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Article ; Online: Tachyphylaxis and reproducibility of desmopressin response in perioperative persons with nonsevere hemophilia A: implications for clinical practice.

Romano, L G R / Schütte, L M / van Hest, R M / Meijer, K / Laros-van Gorkom, B A P / Nieuwenhuizen, L / Eikenboom, J / Heubel-Moenen, F C J I / Uitslager, N / Coppens, M / Fijnvandraat, K / Driessens, M H E / Polinder, S / Cnossen, M H / Leebeek, F W G / Mathôt, R A A / Kruip, M J H A

Research and practice in thrombosis and haemostasis

2024 Volume 8, Issue 3, Page(s) 102367

Abstract: Background: Desmopressin is frequently used perioperatively in persons with nonsevere hemophilia A. However, increase in factor (F)VIII:C after desmopressin use is interindividually highly variable. Tachyphylaxis has only been reported in test setting ... ...

Abstract	Background: Desmopressin is frequently used perioperatively in persons with nonsevere hemophilia A. However, increase in factor (F)VIII:C after desmopressin use is interindividually highly variable. Tachyphylaxis has only been reported in test setting for persons with hemophilia A, with a remaining response of approximately 70% after a second dose compared with that after a first dose. Objectives: To study tachyphylaxis of FVIII:C response after multiple administration(s) of desmopressin in perioperative persons with nonsevere hemophilia A. Methods: We studied FVIII:C levels after desmopressin before (day 0 [D0]) and on days 1 (D1) and 2 (D2) after surgery in 26 patients of the DAVID and Little DAVID studies. We studied tachyphylaxis by comparing the responses at D1 and D2 with that at D0. We also assessed the reproducibility of the D0 response in comparison to an earlier performed desmopressin test. Results: The median absolute FVIII:C increase was 0.50 IU/mL (0.35-0.74; Conclusion: Tachyphylaxis in the surgical setting was considerably more pronounced than previously reported, with FVIII:C at D1 and D2 of 36% to 43% of the initial response. Our results may have important implications for monitoring repeated desmopressin treatment when used perioperatively.
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1016/j.rpth.2024.102367
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Article ; Online: The Performance of Nine Commercial Serological Screening Assays for the Diagnosis of Lyme Borreliosis: a Multicenter Modified Two-Gate Design Study.

Hoeve-Bakker, B J A / Jonker, Mark / Brandenburg, Afke H / den Reijer, P Martijn / Stelma, Foekje F / van Dam, Alje P / van Gorkom, Tamara / Kerkhof, Karen / Thijsen, Steven F T / Kremer, Kristin

Microbiology spectrum

2022 Volume 10, Issue 2, Page(s) e0051022

Abstract: In this retrospective study, the performance of nine serological screening assays for Lyme borreliosis (LB) diagnostics was evaluated using a study population of LB cases and controls. Sera derived from 74 well-defined LB cases and 122 controls were ... ...

Abstract	In this retrospective study, the performance of nine serological screening assays for Lyme borreliosis (LB) diagnostics was evaluated using a study population of LB cases and controls. Sera derived from 74 well-defined LB cases and 122 controls were included. The LB cases were diagnosed with erythema migrans (EM;
MeSH term(s)	Antibodies, Bacterial ; Borrelia ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Lyme Disease/diagnosis ; Retrospective Studies
Chemical Substances	Antibodies, Bacterial ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2022-03-17
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.00510-22
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Article ; Online: Treatment patterns and clinical outcomes of asciminib in a real-world multiresistant chronic myeloid leukemia patient population.

Kockerols, Camille C B / Janssen, Jeroen J W M / Blijlevens, Nicole M A / Klein, Saskia K / Van Hussen-Daenen, Laura G M / Van Gorkom, Gwendolyn G Y / Smit, Willem M / Van Balen, Peter / Biemond, Bart J / Cruijsen, Marjan J / Corsten, Maarten F / Te Boekhorst, Peter A W / Koene, Harry R / Van Sluis, Geerte L / Cornelissen, Jan J / Westerweel, Peter E

Haematologica

2023 Volume 108, Issue 1, Page(s) 240–244

MeSH term(s)	Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Pyrazoles/therapeutic use ; Leukemia, Myeloid/drug therapy ; Niacinamide/therapeutic use ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	asciminib ; Pyrazoles ; Niacinamide (25X51I8RD4) ; Protein Kinase Inhibitors
Language	English
Publishing date	2023-01-01
Publishing country	Italy
Document type	Letter
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.281386
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Article ; Online: Retrospective Evaluation of Various Serological Assays and Multiple Parameters for Optimal Diagnosis of Lyme Neuroborreliosis in a Routine Clinical Setting.

van Gorkom, Tamara / Voet, Willem / van Arkel, Gijs H J / Heron, Michiel / Hoeve-Bakker, B J A / Notermans, Daan W / Thijsen, Steven F T / Kremer, Kristin

Microbiology spectrum

2022 Volume 10, Issue 3, Page(s) e0006122

Abstract: ... functionality, and intrathecal total antibody synthesis), two-tier serology on serum, the CSF level of the B ...

Abstract	Laboratory diagnosis of Lyme neuroborreliosis (LNB) is challenging, and validated diagnostic algorithms are lacking. Therefore, this retrospective cross-sectional study aimed to compare the diagnostic performance of seven commercial antibody assays for LNB diagnosis. Random forest (RF) modeling was conducted to investigate whether the diagnostic performance using the antibody assays could be improved by including several routine cerebrospinal fluid (CSF) parameters (i.e., leukocyte count, total protein, blood-CSF barrier functionality, and intrathecal total antibody synthesis), two-tier serology on serum, the CSF level of the B-cell chemokine (C-X-C motif) ligand 13 (CXCL13), and a
MeSH term(s)	Antibodies ; Borrelia ; Cross-Sectional Studies ; Humans ; Leukocytosis/diagnosis ; Lyme Neuroborreliosis/cerebrospinal fluid ; Lyme Neuroborreliosis/diagnosis ; Prospective Studies ; Retrospective Studies
Chemical Substances	Antibodies
Language	English
Publishing date	2022-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.00061-22
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Article ; Online: Population pharmacokinetics of the von Willebrand factor-factor VIII interaction in patients with von Willebrand disease.

Bukkems, Laura H / Heijdra, Jessica M / de Jager, Nico C B / Hazendonk, Hendrika C A M / Fijnvandraat, Karin / Meijer, Karina / Eikenboom, Jeroen C J / Laros-van Gorkom, Britta A P / Leebeek, Frank W G / Cnossen, Marjon H / Mathôt, Ron A A

Blood advances

2021 Volume 5, Issue 5, Page(s) 1513–1522

Abstract: Recent studies have reported that patients with von Willebrand disease treated perioperatively with a von Willebrand factor (VWF)/factor VIII (FVIII) concentrate with a ratio of 2.4:1 (Humate P/Haemate P) often present with VWF and/or FVIII levels ... ...

Abstract	Recent studies have reported that patients with von Willebrand disease treated perioperatively with a von Willebrand factor (VWF)/factor VIII (FVIII) concentrate with a ratio of 2.4:1 (Humate P/Haemate P) often present with VWF and/or FVIII levels outside of prespecified target levels necessary to prevent bleeding. Pharmacokinetic (PK)-guided dosing may resolve this problem. As clinical guidelines increasingly recommend aiming for certain target levels of both VWF and FVIII, application of an integrated population PK model describing both VWF activity (VWF:Act) and FVIII levels may improve dosing and quality of care. In total, 695 VWF:Act and 894 FVIII level measurements from 118 patients (174 surgeries) who were treated perioperatively with the VWF/FVIII concentrate were used to develop this population PK model using nonlinear mixed-effects modeling. VWF:Act and FVIII levels were analyzed simultaneously using a turnover model. The protective effect of VWF:Act on FVIII clearance was described with an inhibitory maximum effect function. An average perioperative VWF:Act level of 1.23 IU/mL decreased FVIII clearance from 460 mL/h to 264 mL/h, and increased FVIII half-life from 6.6 to 11.4 hours. Clearly, in the presence of VWF, FVIII clearance decreased with a concomitant increase of FVIII half-life, clarifying the higher FVIII levels observed after repetitive dosing with this concentrate. VWF:Act and FVIII levels during perioperative treatment were described adequately by this newly developed integrated population PK model. Clinical application of this model may facilitate more accurate targeting of VWF:Act and FVIII levels during perioperative treatment with this specific VWF/FVIII concentrate (Humate P/Haemate P).
MeSH term(s)	Factor VIII ; Half-Life ; Hemorrhage ; Humans ; von Willebrand Diseases/drug therapy ; von Willebrand Factor
Chemical Substances	von Willebrand Factor ; Factor VIII (9001-27-8)
Language	English
Publishing date	2021-03-08
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.2020003891
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Article ; Online: Specific proteome changes in platelets from individuals with GATA1-, GFI1B-, and RUNX1-linked bleeding disorders.

Van Bergen, M G J M / Marneth, A E / Hoogendijk, A J / Van Alphen, F P J / Van den Akker, E / Laros-Van Gorkom, B A P / Hoeks, M / Simons, A / De Munnik, S A / Janssen, J J W M / Martens, J H A / Jansen, J H / Meijer, A B / Van der Reijden, B A

Blood

2021 Volume 138, Issue 1, Page(s) 86–90

Abstract: Mutations in the transcription factors GATA binding factor 1 (GATA1), growth factor independence 1B (GFI1B), and Runt-related transcription factor 1 (RUNX1) cause familial platelet and bleeding disorders. Mutant platelets exhibit common abnormalities ... ...

Abstract	Mutations in the transcription factors GATA binding factor 1 (GATA1), growth factor independence 1B (GFI1B), and Runt-related transcription factor 1 (RUNX1) cause familial platelet and bleeding disorders. Mutant platelets exhibit common abnormalities including an α-granule reduction resulting in a grayish appearance in blood smears. This suggests that similar pathways are deregulated by different transcription factor mutations. To identify common factors, full platelet proteomes from 11 individuals with mutant GATA1R216Q, GFI1BQ287*, RUNX1Q154Rfs, or RUNX1TD2-6 and 28 healthy controls were examined by label-free quantitative mass spectrometry. In total, 2875 platelet proteins were reliably quantified. Clustering analysis of more than 300 differentially expressed proteins revealed profound differences between cases and controls. Among cases, 44 of 143 significantly downregulated proteins were assigned to platelet function, hemostasis, and granule biology, in line with platelet dysfunction and bleedings. Remarkably, none of these proteins were significantly diminished in all affected cases. Similarly, no proteins were commonly overrepresented in all affected cases compared with controls. These data indicate that the studied transcription factor mutations alter platelet proteomes in distinct largely nonoverlapping manners. This work provides the quantitative landscape of proteins that affect platelet function when deregulated by mutated transcription factors in inherited bleeding disorders.
MeSH term(s)	Blood Platelet Disorders/metabolism ; Blood Platelets/metabolism ; Core Binding Factor Alpha 2 Subunit/metabolism ; GATA1 Transcription Factor/metabolism ; Homeostasis ; Humans ; Mutation/genetics ; Proteome/metabolism ; Proto-Oncogene Proteins/metabolism ; Repressor Proteins/metabolism ; Signal Transduction ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Core Binding Factor Alpha 2 Subunit ; GATA1 Transcription Factor ; GATA1 protein, human ; GFI1B protein, human ; Proteome ; Proto-Oncogene Proteins ; Repressor Proteins ; Transcription Factors
Language	English
Publishing date	2021-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2020008118
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Article ; Online: The bleeding phenotype in people with nonsevere hemophilia.

Kloosterman, Fabienne R / Zwagemaker, Anne-Fleur / Bagot, Catherine N / Beckers, Erik A M / Castaman, Giancarlo / Cnossen, Marjon H / Collins, Peter W / Hay, Charles / Hof, Michel / Laros-van Gorkom, Britta / Leebeek, Frank W G / Male, Christoph / Meijer, Karina / Pabinger, Ingrid / Shapiro, Susan / Coppens, Michiel / Fijnvandraat, Karin / Gouw, Samantha C

Blood advances

2022 Volume 6, Issue 14, Page(s) 4256–4265

Abstract: ... A and B) study, an international multicenter cohort, we included males with nonsevere hemophilia (FVIII ...

Abstract	Detailed information on the onset, frequency, and severity of bleeding in nonsevere hemophilia is limited. We aimed to assess the bleeding phenotype of persons with nonsevere hemophilia and to analyze the association between baseline factor VIII/IX (FVIII/IX) levels and the joint bleeding rate. In the DYNAMO (Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B) study, an international multicenter cohort, we included males with nonsevere hemophilia (FVIII/IX, 0.02-0.35 IU/mL) aged 12 to 55 years. Information on age at first treated (joint) bleed, annual bleeding rates (ABRs), and annual joint bleeding rates (AJBRs) was collected from the medical files. The association between baseline FVIII/IX levels and the joint bleeding rate was assessed by using a frailty model for recurrent events. In total, 304 persons (70 with moderate hemophilia and 234 with mild hemophilia) were included. The median age was 38 years (interquartile range [IQR], 25-49 years), and the median baseline FVIII/IX level was 0.12 IU/mL (IQR, 0.05-0.21 IU/mL). In total, 245 (81%) persons had experienced at least 1 bleed, and 156 (51%) had experienced at least 1 joint bleed. The median age at first bleed and first joint bleed was 8 and 10 years, respectively. The median ABR and AJBR was 0.2 (IQR, 0.1-0.5) and 0.0 (IQR, 0.0-0.2). From baseline FVIII/IX levels 0.02 to 0.05 IU/mL to >0.25 IU/mL, the median ABR decreased from 0.6 (IQR, 0.2-1.4) to 0.1 (IQR, 0.0-0.2) and the AJBR from 0.2 (IQR, 0.0-0.4) to 0.0 (IQR, 0.0-0.0). Baseline FVIII/IX was inversely associated with the joint bleeding rate (P < .001). Low bleeding rates were observed in persons with nonsevere hemophilia. However, one-half of all adolescents and adults had experienced a joint bleed.
MeSH term(s)	Adolescent ; Adult ; Child ; Factor IX ; Hemarthrosis/etiology ; Hemophilia A/complications ; Hemorrhage/etiology ; Hemostatics ; Humans ; Male ; Middle Aged ; Phenotype ; Young Adult
Chemical Substances	Hemostatics ; Factor IX (9001-28-9)
Language	English
Publishing date	2022-05-09
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; 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.2022007620
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Article ; Online: Second nationwide anti-tuberculosis drug resistance survey in Namibia.

Ruswa, N / Mavhunga, F / Roscoe, J C / Beukes, A / Shipiki, E / van Gorkom, J / Sawadogo, S / Agolory, S / Menzies, H / Tiruneh, D / Makumbi, B / Bayer, B / Zezai, A / Campbell, P / Alexander, H / Kalisvaart, N / Forster, N

The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

2019 Volume 23, Issue 7, Page(s) 858–864

Abstract: SETTING: ...

Abstract	SETTING:
MeSH term(s)	Adolescent ; Adult ; Aged ; Antibiotics, Antitubercular/pharmacology ; Antibiotics, Antitubercular/therapeutic use ; Child ; Child, Preschool ; Comorbidity ; Female ; HIV Infections ; Humans ; Infant ; Infant, Newborn ; Male ; Mass Screening ; Microbial Sensitivity Tests ; Middle Aged ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/isolation & purification ; Namibia/epidemiology ; Prevalence ; Surveys and Questionnaires ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/epidemiology ; Tuberculosis, Multidrug-Resistant/microbiology ; Tuberculosis, Multidrug-Resistant/prevention & control ; Tuberculosis, Pulmonary/drug therapy ; Tuberculosis, Pulmonary/epidemiology ; Tuberculosis, Pulmonary/microbiology ; Tuberculosis, Pulmonary/prevention & control ; Young Adult
Chemical Substances	Antibiotics, Antitubercular
Language	English
Publishing date	2019-08-23
Publishing country	France
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1385624-8
ISSN	1815-7920 ; 1027-3719
ISSN (online)	1815-7920
ISSN	1027-3719
DOI	10.5588/ijtld.18.0526
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Article ; Online: Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders.

EClinicalMedicine

2021 Volume 32, Page(s) 100726

Abstract: Background: In recent years, more awareness is raised about sex-specific dilemmas in inherited bleeding disorders. However, no large studies have been performed to assess differences in diagnosis, bleeding phenotype and management of men and women with ... ...

Abstract	Background: In recent years, more awareness is raised about sex-specific dilemmas in inherited bleeding disorders. However, no large studies have been performed to assess differences in diagnosis, bleeding phenotype and management of men and women with bleeding disorders. Therefore, we investigated sex differences in a large cohort of well-defined patients with autosomal inherited bleeding disorders (von Willebrand disease (VWD), rare bleeding disorders (RBDs) and congenital platelet defects (CPDs)). Methods: We included patients from three nationwide cross-sectional studies on VWD, RBDs and CPDs in the Netherlands, respectively the WiN, RBiN and TiN study. In all studies a bleeding score (BS) was obtained, and patients filled in an extensive questionnaire on the management and burden of their disorder. Findings: We included 1092 patients (834 VWD; 196 RBD; 62 CPD), of whom 665 (60.9%) were women. Women were more often referred because of a bleeding diathesis than men (47.9% vs 36.6%, Interpretation: Women with autosomal inherited bleeding disorders are more often referred for bleeding, have a longer diagnostic delay, and often require treatment because of sex-specific bleeding. Funding: The WiN study was supported (in part) by research funding from the Dutch Hemophilia Foundation (Stichting Haemophilia), Shire (Takeda), and CSL Behring (unrestricted grant).
Language	English
Publishing date	2021-01-29
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2021.100726
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Article ; Online: An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31-Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the Netherlands.

van Gorkom, T / Sankatsing, S U C / Voet, W / Ismail, D M / Muilwijk, R H / Salomons, M / Vlaminckx, B J M / Bossink, A W J / Notermans, D W / Bouwman, J J M / Kremer, K / Thijsen, S F T

Journal of clinical microbiology

2018 Volume 56, Issue 4

Abstract: Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular ...

Abstract	Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular immune system are available, but studies evaluating the utility of these tests on well-defined patient populations are lacking. Therefore, we investigated the utility of an enzyme-linked immunosorbent spot (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood mononuclear cells (PBMCs) of various study groups were stimulated by using
MeSH term(s)	Adult ; Antibodies, Bacterial/blood ; Borrelia burgdorferi ; Enzyme-Linked Immunosorbent Assay ; Enzyme-Linked Immunospot Assay ; Female ; Humans ; Immunoglobulin G/blood ; Interferon-gamma/immunology ; Lyme Disease/diagnosis ; Lyme Neuroborreliosis/diagnosis ; Male ; Middle Aged ; Netherlands ; Prospective Studies ; Recombinant Proteins/immunology ; T-Lymphocytes/immunology
Chemical Substances	Antibodies, Bacterial ; Immunoglobulin G ; Recombinant Proteins ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2018-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.01695-17
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