Prevalence of potential underlying aetiology of macrocytic anaemia in Dutch general practice.

BACKGROUND: Macrocytic anaemia (MCV ≥ 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated. METHODS: Between the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results. RESULTS: Of the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001). Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes. CONCLUSION: In addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice.

A comparative study of conventional versus new, magnesium-poor Vacutainer® Sodium Citrate blood collection tubes for determination of prothrombin time and INR.

INTRODUCTION: Conventional Vacutainer® Sodium Citrate blood collection tubes contain a relatively high concentration of contaminating magnesium ions, which may result in shortening of the prothrombin time (PT) and the International Normalized Ratio (INR). Recently the manufacturer of Vacutainer® Sodium Citrate tubes introduced new tubes with a magnesium-poor stopper. The magnesium concentration in the new low-Mg tubes is significantly lower than that in the conventional plastic tubes. The purpose of the present study was to compare PT and INR determined in specimens drawn with the new tubes to those drawn with the conventional tubes. MATERIALS AND METHODS: Venous blood specimens were collected from 22 healthy persons and 65 patients treated with vitamin K-antagonists using conventional Vacutainer® Sodium Citrate tubes and new, low-Mg Vacutainer® tubes. PT and INR were determined with four thromboplastin reagents, i.e., three brands of recombinant human tissue factor and one brand of combined rabbit brain reagent. Magnesium concentrations were determined in the citrate plasmas with a colorimetric method. RESULTS: The differences in PT, INR and International Sensitivity Index (ISI) between the two tubes were significant when using three recombinant human thromboplastin reagents, but were not significant when using the rabbit thromboplastin. The PT and INR differences between the tubes correlated with the magnesium concentration differences (P<0.001). The INR bias between the four reagents was greater for specimens drawn with conventional tubes than the INR bias for specimens drawn with the new tubes. CONCLUSION: Agreement of INR between reagents is improved by using magnesium-poor tubes.

Influence of C-reactive protein levels and age on the value of D-dimer in diagnosing pulmonary embolism.

BACKGROUND: Recently, the number of performed CT-angiographies to diagnose pulmonary embolism (PE) rised markedly, while the incidence of PE hardly increased. This low yield of CT-angiography leads to more patients exposed to radiation and higher costs. AIM: The diagnostic value of age, C-reactive protein (CRP) and D-dimer in PE was investigated. Additionally an age-adjusted D-dimer cutoff level [age-adjusted cutoff = age/100 mg/L] was compared with the conventional cutoff level in diagnosing PE for patients ≥50 yr. METHODS: This observational study (2004-2007) included all consecutive patients suspected for PE presenting on the emergency department with a performed CT-angiography after measuring CRP and D-dimer levels. RESULTS: Of 4609 patients suspected for PE, 1164 patients underwent CT-angiography of whom 309 (26.5%) had PE. Correlation between CRP and D-dimer was 0.42 (P < 0.001). D-dimer and age correlated positively (rs  = 0.33, P < 0.001), but only in patients >50 yr and independent of PE. Multivariate regression analysis showed significant contribution of age, D-dimer and age-adjusted D-dimer for diagnosing PE, but not for CRP. Using an age-adjusted D-dimer cutoff value increased specificity from 37% to 50%, whereas sensitivity declined from 96% to 90%. Applying this age-adjusted cutoff level in patients ≥70 yr, specificity increased from 18% to 40%, while sensitivity decreased from 96% to 88%. CONCLUSIONS: In the prediction of PE, age and D-dimer levels are relevant, while CRP level is not. Using an age-adjusted D-dimer cutoff in older patients remarkably improves the specificity of D-dimer testing with a minor decline in sensitivity. This may increase the yield of CT-angiography in diagnosing PE.

The transferrin/log(ferritin) ratio: a new tool for the diagnosis of iron deficiency anemia.

BACKGROUND: Serum ferritin is the best single laboratory test to diagnose iron deficiency anemia (IDA). Ferritin levels <20 µg/L are highly specific for IDA, and ferritin levels >100 µg/L usually exclude IDA. However, ferritin concentrations between 20 and 100 µg/L are often inconclusive. The objective of this study was to improve the diagnosis of IDA when ferritin levels are inconclusive. METHODS: We evaluated the predictive performance of classic (ferritin, mean corpuscular volume, transferrin and serum iron) and modern [reticulocyte hemoglobin content, serum transferrin receptor and soluble transferrin receptor (sTfR)/log(ferr)] iron status parameters to diagnose IDA in 2084 anemic, non-hospitalized patients. The results were validated in an independent cohort of 274 anemic patients. RESULTS: In our study population, 29% (595 patients) of the patients had a ferritin level between 20 and 100 µg/L, hampering diagnosis of IDA. None of the classic or modern parameters was capable of completely separating the IDA population from the non-IDA population. However, using a new parameter, the transferrin/log(ferritin) ratio, the IDA and non-IDA populations can be completely separated. At a cut-off value of 1.70, the transferrin/log(ferritin) ratio indicates IDA in 29% of the patients with inconclusive ferritin levels. CONCLUSIONS: The transferrin/log(ferritin) ratio is a practical new tool that improves diagnosis of iron deficiency when ferritin levels are inconclusive.

Screening for gastrointestinal malignancy in patients with iron deficiency anemia by general practitioners: an observational study.

BACKGROUND: The prevalence of iron deficiency anemia (IDA) is 2-5% in men and postmenopausal women in the developed world. IDA is commonly caused by chronic gastrointestinal blood loss, and a thorough examination of the gastrointestinal tract must be standard practice. OBJECTIVE: To retrospectively study endoscopic evaluations of patients from general practitioners diagnosed with IDA in a peripheral hospital laboratory in order to determine the cause of IDA and the number of gastrointestinal malignancies. MATERIAL AND METHODS: We retrospectively evaluated all patients with IDA diagnosed in a peripheral hospital laboratory by the general practitioner in the region of our hospital from 1 January 2004 until 31 December 2005. We included women older than 50 and men 18 years and older without a history of IDA in the previous 2 years. RESULTS: In 2 years, 287 patients were newly diagnosed with IDA in our hospital laboratory. Only 90 (31%) patients were endoscopically evaluated within 4 months. Gastrointestinal endoscopy revealed at least one lesion potentially responsible for blood loss in 41 of 90 (46%) patients. The most common lesions identified by gastroduodenal endoscopy were erosive esophagitis, gastritis and duodenitis (14%). Cancer was the most commonly detected lesion in the colon, accounting for 17 of 21 colonic lesions explaining IDA. In total, gastrointestinal malignancy was diagnosed in 2% of screened patients. Factors determining the decision for endoscopic screening were lower hemoglobin level, lower ferritin level and male gender. CONCLUSION: In our retrospective study of patients with IDA, only 31% received any form of endoscopic evaluation. In general practice, IDA is investigated suboptimally, and interventions other than the issuing of guidelines are needed to change practice.