Pedijatrijski moždani udar iz laboratorijske perspektive

Moždani udar kod djece uvelike se razlikuje od moždanog udara odrasle populacije. U radu je opisana definicija, podjela, učestalost, klinička slika, dijagnostika, čimbenici rizika i pristup djetetu s moždanim udarom. Iako nema dijagnostički značaj, laboratorijska dijagnostika u skrbi djeteta s moždanim udarom neizostavna je karika u iznalaženju rizičnih čimbenika koji su doveli do moždanog udara zbog provođenja pravilnog i pravovremenog liječenja te planiranja rehabilitacije i preventivne terapije s krajnjim ciljem sprečavanja opetovanog moždanog udara. Od najučestalijih čimbenika rizika, laboratorijskoj dijagnostici uglavnom pripadaju laboratorijski testovi koji će pomoći u dijagnostici pedijatrima uže specijalizacije za pojedine bolesti (urođene srčane greške, bolesti srpastih stanica, hemolitičke anemije, koagulopatije, metaboličke bolesti, infekcija, trombofilija). Trombofilija u djece s moždanim udarom i njihovih roditelja tema je koja je obrađena u radu na temelju literaturnih podataka i vlastitih rezultata u zadnja dva desetljeća. Na temelju tih rezultata prikazan je i prijedlog laboratorijske dijagnostike trombofilije u pedijatrijskoj laboratorijskoj medicini

Verification of the Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) reference values in Croatian children and adolescents

Introduction: The aim of this study was to examine whether the Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) could be applied to Croatian children and adolescents. Materials and methods: A total of 295 outpatient healthy children and adolescents of age 1 to 18 were selected using the direct a posteriori sampling method. According to current guidelines, 20 samples were tested for each of a total of 51 reference intervals for ferritin, cortisol, dehydroepiandrosterone sulfate, follicle stimulating hormone, lutein stimulating hormone, prolactin, progesterone, sex hormone binding globulin, thyroid stimulating hormone, total testosterone, total thyroxine and total triiodothyronine. Serum samples were analysed on the Beckman Coulter DxI600 immunoassay analyser by chemiluminescence immunoassay method. A reference interval was adopted if < 10% of the results fall outside CALIPER reference interval range. For analytes in which this criterion is not met in the first set of samples, a new set of 20 samples were collected. Results: After the first set of measurements, 96% of all tested reference intervals were adopted for use. The additional sets of 20 reference subjects were tested for only two reference intervals; follicle stimulating hormone for female aged 1 to 9 years, and irrespective of the gender, sex hormone binding globulin for children aged 8 to 11 years. All results of additional samples were within the specified interval limits. Conclusions: CALIPER reference intervals for ferritin and 11 hormones defined for Beckman Coulter DxI600 immunoassay analyser can be implemented into the Croatian laboratories and clinical practice

New perspectives and strategies in the treatment of thromboembolic diseases.

U prevenciji tromboembolijskih događaja različite etiologije, a stoga i kod pacijenata s fibrilacijom atrija (FA) te pacijenata s akutnim koronarnim sindromom (AKS) konvencionalno se primjenjuje acetilsalicilatna kiselina, heparini te antagonisti vitamina K. Dakako, ovisno o indikaciji različite prednosti i nedostatci svake od ovih kategorija lijekova usmjeravaju ili ograničavaju njihovu uporabu. Njihovom primjenom postignut je znatan napredak u liječenju, međutim kako ipak imaju neke neželjene karakteristike, a prevalencija trombotskih događaja generalno je još uvijek vrlo visoka, javila se potreba za razvojem novih protuzgrušavajućih lijekova. U zadnjih nekoliko godina na tržištu je predstavljena nova generacija protuzgrušavajućih lijekova čije je djelovanje usmjereno na inhibiciju trombina ili aktiviranog faktora X. Rezultati provedenih kliničkih istraživanja istakli su potencijal direktnog inhibitora trombina dabigatrana te anti-Xa lijeka rivaroksabana u liječenju i prevenciji duboke venske tromboze te moždanog udara povezanog s FA. Odnedavna je u mnogim zemljama njihova primjena odobrena za navedene indikacije, a preliminarna istraživanja kod pacijenata s AKS su ukazala na to da bi primjena pojedinih lijekova nove generacije mogla biti dobra alternativa za akutno zbrinjavanje ili blagotvorna u sekundarnoj prevenciji ishemije. Ovdje dan kratak pregled spoznaja o farmakologiji novih lijekova, rezultatima kliničkih ispitivanja kod pacijenata s FA i AKS, kao i mogućnostima njihovog monitoringa.In the prevention of tromboembolic events of different etiology and therefore in patients with atrial fibrillation (AF) and patients with acute coronary syndrome (ACS) acetylsalicylic acid, heparins and vitamin K antagonists are traditionally applied. So, depending on the indication, various advantages and disadvantages of each of these categories of drugs direct or restrict their use. Their application has achieved considerable progress in the treatment, but as some of them show undesired characteristcs and considering that general prevalence of thrombotic events is generally still very high, a development of new antithrombotic drugs has been considered. In the last few years, a new generation of antithrombotic drugs with effects directed on the inhibition of thrombin (FIIa) or activated factor X (FXa) has been developed and introduced in the market. The results of the conducted clinical trials have demonstrated the potential of these drugs in the treatment and prevention of deep vein thrombosis and AF related stroke. In many countries their application for the above mentioned indications has been recently approved, while the preliminary trials in patients with ACS have showed that the use of particular new generation drugs could be a good alternative for the acute management or could be beneficial in the secondary prevention of ischemia. Here, we have presented a short overview of insights about pharmacology, results of clinical trials and possibilities of monitoring of new antithrombotic drugs

Troponin i B-tip natrijuretskog peptida: laboratorijska dijagnostika i klinička upotreba u pedijatriji

For years now, troponin and B-type natriuretic peptide are two cardiac biomarkers routinely used in the diagnosis of cardiac disease in general population, but the knowledge of their usability in pediatric population is very low. This review covers the issues of determination, interpretation of laboratory test results, and usefulness of troponin and B-type natriuretic peptide in pediatrics, based on published data and our own experience. It is intended for pediatricians and laboratory specialists who work with pediatric population.Troponin i B-tip natrijuretskog peptida su dva srčana biljega koja se u općoj odrasloj populaciji već dugi niz godina rutinski primjenjuju u dijagnostici srčanih bolesti, no malo je spoznaja o njihovoj korisnoj upotrebi u pedijatrijskoj praksi. Ovaj pregledni rad obuhvaća svu problematiku određivanja, tumačenja nalaza i korisnost troponina i B-tipa natrijuretskog peptida u pedijatriji na temelju podataka iz literature i vlastitog iskustva. Namijenjen je liječnicima pedijatrima i laboratorijskim stručnjacima koji se u svom radu susreću s dječjom populacijom

Analytical verification of the Dymind D7-CRP automated analyser

IntroductionThe aim of this study was to perform a verification of the Dymind D7-CRP automated analyser and compare it with established analysers. Materials and methodsAnalytical verification included estimation of repeatability, between run precision, within-laboratory precision, and bias in control samples with low, normal and high levels. The acceptance criteria for analytical verification were defined using the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) 2019 Biological Variation Database. Method comparison between the Dymind D7-CRP and the Sysmex XN1000 for haematological parameters and the Dymind D7-CRP and the Beckman Coulter AU680 for CRP values was performed on 40 patient samples. ResultsAnalytical verification criteria were adequately met with the exception of monocyte count for repeatability and within-laboratory precision (13.4% and 11.5%, respectively, acceptance criteria 10.1%) and measurement uncertainty (23.0, acceptance criteria 20.0%) at low level, eosinophil count for BIAS at the low level (37.7%, acceptance criteria 25.2%), basophil count (BAS) for BIAS at the high level (14.2%, acceptance criteria 10.9%), and mean platelet volume (MPV) for repeatability (4.2% and 6.8%), between run precision (2.2% and 4.7%), within-laboratory precision (4.0% and 7.3%) (acceptance criteria 1.7%), and measurement uncertainty (8.0 and 14.6%, acceptance criteria 3.4%) at both the low and high concentrations. Method comparison showed no clinically significant constant or proportional differences for all parameters except BAS and MPV. ConclusionThe analytical verification of the Dymind D7-CRP showed adequate analytical characteristics. The Dymind D7-CRP can be used interchangeably with the Sysmex XN-1000 for all parameters tested, except BAS and MPV, and with the Beckman Coulter AU-680 for the determination of CRP

Routine coagulation testing in acute stroke

Uvod: Promjene u sustavu hemostaze mogu pridonijeti razvoju tromboembolijskih i hemoragijskih bolesti. Stoga je glavni cilj ovoga rada bio istražiti povezanost koagulacijskih pretraga koje se uobičajeno određuju po prijemu bolesnika s akutnim moždanim udarom (MU), njihov odnos s (pod)tipovima MU-a i ishodom nakon akutnoga MU-a. Materijali i metode: Retrospektivno su pregledani podatci o 262 pacijenta hospitaliziranih u razdoblju od siječnja do lipnja 2011. godine na Klinici za neurologiju Zavoda za cerebrovaskularne bolesti Kliničke bolnice „Sveti Duh” suspektnih na akutni moždani udar. Klasifikacija MU-a temeljena je na kliničkoj slici i nalazima neuroradiološke obrade, dok se ishod MU-a procjenjivao pomoću modificirane Rankinove ljestvice. Analizirani su rezultati koagulacijskih pretraga: PV-INR APTV, fibrinogena i D-dimera prilikom prijema pacijenata u bolnicu. Za sve pacijente izračunat je i omjer D-dimera i fibrinogena. Rezultati: U konačnu analizu uključena su 74 pacijenta, 67 s ishemijskim MU-om, od čega je u 22 pacijenta MU klasificiran kao lakunarni, a u 10 pacijenata kao hemoragijski. Nađena je umjerena, ali značajna pozitivna korelacija između vrijednosti D-dimera i modificirane Rankinove ljestvice (r = 0,470, CI% = 0,271-0,631; P < 0,0001). Tijekom hospitalizacije preminulo je 16 % bolesnika. Vrijednosti D dimera po primitku u bolnicu bile su statistički značajno više u bolesnika koji nisu preživjeli u odnosu na bolesnike koji su preživjeli MU (604 naspram 224 μg/L, P < 0,0001) kao i u bolesnika s dijagnosticiranim ishemijskim MU-om klasificiranim kao nelakunarni u odnosu na bolesnike s klasificiranim lakunarnim MU-om (294 naspram 206 μg /L. P = 0,02). Vrijednosti drugih koagulacijskih pretraga i omjera D-dimera i fibrinogena nisu se značajno razlikovale među ispitivanim grupama. Zaključak: Istraživanje je pokazalo da su povišene vrijednosti D-dimera povezane s lošijim ishodom nakon akutnoga MU-a te da njihovo određivanje po primitku može biti indikativno u smislu prognoze i ishodaIntroduction: Changes in haemostatic system could contribute to the development of thromboembolic and haemorrhagic disease. The main objective of this study was to explore the relationship between coagulation tests commonly used in the clinical settings on patient’s admission, stroke types and patient’s outcome. Patients and methods: Patients’ hospital charts and documentation were retrospectively reviewed for 262 patients admitted to the Stroke and Intensive Care Unit, Department of Neurology at “Sveti Duh” University Hospital, Zagreb, Croatia from January to June 2011 under the suspected diagnosis of acute stroke. Classification of stroke types was primarily based on clinical picture and imaging studies, whereas degree of patients’ disability and outcome was measured by modified Rankin Scale (mRS). Results of the coagulation test PT-INR, APTT, fibrinogen and D-dimer performed on admission were recorded. For all patients the D-dimer to fibrinogen ratio was also calculated. Results: Total of 74 patients were enrolled in the study, 67 with ischemic stroke whereby 22 of them were classified as patients with lacunar stroke and 10 as patients with haemorrhagic stroke. During hospitalisation 16% of patients did not survive. The median D-dimer value on admission was significantly higher in non-survivors than in survivors (604 vs. 224μg/L, P < 0.0001), as well as in patients with ischemic non-lacunar stroke in comparison to lacunar stroke (294 vs. 206 μg /L. P = 0.02). Although moderate, significant correlation was observed between elevated DD levels and mRS scale (r = 0.470, CI% = 0.271-0.631; P < 0.0001). Other coagulation parameters, as well as D-dimer/fibrinogen ratio, considered in the study did not show any significant difference between stroke type or survival. Conclusions: Our study revealed that increased DD levels in acute phase of the stroke are associated with stroke outcome and that their determination on admission could be indicative of prognosis and outcome

Fecal Calprotectin as a Biomarker of Food Allergy and Disease Severity in Children with Atopic Dermatitis without Gastrointestinal Symptoms

Fecal calprotectin (FCP) is a biomarker of intestinal inflammation and has recently been proposed as a diagnostic biomarker of food allergy (FA) in children. The aim of this study was to compare FCP level in infants and children under 4 years old with 1) atopic dermatitis (AD) with food allergy (FA) and 2) children with AD and without FA with the results in healthy controls. In total, 46 infants and children (mean age 14 months ± 12) diagnosed with AD were divided into two groups: G1, children with atopic AD with FA (n=28) and G2, children with AD without FA (n=18). The control group (G3) was made up of healthy children of the same age (n=18). The median FCP was significantly higher in G1 compared with G2 (G1: median 154, IQR 416 μg/g vs G2: median 41.3, IQR 59 μg/g; P=0.0096). The median FCP in children with AD and FA was significantly higher before elimination diet in comparison with FCP after 3 months of elimination diet (median 154, IQR 416 μg/g vs median 35, IQR 23 μg/g; P=0.0039). The level of FCP was significantly positively correlated with the SCORAD score (r=0.5544, P=0.0022). Our study showed a significant difference in level of FCP in patients with AD without FA compared with patients with AD and FA. We also found a positive correlation of FCP with SCORAD score, a biomarker of AD severity. New studies are needed to investigate the role of FCP as a biomarker of FA in children with AD

Reporting of activated partial thromboplastin time (aPTT): Could we achieve better comparability of the results?

Activated partial thromboplastin time (aPTT) is determined and reported as clotting time in seconds aPTT(s), but it is presumed that reporting results as patient-to-normal clotting time ratio, aPTT(r), could minimize within-laboratory variability. The aim of study was to investigate differences in reporting aPTT results that can affect comparability of the results among Croatian laboratories and suggest further steps for its harmonization. The questionnaire on aPTT reporting practice was distributed to 83 laboratories through Survey Monkey application in March 2019 as the part of the first regular round of Croatian Centre for Quality Assessment in Laboratory Medicine proficiency testing. The survey response rate was 0.49. Majority of laboratories report aPTT results as both, seconds and ratio. Participants reported use of 23 different aPTT(s) reference intervals along with 17 different combinations of reagent/coagulometer and 25 aPTT(s) denominators of different origin for aPTT(r) calculation. Despite the same aPTT(s) results, the use of different denominators caused a dispersion of aPTT(r) results that can lead to exceeding external quality assessment performance criteria of 7%, particularly when results were compared for the same reagent group only. By applying aPTT(s) reference interval mean as denominator for calculation of aPTT(r) reference interval better concordance to harmonized one was obtained (17 vs. 27; χ2 = 3.972; P = 0.046). In order to improve comparability of the results, laboratories are advised to use mean of aPTT(s) reference interval as denominator for aPTT(r) calculation. Type of coagulometer need to be considered when evaluating aPTT proficiency test results and its currently acceptable limit of performance evaluated accordingly