity. CONCLUSIONS: Sampling site does not influence levels of fT4 and TSH.

Urinary matrix metalloproteinase-8 and -9 activities in type 2 diabetic subjects: A marker of incipient diabetic nephropathy?

Matrix metalloproteinases (MMPs) may play a pathophysiological role in the development of diabetic nephropathy (DN). We hypothesized that urinary MMP activity in patients with type 2 diabetes mellitus (T2DM) is related to a decline in renal function. We determined MMP-2, -8 and -9 activity in 24-h urine collections in relation to risk factors for DN in T2DM patients with (UA, n=27) and without albuminuria (NA, n=48) and controls (CO, n=28). MMP-8 and -9 levels were highest in UA patients (P<0.01). Of UA patients, 93% had at least one MMP increased, compared to 78% of NA patients and 46% of CO (P=0.001). Age, diabetes duration, BMI, systolic blood pressure, fasting plasma glucose, HbA1c and renal function were determinants of MMP-8 and -9 (P<0.05). In summary, MMP-8 and -9 are highest in T2DM UA patients. MMP-9, showed the strongest associations with clinical parameters related to DN.