The reliability of the HIL indices assessment on coagulation analysers

HIL indeksi rezultat su automatske detekcije hemolize, lipemije i ikterije na automatskim analizatorima. Danas su implementirani u sustav većine biokemijskih i koagulacijskih analizatora te su postali zlatni standard u evaluaciji kvalitete uzoraka. HIL indeksi su u sustav koagulacijskih analizatora implementirani tek unazad nekoliko godina te se u praksi rijetko koriste i ne postoji mnogo verifikacijskih studija, iako su nužni zbog postojećeg utjecaja hemolize, lipemije i ikterije na rezultate koagulacijskih pretraga. Cilj ovog rada je stoga bio provjeriti pouzdanost određivanja HIL indeksa na koagulacijskim analizatorima Sysmex CS-5100 i Attelica COAG 360 (Siemens Healthcare, Marburg, Njemačka). Pouzdanost određivanja HIL indeksa provjerena je usporedbom rezultata određivanja kvalitativnih HIL indeksa na analizatoru Sysmex CS-5100 i Attelica COAG 360 s rezultatima određivanja kvantitativnih HIL indeksa na biokemijskom analizatoru Cobas c501 (Roche Diagnostics, Mannheim, Njemačka) i s točnim koncentracijama slobodnog hemoglobina za H indeks, triglicerida za L indeks i ukupnog bilirubina za I indeks u analiziranim uzorcima. Zaključci ovog rada su da rezultati određivanja HIL indeksa na Sysmex-u CS-5100 i Attelici COAG 360 koreliraju s točnim koncentracijama mjerenih interferenata u uzorku i sa kvantitativnim HIL indeksima na Cobasu c501, da oba analizatora detektiraju prisutnost interferenata već kod vrlo niskih koncentracija te da su HIL indeksi na Sysmex-u CS-5100 i Attelici COAG 360 pouzdani za korištenje u rutinskom radu.HIL indices are the result of automatic detection of haemolysis, lipemia and icterus on automatic analysers. They are determined on most biochemistry and coagulation analysers and have become the golden standard in sample quality evaluation. Only recently HIL indices have been introduced on coagulation analysers, they are rarely used in routine work and there have not been many verification studies regardless of the fact that haemolysis, lipemia and icterus influence coagulation assays. Therefore, the main goal of this study was to verify the reliability of the HIL indices assessment on coagulation analysers Sysmex CS-5100 and Attelica COAG 360 (Siemens Healthcare, Marburg, Germany).The reliability of the HIL indices assessment was examined by comparison of qualitative HIL indices assessment results on coagulation analysers Sysmex CS-5100 and Attelica COAG 360 with the results of the quantitative HIL indices assessment on biochemistry analyser Cobas c501 (Roche Diagnostics, Mannheim, Germany) and with the exact concentrations of free haemoglobin for H index, of triglycerides for L index and of total bilirubin for I index in analysed samples. Main findings of this study are that the HIL indices assessment results on coagulation analysers Sysmex CS-5100 and Attelica COAG 360 are in correlation with measured interference concentrations and with quantitative HIL indices on Cobas c501; further, that both analysers detect very low concentrations of interferences and that the HIL indices on coagulation analysers Sysmex CS-5100 and Attelica COAG 360 are reliable for usage in everyday routine practice

The reliability of the HIL indices assessment on coagulation analysers

HIL indeksi rezultat su automatske detekcije hemolize, lipemije i ikterije na automatskim analizatorima. Danas su implementirani u sustav većine biokemijskih i koagulacijskih analizatora te su postali zlatni standard u evaluaciji kvalitete uzoraka. HIL indeksi su u sustav koagulacijskih analizatora implementirani tek unazad nekoliko godina te se u praksi rijetko koriste i ne postoji mnogo verifikacijskih studija, iako su nužni zbog postojećeg utjecaja hemolize, lipemije i ikterije na rezultate koagulacijskih pretraga. Cilj ovog rada je stoga bio provjeriti pouzdanost određivanja HIL indeksa na koagulacijskim analizatorima Sysmex CS-5100 i Attelica COAG 360 (Siemens Healthcare, Marburg, Njemačka). Pouzdanost određivanja HIL indeksa provjerena je usporedbom rezultata određivanja kvalitativnih HIL indeksa na analizatoru Sysmex CS-5100 i Attelica COAG 360 s rezultatima određivanja kvantitativnih HIL indeksa na biokemijskom analizatoru Cobas c501 (Roche Diagnostics, Mannheim, Njemačka) i s točnim koncentracijama slobodnog hemoglobina za H indeks, triglicerida za L indeks i ukupnog bilirubina za I indeks u analiziranim uzorcima. Zaključci ovog rada su da rezultati određivanja HIL indeksa na Sysmex-u CS-5100 i Attelici COAG 360 koreliraju s točnim koncentracijama mjerenih interferenata u uzorku i sa kvantitativnim HIL indeksima na Cobasu c501, da oba analizatora detektiraju prisutnost interferenata već kod vrlo niskih koncentracija te da su HIL indeksi na Sysmex-u CS-5100 i Attelici COAG 360 pouzdani za korištenje u rutinskom radu.HIL indices are the result of automatic detection of haemolysis, lipemia and icterus on automatic analysers. They are determined on most biochemistry and coagulation analysers and have become the golden standard in sample quality evaluation. Only recently HIL indices have been introduced on coagulation analysers, they are rarely used in routine work and there have not been many verification studies regardless of the fact that haemolysis, lipemia and icterus influence coagulation assays. Therefore, the main goal of this study was to verify the reliability of the HIL indices assessment on coagulation analysers Sysmex CS-5100 and Attelica COAG 360 (Siemens Healthcare, Marburg, Germany).The reliability of the HIL indices assessment was examined by comparison of qualitative HIL indices assessment results on coagulation analysers Sysmex CS-5100 and Attelica COAG 360 with the results of the quantitative HIL indices assessment on biochemistry analyser Cobas c501 (Roche Diagnostics, Mannheim, Germany) and with the exact concentrations of free haemoglobin for H index, of triglycerides for L index and of total bilirubin for I index in analysed samples. Main findings of this study are that the HIL indices assessment results on coagulation analysers Sysmex CS-5100 and Attelica COAG 360 are in correlation with measured interference concentrations and with quantitative HIL indices on Cobas c501; further, that both analysers detect very low concentrations of interferences and that the HIL indices on coagulation analysers Sysmex CS-5100 and Attelica COAG 360 are reliable for usage in everyday routine practice

Učestalost polimorfizma UGT2B7 c.-161C>T u hrvatskoj populaciji

Uridine diphosphate glucuronosyltransferase-2B7 (UGT2B7), enzyme responsible for the elimination of a number of xenobiotics through glucuronidation, is expressed in the gut, kidneys, intestines, and brain. However, data on the frequency of UGT2B7 polymorphisms in the Croatian population are limited. The aim of this study was to assess the frequency of the UGT2B7 c.-161C>T (rs7668258) polymorphism in the Croatian population and to compare it with reported frequencies in other populations. This polymorphism is in complete linkage disequilibrium with the UGT2B7 c.802C>T (UGT2B7*2, rs7439366) variant, which is important in clinical medicine. The study reports data of 501 participants from University Hospital Centre Zagreb. All data were collected and analysed retrospectively. Genotyping was performed by real-time polymerase chain reaction (PCR) using the TaqMan® Drug Metabolism Genotyping Assay for UGT2B7 c.-161C>T (rs7668258). We found that 120 (23.95 %) participants were carriers of the UGT2B7 c.-161CC genotype and 255 (50.9 %) were heterozygous carriers (UGT2B7 c.-161CT), while 126 (25.15 %) were homozygous carriers of the variant allele (UGT2B7 c.-161TT). The frequency of the variant UGT2B7 c.-161C>T allele in this study was T=0.506. The frequency of the UGT2B7 c.-161C>T allelic variants and genotypes in the Croatian population is similar to other European populations.Najčešći metabolički put konjugacije u ljudi je glukuronidacija zbog svojih različitih i brojnih potencijalnih supstrata. Enzim UGT2B7, kodiran genom UGT2B7, eksprimiran je u bubrezima i crijevima, a aktivan je i u mozgu. Podatci o učestalosti polimorfizma UGT2B7 u hrvatskoj populaciji vrlo su ograničeni. Cilj ovog istraživanja bio je procijeniti učestalost polimorfizma UGT2B7 c.-161C>T (rs7668258), povezanoga s promijenjenom aktivnošću enzima, u hrvatskoj populaciji te ga usporediti s učestalošću u drugim etničkim skupinama. Ovaj je polimorfizam u potpunoj neravnoteži vezanosti s potvrđenom važnom varijantom UGT2B7 c.802C>T (UGT2B7*2, rs7439366) u kliničkoj medicini. Svi ispitanici redovito su upućivani na farmakogenetičko ispitivanje u KBC Zagreb, a svi podatci prikupljani su nekoliko godina i retrospektivno analizirani. Genotipizacija je provedena lančanom reakcijom polimeraze u stvarnom vremenu (PCR) korištenjem TaqMan® testa genotipizacije metabolizma lijekova za UGT2B7 c.-161C>T (rs7668258). Ukupno je bio uključen 501 pacijent: njih 120 (23,95 %) bili su nositelji genotipa UGT2B7 c.-161CC, njih 255 (50,9 %) bili su heterozigotni nositelji (UGT2B7 c.-161CT), a 126 (25,15 %) ispitanika homozigotni nositelji UG2TB7 c.-161TT. Učestalost alela varijante UGT2B7 c.-161C>T u ovom istraživanju bila je T=0,506. Kao zaključak, učestalost alelnih varijanti i genotipova UGT2B7 c.-161C>T u hrvatskoj populaciji u skladu je s ostalim europskim populacijama

Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series

Non-vitamin K antagonist oral anticoagulants’ interindividual trough concentration variability affects efficacy and safety, especially in bleeding events. Rivaroxaban is metabolised via CYP3A4/5-, CYP2J2-, and CYP-independent mechanisms and is a substrate of two transporter proteins: ABCB1 (MDR1, P-glycoprotein) and ABCG2 (BCRP; breast-cancer-resistance protein). The polymorphisms of these genes may possibly affect the pharmacokinetics of rivaroxaban and, consequently, its safety profile. Rivaroxaban variability may be associated with age, liver and kidney function, concomitant illness and therapy, and pharmacogenetic predisposition. This case series is the first, to our knowledge, that presents multiple risk factors for rivaroxaban-related bleeding (RRB) including age, renal function, concomitant diseases, concomitant treatment, and pharmacogenetic data. It presents patients with RRB, along with their complete clinical and pharmacogenetic data, as well as an evaluation of possible risk factors for RRB. Thirteen patients were carriers of ABCB1, ABCG2, CYP2J2, and/or CYP3A4/5 gene polymorphisms. Possible drug–drug interactions with increased bleeding risk were identified in nine patients. Six patients had eGFR 2. Our data suggest a possible role of multiple factors and their interactions in predicting RRB; however, they also indicate the need for further comprehensive multidisciplinary research to enable safer use of this product based on a personalised approach

Risk Factors for Rivaroxaban-Related Bleeding Events—Possible Role of Pharmacogenetics: Case Series

Non-vitamin K antagonist oral anticoagulants’ interindividual trough concentration variability affects efficacy and safety, especially in bleeding events. Rivaroxaban is metabolised via CYP3A4/5-, CYP2J2-, and CYP-independent mechanisms and is a substrate of two transporter proteins: ABCB1 (MDR1, P‑glycoprotein) and ABCG2 (BCRP; breast-cancer-resistance protein). The polymorphisms of these genes may possibly affect the pharmacokinetics of rivaroxaban and, consequently, its safety profile. Rivaroxaban variability may be associated with age, liver and kidney function, concomitant illness and therapy, and pharmacogenetic predisposition. This case series is the first, to our knowledge, that presents multiple risk factors for rivaroxaban-related bleeding (RRB) including age, renal function, concomitant diseases, concomitant treatment, and pharmacogenetic data. It presents patients with RRB, along with their complete clinical and pharmacogenetic data, as well as an evaluation of possible risk factors for RRB. Thirteen patients were carriers of ABCB1, ABCG2, CYP2J2, and/or CYP3A4/5 gene polymorphisms. Possible drug–drug interactions with increased bleeding risk were identified in nine patients. Six patients had eGFR <60 mL/min/1.73 m2. Our data suggest a possible role of multiple factors and their interactions in predicting RRB; however, they also indicate the need for further comprehensive multidisciplinary research to enable safer use of this product based on a personalised approach