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Article ; Online: Comparison Evaluation of Automated Nucleated Red Blood Cell Enumeration by Sysmex XN 1000 in Comparison With Microscopic Reference in Children Under 1 Year.

Brunner-Ziegler, Sophie / Jilma, Bernd / Grimm, Gabriele / Jilma-Stohlawetz, Petra

2024 , Page(s) e25037

Abstract: Background: In newborns, elevated nucleated red blood cell (NRBC) levels can be associated with enhanced erythropoietic stress and might be predictive for adverse outcome. Also, the presence of NRBC in peripheral blood might lead to erroneous ... ...

Abstract	Background: In newborns, elevated nucleated red blood cell (NRBC) levels can be associated with enhanced erythropoietic stress and might be predictive for adverse outcome. Also, the presence of NRBC in peripheral blood might lead to erroneous enumeration results of white blood cells in automated hematology analyzers. We aimed to assess the comparability of the Sysmex XN 1000 to manual slide reviews and correlation of NRBC with inflammation markers. Methods: Specimens of 3397 children under 1 year were compared by automated and microscopic NRBC enumeration. Additionally, potential correlations between NRBC and age and inflammation markers were examined. Results: Overall, there was good correlation (r = 0.97) between automated (range: 0%-3883%) and microscopic enumeration (range: 0%-3694%) of NRBC with high comparability up to a NRBC value of 200% and an increase in the variation between the two methods with increasing NRBC numbers. When 94 samples with ≤ 200% NRBC and ≥ 30% divergence between methods were separately reanalyzed with respect to overlapping cell populations in their scattergrams, Sysmex would have generated unrecognized incorrect automated results in 47 samples, corresponding to 1.4% of total study samples. NRBC counts were negatively correlated to age, but not to inflammation markers. Conclusion: Sysmex XN 1000 is highly precise in the enumeration of NRBC in children under 1 year up to counts of 200% and might replace time-intense manual counting in routine diagnostics. In the setting of neonatal and intensive care diagnostics, microscopic control and supervision of scattergrams are highly recommended for any automated NRBC enumeration processes.
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	645095-7
ISSN	1098-2825 ; 0887-8013
ISSN (online)	1098-2825
ISSN	0887-8013
DOI	10.1002/jcla.25037
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Article ; Online: Interference in specialized coagulation assays affecting the protein C pathway: Effects of marked haemolysis, hyperbilirubinaemia and lipaemia on chromogenic and clotting tests on two coagulation platforms.

Jilma-Stohlawetz, Petra / Lysy, Katharina / Belik, Sabine / Jilma, Bernd / Quehenberger, Peter

International journal of laboratory hematology

2019 Volume 41, Issue 3, Page(s) 404–411

Abstract: Background: Haemolysis, lipaemia and hyperbilirubinaemia represent important challenges in the coagulation laboratory. Test results are influenced not only by the degree of the interfering substance but also by the detection system.: Methods: We ... ...

Abstract	Background: Haemolysis, lipaemia and hyperbilirubinaemia represent important challenges in the coagulation laboratory. Test results are influenced not only by the degree of the interfering substance but also by the detection system. Methods: We investigated the interference of free haemoglobin, triglycerides and bilirubin on a "modified activated protein C (APC) resistance test," protein C activity and protein S (antigen and activity) with two coagulation analysers, the STA-R Evolution and the ACL TOP. Results: Haemolysis interfered with all assays on the STA-R Evolution resulting in higher levels of protein C activity and lower levels of protein S and a decreased APC ratio compared with baseline levels. On the ACL TOP, haemolysis only diminished protein S antigen levels and the APC ratio. Lipaemia increased protein C activity and protein S activity levels on the STA-R Evolution, whereas APC-R decreased on the ACL TOP and protein S antigen could not be measured in any lipaemic samples. Hyperbilirubinaemia caused an increase in protein C activity and in protein S antigen and a decrease in APC-R on the STA-R Evolution, whereas a decline of protein C activity, of protein S antigen and of the APC-R could be observed in icteric samples on the ACL TOP. Conclusions: Our data show that the degree of interference associated with haemolysis, lipaemia and hyperbilirubinaemia is different in several assays. Some assay limitations were not reproduced, and limitations stated in kit inserts cannot be assumed to apply to all analysers.
MeSH term(s)	Activated Protein C Resistance ; Bilirubin/blood ; Blood Coagulation ; Blood Coagulation Tests/methods ; Blood Coagulation Tests/standards ; Hemoglobins ; Hemolysis ; Humans ; Hyperbilirubinemia/blood ; Hyperlipidemias/blood ; Protein C/metabolism ; Protein S ; Reproducibility of Results ; Signal Transduction
Chemical Substances	Hemoglobins ; Protein C ; Protein S ; Bilirubin (RFM9X3LJ49)
Language	English
Publishing date	2019-03-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2268590-X
ISSN	1751-553X ; 1751-5521 ; 0141-9854
ISSN (online)	1751-553X
ISSN	1751-5521 ; 0141-9854
DOI	10.1111/ijlh.13000
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Zs.A 1499: Show issues

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Article ; Online: The VWF binding aptamer rondoraptivon pegol increases platelet counts and VWF/FVIII in type 2B von Willebrand disease.

Ay, Cihan / Pabinger, Ingrid / Kovacevic, Katarina D / Gelbenegger, Georg / Schörgenhofer, Christian / Quehenberger, Peter / Jilma-Stohlawetz, Petra / Sunder-Plassman, Raute / Gilbert, James C / Zhu, Shuhao / Jilma, Bernd / Derhaschnig, Ulla

Blood advances

2022 Volume 6, Issue 18, Page(s) 5467–5476

Abstract: Type 2B von Willebrand disease (VWD) is characterized by an increased binding affinity of von Willebrand factor (VWF) to platelet glycoprotein Ib. This can lead to clearance of high-molecular-weight (HMW) multimers and thrombocytopenia with a resulting ... ...

Abstract	Type 2B von Willebrand disease (VWD) is characterized by an increased binding affinity of von Willebrand factor (VWF) to platelet glycoprotein Ib. This can lead to clearance of high-molecular-weight (HMW) multimers and thrombocytopenia with a resulting moderate-severe bleeding phenotype. Rondoraptivon pegol (BT200) is a pegylated aptamer binding to the A1 domain of VWF with a novel mechanism of action: it enhances VWF/factor VIII (FVIII) levels by decreasing their clearance. To study the potential benefit of rondoraptivon pegol in patients with type 2B VWD, we conducted a prospective phase 2 trial. Patients with type 2B VWD received 3 mg rondoraptivon pegol subcutaneously on study days 1, 4, and 7, followed by 6 to 9 mg every week until day 28. Five patients (male:female ratio = 3:2) were included. Rondoraptivon pegol rapidly tripled platelet counts from a median of 60 to 179 × 10E9/L (P < .001). Circulating VWF antigen increased from a median of 64% to 143%, which doubled FVIII activity levels from 67% to 134%. In all thrombocytopenic patients, plasma levels of VWF:GPIbM normalized, VWF ristocetin cofactor and VWF collagen-binding activity increased, and HMW multimers appeared. These pronounced improvements reversed during washout of the drug, thus demonstrating causality. The A1 domain binding aptamer directly corrects the underlying defect of type 2B VWD, thus providing a novel potential option for prophylaxis and treatment of patients with this VWD type. These data provide the basis for a phase 2b/3 trial in such patients. This trial was registered at www.clinicaltrials.gov as #NCT04677803.
MeSH term(s)	Collagen ; Factor VIII/therapeutic use ; Female ; Hemostatics/therapeutic use ; Humans ; Male ; Platelet Count ; Platelet Glycoprotein GPIb-IX Complex/metabolism ; Polyethylene Glycols/therapeutic use ; Prospective Studies ; von Willebrand Disease, Type 2 ; von Willebrand Diseases/drug therapy ; von Willebrand Factor/metabolism
Chemical Substances	Hemostatics ; Platelet Glycoprotein GPIb-IX Complex ; von Willebrand Factor ; Polyethylene Glycols (3WJQ0SDW1A) ; Factor VIII (9001-27-8) ; Collagen (9007-34-5)
Language	English
Publishing date	2022-07-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022007805
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Zs.A 7153: Show issues

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Article ; Online: The von Willebrand factor A-1 domain binding aptamer BT200 elevates plasma levels of von Willebrand factor and factor VIII: a first-in-human trial.

Kovacevic, Katarina D / Grafeneder, Jürgen / Schörgenhofer, Christian / Gelbenegger, Georg / Gager, Gloria / Firbas, Christa / Quehenberger, Peter / Jilma-Stohlawetz, Petra / Bileck, Andrea / Zhu, Shuhao / Gilbert, James C / Beliveau, Martin / Jilma, Bernd / Derhaschnig, Ulla

Haematologica

2022 Volume 107, Issue 9, Page(s) 2121–2132

Abstract: Von Willebrand factor (VWF) and factor VIII (FVIII) circulate in a noncovalent complex in blood and promote primary hemostasis and clotting, respectively. A new VWF A1-domain binding aptamer, BT200, demonstrated good subcutaneous bioavailability and a ... ...

Abstract	Von Willebrand factor (VWF) and factor VIII (FVIII) circulate in a noncovalent complex in blood and promote primary hemostasis and clotting, respectively. A new VWF A1-domain binding aptamer, BT200, demonstrated good subcutaneous bioavailability and a long half-life in non-human primates. This first-in-human, randomized, placebo-controlled, doubleblind trial tested the hypothesis that BT200 is well tolerated and has favorable pharmacokinetic and pharmacodynamic effects in 112 volunteers. Participants received one of the following: a single ascending dose of BT200 (0.18-48 mg) subcutaneously, an intravenous dose, BT200 with concomitant desmopressin or multiple doses. Pharmacokinetics were characterized, and the pharmacodynamic effects were measured by VWF levels, FVIII clotting activity, ristocetin-induced aggregation, platelet function under high shear rates, and thrombin generation. The mean half-lives ranged from 7-12 days and subcutaneous bioavailability increased dose-dependently exceeding 55% for doses of 6-48 mg. By blocking free A1 domains, BT200 dose-dependently decreased ristocetin-induced aggregation, and prolonged collagen-adenosine diphosphate and shear-induced platelet plug formation times. However, BT200 also increased VWF antigen and FVIII levels 4-fold (P<0.001), without increasing VWF propeptide levels, indicating decreased VWF/FVIII clearance. This, in turn, increased thrombin generation and accelerated clotting. Desmopressin-induced VWF/FVIII release had additive effects on a background of BT200. Tolerability and safety were generally good, but exaggerated pharmacology was seen at saturating doses. This trial identified a novel mechanism of action for BT200: BT200 dose-dependently increases VWF/FVIII by prolonging half-life at doses well below those which inhibit VWF-mediated platelet function. This novel property can be exploited therapeutically to enhance hemostasis in congenital bleeding disorders.
MeSH term(s)	Deamino Arginine Vasopressin ; Factor VIII ; Humans ; Ristocetin/pharmacology ; Thrombin ; von Willebrand Diseases ; von Willebrand Factor/metabolism
Chemical Substances	von Willebrand Factor ; Ristocetin (1404-55-3) ; Factor VIII (9001-27-8) ; Thrombin (EC 3.4.21.5) ; Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2022-09-01
Publishing country	Italy
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2021.279948
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Article ; Online: Limitations of a calibrated, quantitative APC-R assay under routine conditions.

Jilma-Stohlawetz, Petra / Lysy, Katharina / Sunder-Plassmann, Raute / Belik, Sabine / Jilma, Bernd / Pabinger, Ingrid / Quehenberger, Peter

International journal of laboratory hematology

2020 Volume 43, Issue 2, Page(s) 318–323

Abstract: Introduction: The aim of this study was to evaluate the Hemoclot Quanti. V-L assay in various clinical conditions.: Methods: We compared the Hemoclot Quanti.V-L assay with DNA testing and with the Pefakit assay in 60 normal (no mutation) vs carriers ... ...

Abstract	Introduction: The aim of this study was to evaluate the Hemoclot Quanti. V-L assay in various clinical conditions. Methods: We compared the Hemoclot Quanti.V-L assay with DNA testing and with the Pefakit assay in 60 normal (no mutation) vs carriers of the factor V (FV) Leiden mutation (56 heterozygous and three homozygous). We further investigated the interference of lupus anticoagulant on test results in normal and heterozygous individuals and of direct oral anticoagulants (DOACs) at trough and peak levels. Additionally, DOAC-Remove was tested in samples containing DOACs at peak levels. We further evaluated the influence of FV deficiency on this quantitative assay. Results: There was a 100% agreement between the Quant. V-L assay and DNA testing in 60 normal individuals. However, 1.85% of heterozygous and 33% of homozygous samples were falsely classified with the quantitative assay, and no misclassification was observed with the Pefakit assay. Lupus anticoagulant did not influence the test results of the quantitative assay. DOACs also interfered with test results in heterozygous patients, but this effect was prevented with the DOAC-Remove procedure. Even mild FV deficiency affected the test results of the quantitative assay in heterozygous patients leading either to misclassification or the need for subsequent PCR testing. Conclusion: The quantitative FV-L assay has several limitations, especially FV deficiency and the presence of DOACs have to be ruled out before running this quantitative assay.
MeSH term(s)	Anticoagulants/administration & dosage ; Anticoagulants/adverse effects ; Blood Coagulation Tests/methods ; Blood Coagulation Tests/standards ; Factor V/genetics ; Factor V Deficiency/blood ; Factor V Deficiency/diagnosis ; Factor V Deficiency/genetics ; Genetic Testing/methods ; Genetic Testing/standards ; Heterozygote ; Homozygote ; Humans ; Lupus Coagulation Inhibitor/adverse effects ; Mutation ; Reproducibility of Results ; Sensitivity and Specificity
Chemical Substances	Anticoagulants ; Lupus Coagulation Inhibitor ; Factor V (9001-24-5)
Language	English
Publishing date	2020-11-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2268590-X
ISSN	1751-553X ; 1751-5521 ; 0141-9854
ISSN (online)	1751-553X
ISSN	1751-5521 ; 0141-9854
DOI	10.1111/ijlh.13378
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Zs.A 1499: Show issues

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Article ; Online: The von Willebrand factor-binding aptamer rondaptivon pegol as a treatment for severe and nonsevere hemophilia A.

Ay, Cihan / Kovacevic, Katarina D / Kraemmer, Daniel / Schoergenhofer, Christian / Gelbenegger, Georg / Firbas, Christa / Quehenberger, Peter / Jilma-Stohlawetz, Petra / Gilbert, James C / Zhu, Shuhao / Beliveau, Martin / Koenig, Franz / Iorio, Alfonso / Jilma, Bernd / Derhaschnig, Ulla / Pabinger, Ingrid

Blood

2022 Volume 141, Issue 10, Page(s) 1147–1158

Abstract: Factor VIII (FVIII) circulates in a noncovalent complex with von Willebrand Factor (VWF), the latter determining FVIII half-life. The VWF-binding aptamer rondaptivon pegol (BT200) increases plasma levels of VWF/FVIII in healthy volunteers. This trial ... ...

Abstract	Factor VIII (FVIII) circulates in a noncovalent complex with von Willebrand Factor (VWF), the latter determining FVIII half-life. The VWF-binding aptamer rondaptivon pegol (BT200) increases plasma levels of VWF/FVIII in healthy volunteers. This trial assessed its safety, pharmacokinetics, and pharmacodynamics in hemophilia A. Nineteen adult patients (ages 20-62 years, 4 women) with hemophilia A (8 mild, 2 moderate, and 9 severe) received subcutaneous injections of rondaptivon pegol. After an initial fixed dose of 3 mg on days 0 and 4, patients received weekly doses of 2 to 9 mg until day 28. Severe hemophilia A patients underwent sparse-sampling population pharmacokinetics individual profiling after the final dose of rondaptivon pegol. Adverse events, pharmacokinetics, and pharmacodynamics were assessed. FVIII activity and VWF levels were measured. All patients tolerated rondaptivon pegol well. The geometric mean half-life of rondaptivon pegol was 5.4 days and rondaptivon pegol significantly increased VWF levels. In severe hemophilia A, 6 doses of rondaptivon pegol increased the half-lives of 5 different FVIII products from a median of 10.4 hours to 31.1 hours (range, 20.8-56.0 hours). Median FVIII increased from 22% to 48% in mild hemophilia A and from 3% to 7.5% in moderate hemophilia A. Rondaptivon pegol is a first-in-class prohemostatic molecule that extended the half-life of substituted FVIII approximately 3-fold and increased endogenous FVIII levels approximately 2-fold in hemophilia patients. This trial was registered at www.clinicaltrials.gov as #NCT04677803.
MeSH term(s)	Adult ; Humans ; Female ; Young Adult ; Middle Aged ; von Willebrand Factor/therapeutic use ; Hemophilia A/drug therapy ; Factor VIII ; Hemostatics/therapeutic use ; Half-Life
Chemical Substances	von Willebrand Factor ; Factor VIII (9001-27-8) ; Hemostatics
Language	English
Publishing date	2022-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022016571
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

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Article ; Online: The use of frozen plasma samples in thromboelastometry.

Schoergenhofer, Christian / Buchtele, Nina / Schwameis, Michael / Bartko, Johann / Jilma, Bernd / Jilma-Stohlawetz, Petra

Clinical and experimental medicine

2017 Volume 17, Issue 4, Page(s) 489–497

Abstract: Thromboelastometry is increasingly used in the clinical and scientific setting. The use of frozen plasma samples may be useful in overcoming certain limitations such as local and timely availability. Whole blood (WB) samples of 20 healthy volunteers were ...

Abstract	Thromboelastometry is increasingly used in the clinical and scientific setting. The use of frozen plasma samples may be useful in overcoming certain limitations such as local and timely availability. Whole blood (WB) samples of 20 healthy volunteers were obtained, and plasma was generated. NATEM (n = 20), EXTEM (n = 20) and INTEM (n = 8) analyses were performed in WB, fresh plasma and frozen and thawed plasma. Dabigatran (500, 1000 ng/ml), rivaroxaban (100, 200 ng/ml) or alteplase (333 ng/ml) were added ex vivo to WB, and thromboelastometry was performed in WB and in frozen and thawed plasma samples. Clot formation time, mean clot firmness and the area under the curve were significantly altered in plasma compared to WB. In INTEM and EXTEM analysis, clotting time (CT) was comparable between WB (100%) and fresh (INTEM 114% and EXTEM 93%, ratio of the means) and frozen plasma samples (85 and 99%), whereas in NATEM analysis, the CT increased in fresh (193%) and frozen plasma samples (130%). Dabigatran dose-dependently increased the CT approximately 5- and 9-fold in WB and even more pronounced 10- and 26-fold in plasma. Accordingly, rivaroxaban dose-dependently increased the CT 2- and 2.7-fold in WB, and 3.5- and 4-fold in plasma samples. Hyperfibrinolysis was achieved by addition of alteplase in all WB samples and was reproducible in plasma samples. In conclusion, thromboelastometry, especially INTEM and EXTEM analyses, is possible using frozen and stored plasma samples with comparable results to the corresponding whole blood samples.
Language	English
Publishing date	2017-11
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-017-0454-5
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Zs.A 5481: Show issues

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Article ; Online: Effect of preanalytical time-delay on platelet function as measured by multiplate, PFA-100 and VerifyNow.

Jilma-Stohlawetz, Petra / Ratzinger, Franz / Schörgenhofer, Christian / Jilma, Bernd / Quehenberger, Peter

Scandinavian journal of clinical and laboratory investigation

2016 Volume 76, Issue 3, Page(s) 249–255

Abstract: Background and aims: Platelet function testing may help to identify poor responders to antiplatelet drugs. The aim of this study was to compare three commonly used platelet function tests with special focus on the pre-analytical influence of time-delay ... ...

Abstract	Background and aims: Platelet function testing may help to identify poor responders to antiplatelet drugs. The aim of this study was to compare three commonly used platelet function tests with special focus on the pre-analytical influence of time-delay on the tested parameters. Methods: We assessed ADP-induced platelet function by the Multiplate, Platelet Function Analyzer-100 (PFA-100) and VerifyNow in nine healthy volunteers and 36 patients receiving clopidogrel or prasugrel 1 and 3 hours after sampling. Results: The PFA-100 demonstrated non-closure time in 23 patients. A more graded response could be detected with the two other devices. Aggregation in whole blood (Multiplate) decreased after 3 hours compared to 1 hour in all subjects (p < 0.05). Furthermore, aggregation levels obtained by the VerifyNow showed a decrease in patients taking P2Y12 inhibitors after 3 hours (p < 0.05), except in three patients, in whom an increase was observed. Conclusion: Responses to ADP are time-dependent after blood sampling for the Multiplate in all subjects and for the VerifyNow in patients on antiplatelet drugs. For both devices, platelet aggregation was reduced 3 hours after sampling which may affect data interpretation and clinical consequences.
MeSH term(s)	Aged ; Blood Platelets/drug effects ; Blood Platelets/physiology ; Case-Control Studies ; Humans ; Middle Aged ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; Platelet Function Tests/methods ; Prasugrel Hydrochloride/pharmacology ; Prasugrel Hydrochloride/therapeutic use ; Ticlopidine/analogs & derivatives ; Ticlopidine/pharmacology ; Ticlopidine/therapeutic use ; Time Factors
Chemical Substances	Platelet Aggregation Inhibitors ; clopidogrel (A74586SNO7) ; Prasugrel Hydrochloride (G89JQ59I13) ; Ticlopidine (OM90ZUW7M1)
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article
ZDB-ID	3150-1
ISSN	1502-7686 ; 0036-5513
ISSN (online)	1502-7686
ISSN	0036-5513
DOI	10.3109/00365513.2016.1143115
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Article ; Online: Regulation of histamine and diamine oxidase in patients undergoing orthotopic liver transplantation.

Schiefer, Judith / Baron-Stefaniak, Joanna / Boehm, Thomas / Wadowski, Patricia / Berlakovich, Gabriela / Kuessel, Lorenz / Mühlbacher, Jakob / Jilma-Stohlawetz, Petra / Schwameis, Michael / Jilma, Bernd / Faybik, Peter

Scientific reports

2020 Volume 10, Issue 1, Page(s) 822

Abstract: Increased concentrations of the vasodilator histamine have been observed in patients undergoing abdominal surgery. The role of histamine during orthotopic liver transplantation (OLT) has only been studied in animals. The aim of this study was to measure ... ...

Abstract	Increased concentrations of the vasodilator histamine have been observed in patients undergoing abdominal surgery. The role of histamine during orthotopic liver transplantation (OLT) has only been studied in animals. The aim of this study was to measure plasma concentrations of histamine and its degrading enzyme diamine oxidase (DAO) in patients undergoing orthotopic liver transplantation, and assess whether histamine or DAO correlate with intraoperative noradrenaline requirements. Histamine and DAO concentrations were measured in 22 adults undergoing liver transplantation and 22 healthy adults. Furthermore, norepinephrine requirements during liver transplantation were recorded. Baseline concentrations of histamine and DAO were greater in patients, who underwent liver transplantation, than in healthy individuals (Histamine: 6.4 nM, IQR[2.9-11.7] versus 4.3 nM, IQR[3.7-7.1], p = 0.029; DAO: 2.0 ng/mL, IQR[1.5-4.1] versus <0,5 ng/mL, IQR[<0.5-1.1], p < 0.001). During liver transplantation, histamine concentrations decreased to 1.8 nM, IQR[0.5-4.9] in the anhepatic phase (p < 0.0001 versus baseline), and to 1.5 nM, IQR[0.5-2.9] after reperfusion (p < 0.0001 versus baseline). In contrast, DAO concentrations increased to 35.5 ng/ml, IQR[20-50] in the anhepatic phase (p = 0.001 versus baseline) and to 39.5 ng/ml, IQR[23-64] after reperfusion (p = 0.001 versus baseline), correlating inversely with histamine. Norepinephrine requirements during human liver transplantation correlated significantly with DAO concentrations in the anhepatic phase (r = 0.58, p = 0.011) and after reperfusion (r = 0.56; p = 0.022). In patients undergoing orthotopic liver transplantation, histamine concentrations decrease whereas DAO concentrations increase manifold. Diamine oxidase correlates with intraoperative norepinephrine requirements in patients undergoing OLT.
MeSH term(s)	Aged ; Amine Oxidase (Copper-Containing)/blood ; Biomarkers/blood ; End Stage Liver Disease/blood ; End Stage Liver Disease/physiopathology ; End Stage Liver Disease/surgery ; Female ; Hemodynamics ; Histamine/blood ; Humans ; Hypotension/diagnosis ; Hypotension/diagnostic imaging ; Hypotension/etiology ; Intraoperative Care ; Intraoperative Complications/diagnosis ; Intraoperative Complications/drug therapy ; Intraoperative Complications/etiology ; Liver Transplantation/adverse effects ; Liver Transplantation/methods ; Male ; Middle Aged ; Norepinephrine/administration & dosage
Chemical Substances	Biomarkers ; Histamine (820484N8I3) ; Amine Oxidase (Copper-Containing) (EC 1.4.3.21) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2020-01-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-57728-x
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Article ; Online: Comparison of a new ELISA-based with the flow cytometric assay for vasodilator-associated stimulated phosphoprotein phosphorylation to assess P2Y12 -inhibition after ticagrelor intake.

Hobl, Eva-Luise / Jilma, Bernd / Derhaschnig, Ulla / Schoergenhofer, Christian / Schwameis, Michael / Jilma-Stohlawetz, Petra

Cytometry. Part B, Clinical cytometry

2015 Volume 88, Issue 6, Page(s) 385–388

Abstract: Background: Ticagrelor is a P2Y12 receptor antagonist, with superior effects but also ensuing enhanced bleeding risk as compared to clopidogrel. Determination of platelet inhibition may be useful to confirm efficient platelet inhibition on an individual ...

Abstract	Background: Ticagrelor is a P2Y12 receptor antagonist, with superior effects but also ensuing enhanced bleeding risk as compared to clopidogrel. Determination of platelet inhibition may be useful to confirm efficient platelet inhibition on an individual patient level and to identify patients at risk for bleeding. The vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay specifically measures platelet P2Y12 inhibition, but has so far required individual sample processing. A new ELISA-based VASP assay has been developed, which allows batch analysis after initial platelet activation. Because of the reversible binding of ticagrelor it is unclear if the ELISA and flow cytometric assays provide comparable results; several washing steps of the ELISA may potentially result in false low results through dilution. Methods: We hypothesized that the conventional and new methods may be comparable when ticagrelor is used. We pair-wise compared the platelet reactivity index (PRI) between assays in a prospective clinical trial. Six healthy volunteers received a single 180 mg loading dose of ticagrelor. Results: PRI-values of the two methods correlated well (r = 0.97, P < 0.001). Ticagrelor rapidly decreased PRI values on average after 50 min, but nadir levels 2-6 h after ticagrelor intake were 15% higher when PRI% was measured with the flow cytometric method. Bland-Altman analysis showed that the flow cytometric assay measured markedly higher PRI levels than the new ELISA-based technique (mean difference 13%). Conclusions: The new ELISA-based VASP assay offers an alternative to the currently used flow cytometric method, but measures lower PRI levels, particularly when PRI falls below 20% after ticagrelor intake.
MeSH term(s)	Adenosine/analogs & derivatives ; Adenosine/pharmacology ; Adolescent ; Adult ; Cell Adhesion Molecules/pharmacology ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; Flow Cytometry/methods ; Humans ; Male ; Microfilament Proteins/pharmacology ; Phosphoproteins/pharmacology ; Phosphorylation/drug effects ; Platelet Activation/drug effects ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/pharmacology ; Prospective Studies ; Receptors, Purinergic P2Y12/immunology ; Ticlopidine/analogs & derivatives ; Ticlopidine/pharmacology ; Young Adult
Chemical Substances	Cell Adhesion Molecules ; Microfilament Proteins ; P2RY12 protein, human ; Phosphoproteins ; Platelet Aggregation Inhibitors ; Receptors, Purinergic P2Y12 ; vasodilator-stimulated phosphoprotein ; clopidogrel (A74586SNO7) ; Ticagrelor (GLH0314RVC) ; Adenosine (K72T3FS567) ; Ticlopidine (OM90ZUW7M1)
Language	English
Publishing date	2015-11
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2099657-3
ISSN	1552-4957 ; 1552-4949 ; 0196-4763
ISSN (online)	1552-4957
ISSN	1552-4949 ; 0196-4763
DOI	10.1002/cyto.b.21119
Database	MEDical Literature Analysis and Retrieval System OnLINE

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