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IntroductionLaboratory plays important part in screening, diagnosis, and management of thyroid disorders. The aim of this study was to estimate current laboratory preanalytical, analytical and postanalytical practices and policies in Croatia. Materials and methodsWorking Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine designed a questionnaire with 27 questions and statements regarding practices and protocols in measuring thyroid function tests. The survey was sent to 111 medical biochemistry laboratories participating in external quality assurance scheme for thyroid hormones organized by Croatian Centre for Quality Assessment in Laboratory Medicine. Data is presented as absolute numbers and proportions. ResultsFifty-three participants returned the questionnaire. Response rate varied depending on question, yielding a total survey response rate of 46-48%. All respondents perform thyroid stimulating hormone (TSH). From all other thyroid tests, most performed is free thyroxine (37/53) and least TSH-stimulating immunoglobulin (1/53). Laboratories are using nine different immunoassay methods. One tenth of laboratories is verifying manufacturer’s declared limit of quantification for TSH and one third is verifying implemented reference intervals for all performed tests. Most of laboratories (91%) adopt the manufacturer’s reference interval for adult population. Reference intervals for TSH are reported with different percentiles (90, 95 or 99 percentiles). ConclusionThis survey showed current practices and policies in Croatian laboratories regarding thyroid testing. The results identified some critical spots and will serve as a foundation in creating national guidelines in order to harmonize laboratory procedures in thyroid testing in Croatia.

In the final phase of clot formation, fibrinogen constitutes frame, whereas factor XIII (FXIII) active form is responsible for the covalent cross-linking of fibrin fibres and plasmin inhibitor (PI), thus contributing to clot stability. It could be expected that any change of coagulation factors' structure affects the clot formation and modulates the atherothrombotic risk. The aim was to determine the frequency of four single nucleotide polymorphisms: (We performed the unrelated case-control association study on the consecutive sample of patients 18 years old, who had undergone coronary angiography for investigation of chest pain and suspected CAD. The cases were patients with confirmed CAD (N=201), and the controls were the subjects with no CAD (N=119). Samples were genotyped using PCR-RFLP analysis.Observed frequencies of the rare alleles of Thr312Ala FGA, 10034CT FGG, Leu564Pro FXIII-A and Arg6Trp PI polymorphisms were 21%, 17%, 14%, 20%, respectively. Patients with 10034CT FGG CC genotype had 3.5 times (95% CI 1.02-12.03) higher adjusted odds for CAD than patients with 10034CT FGG TT genotype. Patients with Arg6Trp PI CC genotype had 3.86 times (95% CI 1.23-12.12) higher odds for CAD than patients with Arg6Trp PI TT genotype. It seems that those genotype-related higher odds are also male-gender related. No difference was observed regarding any other investigated polymorphism.Our finding suggests that 10034CT FGG and Arg6Trp PI are associated with CAD.U završnoj fazi stvaranja ugruška fibrinogen čini okvir, dok je aktivni oblik faktora XIII (FXIII) odgovoran za kovalentno umrežavanje vlakana fibrina i inhibitora plazmina (PI), doprinoseći tako stabilnosti ugruška. Moglo bi se očekivati da svaka promena strukture faktora koagulacije utiče na stvaranje ugruška i modulira rizik od aterotrom - bota. Cilj je bio da se odredi frekvencija četiri pojedinačna nukleotidna polimorfizma: (I) AG u kodonu 312 gena a-lanca fibrinogena (rs6050, Thr312AlaFGA), (II) CT na položaju 10034 3' netransliranog regiona u genu g-lanca fibrinogena (rs2066865, 10034CTFGG), (III) CT u kodonu 564 gena podjedinice FXIII-A (rs5982, Pro564LeuFXIII-A), i (IV) CT u kodonu 6 gena inhibitora plazmina (rs2070863, Arg6TrpPI) kod hrvatskih pacijenata, i njihovu povezanost sa koronarnom arterijskom bolešću (CAD).Obavljeno je nepovezano istraživanje slučajeva i kontrola na uzastopnom uzorku pacijenata sa 18 i više godina koji su bili podvrgnuti koronarnoj angiografiji radi ispitivanja bola u grudima i sumnje na CAD. Slučajevi su bili pacijenti sa potvrđenom CAD (N = 201), a kontrolna grupa su bili oni koji nisu imali CAD (N = 119). Genetska konstrukcija uzoraka istražena je pomoću PCR-RFLP analize.Posmatrane frekvencije retkih alela Thr312Ala FGA, 10034 CT FGG, Leu564Pro FXIII-A i Arg6Trp PI polimorfizma bile su, redom, 21%, 17%, 14%, 20%. Pacijenti sa 10034 CT FGG CC genotipom imali su 3,5 puta (95% CI 1,02-12,03) veće prilagođene izglede za dobijanje CAD u odnosu na pacijente sa 10034 CT FGG TT genotipom. Pacijenti sa Arg6Trp PI CC genotipom imali su 3,86 puta (95% CI 1,23-12,12) veće izglede za CAD u odnosu na pacijente sa Arg6Trp PI TT genotipom. čini se da ti veći izgledi vezani za genotip takođe imaju veze i sa muškim polom. Nije uočena razlika u odnosu na bilo koji drugi istraženi polimorfizam.Dobijeni rezultati ukazuju na to da su 10034 CT FGG i Arg6Trp PI povezani sa CAD.

European Union (EU) Directive 2013/55/EC (The Recognition of Professional Qualifications) allows Member States to decide on a common set of minimum knowledge, skills and competences that are needed to pursue a given profession through a Common Training Framework. To be adopted the framework must combine the knowledge, skills and competences of at least one third of the Member States. Professionals who have gained their qualifications under a Common Training Framework will be able to have these recognised automatically within the Union. The backbone of the European Federation of Clinical Chemistry and Laboratory Medicine’s (EFLM) proposed Common Training Framework for non-medical Specialists in Laboratory Medicine is outlined here. It is based on an Equivalence of Standards in education, training, qualifications, knowledge, skills, competences and the professional conduct associated with specialist practice. In proposing the recognition of specialist practice EFLM has identified 15 EU Member States able to meet Equivalence and in whom the profession and/or its training is regulated (an additional EU Commission requirement). The framework supports and contributes to the Directive’s enabling goals for increasing professional mobility, safeguarding consumers and ensuring a more equitable distribution of skills and expertise across the Member States. It represents EFLM’s position statement and provides a template for professional societies and/or competent authorities to engage with the EU Commission.

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.

The sweat test (ST) is a cornerstone in the diagnosis of cystic fibrosis (CF), together with newborn screening and genetic testing. However, the performance of the ST can depend on the operator's skill, so several international guidelines have been published to standardise the ST, but inconsistencies remain. The joint Working Group for ST Standardisation (WG STS) of the Croatian Society of Medical Biochemistry and Laboratory Medicine, in association with cistic fybrosis health professional and the Cistic Fibrosis Centre for Paediatrics and Adults, have issued National Guidelines for the Performance of the Sweat Test in order to ensure consistency in ST performance and accuracy of reported results. Many of the standards were taken from the 2nd Edition of the UK Guidelines for Performance of the ST for the Diagnosis of CF, while others were taken from independent consensus statements from the WG STS based on local ST equipment and practices. The standards cover every step of the ST, from the indications for testing to reporting of results and their interpretation, including the analytical phase and quality control. In addition, National Guidelines include appendices with practical examples in order to aid implementation of the recommendations in routine practice. Croatian Society of Medical Biochemistry and Laboratory Medicine.

Introduction: 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. Materials and methods: 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. Results: 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). Conclusion: 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.

Aim To assess the role of human platelet antigens (HPA), P-selectin gene (SELP) polymorphisms, and HPA and SELP haplotypes with factor V (FV) R506Q in ischemic pediat - ric stroke (IPS) subtypes: cerebral sinovenous thrombosis (CSVT), perinatal (PAIS), and childhood (CAIS) arterial isch - emic stroke. Methods This case-control study enrolled 150 children with confirmed IPS and 150 age- and sex-matched con - trols. FV R506Q and HPA-1 were genotyped with CVD Stri - pAssay®, HPA-2 and HPA-3 with real-time polymerase chain reaction, SELP S290N, V599L, and T715P with high resolu - tion melting analysis, and SELP N562D with sequence-spe - cific polymerase chain reaction. Results HPA-1b allele (odds ratio [OR] 2.75, 95% confidence interval [CI] 1.02-7.42, P =0.048) and HPA-1a2a3b (OR 5.46, 95% CI 1.51-19.76, P =0.011), HPA-1b2a3a (OR 7.00, 95% CI 1.25-39.13, P =0.028), and HPA-1b2b3a (OR 11.39, 95% CI 1.39-92.95, P =0.024) haplotypes increased the risk for CSVT. HPA-3b allele was significantly associated with 2-fold lower risk for PAIS (OR 0.49, 95% CI 0.26-0.89, P =0.020) and CAIS (OR 0.47, 95% CI 0.26-0.86, P =0.014) and non-signifi - cantly associated with increased risk for CSVT (OR 6.43, 95% CI 0.83-50.00, P =0.022). HPA-1a2b3a haplotype was significantly associated with CAIS (OR 6.76, 95% CI 2.13-21.44, P=0.001). The inclusion of FV R506Q in SELP haplotype analysis increased the risk for PAIS 4-fold in QNDVT carri - ers (OR 8.14, 95% CI 0.93-71.33, P =0.060) compared with NDVT haplotype (OR 2.45, 95% CI 0.98-6.18, P =0.058), but the result was not significant. Conclusion Individual HPAs, and particularly HPA haplo - types, are involved in IPS subtypes pathogenesis. A possi - ble risk-inducing synergistic effect of SELP haplotypes with FV R506Q is restricted to PAIS only.

Background Although Immulite®2000XPi (Siemens) allergy testing is routinely used in laboratories worldwide; a well-designed comprehensive third-party verification of its analytical performance has not yet been published. Our aim was to verify stability, precision and reference intervals for total and some frequent specific IgEs, test trueness for several most common allergens and assess the comparability of fluorescent- and chemiluminescent-enzyme immunoassay for total IgE. Methods Verification was based on EP15-A3, EP9-A3 and EP28-A3c CLSI guidelines. Stability was tested on serum pools stored at 2–8 °C, during 7 days. Manufacturer’s reference intervals were verified for children and adults. Acceptance criteria were based on manufacturer specifications and national External Quality Assessment provider data. Results Samples for total IgE analysis were stable at 2–8 °C for 7 days. Precision was within manufacturer’s specifications for most of tested allergens, except for total IgE (92.5 kIU/L, CVs 5.6% and 7.6%) and w1 (9.3 kU/L, CV = 5.9%). Bland-Altman plot revealed statistically significant constant (−32.4 kIU/L) and proportional bias (−20.2%) for total IgE between two methods. Passing Bablok showed statistically but not clinically significant biases between two Immulite analyzers for betula verrucosa (constant and proportional), house dust mite and egg white allergens (proportional). For adults and children, total IgE results were within reference intervals declared by Siemens. Conclusions Immulite®2000XPi assay has acceptable precision and trueness. Samples for total IgE are stable even longer than declared by the manufacturer. Declared reference intervals can safely be adopted for both adult and children population in our laboratory. Fluorescent- and chemiluminescent-enzyme immunoassay results of total IgE are not comparable.

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.

Introduction: Variability among manufacturers of urine dipsticks, respective to their accuracy and measurement range, may lead to diagnostic errors and thus create a serious risk for the patient. Our aims were to determine the level of agreement between 12 most commonly used urine dipsticks in Croatia, examine their accuracy for glucose and total protein and to test their repeatability. Materials and methods: A total of 75 urine samples were used to examine comparability and accuracy of 12 dipstick brands (Combur 10 TestM, ChoiceLine 10, Combur 10 TestUX, ComboStik 10M, ComboStik 11M, CombiScreen 11SYS, CombiScreen 10SL, Combina 13, Combina 11S, Combina 10M, UriGnost 11, Multistix 10SG). Agreement between each dipstick and the reference (Combur 10 TestM) was expressed as kappa coefficient (acceptable κ ≥ 0.80). Accuracy for glucose and total protein was tested by comparison with quantitative measurements on analysers: AU400 (Beckman Coulter, USA), Cobas 6000 c501 (Roche Diagnostics, Germany) and Architect plus c4000 (Abbott, USA). Repeatability was assessed on 20 replicates (acceptable > 90%). Results: Best agreement was achieved for glucose, total protein and nitrite (11/11, k > 0.80) and the lowest for bilirubin (5/5, k < 0.60). Sensitivities for total protein were 41-75% (AU400) and 56-92% (Cobas and Architect); while specificities were 41-75% (AU400, Cobas, Architect). Dipsticks’ sensitivity and specificity for glucose were 68-98%. Most of the dipsticks showed unacceptable repeatability (6/12, < 90%) for one parameter, most prominently for pH (3/12, < 90%). Conclusions: Most commonly used dipsticks in Croatia showed low level of agreement between each other. Moreover, their repeatability varies among manufacturers and their accuracy for glucose and proteins is poor.

Introduction: In line with the national recommendations, Croatian medical laboratories report urine test strip qualitative analysis results using a categorized scale with defined number of categories. Since concentration ranges for measured analytes have not been provided by national professional authority, it is up to the laboratories to define their own categories. The aim of study was to assess the comparability of concentrations assigned to different categories used in reporting the results of dipstick urinalysis in Croatian laboratories. Material and methods: A questionnaire was e-mailed to all Croatian medical laboratories (N = 195). They were asked to provide the number of categories and respective concentrations for each parameter. Data were described as numbers and percentages. Values above the upper reference range limit, which were assigned as normal and/or trace category, were considered as false negative. Results: Response rate was 71% (139/195). Seventy percent (98/139) of laboratories report their results with either higher (77/98; 79%) or lower (2/98; 2%) number of categories, relative to the national recommendation, whereas 19/98 (19%) report their results as concentrations. Great heterogeneity of reporting categories was observed. Multiple categories were assigned to same concentrations and there was a large overlap of concentrations for most categories. Considerable proportion of laboratories reported false negative results for ketones (42%), leukocytes (30%) and glucose (21%). Conclusions: The concentrations assigned to categories used to report the results of dipstick urinalysis are not comparable among Croatian medical laboratories. There is an urgent need for harmonization and standardization of reporting the results of urine dipstick analysis in Croatia.

Pediatric solid central nervous system (CNS) tumors are rarely detected at an early stage. The reasons for this include the tumor site, acute intracranial bleeding, unavailable imaging tests, inconsistent conduct of clinical diagnostic procedures, etc (1). CNS tumors account for 20% of all childhood cancers, and their incidence rates are rising (2). Treatment results are better if the disease is detected early, which requires sufficiently sensitive and specific diagnostic methods. This is why new biomarkers indicating the presence of CNS tumors are needed. One of the biological materials used for biomarker testing is cerebrospinal fluid (CSF) (3). CSF washes the structures of the CNS including the tumors present there, enabling the detection of tumor proteins in the CSF. PChE has a role in tumorogenesis and oncogenesis and has been proven to be a good indicator of the presence of tumors (4-6). PChE in serum has already been recognized and confirmed as a good diagnostic and prognostic marker for head and neck tumors (7). Studies of PChE in tumor tissue showed that its concentration in some tumor samples was high, eg, in glioma tissue samples (4). In tissue samples, PChE has higher activity levels in astrocytomas than in meduloblastomas, neuromas, or meningeomas (4). It is included in the myelin metabolism of, eg, the corpus callosum, nervus opticus, and spinal cord. Subcortical white matter has much greater PChE activity than gray matter (8) and PChE activity decreases as we descend from the cerebrum toward the spinal cord. After blood removal, PChE activity is present in the vessels of the brain and it is higher in arteries than in veins (4) PChE is an enzyme (EC 3.1.1.8) synthesized in the liver and distributed to body tissue and fluids. Cholinesterases (acetylcholinesterase – AChE and PChE) activity changes in an abnormal tissue metabolism and/or they become part of the oncogenic process (7). Cholinesterase genes are amplified, aberrant, and mutated in numerous types of human tumors. The PChE and AChE found in these tumors contain the peptide motif S/T-P-X-Z found in many cdc2 gene-dependent protein kinase substrates (5). Phosphorylation of cdc2-dependent protein kinases is a possible molecular mechanism that connects cholinesterases with tumor proliferation. Moreover, the inhibition or reduction of AChE, PChE, and some other enzymes especially with organophosphorous and perhaps carbamate poisons used as insecticides in home and local environment may result in the formation of brain tumors in children partially depending on the genetic polymorphisms that affect insecticide metabolism (9,10). PChE activity in CSF in healthy people is rarely investigated, most often as a part of studies on specific diseases or anesthetics (11-13). Lumbar puncture is an invasive procedure and for ethical reasons the number of healthy participants in studies is always small, especially in case of children. For this reason the information about the normal values of PChE activity in CSF in relation to age at all ages is scarce. In adults, PChE activity in CSF ranges from 1/20 to 1/100 of the value of serum (13). In children, the values are age-dependent (14). PChE activity in serum is low at birth, which is followed by a sudden increase in activity over the next three weeks, with values exceeding those in adulthood. This remains unchanged until the age of three. Between three and six years, PChE activity is 30% above the adult level and it begins to slowly drop between the age of five and puberty, when it reaches the adulthood value, which remains relatively stable (14). In this study, we tested whether PChE could be used as a potential biomarker for solid CNS tumors in children.

Aim To determine the frequency of inherited and acquired prothrombotic risk factors in children with arterial ischemic stroke (AIS) and transient ischemic attacks (TIA) in Croatia. Methods We investigated 14 prothrombotic risk factors using blood samples from 124 children with AIS or TIA and 42 healthy children. Prothrombotic risk factors were classified into five groups: natural coagulation inhibitors (antithrombin, protein C, protein S), blood coagulation factors (FV Leiden and FII 20210), homocysteine, lipid and lipoprotein profile (lipoprotein (a), triglycerides, total, high- and low-density lipoprotein), and antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and antiphosphatidylserine antibodies). Results The most common prothrombotic risk factor was elevated lipoprotein (a), which was identified in about 31% of patients and in 24% of controls. Natural coagulation inhibitors were decreased in about 19% of patients, but not in controls. Pathological values of homocysteine, blood coagulation factor polymorphisms, and antiphospholipid antibodies were found in similar frequencies in all groups. Fourteen children with AIS and TIA (11.3%) and no children from the control group had three or more investigated risk factors. Conclusion The presence of multiple prothrombotic risk factors in children with cerebrovascular disorder suggests that a combination of risk factors rather than individual risk factors could contribute to cerebrovascular disorders in children.

Background: Laboratory evaluation through external quality assessment (EQA) schemes is often performed as ‘peer group’ comparison under the assumption that matrix effects influence the comparisons between results of different methods, for analytes where no commutable materials with reference value assignment are available. With EQA schemes that are not large but have many available instruments and reagent options for same analyte, homogenous peer groups must be created with adequate number of results to enable satisfactory statistical evaluation. We proposed a multivariate analysis of variance (MANOVA)-based test to evaluate heterogeneity of peer groups within the Croatian EQA biochemistry scheme and identify groups where further splitting might improve laboratory evaluation. Methods: EQA biochemistry results were divided according to instruments used per analyte and the MANOVA test was used to verify statistically significant differences between subgroups. The number of samples was determined by sample size calculation ensuring a power of 90% and allowing the false flagging rate to increase not more than 5%. When statistically significant differences between subgroups were found, clear improvement of laboratory evaluation was assessed before splitting groups. Results: After evaluating 29 peer groups, we found strong evidence for further splitting of six groups. Overall improvement of 6% reported results were observed, with the percentage being as high as 27.4% for one particular method. Conclusions: Defining maximal allowable differences between subgroups based on flagging rate change, followed by sample size planning and MANOVA, identifies heterogeneous peer groups where further splitting improves laboratory evaluation and enables continuous monitoring for peer group heterogeneity within EQA schemes.

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 ishoda, Introduction: 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.

Cerebrovascular disorders (CD) are an important cause of mortality and morbidity in children, and an emerging area for clinical research. There is increasing evidence that inherited or acquired prothrombotic disorders may be implicated in the etiology of CD in childhood. We have investigated the prevalence of genetic polymorphisms associated with thrombosis: factor V G1619A (FVL), factor II G20210A (PT), methylenetetrahidropholate reductase C677T (MTHFR), and human platelet antigens (HPA-1, -2, -3 and -5) in 151 children with CD and compared the data with those obtained for the control group (112 children from the same geographical region). Children with CD were classified into 5 groups according to diagnosis based on clinical symptoms, neurological examination, computed tomography and magnetic resonance imaging of the brain: children with arterial ischemic stroke (AIS ; n=36), perinatal arterial ischemic stroke (PAIS ; n=26), transient ischemic attack (TIA ; n=36), migraine (n=35) and intracranial hemorrhage (ICH ; n=18). Similar genotype distributions of all studied polymorphisms were found only between children with ICH and controls. Statistically significant differences between controls and other groups of children with CD were observed for at least one polymorphism: for FVL in children with AIS and TIA (p=0.048), for MTHFR in children with AIS (p=0.036), PAIS (p=0.034) and migraine (p=0.037), for HPA-2 and -5 (p=0.037) in children with TIA. Furthermore, higher frequencies of the HPA-3a allele in children with AIS were found to be statistically significant (p=0.027), as compared to the control group. Obtained results indicate that different polymorphisms are implicated in the etiology of CD in childhood.

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.