Olav Inge Klingenberg

• Fjeld, Bente; Jørgensen, Markus; Lillemoen, Paul Kjetel Soldal; Holstad, Kristin & Klingenberg, Olav Inge (2026). Mild Thalassemic Effect of Heterozygous Hb Sogn in a Large Cohort from Routine Hemoglobinopathy Investigation. Hemoglobin. ISSN 0363-0269. 50(1), p. 49–55. doi: 10.1080/03630269.2026.2613682. Full text in Research Archive
• Klingenberg, Olav Inge; Fjeld, Bente & Lundbye, Ingunn B.O. (2026). Hemoglobin fraction quantitation with Capillarys 2 FP HbA1c mode in patients with known sickle cell disease. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 86(4), p. 361–368. doi: 10.1080/00365513.2026.2671961. Full text in Research Archive Show summary

  Objective: To evaluate the feasibility of using Sebia Capillarys HbA1c mode for quantifying hemoglobin fractions in patients with known sickle cell disease to reduce turnaround time. Methods: Hemoglobin fractions were analyzed in 58 samples from patients with previously diagnosed sickle cell disease using the Sebia Capillarys 2 FP HbA1c mode (A1c mode) and Sebia Capillarys 2 FP, HEMOGLOBIN(E) mode (Hb mode). Method comparison was performed using Bland-Altman and linear regression analyses. Precision was determined by repeated analysis of internal control material and patient samples, while linearity was studied by serial dilution of a sample containing HbS with a sample without HbS. Results: The A1c mode showed good agreement with the Hb mode for quantification of HbA, HbS, and HbF fractions, with small biases of 1.44%, −1.66%, and 0.−02% respectively. Good linearity was demonstrated for HbS and HbA quantification (R2=0.9995). Conclusion: The A1c mode is appropriate for quick measurement of hemoglobin fractions in patients with known sickle cell disease, allowing for improved turnaround times in clinical settings. Due to occasional peak shifts and peak mislabeling by the software, a flow chart is included to guide proper A1c mode electropherogram interpretation.

• Sagedal, Solbjørg; Hovd, Markus; Åsberg, Anders; Mollnes, Tom Eirik; Klingenberg, Olav Inge & Heldal, Torbjørn Fossum [Show all 10 contributors for this article] (2025). Increased levels of ficolin-1 and of C3dg are independently associated with high risk of infection in patients with chronic kidney disease: a prospective cohort study. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1645347. Full text in Research Archive Show summary

  Background and hypothesis: Infection is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). The complement system provides crucial first-line defense against pathogens. Mannose-binding lectin (MBL), ficolins (1, 2 and 3), and collectin-LK 1 (CL-LK) are pattern recognition molecules (PRMs) of the lectin pathway (LP) that recognize microbial surfaces and activate complement. C3dg is a complement cleavage fragment indicating complement activation. The aim of the study was to investigate whether levels of PRMs and C3dg are associated with the risk of significant infections requiring hospitalization in patients with CKD. Methods: This prospective cohort study included 518 patients ≥18 years with CKD (eGFR<60 mL/min/1.73 m2), consecutively recruited between 2008-2022. About half (270/518) were in dialysis at inclusion. None of the patients were previously transplanted with any organ or stem cells. The primary endpoint was non-access-related infections requiring hospitalization. Patients were followed until kidney transplantation or death or until 31.12.2024. Plasma concentrations of the biomarkers were measured at inclusion. Time-to-event analyses using Cox regression were employed to assess associations with infection, adjusting for age, sex, diabetes, dialysis status, and dialysis vintage. Results: During a median (interquartile range [IQR]) time of follow-up of 1.24 (0.49-2.76) years, 182 patients (35%) were hospitalized due to non-access infection. Higher baseline levels of ficolin-1 and C3dg were independently associated with infection risk, HR 3.05, 95% CI 1.25-7.43, p=0.01 and HR 2.97, 95% CI 1.37-6.44, p=0.006, respectively, for each log10 unit increase. In multivariable models including all biomarkers, only C3dg remained independently associated with infection (HR 2.81, 95% CI 1.23-6.43, p=0.01). Conclusions: High levels of complement activation (C3dg) and ficolin-1 were independently associated with increased infection risk in patients with CKD. A dysregulated complement activation rather than PRM deficiency seems to be a key pathogenic mechanism resulting in increased infection risk in advanced CKD.

• Bekkenes, Maria Egeland; Jørgensen, Marte Morin; Jacobsen, Anne Flem; Fagerland, Morten Wang; Rakstad-Larsen, Helene & Aaberge, Lars [Show all 10 contributors for this article] (2025). Effects of Prophylactic Oxytocin or Carbetocin on Troponin Release and Postpartum Haemorrhage at Planned Caesarean Delivery: A Double-Blind Randomised Controlled Trial. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. 132(12), p. 1742–1752. doi: 10.1111/1471-0528.18312. Full text in Research Archive
• Bos, Steffan Daniel; Lauritzen, Marianne; Gislefoss, Randi Elin; Støer, Nathalie Charlotte; Klingenberg, Olav Inge & Langseth, Hilde (2025). Effect of Storage Time up to Nine Years at −25°C on 15 Selected Biochemical Serum Components. Biopreservation and Biobanking. ISSN 1947-5535. doi: 10.1177/19475535251371418. Full text in Research Archive
• Fjeld, Bente; Sudmann-Day, Åshild Amelie; Grimholt, Runa Marie; Larstorp, Anne Cecilie Kjeldsen; Urdal, Petter & Klingenberg, Olav Inge (2022). Additional value of red blood cell parameters in predicting uncommon α-thalassemia; experience from 10 years of α-globin gene sequencing and copy number variation analysis. International Journal of Laboratory Hematology (IJLH). ISSN 1751-5521. 45(2), p. 250–259. doi: 10.1111/ijlh.14010. Full text in Research Archive Show summary

  Introduction The diagnosis of rare forms of α-thalassemia requires laborious genetic analyses. Accurate sample selection for such evaluation is therefore essential. The main objectives of this study were to investigate the predictive power of red blood cell parameters to detect rare forms of α-thalassemia (substudy 1), and to explore the frequency of rare versus common forms of α-thalassemia in our sample population (substudy 2). Methods In substudy 1, we reviewed all blood samples selected for extended α-hemoglobinopathy evaluation at our laboratory during 2011–2020 (n = 1217), which included DNA sequencing and/or copy number variation analysis. We assessed α-thalassemia positive samples at different levels of mean corpuscular hemoglobin (MCH) alone and in combination with results for red blood cell count (RBC) or red cell distribution width (RDW). In substudy 2, we examined the distribution of α-thalassemia genotypes for all samples submitted to a first-tier hemoglobinopathy evaluation at our laboratory during 2014–2020 (n = 6495). Results In substudy 1, both RBC and RDW added predictive value in detecting rare forms of α-thalassemia in samples from adults and children. In adult samples with MCH ≤ 23 pg, the presence of erythrocytosis increased the detection rate from 27% to 74% as compared to non-erythrocytosis, while normal RDW increased the detection rate from 36% to 86% as compared to elevated RDW. In substudy 2, rare forms of α-thalassemia were detected in 12% of α-thalassemia positive samples. Conclusion Initial assessment of MCH, RBC, and RDW provided valuable predictive information about the presence of rare forms of α-thalassemia during hemoglobinopathy evaluation.

• Bekkenes, Maria Egeland; Fagerland, Morten; Solberg, Ole Geir; Aaberge, Lars; Klingenberg, Olav Inge & Norseth, Jon [Show all 7 contributors for this article] (2022). Exploring cardiac effects after oxytocin 2.5 IU or carbetocin 100 μg: A randomised controlled trial in women undergoing planned caesarean delivery. European Journal of Anaesthesiology. ISSN 0265-0215. 39(12), p. 928–938. doi: 10.1097/EJA.0000000000001763. Full text in Research Archive Show summary

  BACKGROUND Oxytocin can stimulate release of myocardial biomarkers troponin I and T, prolong QTc and induce ST-depression. OBJECTIVE To explore cardiac changes after either intravenous carbetocin or oxytocin. STUDY DESIGN Exploratory phase 4 randomised controlled trial. SETTING Obstetrics units of Oslo University Hospital, Norway between September 2015 and May 2018. PARTICIPANTS Forty healthy, singleton pregnant women aged 18 to 50 years at gestational age at least 36 weeks with a planned caesarean delivery. INTERVENTIONS Participants were randomised to receive either oxytocin 2.5 IU or carbetocin 100 μg immediately after delivery. MAIN OUTCOME MEASURES The primary endpoint was the assessment of troponin I within 48 h of study drug administration. Troponin I and T, and creatine kinase myocardial band assessments were measured before spinal anaesthesia (baseline), and again at 4, 10 and 24 h after delivery. QTc, ST-depression and relative increase in heart rate were recorded from start of study drug administration to 10 min after delivery. All adverse events were monitored. RESULTS Compared with the carbetocin group, higher troponin I levels were observed in the oxytocin group at 4 h and 10 h after delivery. For both treatment groups, an increase from baseline in troponin I and T was most pronounced at 10 h after delivery, and it had begun to decline by 24 h. QTc increased with time after administration of both study drugs, with a mean maximum increase of 10.4 ms observed at 9 min (P< 0.001). No statistical differences were observed in QTc (P = 0.13) or ST-depression (P = 0.11) between the treatment groups. CONCLUSIONS Oxytocin 2.5 IU and carbetocin 100 μg caused a similar increase in QTc. The trial was underpowered with regards to ST-depression and the release of myocardial biomarkers and these warrant further investigation. Data from this trial will inform a larger phase 4 trial to determine potential drug differences in troponin release. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02528136

• Larstorp, Anne Cecilie Kjeldsen; Salvador, Cathrin Lytomt; Svensvik, Bjørn Andreas; Klingenberg, Olav Inge & Distante, Sonia (2022). Neutrophil Gelatinase-Associated Lipocalin (NGAL) and cystatin C are early biomarkers of acute kidney injury associated with cardiac surgery. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 82(5), p. 410–418. doi: 10.1080/00365513.2022.2114105. Full text in Research Archive Show summary

  Acute kidney injury (AKI) is a serious complication in as much as half of the patients undergoing cardiac surgery, and early diagnosis and treatment are of the utmost importance. There is a need for robust biomarkers that can detect cardiac surgery-associated AKI (CSA-AKI) prior to rise in plasma creatinine, which typically occurs at least 48 h postoperatively. We compared pre- and 4, 12 and 48 h postoperative plasma (P) neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, urea and creatinine, and urine (U) NGAL, as markers of AKI, in 49 patients (67% men, median age 65 years) scheduled for elective cardiac surgery (e.g. coronary artery bypass graft and/or valve replacement surgery) with the use of extracorporeal circulation. Patients with preoperative sepsis, renal replacement therapy, or estimated glomerular filtration rate <30 mL/min/1.73m2 were excluded. P- and U-NGAL were measured using the Roche Modular P (Roche Diagnostics®) NGAL immunoassay. According to AKIN/KDIGO criteria, nine patients (18%) were diagnosed with CSA-AKI. Compared to patients without CSA-AKI, these patients had significantly higher P-NGAL and P-cystatin C values 4 h (p-values .002 and <.001) and 12 h (p-values <.001 and <.001) postoperatively. The same differences were not observed for U-NGAL. Patients with AKI also had significantly higher P-creatinine 4 and 12 h postoperatively (p-values .001 and <.001), however the rise in P-creatinine was just above the upper reference limit. In conclusion, plasma NGAL and cystatin C seem to detect CSA-AKI earlier than the more commonly used biomarkers creatinine and urea.

• Grimholt, Runa Marie; Fjeld, Bente & Klingenberg, Olav (2021). Hemoglobinopathy gone astray—three novel forms of α-thalassemia in Norwegian patients characterized by quantitative real-time PCR and DNA sequencing. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 81(8), p. 670–678. doi: 10.1080/00365513.2021.2004218. Full text in Research Archive Show summary

  α-thalassemia is one of the most common monogenic diseases worldwide and is caused by reduced or absent synthesis of α-globin chains, most commonly due to deletions of one or more of the α-globin genes. α-thalassemia occurs with high frequency in tropical and subtropical regions of the world and are very rarely found in the indigenous Scandinavian population. Here, we describe four rare forms of α-thalassemia out of which three are novel, found in together 20 patients of Norwegian origin. The study patients were diagnosed during routine hemoglobinopathy evaluation carried out at the Department of Medical Biochemistry, Oslo University Hospital, Norway. The patients were selected for their thalassemic phenotype, despite Norway as country of origin. All samples went through standard hemoglobinopathy evaluation. DNA sequencing and copy number variation (CNV) analysis using quantitative real-time polymerase chain reaction (qPCR) was applied to detect sequence variants and uncommon deletions in the α-globin gene cluster, respectively. Deletion breakpoints were characterized using gap-PCR and DNA sequencing. DNA sequencing revealed a single nucleotide deletion in exon 3 of the HBA2 gene (NM_000517.4(HBA2):c.345del) and a novel deletion of 20 nucleotides in exon 2 of the HBA2 gene (NM_000517.4(HBA2):c.142_161del). qPCR CNV analysis detected two novel large deletions in the α-globin gene cluster, –(NOR) deletion covering both α-globin genes and (αα)Aurora Borealis affecting the regulatory region, leaving the downstream α-globin genes intact. Even though inherited globin gene disorders are extremely rare in indigenous Scandinavians, the possibility of a carrier state should not be ignored.

• Georgina, Martin; Grimholt, Runa Marie; Le, Doan; Bechensteen, Anne Grete; Klingenberg, Olav Inge & Fjeld, Bente [Show all 11 contributors for this article] (2021). Hb Calgary (HBB: c.194G>T): A Highly Unstable Hemoglobin Variant with a β-Thalassemia Major Phenotype. Hemoglobin. ISSN 0363-0269. 45(4), p. 215–219. doi: 10.1080/03630269.2021.1956947. Full text in Research Archive Show summary

  We describe two unrelated patients, both heterozygous for an unstable hemoglobin (Hb) variant named Hb Calgary (HBB: c.194G>T) that causes severe hemolytic anemia and dyserythorpoietic, resulting in transfusion dependence and iron overload. The molecular pathogenesis is a missense variation on the β-globin gene, presumed to lead to an unstable Hb. The phenotype of Hb Calgary is particularly severe presenting as transfusion-dependent anemia in early infancy, precluding phenotypic diagnosis and highlighting the importance of early genetic testing in order to make an accurate diagnosis.

• Amundsen, Erik Koldberg; Binde, Christina; Christensen, Erik Egeland; Klingenberg, Olav Inge; Kvale, Dag & Holten, Aleksander Rygh (2021). Prognostic Value of Nucleated RBCs for Patients With Suspected Sepsis in the Emergency Department: A Single-Center Prospective Cohort Study. Critical Care Explorations. 3(7), p. 1–9. doi: 10.1097/CCE.0000000000000490. Full text in Research Archive Show summary

  Objectives: Increase of nucleated RBCs in peripheral blood has been shown to be predictive of mortality in ICU patients. The aim of this study was to explore the prognostic value of nucleated RBCs in the first blood sample taken at admission to the emergency department from patients with suspected sepsis. Design: Single-center prospective cohort study. Setting: Emergency department. Patients: One-thousand two-hundred thirty-one consecutive adult patients with suspected sepsis were included in a prospective quality register-based co-hort study. Inclusion criteria were as follows: patients received in rapid response team with blood cultures taken and immediate antibiotics given in the emergency department. Intervention: Not applicable. Measurement and main results: Nucleated RBCs, Sequential Organ Failure Assessment score, Quick Sequential Organ Failure Assessment, Charlson Comorbidity Index, and commonly used laboratory tests measured in the emergency department were compared with 30-day mortality. Nvaucleated RBC counts were divided into five groups, called “Nucleated RBC score,” according to nucleated RBC count levels and analyzed with logistic regression together with the Sequential Organ Failure Assessment score and Charlson Comorbidity Index. Of the 262 patients with nucleated RBCs equal to or higher than the detection limit (0.01 × 109/L), 26% died within 30 days, compared with 12% of the 969 patients with nucleated RBCs below the detection limit (p < 0.0001). Mortality was significantly higher for each increase in Nucleated RBC score, except from score 2 to 3, and was 62% in the highest group. In multivariate logistic regression, odds ratios for 30-day mortality were as follows: Nucleated RBC score: 1.33 (95% CI, 1.13–1.56), Sequential Organ Failure Assessment score: 1.32 (1.29–1.56), and Charlson Comorbidity Index: 1.17 (1.09–1.25). Conclusions: Most patients with suspected sepsis in emergency department had undetectable nucleated RBCs at admission to the emergency department. However, increased nucleated RBCs significantly predicted 30-day mortality. Nucleated RBCs may provide additional prognostic information to Sequential Organ Failure Assessment score and other laboratory tests.

• Holm, Are Martin; Andreassen, Siw Lillevik; Christensen, Vivi Lycke; Kongerud, Johny; Almås, Øystein & Auråen, Henrik [Show all 10 contributors for this article] (2020). Hypogammaglobulinemia and risk of exacerbation and mortality in patients with COPD. The International Journal of Chronic Obstructive Pulmonary Disease. ISSN 1176-9106. 15, p. 799–807. doi: 10.2147/COPD.S236656. Full text in Research Archive Show summary

  Introduction: Chronic obstructive pulmonary disease (COPD) may, in some patients, be characterized by recurring acute exacerbations. Often these exacerbations are associated with airway infections. As immunoglobulins (Ig) are important parts of the immune defence against airway infections, the aim of this study was to relate the levels of circulating immunoglobulins to clinical features in unselected patients with COPD included in a Norwegian multicenter study. Methods: Clinical and biological data, including circulating levels of immunoglobulins, were assessed in 262 prospectively included patients with COPD GOLD stage II–IV at five hospitals in south-eastern Norway. A revisit was done after one year, and survival was assessed after five years. Clinical features and survival of those with immunoglobulin levels below reference values were compared to those with normal levels. Results: In total, 11.5% of all COPD patients and 18.5% of those with GOLD stage IV had IgG concentrations below reference values. These patients were more likely to use inhaled or oral steroids, had lower BMI, and lower FEV1%. Moreover, they had significantly more COPD-related hospital admissions (2.8 vs 0.6), number of prednisolone courses (3.9 vs 1.2), and antibiotic treatments (3.7 vs 1.5) in the preceding year. Importantly, hypogammaglobulinemia was significantly associated with reduced survival in a log-rank analysis. In multivariate regression analysis, we found that the higher risk for acute exacerbations in these patients was independent of other risk factors and was associated with impaired survival. Conclusion: In conclusion, our study suggests that hypogammaglobulinemia may be involved in poor outcome in COPD and may thus be a feasible therapeutic target for interventional studies in COPD.

• Grimholt, Runa Marie; Fjeld, Bente; Selsås, Hilde; Schwettmann, Lutz & Klingenberg, Olav (2019). Hb Aalesund (HBA2: c.400_406delAGCACCG), an Unstable α-Globin Variant Found in a Norwegian Patient Causing Moderate Hemolytic Anemia and Falsely High Hb A1c Using Ion Exchange High Performance Liquid Chromatography. Hemoglobin. ISSN 0363-0269. 43(2), p. 122–125. doi: 10.1080/03630269.2019.1614048. Full text in Research Archive Show summary

  A new unstable hemoglobin (Hb) variant, named Hb Aalesund, was detected during Hb A1c measurement in a patient with a nearly compensated hemolytic anemia. Sequencing of the α-globin genes revealed a 7 bp deletion in exon 3 of the HBA2 gene (HBA2: c.400_406delAGCACCG) (NM_000517.4) causing a frameshift and a premature termination codon (PTC) two positions downstream. Apparently, the transcript bypassed nonsense-mediated decay (NMD), and a truncated protein was translated. The unstable Hb variant presumably underwent rapid denaturation, as heterozygosity of Hb Aalesund was associated with mild hemolytic anemia. In addition, the Hb variant interfered with Hb A1c measurement by cation exchange high performance liquid chromatography (HPLC), causing a falsely high Hb A1c result when using the Bio-Rad D10™ Hemoglobin Analyzer fast Hb A1c Program.

• Grimholt, Runa Marie; Vestli, Anne; Urdal, Petter; Bechensteen, Anne Grete; Fjeld, Bente & Dalhus, Bjørn [Show all 7 contributors for this article] (2018). Hb Oslo [β42(CD1)Phe→Ile; HBB: c.127T>A]: A novel unstable hemoglobin variant found in a Norwegian patient. Hemoglobin. ISSN 0363-0269. 42(2), p. 78–83. doi: 10.1080/03630269.2018.1468773. Full text in Research Archive Show summary

  Unstable hemoglobin (Hb) variants are the result of sequence variants in the globin genes causing precipitation of Hb molecules in red blood cells (RBCs). Intracellular inclusions derived from the unstable Hb reduce the life-span of the red cells and may cause hemolytic anemia. Here we describe a patient with a history of hemolytic anemia and low oxygen saturation. She was found to be carrier of a novel unstable Hb variant, Hb Oslo [β42(CD1)Phe→Ile (TTT>ATT), HBB: c.127T>A] located in the heme pocket of the β-globin chain. Three-dimensional modeling suggested that isoleucine at position 42 creates weaker interactions with distal histidine and with the heme itself, which may lead to altered stability and decreased oxygen affinity. At steady state, the patient was in good clinical condition with a Hb concentration of 8.0–9.0 g/dL. During virus infections, the Hb concentration fell and on six occasions during 4 years, the patient needed a blood transfusion.

• Grimholt, Runa Marie; Harteveld, Cornelis; Arkesteijn, Sandra G J; Fjeld, Bente & Klingenberg, Olav (2018). Characterization of Two Deep Intronic Variants on the β-Globin Gene with Inconsistent Interpretations of Clinical Significance. Hemoglobin. ISSN 0363-0269. 42(2), p. 126–128. doi: 10.1080/03630269.2018.1473255. Full text in Research Archive Show summary

  Sequence variants located in the introns of the β-globin gene may affect the mRNA processing and cause β-thalassemia (β-thal). Sequence variants that change one of the invariant dinucleotides at the exon-intron boundaries may have fatal consequences for normal mRNA splicing. Intronic variants located far from obvious regulatory sequences can be more difficult to evaluate. There is a potential for misinterpretation of such sequence variants. Hence, thorough evaluation of patient data together with critical use of databases and in silico prediction tools are important. Here, we describe two rare sequence variants in the second intron of the β-globin gene, HBB: c.316-70C>G and HBB: c.316-125A>G (NM_000518.4), both previously reported as variants causing β-thal, and later as benign sequence variants. Due to the limited number of published cases and inconsistent interpretations, the significance of these sequence variants has been unclear. We have identified these two sequence variants in multiple individuals, alone and in a variety of combinations with other δ- and β-globin defects, and we find no influence of the sequence variants on the phenotype.

• Sagedal, Solbjørg; Sandvik, Leiv; Klingenberg, Olav & Sandset, Per Morten (2017). β-Thromboglobulin may not reflect platelet activation during haemodialysis with the HeprAN membrane. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 77(8), p. 679–684. doi: 10.1080/00365513.2017.1397288. Full text in Research Archive
• Klingenberg, Olav; Furuset, Torill; Hestbråten, Camilla Røising; Hallberg, Marit Hansen; Steiro, Astrid & Orset, Iren Røstbakken [Show all 7 contributors for this article] (2017). HbA1c analysis by capillary electrophoresis?comparison with chromatography and an immunological method. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 77(6), p. 458–464. doi: 10.1080/00365513.2017.1338747. Full text in Research Archive Show summary

  Background: Haemoglobin A1c (HbA1c) has become an even more important analyte for clinical laboratories during recent years with the introduction of its diagnostic use for diabetes mellitus. Several different analytical principles can be used, each with their advantages and disadvantages. Aim: We wanted to compare Sebia Capillarys 2 Flex Piercing (Capillarys) with our routine HbA1c methods, which were an HPLC method (Tosoh G7) and an immunoassay (Tina-Quant on Roche Modular P) by analysing a large clinical material. Furthermore, we investigated sample stability. Methods: HbA1c analysis was performed in parallel by all three methods for more than 600 patient samples including common and some rare haemoglobin variants, as well as for several controls, some with set target values. Sample stability at room temperature and refrigerated was assessed for up to seven days. Results: Capillarys produced generally somewhat lower HbA1c values than both comparison methods, apparently due to positive bias for the comparison methods. Leaving out samples with haemoglobin variants, we found a mean bias (95% CI) for Capillarys compared to Tosoh G7 (without factorization) and Modular of −0.39 (−0.40 to −0.38) and −0.16 (−0.17 to −0.14) % HbA1c, respectively. HbA1c results were similar between instruments for samples from dialysis patients and for samples with heterozygous common haemoglobin variants, except that Tosoh G7 reported too low results in the presence of Hb E. For heterozygous Hb Raleigh, Capillarys and the immunoassay gave similar results. Conclusion: Capillarys is a convenient instrument for routine HbA1c analysis. © 2017 Taylor & Francis

• Berntsen, Natalie Lie; Klingenberg, Olav; Juran, Brian D.; Valle, Maria Benito De; Lindkvist, Björn & Lazaridis, Konstantinos N. [Show all 9 contributors for this article] (2015). Association between HLA haplotypes and increased serum levels of IgG4 in patients with primary sclerosing cholangitis. Gastroenterology. ISSN 0016-5085. 148(5), p. 924–927.e2. doi: 10.1053/j.gastro.2015.01.041. Full text in Research Archive
• Sudmann, Åshild Amelie; Piehler, Armin; Klingenberg, Olav & Urdal, Petter (2015). Six-day stability of erythrocyte and reticulocyte parameters in-vitro: A comparison of blood samples from healthy, iron-deficient, and thalassemic individuals. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 75(3), p. 247–253. doi: 10.3109/00365513.2014.1000370. Full text in Research Archive
• Grimholt, Runa Marie; Sudmann, Åshild Amelie; Piehler, Armin; Urdal, Petter & Klingenberg, Olav (2014). Hb Ullevaal [β78(EF2)Leu→Val; HBB: c.235C>G], a New Hemoglobin Variant Interfering with Hb A1c Measurement Using a Cation Exchange High Performance Liquid Chromatography Method. Hemoglobin. ISSN 0363-0269. 38(2), p. 130–132. doi: 10.3109/03630269.2013.858640. Full text in Research Archive
• Urdal, Petter; Amundsen, Erik Koldberg; Toska, Karin & Klingenberg, Olav (2014). Automated alarm to detect antigen excess in serum free immunoglobulin light chain kappa and lambda assays. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 74(7), p. 575–581. doi: 10.3109/00365513.2014.915426. Full text in Research Archive
• Grimholt, Runa Marie; Urdal, Petter; Klingenberg, Olav & Piehler, Armin (2014). Rapid and reliable detection of alpha-globin copy number variations by quantitative real-time PCR. BMC Hematology. doi: 10.1186/2052-1839-14-4. Full text in Research Archive Show summary

  Background Alpha-thalassemia is the most common human genetic disease worldwide. Copy number variations in the form of deletions of α-globin genes lead to α-thalassemia while duplications of α-globin genes can cause a severe phenotype in β-thalassemia carriers due to accentuation of globin chain imbalance. It is important to have simple and reliable methods to identify unknown or rare deletions and duplications in cases in which thalassemia is suspected but cannot be confirmed by multiplex gap-PCR. Here we describe a copy number variation assay to detect deletions and duplications in the α-globin gene cluster (HBA-CNV). Results Quantitative real-time PCR was performed using four TaqMan® assays which specifically amplify target sequences representing both the α-globin genes, the –α3.7 deletion and the HS-40 region. The copy number for each target was determined by the 2-ΔΔCq method. To validate our method, we compared the HBA-CNV method with traditional gap-PCR in 108 samples from patients referred to our laboratory for hemoglobinopathy evaluation. To determine the robustness of the four assays, we analyzed samples with and without deletions diluted to obtain different DNA concentrations. The HBA-CNV method identified the correct copy numbers in all 108 samples. All four assays showed the correct copy number within a wide range of DNA concentrations (3.2-100 ng/μL), showing that it is a robust and reliable method. By using the method in routine diagnostics of hemoglobinopathies we have also identified several deletions and duplications that are not detected with conventional gap-PCR. Conclusions HBA-CNV is able to detect all known large deletions and duplications affecting the α-globin genes, providing a flexible and simple workflow with rapid and reliable results.

• Bachmann-Harildstad, Gregor; Stenklev, Niels Chr.; Myrvoll, Elin Alise; Jablonski, Greg & Klingenberg, Olav (2011). Beta-Trace Protein as a Diagnostic Marker for Perilymphatic Fluid Fistula: A Prospective Controlled Pilot Study to Test a Sample Collection Technique. Otology & Neurotology. ISSN 1531-7129. 32(1), p. 7–10. doi: 10.1097/MAO.0b013e3181fc74d0. Full text in Research Archive
• Sagedal, Solbjørg; Witczak, Bartlomiej J; Osnes, Kåre; Hartmann, Anders; Os, Ingrid & Eikvar, Lars Kristian [Show all 8 contributors for this article] (2011). A Heparin-Coated Dialysis Filter (AN69 ST) Does Not Reduce Clotting during Hemodialysis when Compared to a Conventional Polysulfone Filter (F x 8). Blood Purification. ISSN 0253-5068. 32(3), p. 151–155. doi: 10.1159/000325227. Full text in Research Archive
• Henriksson, Carola Elisabeth; Hellum, Marit Synnøve; Haug, Kari Bente Foss; Aass, Hans Christian; Joø, Gun Brit & Øvstebø, Reidun [Show all 9 contributors for this article] (2011). Anticoagulant effects of an antidiabetic drug on monocytes in vitro. Thrombosis Research. ISSN 0049-3848. 128(5), p. E100–E106. doi: 10.1016/j.thromres.2011.07.007. Full text in Research Archive
• Jensen, Torstein; Kierulf, Peter; Sandset, Per Morten; Klingenberg, Olav; Joø, Gun Brit & Godal, Hans Chr [Show all 7 contributors for this article] (2007). Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from peripheral blood mononuclear cells. Thrombosis and Haemostasis. ISSN 0340-6245. 97(5), p. 822–829. doi: 10.1160/TH07-01-0039. Full text in Research Archive Show summary

  Fibrinogen in plasma includes three main fractions; high-molecular-weight (HMW)-fibrinogen, low-molecular-weight (LMW)-fibrinogen, and very-low-molecular-weight (LMW')-fibrinogen. During acute-phase conditions, plasma fibrinogen levels and the HMW-/LMW-fibrinogen ratio increase rapidly due to increased synthesis of HMW-fibrinogen. The consequences of elevated plasma fibrinogen levels and local deposition of fibrin in inflammatory tissues observed during acute-phase conditions are not clear. We wanted to investigate proinflammatory effects of fibrinogen and fibrin on peripheral blood mononuclear cells (PBMC) as reflected by altered mRNA expression and synthesis of the proinflammatory cytokines IL-6, TNF-alpha and IL-1beta, and to explore the significance of altered HMW-/LMW-fibrinogen ratio. PBMC were isolated from whole blood using Lymphoprep((R)). HMW-fibrinogen was separated from unfractioned fibrinogen by ammonium sulphate precipitation. Cells were incubated with unfractioned fibrinogen, HMW-fibrinogen or fibrin. Cytokine levels in cell lysates were determined using ELISA assays. Real-time PCR was used for mRNA quantification. We found that fibrinogen significantly increased mRNA levels, and induced synthesis of the proinflammatory cytokines IL-6 and TNF-alpha in PBMC in a dose dependent manner. Median (25, 75 percentile) IL-6 and TNF-alpha concentrations were 12 (5, 40) pg/ml and 16 (0,61) pg/ml, respectively. Median mRNA quantity was increased 12.3- (6.6, 48.6) and 1.7- (1.5, 6.5) fold for IL-6 and TNF-alpha compared to controls. The stimulatory effect of unfractioned fibrinogen was not significantly different from HMW-fibrinogen. Fibrinogen and fibrin were equally effective in promoting cytokine synthesis from PBMC. The results support that fibrin and fibrinogen may actively modulate the inflammatory process by inducing synthesis of proinflammatory cytokines from PBMC.

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• Vinnes, Erik Wilhelm; Lillemoen, Paul Kjetel Soldal; Klingenberg, Olav Inge; Fjeld, Bente; Iversen, Per Ole & Brodwall, Kristoffer [Show all 7 contributors for this article] (2023). Sigdcellesykdom – kliniske manifestasjoner og diagnostikk. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(3). doi: 10.4045/tidsskr.22.0353. Full text in Research Archive Show summary

  Sigdcellesykdom er en sykdomsgruppe med en rekke typiske akutte og kroniske manifestasjoner. Sigdcellesykdom har vært uvanlig i den nordeuropeiske befolkningen, men grunnet endret demografi er dette en sykdom som også norske klinikere bør være oppmerksomme på. I denne kliniske oversiktsartikkelen ønsker vi å gi en kortfattet introduksjon til sigdcellesykdom, med vekt på etiologi, patofysiologi, klinisk bilde og hvordan diagnosen stilles basert på laboratorieundersøkelser.

• Bekkenes, Maria Egeland; Fagerland, Morten; Solberg, Ole Geir; Aaberge, Lars; Klingenberg, Olav Inge & Norseth, Jon [Show all 7 contributors for this article] (2023). Reply to: Exploring cardiac effects after oxytocin 2.5 IU or carbetocin 100 μg - A randomised controlled trial in women undergoing planned caesarean delivery. European Journal of Anaesthesiology. ISSN 0265-0215. 40(6), p. 453–454. doi: 10.1097/EJA.0000000000001841. Full text in Research Archive
• Bekkenes, Maria Egeland; Jørgensen, Marte Morin; Jacobsen, Anne Flem; Fagerland, Morten; Rakstad-Larsen, Helene & Solberg, Ole Geir [Show all 10 contributors for this article] (2021). A study protocol for the cardiac effects of a single dose of either oxytocin 2.5 IU or carbetocin 100 µg after caesarean delivery: A prospective randomized controlled multi-centre trial in Norway. F1000 Research. 10:973, p. 1–17. doi: 10.12688/f1000research.73112.1. Full text in Research Archive Show summary

  Background: Both oxytocin and carbetocin are used to prevent uterine atony and post-partum haemorrhage after caesarean delivery in many countries, including Norway. Oxytocin causes dose-dependent ST-depression, troponin release, prolongation of QT-time and arrythmia, but little is known about myocardial effects of carbetocin. We have previously demonstrated comparable vasodilatory effects of oxytocin and carbetocin and are now undertaking a Phase 4 trial to investigate whether carbetocin causes similar changes to myocardial markers compared with oxytocin. Methods: Our randomized controlled trial will be conducted at three obstetrics units at Oslo University Hospital and Akershus University Hospital, Norway. Planned enrolment will be of 240 healthy, singleton pregnant women aged 18 to 50 years undergoing planned caesarean delivery. Based on pilot study data, each participant will receive a one-minute intravenous injection of either oxytocin 2.5 IU or carbetocin 100 µg during caesarean delivery. The prespecified primary outcome is the change from baseline in high-sensitive troponin I plasma concentrations at 6–10 hours after study drug administration. Secondary outcomes include uterine tone grade at 2.5 and five minutes after study drug administration, adverse events for up to 48 hours after study drug administration, estimated blood loss within eight hours of delivery, need for rescue treatment and direct/indirect costs. Enrolment and primary analysis are expected to be completed by the end of 2021. Discussion: Women undergoing caesarean delivery should be assessed for cardiovascular risk particularly as women with an obstetric history of pregnancy induced hypertension, gestational diabetes mellitus, preterm birth, placental abruption, and stillbirth are at increased risk of future cardiovascular disease. Any additional ischaemic myocardial risk from uterotonic agents will need to be balanced with the benefit of reducing the risk of postpartum haemorrhage. Any potential cardiotoxicity difference between oxytocin and carbetocin will help inform treatment decisions for pregnant women. Registration: Clinicaltrials.gov NCT03899961 (02/04/2019).

• Hildrum, Jonas Meek; Fjeld, Bente; Risahagen, Siv Mørkestøl; Bernatek, Barbara Jean & Klingenberg, Olav Inge (2021). Assessment of Hemoglobin A2 stability at room temperature during 24 or 25 days as measured by high pressure liquid chromatography and capillary electrophoresis. International Journal of Laboratory Hematology (IJLH). ISSN 1751-5521. 43(5), p. e266–e270. doi: 10.1111/ijlh.13555. Full text in Research Archive
• Fjeld, Bente; Sudmann-Day, Åshild Amelie; Grimholt, Runa Marie & Klingenberg, Olav (2019). Kan pasienten ha talassemi eller en hemoglobinvariant? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 139(17). doi: 10.4045/tidsskr.19.0121. Full text in Research Archive
• Grimholt, Runa Marie; Urdal, Petter; Klingenberg, Olav Inge & Piehler, Armin (2019). Correction to: Rapid and reliable detection of α-globin copy number variations by quantitative real-time PCR (BMC Hematology (2014) 14 (4) DOI: 10.1186/2052-1839-14-4). BMC Hematology. 19(1). doi: 10.1186/s12878-019-0144-5. Full text in Research Archive
• Klingenberg, Olav (2017). Hemoglobin amino acids by the numbers. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 77(1), p. 1–1. doi: 10.1080/00365513.2017.1267428. Full text in Research Archive
• Grimholt, Runa Marie; Fjeld, Bente; Piehler, Armin & Klingenberg, Olav (2017). Chasing the Northern Light - (--)NOR and (αα) Aurora Borealis; two novel deletions causing alpha-thalassemia found in Norwegian patients. Full text in Research Archive Show summary

  Introduction: Alpha-thalassemia is one of the most common monogenic diseases worldwide and is caused by reduced or absent synthesis of alpha-globin chains, most commonly due to deletions of one or more of the alpha-globin genes. Sequence variants that alter gene expression or deletions involving upstream regulatory elements are less frequent. Alpha-thalassemia occurs with high frequency in tropical and subtropical regions of the world. For people of Northern European origin, inherited hemoglobin disorders, such as alpha-thalassemia, are extremely rare. Here, we describe two novel deletions causing alpha-thalassemia found in patients of Norwegian origin. Materials and Methods: The study patients were diagnosed during routine hemoglobinopathy evaluation carried out at the Department of Medical Biochemistry, Oslo University Hospital, Norway. The patients were selected for their thalassemic phenotype, despite Norway as country of origin. All samples went through standard hemoglobinopathy evaluation. Quantitative real-time PCR copy number variation (CNV) analysis was applied to detect uncommon deletions in the alpha-globin gene cluster. Deletion breakpoints were characterized using gap-PCR and DNA sequencing. Results: Two novel deletions, (--)NOR and (αα)Aurora Borealis, were identified in altogether nine patients from two and one families, respectively, all of Norwegian origin presenting with microcytosis. The (--)NOR deletion was a result of homologous recombination deleting both alpha-globin genes. The (αα)Aurora Borealis deletion caused alpha-thalassemia by affecting the upstream regulatory element, HS-40, leaving the alpha-globin genes intact. Conclusions: Even though inherited hemoglobin disorders are extremely rare in indigenous Northern Europeans, the possibility of a carrier state should not be ignored.

• Grimholt, Runa Marie; Fjeld, Bente; Klingenberg, Olav & Piehler, Armin P (2017). Alfa-thalassemi på avveie – sjeldne former for alfa-thalassemi funnet hos norske pasienter. Full text in Research Archive Show summary

  Bakgrunn: Alfa-thalassemi er en av de vanligste monogene sykdommene i verden og skyldes i hovedsak delesjoner av alfa-globingenene, som gir nedsatt eller ingen produksjon av alfa-globinkjeder. Sekvensvarianter og delesjoner av det regulerende området oppstrøms for alfa-globingenene, HS-40, forekommer langt sjeldnere. Alfa-thalassemi er hyppig forkommende i områder der malaria er eller har vært vanlig. Med dagens globale migrasjonsmønster er hemoglobinopatier blitt stadig vanligere forekommende også i det norske helsevesen, men hos individer av norsk opprinnelse er det svært sjelden. Her beskriver vi tre former for alfa-thalassemi påvist hos etnisk norske pasienter. Material og metode: Pasientene ble diagnostisert gjennom rutinemessig hemoglobinopati-utredning ved Avdeling for medisinsk biokjemi, Oslo universitetssykehus, Ullevål. Standard hemoglobinopati-utredning, som innebærer analytisk hematologi, måling av ferritin og CRP, hemoglobintyping og gap-PCR som påviser de syv vanligste delesjonene som gir alfa-thalassemi, ble utført på alle pasientene. DNA sekvensering av alfa-globingenene ble brukt til å påvise sekvensvarianter og sanntids PCR ble brukt til å påvise sjeldne delesjoner i alfa-globin genclusteret. Resultater: To nye delesjoner, (αα)Aurora Borealis og (--)NOR ble påvist ved sanntids PCR hos til sammen ni pasienter fra henholdsvis en og to familier. (αα)Aurora Borealis fører til alfa-thalassemi ved at det regulatoriske området, HS-40, er deletert. (--)NOR er et resultat av homolog overkryssing og rammer begge alfa-globingenene. I tillegg ble det påvist en sjelden sekvensvariant i HBA2 genet som gir alfa-thalassemi hos åtte pasienter fra fem ulike familier. Alle pasientene var av norsk opprinnelse og hadde mikrocytose med eller uten anemi. Konklusjon: Selv om thalassemi er svært sjelden hos etnisk norske individer, skal muligheten for bærertilstand likevel ikke utelukkes.

• Hausken, Jon; Klingenberg, Olav; Mørkrid, Lars; Rollag, Halvor; Foss, Aksel & Midtvedt, Karsten (2012). Elevated Troponin I and NT-proBNP at the Time of Transplantation May Predict a Major Adverse Cardiac Event in the Early Postoperative Period After Renal Transplantation. Transplantation. ISSN 0041-1337. 94(2), p. E15–E16. doi: 10.1097/TP.0b013e31825b7633. Full text in Research Archive

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