26 results on '"A.J. Gerard Jansen"'
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2. Anti-HLA antibodies with complementary and synergistic interaction geometries promote classical complement activation on platelets
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Maaike Rijkers, David Schmidt, Nina Lu, Cynthia S.M. Kramer, Sebastiaan Heidt, Arend Mulder, Leendert Porcelijn, Frans H.J. Claas, Frank W.G. Leebeek, A.J. Gerard Jansen, Ilse Jongerius, Sacha S. Zeerleder, Gestur Vidarsson, Jan Voorberg, and Masja de Haas
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
High titers of HLA antibodies are associated with platelet refractoriness, causing poor platelet increments after transfusions in a subset of patients with HLA antibodies. Currently, we do not know the biological mechanisms that explain the variability in clinical responses in HLA alloimmunized patients receiving platelet transfusions. Previously we showed that a subset of anti-HLA IgG-antibodies induces FcγRIIa-dependent platelet activation and enhanced phagocytosis. Here, we investigated whether anti-HLA IgG can induce complement activation on platelets. We found that a subset of anti-HLA IgG induced complement activation via the classical pathway, causing C4b and C3b deposition and formation of the membrane-attack complex. This resulted in permeabilization of platelet membranes and increased calcium influx. Complement activation also caused enhanced α-granule release, as measured by CD62P surface exposure. Blocking studies revealed that platelet activation was caused by FcγRIIa-dependent signaling as well as HLA antibody induced complement activation. Synergistic complement activation employing combinations of monoclonal IgGs suggested that assembly of oligomeric IgG complexes strongly promoted complement activation through binding of IgGs to different antigenic determinants on HLA. In agreement with this, we observed that preventing anti-HLA-IgG hexamer formation using an IgG-Fc:Fc blocking peptide, completely inhibited C3b and C4b deposition. Our results show that HLA antibodies can induce complement activation on platelets including membrane attack complex formation, pore formation and calcium influx. We propose that these events can contribute to fast platelet clearance in vivo in patients refractory to platelet transfusions with HLA alloantibodies, who may benefit from functional-platelet matching and treatment with complement inhibitors.
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- 2019
- Full Text
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3. A subset of anti-HLA antibodies induces FcγRIIa-dependent platelet activation
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Maaike Rijkers, Anno Saris, Sebastiaan Heidt, Arend Mulder, Leendert Porcelijn, Frans H.J. Claas, Ruben Bierings, Frank W.G. Leebeek, A.J. Gerard Jansen, Gestur Vidarsson, Jan Voorberg, and Masja de Haas
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
HLA antibodies are associated with refractoriness to platelet transfusion, leading to rapid platelet clearance, sometimes coinciding with clinical side effects such as fever and chills. The presence of HLA antibodies is not always manifested by clinical symptoms. It is currently unclear why refractoriness to platelet transfusion is only observed in a subset of patients. Here, we utilized the availability of a unique panel of human monoclonal antibodies to study whether these were capable of activating platelets. Three out of eight human HLA-specific monoclonal antibodies induced activation of HLA-matched platelets from healthy donors as evidenced by enhanced α-granule release, aggregation, and αIIbb3 activation. The propensity of HLA monoclonal antibodies to activate platelets was independent of the HLA subtype to which they were directed, but was dependent on the recognized epitope. Activation was fully inhibited either by blocking FcγRIIa, or by blocking FcγRIIa-dependent signaling with Syk inhibitor IV. Furthermore, activation required the presence of the IgG-Fc part, as F(ab’)2 fragments of HLA monoclonal antibodies were unable to induce platelet activation. Mixing experiments revealed that activation of platelets occurred in an intra-platelet dependent manner. Accordingly, a proportion of sera from refractory patients with HLA antibodies induced FcγRIIa-dependent platelet activation. Our data show that a subset of HLA antibodies is capable of crosslinking HLA and FcγRIIa thereby promoting platelet activation and enhancing these cells’ phagocytosis by macrophages. Based on these findings we suggest that FcγRIIa-dependent platelet activation may contribute to the decreased platelet survival in platelet-transfusion-dependent patients with HLA antibodies.
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- 2018
- Full Text
- View/download PDF
4. Safety and Efficacy of SARS-CoV-2 Vaccination in Patients with Immune Thrombocytopaenia: a Multi-Centre Review
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Sara Stefani, Rocel C. Saputil, Michelle MH Tan, Noora Buti, Deena Paul, Naghma Rizvi, Vashti Ragoonanan, Emma Thorley, Ariam Teklemichael, Camelia Vladescu, Amna Malik, Christine Ademokun, Alice C J Hart, Richard Szydlo, George Adams, James B. Bussel, A.J. Gerard Jansen, and Nichola Cooper
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia
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David J. Kuter, Merlin Efraim, Jiri Mayer, Marek Trněný, Vickie McDonald, Robert Bird, Thomas Regenbogen, Mamta Garg, Zane Kaplan, Nikolay Tzvetkov, Philip Y. Choi, A.J. Gerard Jansen, Milan Kostal, Ross Baker, Jaromir Gumulec, Eun-Ju Lee, Ilona Cunningham, Isaac Goncalves, Margaret Warner, Ralph Boccia, Terry Gernsheimer, Waleed Ghanima, Olga Bandman, Regan Burns, Ann Neale, Dolca Thomas, Puneet Arora, Beiyao Zheng, Nichola Cooper, and Hematology
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Purpura, Thrombocytopenic, Idiopathic ,Treatment Outcome ,Platelet Count ,Agammaglobulinaemia Tyrosine Kinase ,Administration, Oral ,Humans ,General Medicine ,Protein Kinase Inhibitors - Abstract
BACKGROUND Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (Fcγ receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies. METHODS In an international, adaptive, open-label, dose-finding, phase 1-2 clinical trial, we evaluated rilzabrutinib therapy in previously treated patients with immune thrombocytopenia. We used intrapatient dose escalation of oral rilzabrutinib over a period of 24 weeks; the lowest starting dose was 200 mg once daily, with higher starting doses of 400 mg once daily, 300 mg twice daily, and 400 mg twice daily. The primary end points were safety and platelet response (defined as at least two consecutive platelet counts of ≥50×103 per cubic millimeter and an increase from baseline of ≥20×103 per cubic millimeter without the use of rescue medication). RESULTS Sixty patients were enrolled. At baseline, the median platelet count was 15×103 per cubic millimeter, the median duration of disease was 6.3 years, and patients had received a median of four different immune thrombocytopenia therapies previously. All the treatment-related adverse events were of grade 1 or 2 and transient. There were no treatment-related bleeding or thrombotic events of grade 2 or higher. At a median of 167.5 days (range, 4 to 293) of treatment, 24 of 60 patients (40%) overall and 18 of the 45 patients (40%) who had started rilzabrutinib treatment at the highest dose met the primary end point of platelet response. The median time to the first platelet count of at least 50×103 per cubic millimeter was 11.5 days. Among patients with a primary platelet response, the mean percentage of weeks with a platelet count of at least 50×103 per cubic millimeter was 65%. CONCLUSIONS Rilzabrutinib was active and associated with only low-level toxic effects at all dose levels. The dose of 400 mg twice daily was identified as the dose for further testing. Overall, rilzabrutinib showed a rapid and durable clinical activity that improved with length of treatment.
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- 2022
6. Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia
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Floor L.F. van Baarle, Emma K. van de Weerdt, Walter J.F.M. van der Velden, Roelof A. Ruiterkamp, Pieter R. Tuinman, Paula F. Ypma, Walter M. van den Bergh, Astrid M.P. Demandt, Emile D. Kerver, A.J. Gerard Jansen, Peter E. Westerweel, Sesmu M. Arbous, Rogier M. Determann, Walther N.K.A. van Mook, Mirelle Koeman, Anja B.U. Mäkelburg, Krijn P. van Lienden, Jan M. Binnekade, Bart J. Biemond, Alexander P.J. Vlaar, Hematology, Graduate School, AII - Inflammatory diseases, APH - Quality of Care, CCA - Cancer Treatment and Quality of Life, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Cancer immunology, AII - Infectious diseases, CCA - Cancer biology and immunology, Clinical Haematology, ACS - Microcirculation, and Intensive care medicine
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All institutes and research themes of the Radboud University Medical Center ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,General Medicine - Abstract
Item does not contain fulltext BACKGROUND: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).
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- 2023
7. Quantitative super-resolution imaging of platelet degranulation reveals differential release of VWF and VWF propeptide from alpha-granules
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Maurice Swinkels, Sophie Hordijk, Petra E. Bürgisser, Johan A. Slotman, Tom Carter, Frank W.G. Leebeek, A.J. Gerard Jansen, Jan Voorberg, and Ruben Bierings
- Abstract
BackgroundPlatelet alpha-granules contain Von Willebrand factor (VWF), which is stored in eccentric alpha-granule nanodomains, and VWF propeptide (VWFpp). Differential release of VWF and VWFpp has been reported from endothelial cells. It is unclear if this also occurs during platelet alpha-granule exocytosis. We have recently developed a 3D super-resolution imaging workflow for quantification of platelet alpha-granule content based on Structured Illumination Microscopy (SIM). With this we can study alpha-granule cargo release following platelet activation in hundreds of platelets simultaneously.AimsTo study release of VWF and VWFpp from alpha-granules using quantitative super-resolution microscopy.MethodsPlatelets were activated with PAR-1 activating peptide (PAR-1 ap) or collagen-related peptide (CRP-XL). Alpha-tubulin, VWF, VWFpp, SPARC and fibrinogen were imaged using 3D-SIM, followed by semi-automated analysis in FIJI. Uptake of anti-VWF nanobody during degranulation was used to identify alpha-granules that partially released content.ResultsVWF+ and VWFpp+ structures overlapped nearly completely (∼90%) in resting platelets, implying they are stored in similar eccentric alpha-granule nanodomains. A subset of VWF+/VWFpp+-structures was released completely at 0.6 µM PAR-1 ap, but at higher concentration (20 µM) significantly more VWFpp (85.3±1.6%) was released than VWF (37.6±1.4%). Release of other cargo was intermediate at 20 µM (SPARC: 62.2±1.4%; fibrinogen: 51.9±2.9%), providing further evidence for differential cargo release. Similar results were obtained using CRP-XL. Anti-VWF nanobody was taken up by VWF+/VWFpp-structures and increased with stimulus strength, demonstrating these were post-exocytotic structures.ConclusionsVWF and VWFpp are differentially released from alpha-granules. This may affect how platelet-derived VWF and VWFpp contribute to formation and stabilization of hemostatic clots.Key pointsVWFpp and VWF are localized in the same, eccentric alpha-granule subdomain in resting platelets and do not overlap with other alpha-granule cargo proteins such as fibrinogenVWFpp and VWF are differentially secreted from individual alpha-granules upon activation with platelet agonists PAR-1 activating peptide and collagen-related peptide
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- 2022
8. Predicting Platelet Age Using Artificial Intelligence Techniques
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Johan Slotman, Maurice Swinkels, Petra E. Burgisser, Joyce Bestebroer, Thomas R.L. Klei, Adriaan B. Houtsmuller, Frank W.G. Leebeek, Ruben Bierings, and A.J. Gerard Jansen
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
9. First line treatment of adult patients with primary immune thrombocytopenia: a real-world study
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Lei Xu, Liang Wang, Honglei Li, Yajing Zhao, Hongyuan Hao, Guoqiang Liu, A.J. Gerard Jansen, Ming Hou, Xinguang Liu, Jun Peng, and Hematology
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Adult ,Blood Platelets ,0301 basic medicine ,medicine.medical_specialty ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Dexamethasone ,03 medical and health sciences ,0302 clinical medicine ,Prednisone ,Internal medicine ,Humans ,Medicine ,Adverse effect ,Autoantibodies ,Autoimmune disease ,Purpura, Thrombocytopenic, Idiopathic ,Adult patients ,biology ,business.industry ,Incidence ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Immune thrombocytopenia ,First line treatment ,030104 developmental biology ,biology.protein ,Female ,Antibody ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Immune thrombocytopenia (ITP) is an autoimmune disease with a mild to severe risk of bleeding complications. First line treatment includes corticosteroids, immunoglobulins, or other. In this large cohort study, first-line strategies for treatment-naive adult primary ITP was studied in a real-world setting. Records from all adult ITP patients who received first-line treatment between January 2010 and December 2017 at Qilu Hospital were reviewed retrospectively (n = 699). During the study period, 271 patients were treated with high-dose dexamethasone (HDD) and 289 patients were treated with conventional prednisone (alone or in combination with other drugs). Initial responses were similar for the two groups (88.56% vs. 86.51%, P = 0.462), but patients in the HDD group responded earlier than the prednisone group (3 days vs. 5 days, P 0.05). Adverse events were more frequent and long-lasting in the prednisone group. Our study showed that HDD provided an effective and more rapid response as initial treatment of ITP, with comparable long-term prognosis and better tolerance when compared with conventional PDN (less than 3 months) in the real-world setting.
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- 2019
10. Indication and outcome of lupus anticoagulant and antiphospholipid antibodies testing in routine clinical practice
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Frank W.G. Leebeek, Eva K Kempers, A.J. Gerard Jansen, Annemarie G.M.G.J. Mulders, Virgil A. S. H. Dalm, Marie Josee Van Rijn, Moniek P.M. de Maat, Hematology, Immunology, Internal Medicine, Surgery, and Obstetrics & Gynecology
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medicine.medical_specialty ,Lupus anticoagulant ,biology ,business.industry ,obstetric complications ,medicine.disease ,Outcome (game theory) ,aPL ,Rheumatology ,immune system diseases ,medicine ,biology.protein ,Original Article ,Routine clinical practice ,blood coagulation disorders ,Antibody ,AcademicSubjects/MED00010 ,Intensive care medicine ,business ,antiphospholipid syndrome ,neoplasms ,thrombosis - Abstract
Objectives Lupus anticoagulans (LACs) and aPLs, both further summarized as aPL, are frequently assessed in routine daily clinical practice in diagnostic workups for suspected autoimmune diseases or to test for underlying risk factors in patients with thrombosis or obstetric complications. The aim of this study was to determine the prevalence of aPL positivity in patients with an indication for aPL testing in routine clinical practice. Methods In this retrospective single-centre study, indication for aPL testing, aPL test results and clinical data were collected for patients tested between June 2015 and April 2018. Results During the study period, 16 847 single aPL tests were performed in 2139 patients. In 212 patients one or more positive aPL test was found, confirmed in 43.9% with a second positive test. Indications for aPL testing were diagnostic workup/follow-up of autoimmune diseases (33.6%), thrombosis (21.4%) and obstetric complications (28%). Seventy-four patients (3.5% of all patients) fulfilled the criteria of APS, of whom 51% were newly diagnosed. Second positive aPL titres and titres of APS patients were significantly higher compared with positive aPL titres at the first measurement (P < 0.05). Patients with indications of arterial thrombosis and diagnostic workup/follow-up of autoimmune diseases had significantly higher levels of aCL IgG and anti-β2 glycoprotein I (β2GPI) IgG compared with patients with other indications. Conclusion The prevalence of one or more positive aPL test was 9.9% and APS was diagnosed in 3.5% of the patients. Patients with arterial thrombosis had significantly higher anti-β2GPI IgG and aCL IgG, which should be confirmed in future studies.
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- 2021
11. COVID‐19‐associated immune thrombocytopenia
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Pim G N J Mutsaers, Johannes Hofland, Gienke Bomhof, Peter A. W. te Boekhorst, A.J. Gerard Jansen, Frank W.G. Leebeek, F. Nanne Croles, Hematology, and Internal Medicine
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Autoimmune disease ,Disseminated intravascular coagulation ,business.industry ,Hematology ,medicine.disease ,Malignancy ,Sepsis ,03 medical and health sciences ,Pneumonia ,Purpura ,0302 clinical medicine ,030220 oncology & carcinogenesis ,hemic and lymphatic diseases ,Immunology ,medicine ,Platelet ,Letters ,medicine.symptom ,Risk factor ,business ,030215 immunology - Abstract
Thrombocytopenia is a risk factor for increased morbidity and mortality in patients with the new severe acute respiratory syndrome corona virus, SARS‐CoV‐2 infection (COVID‐19 infection).1 Thrombocytopenia in COVID‐19 patients may be caused by disseminated intravascular coagulation (DIC), sepsis or drug‐induced. Recently a single case report suggested immune thrombocytopenia (ITP) may be associated with COVID‐19 infection.2 ITP is a rare autoimmune disease characterized by a platelet count < 100x109/L, leading to an increased bleeding risk.3 Several risk factors have been described for ITP including environmental (e.g. infection, malignancy and drugs) and genetic predisposition.4 We report here the first case series of three patients with ITP associated with COVID‐19 infection.
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- 2020
12. Results of the prematurely terminated TEMPLE randomized controlled trial in patients with myelodysplastic syndrome: liberal versus restrictive red blood cell transfusion threshold
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A.J. Gerard Jansen, Erik A M Beckers, Peter A. W. te Boekhorst, Martin R. Schipperus, Joan van den Bosch, Hematology, Interne Geneeskunde, MUMC+: MA Hematologie (9), and RS: Carim - B01 Blood proteins & engineering
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medicine.medical_specialty ,business.industry ,Immunology ,Red Blood Cell Transfusion ,Hematology ,Surgery ,law.invention ,Randomized controlled trial ,law ,Myelodysplastic Syndromes ,medicine ,Immunology and Allergy ,Humans ,In patient ,business ,Erythrocyte Transfusion ,Randomized Controlled Trials as Topic - Published
- 2020
13. A subset of anti-HLA antibodies induces Fc gamma RIIa-dependent platelet activation
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Jan Voorberg, Sebastiaan Heidt, Anno Saris, Masja de Haas, Maaike Rijkers, Ruben Bierings, Frans H.J. Claas, Frank W.G. Leebeek, A.J. Gerard Jansen, Arend Mulder, Gestur Vidarsson, Leendert Porcelijn, Graduate School, Landsteiner Laboratory, ACS - Microcirculation, Experimental Vascular Medicine, and Hematology
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Blood Platelets ,medicine.drug_class ,Syk ,Human leukocyte antigen ,030204 cardiovascular system & hematology ,Monoclonal antibody ,Epitope ,Article ,03 medical and health sciences ,Immunoglobulin Fab Fragments ,0302 clinical medicine ,HLA Antigens ,medicine ,Humans ,Platelet ,Blood Transfusion ,Platelet activation ,biology ,Chemistry ,Receptors, IgG ,Antibodies, Monoclonal ,Hematology ,Platelet Activation ,Immunoglobulin Fc Fragments ,Platelet transfusion ,Immunoglobulin G ,Immunology ,biology.protein ,Antibody ,030215 immunology - Abstract
HLA antibodies are associated with refractoriness to platelet transfusion, leading to rapid platelet clearance, sometimes coinciding with clinical side effects such as fever and chills. The presence of HLA antibodies is not always manifested by clinical symptoms. It is currently unclear why refractoriness to platelet transfusion is only observed in a subset of patients. Here, we utilized the availability of a unique panel of human monoclonal antibodies to study whether these were capable of activating platelets. Three out of eight human HLA-specific monoclonal antibodies induced activation of HLA-matched platelets from healthy donors as evidenced by enhanced α-granule release, aggregation, and αIIbb3 activation. The propensity of HLA monoclonal antibodies to activate platelets was independent of the HLA subtype to which they were directed, but was dependent on the recognized epitope. Activation was fully inhibited either by blocking FcγRIIa, or by blocking FcγRIIa-dependent signaling with Syk inhibitor IV. Furthermore, activation required the presence of the IgG-Fc part, as F(ab’)2 fragments of HLA monoclonal antibodies were unable to induce platelet activation. Mixing experiments revealed that activation of platelets occurred in an intra-platelet dependent manner. Accordingly, a proportion of sera from refractory patients with HLA antibodies induced FcγRIIa-dependent platelet activation. Our data show that a subset of HLA antibodies is capable of crosslinking HLA and FcγRIIa thereby promoting platelet activation and enhancing these cells’ phagocytosis by macrophages. Based on these findings we suggest that FcγRIIa-dependent platelet activation may contribute to the decreased platelet survival in platelet-transfusion-dependent patients with HLA antibodies.
- Published
- 2018
14. Low platelet count as risk factor for infections in patients with primary immune thrombocytopenia: a retrospective evaluation
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Heyu Ni, Ming Hou, Hongguo Zhao, Qiang Liu, Mingming Qu, Jun Peng, A.J. Gerard Jansen, Landsteiner Laboratory, and Hematology
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Platelet Transfusion ,030204 cardiovascular system & hematology ,Infections ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Risk Factors ,Prednisone ,law ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Platelet ,Risk factor ,Dexamethasone ,Retrospective Studies ,Purpura, Thrombocytopenic, Idiopathic ,Hematology ,Platelet Count ,business.industry ,Incidence ,General Medicine ,Length of Stay ,Middle Aged ,Thrombocytopenia ,030104 developmental biology ,Platelet transfusion ,Cohort ,ITP ,Original Article ,Female ,Infection ,business ,medicine.drug - Abstract
Infectious complications are common and sometimes life threatening in patients with immune thrombocytopenia (ITP), mainly due to the immune-suppressive therapy. Recent evidence suggests a potential role of platelets in the inflammation process. In this clinical study, we further investigated the role of thrombocytopenia on infections in patients with primary ITP. We retrospectively evaluated data from the recently published large randomized clinical trial of a cohort of 195 patients with primary ITP, who were randomized for prednisone or high-dose dexamethasone. From 158 patients (81%), data on platelet count and infections within the first month of treatment were collected. In this period, 24% of the ITP patients had an infection. Patients with infection had significant lower platelet counts during the first month of treatment leading to a significant lower therapy response at 1 month and a significant longer hospital stay (14.0 versus 9.8 days). Additionally, Cox regression analysis showed that an increase in platelet count of 20 × 109/L led to a reduction of 52% in infections in the next week, showing low platelet count is a significant risk factor for infection. Platelet transfusion led to an increase in platelet count in ITP patients without infection, but not in patients with infection. In conclusion, infections are common in patients with primary ITP leading to significant worse response rates and a longer hospital stay. Interestingly, low platelet count was independently correlated with an increased risk of infection.
- Published
- 2018
15. Updated Phase I/II Safety and Efficacy Results for Oral Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients with Relapsed/Refractory Immune Thrombocytopenia
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Olga Bandman, J. Gumulec, Milan Kostal, A.J. Gerard Jansen, Terry B. Gernsheimer, Ahmed Daak, Ann Neale, Regan Burns, Fareha Iqbal, Philip Young-Ill Choi, David J. Kuter, Ross I. Baker, Nichola Cooper, Mamta Garg, Timothee Sourdille, Waleed Ghanima, Jiří Mayer, Mengjie Yao, Vickie McDonald, Puneet Arora, Zane Kaplan, Nikolay Tzvetkov, Dolca Thomas, Merlin Efraim, and Robert Bird
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0303 health sciences ,biology ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Immune thrombocytopenia ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Phase i ii ,Relapsed refractory ,Cancer research ,biology.protein ,Bruton's tyrosine kinase ,Medicine ,In patient ,business ,030304 developmental biology ,030215 immunology - Abstract
Introduction: Key characteristics of immune thrombocytopenia (ITP) include immune-mediated platelet destruction/impaired production, with resultant thrombocytopenia and increased bleeding risk. Durable response to current therapies remains an unmet need, particularly in the relapsed/refractory setting. Rilzabrutinib is the first oral, reversible, covalent inhibitor of Bruton tyrosine kinase designed to target immune-mediated pathways in ITP without inhibiting normal platelet aggregation. Initial phase I/II results in ITP demonstrated rapid and durable efficacy with rilzabrutinib that was well-tolerated at all dose levels, including the optimal 400 mg bid dose. Interim results on rilzabrutinib effects in patients with relapsed/refractory ITP were previously reported. Here we present long-term data from a larger group of patients who initiated rilzabrutinib at 400 mg bid and are continuing in the long-term extension (LTE) period. Methods: This ongoing, global phase I/II study (NCT03395210) enrolled adult patients from 8 countries with relapsed or refractory ITP who previously responded to ≥1 prior ITP therapy. Eligible patients with 2 baseline platelet counts of Results: As of June 1, 2021 in 60 patients, 45 patients initiated rilzabrutinib 400 mg bid and to date, 16 patients with durable, stable response proceeded to LTE at 400 mg bid. At enrollment for patients initiating rilzabrutinib 400 mg bid, median age was 49 y (range, 19-74), median duration of ITP was 6.1 y (range, 0.4-52.5), and median platelet count was 15×10 9/L (range, 2-33×10 9/L). Patients were heavily pretreated with a median of 6 prior treatment events (range, 1-53), including 24% with prior splenectomy. Overall, 18/45 patients (40%) achieved the primary endpoint. In primary responders, platelet counts of ≥30×10 9/L, ≥30×10 9/L with ≥20×10 9/L above baseline, and ≥50×10 9/L were maintained for a median of 95%, 86%, and 72% of weeks, respectively. Median time to first platelet counts of ≥30×10 9/L, ≥30×10 9/L with ≥20×10 9/L above baseline, and ≥50×10 9/L were 8.5 (7-134), 11.5 (7-134), and 12.5 (8-142) days, respectively. According to subgroup analyses, primary platelet responses were consistently >30% irrespective of baseline platelet counts, the use of concomitant therapy, duration of ITP, or number of prior therapies (Table). LTE patients received rilzabrutinib for an overall median duration of 462 days (range, 303-764). At LTE entry, patients had a median platelet count of 87×10 9/L (range, 16-321×10 9/L). In addition to all LTE patients achieving the primary endpoint during the main treatment period, these patients maintained platelet counts of ≥30×10 9/L, ≥30×10 9/L with ≥20×10 9/L above baseline, and ≥50×10 9/L, for a median of 100%, 96%, and 90%, of weeks, respectively, during the LTE period (Figure). Treatment-related treatment-emergent adverse events (TEAEs; all grade 1/2) were reported in 27/45 patients (60%); the most common were 36% diarrhea and 31% nausea, and all others were Conclusion: Oral rilzabrutinib 400 mg bid was well-tolerated and had durable, clinically significant platelet responses across subgroups and with extended treatment in patients with heavily pretreated ITP. Continued study in the ongoing, randomized phase III LUNA3 trial (NCT04562766) will further assess the magnitude and durability of rilzabrutinib's clinical benefit in ITP. Figure 1 Figure 1. Disclosures Kuter: Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb (BMS), Immunovant, Kezar, Principia, Protalex, Rigel, Takeda (Bioverativ), UCB: Research Funding; Up-to-Date: Patents & Royalties: Up-To-Date; Rubius: Current equity holder in publicly-traded company; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa-Kirin, Merck Sharp Dohme, Momenta, Novartis, Pfizer, Principia, Protalex, Protalix, Rigel: Consultancy, Other: grant support and consulting fees; Platelet Disorder Support Association: Membership on an entity's Board of Directors or advisory committees. Mayer: Principia: Research Funding. Jansen: 3SBIO, Novartis: Other: Travel, accomodations, expenses; Advisory Board Novartis: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Other: Travel, Accommodations, Expenses. McDonald: Bayer, Sobi, Novartis, Amgen, argenx: Honoraria; Grifols: Research Funding. Baker: Roche, Janssen-Celeg: Membership on an entity's Board of Directors or advisory committees; Bayer, Takeda, Pfizer, Daiichi Sankyo, CSL Behring, Roche, Amgen, Celgene, Rigel Pharmaceuticals, Abbvie, Sanofi, MorphoSys AG, Acerta Pharma, Jansen-Cileg, Bristol-Myers Squibb, Boehringer Ingelheim, Portola, Technoclone, Alexion: Research Funding. Bird: Novartis, Amgen: Speakers Bureau. Garg: Amgen Janssen Novartis Sanofi Takeda: Honoraria; Takeda Janssen Novartis Sanofi: Other: Travel Accommodations, Expenses; University Hospital Leicester: Current Employment. Gernsheimer: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: personal fees ; Amgen: Honoraria; Cellphire: Consultancy; Dova: Consultancy, Honoraria; Principia: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees, Research Funding; NHLBI: Research Funding. Ghanima: Amgen, Novartis, Pfizer, Principia Biopharma Inc- a Sanofi Company, Sanofi, SOBI, Griffols, UCB, Argenx: Consultancy; Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Griffols, Sanofi: Honoraria; Bayer, BMS/Pfizer: Research Funding. Bandman: Sanofi: Ended employment in the past 24 months. Arora: Principia Biopharma Inc, a Sanofi Company: Ended employment in the past 24 months. Burns: Sanofi: Ended employment in the past 24 months. Yao: Sanofi: Current Employment. Daak: Sanofi: Current Employment. Sourdille: Sanofi: Current Employment. Thomas: Chinook and Equillium Biopharma: Current holder of individual stocks in a privately-held company; Chinook: Membership on an entity's Board of Directors or advisory committees; Equillium Biopharma: Current Employment; Principia, a Sanofi Company: Ended employment in the past 24 months; Equillium Biopharma: Current equity holder in publicly-traded company. Neale: Principia Biopharma/Sanofi: Ended employment in the past 24 months; Principia Biopharma: Divested equity in a private or publicly-traded company in the past 24 months. Cooper: Sanofi and Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations expenses; Principia and Sanofi: Consultancy. OffLabel Disclosure: Rilzabrutinib is an investigational therapy being evaluated in a clinical study for the treatment of patients with immune thrombocytopenia.
- Published
- 2021
16. The Effect of COVID-19 Vaccine in Patients with Immune Thrombocytopenia
- Author
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Chantal Visser, Maurice Swinkels, Erik D. van Werkhoven, F. Nanne Croles, Heike Noordzij, Matthijs Eefting, Suzanne M. Last-Koopmans, Cecile Idink, Peter E. Westerweel, Bart Santbergen, Pieter A. Jobse, Fazil Baboe, Recovac-IR Consortium, Mark-David Levin, Marieke J.H.A. Kruip, and A.J. Gerard Jansen
- Subjects
Coronavirus disease 2019 (COVID-19) ,business.industry ,Immunology ,Medicine ,In patient ,Cell Biology ,Hematology ,business ,Biochemistry ,Immune thrombocytopenia - Abstract
Background: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder against platelets characterized by a low platelet count and increased bleeding risk. ITP is likely to rise from defective immune tolerance in addition to a triggering event, such as vaccination. COVID-19 vaccination is associated with a small increased risk of development of de novo ITP. In patients historically diagnosed with ITP, relapse of thrombocytopenia after COVID-19 vaccination has been described. However, the precise platelet dynamics in previously diagnosed ITP patients after COVID-19 vaccination is unknown Aims: To investigate the effect of the COVID-19 vaccine on platelet count, the occurrence of severe bleeding complications and necessity of rescue medication in patients historically diagnosed with ITP. Methods: Platelet counts of ITP patients and healthy controls were collected immediately before, 1 and 4 weeks after the first and second vaccination. Linear mixed effects modelling was applied to analyse platelet count dynamics over time. Results: We included 218 ITP patients (50.9% women) with a mean (SD) age of 58 (17) years and 200 healthy controls (60.0% women) with a mean (SD) age of 58 (13) years. Healthy controls and ITP patients had similar baseline characteristics (Table 1). 201/218 (92.2%)ITP patients received the mRNA-1273 vaccine, 16/218 (7.3%) the BNT162b vaccine and 1/218 (0.46%) the Vaxzevria vaccine. All healthy controls received the mRNA-1273 vaccine. Fifteen (6.8%) patients needed rescue medication (Table 1). Significantly more ITP patients who needed rescue medication were on ITP treatment prior COVID-19 vaccination compared to patients without exacerbation (56.2% (7/16) vs 27.4% (55/202), p=0.016). We found a significant effect of vaccination on platelet count over time in both ITP patients and healthy controls (Figure 1A). Platelet counts of ITP patients decreased 7.9% between baseline and 4 weeks after second vaccination (p=0.045). Rescue medication and prior treatment significantly increased platelet count over time (p=0.042 and p=0.044). Healthy controls decreased 4.5% in platelet count (p IPT patients with a baseline platelet count of >150x10 9/L had a significant decrease of platelet count 4 weeks after second vaccination compared to baseline (median platelet count (IQR) 205 (94) vs 203 x10 9/L (109) p=0.001). No significant decrease was seen in ITP patients with a baseline platelet count Median (IQR) platelet counts were similar between patients with and without exacerbation, except for 4 weeks after second vaccination (112 (105) vs 45 x 10 9/L (70), p=0.025) (Figure 1B). No significant effect was observed over time in ITP patients with rescue medication (p=0.478) (Figure 1C). In ITP patients without rescue medication, COVID-19 vaccination had a significant effect over time (p=0.001), especially 1 week after second vaccination (Figure1B). Of the 15 patients who needed rescue medication, 8/15 patients (53.3%) received rescue medication within 4 weeks after first vaccination and 4/15 (26.67%) needed rescue medication after the first as well as after the second vaccination. 3/15 (20.0%) patients needed rescue medication after the second vaccination. In the total ITP population, 5/218 (2.2%) experienced a WHO grade 2-4 bleeding complication and 3/218 (1.4%) needed platelet transfusion. 4/5 (80%) bleedings occurred before the second vaccination. One of these patients had fatal varices bleeding, although platelet count was normal. Conclusion: COVID-19 vaccination has a significant effect on platelet count in ITP patients and healthy controls. In 6.8% of ITP patients rescue medication was needed and in 2.2% of ITP patients a WHO grade 2-4 bleeding occurred. The majority of rescue medication was given and the majority bleeding complications occurred in the 4 weeks after the first vaccination. Our results demonstrate that close monitoring of platelet count after COVID-19 vaccination is important in patients historically diagnosed with ITP. Figure 1 Figure 1. Disclosures Westerweel: Pfizer: Consultancy; BMS / Celgene: Consultancy; Incyte: Consultancy; Novartis: Research Funding. Levin: Roche, Janssen, Abbvie: Other: Travel Expenses, Ad-Board. Kruip: Bayer: Honoraria, Research Funding; Daiichi Sankyo: Research Funding. Jansen: Novartis: Consultancy, Other: Travel, Accommodations, Expenses; Advisory Board Novartis: Membership on an entity's Board of Directors or advisory committees; 3SBIO, Novartis: Other: Travel, accomodations, expenses.
- Published
- 2021
17. Therapeutic plasma exchange for anticoagulant-refractory antiphospholipid syndrome with severe ischemic and necrotic skin lesions: A case series
- Author
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Frank W.G. Leebeek, Peter A. W. te Boekhorst, A.J. Gerard Jansen, F. Nanne Croles, and Hematology
- Subjects
Male ,medicine.medical_specialty ,Necrosis ,medicine.drug_class ,Skin Diseases ,Gastroenterology ,Refractory ,Ischemia ,Antiphospholipid syndrome ,Internal medicine ,Humans ,Medicine ,Glucocorticoids ,Aged ,Lupus anticoagulant ,Plasma Exchange ,biology ,business.industry ,Anticoagulant ,Anticoagulants ,Thrombosis ,Hematology ,Heparin ,Heparin, Low-Molecular-Weight ,Middle Aged ,Antiphospholipid Syndrome ,medicine.disease ,Immunoglobulin M ,beta 2-Glycoprotein I ,Antibodies, Anticardiolipin ,Immunoglobulin G ,Lupus Coagulation Inhibitor ,biology.protein ,Female ,medicine.symptom ,Antibody ,business ,medicine.drug - Abstract
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by clinical findings including thrombosis and/or obstetric complication and laboratory findings, e.g. ≥1 positive antiphospholipid antibodies (aPL) (lupus anticoagulant, anticardiolipin IgG/IgM and/or anti-β2-glycoprotein IgG/IgM). A rare APS clinical entity is severe necrosis which is difficult to treat and often does not respond to anticoagulant therapy. Three consecutive patients with primary or secondary APS who presented with necrotic skin lesions secondary to APS were treated with therapeutic plasma exchange (TPE), glucocorticoids and low-molecular-weight heparin. All patients had a rapid-onset, either full or significant recovery of their APS-related necrotic lesions. Upon treatment, one patients showed resolution of lupus anticoagulant. Two patients had a decrease of at least 88 % in aPL titers after the initial treatment, and were kept on TPE maintenance every 5–6 weeks. None of the patients experienced significant side effects of the TPE. This is the first case series showing the clinical benefits of TPE in patients with ischemic and necrotic skin lesions due to severe anticoagulant-refractory vascular APS.
- Published
- 2021
18. Severe postpartum haemorrhage as first presenting symptom of an inherited bleeding disorder
- Author
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Johannes J. Duvekot, Moniek P.M. de Maat, Frank W G Leebeek, Willy Visser, Caroline S B Veen, Celesta W. A. Schipaanboord, Irene S van der Reijken, Marieke J. H. A. Kruip, A.J. Gerard Jansen, Hematology, and Obstetrics & Gynecology
- Subjects
Adult ,medicine.medical_specialty ,Pediatrics ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,Blood loss ,Risk Factors ,Internal medicine ,medicine ,Von Willebrand disease ,Outpatient clinic ,Humans ,Genetics (clinical) ,Retrospective Studies ,Hematology ,biology ,business.industry ,Postpartum Hemorrhage ,General Medicine ,Bleed ,Blood Coagulation Disorders ,medicine.disease ,Postpartum haemorrhage ,biology.protein ,Maternal death ,Female ,business ,030215 immunology - Abstract
Introduction: Postpartum haemorrhage (PPH) is the major cause of maternal death worldwide. Haemostatic abnormalities are independently associated with a signifi‐ cantly increased risk for severe PPH. In this study, the value of haemostatic evalua‐ tion in women with severe PPH was explored. Aim: To investigate the occurrence of previously unknown inherited bleeding disor‐ ders in women with severe PPH. Methods: Women with severe PPH (blood loss of ≥2000 mL) between 2011 and 2017, referred to the haematology outpatient clinic for haemostatic evaluation, were retrospectively included. A bleeding disorder was diagnosed based on (inter)national guidelines, or when having a clear bleeding phenotype, not fulfilling any diagnos‐ tic criteria or laboratory abnormalities, this being classified as Bleeding of Unknown Cause (BUC). Logistic regression was used to model the association between diagno‐ sis and obstetrical causes and risk factors for PPH. Results: In total, 85 women with PPH were included. In 23% (n = 16), a mild bleed‐ ing disorder was diagnosed, including low von Willebrand factor (Low VWF 8/16), platelet function disorders (PFD 5/16), BUC (2/16) and von Willebrand disease type 1 (1/16). No significant associations were found between obstetrical causes or risk factors for PPH and the presence of a bleeding disorder. Conclusion: In 23% of women with severe PPH, a mild bleeding disorder was di‐ agnosed, independent of obstetrical causes or risk factors for PPH. This implies that severe PPH can be the first clinical symptom of an inherited bleeding disor‐ der. Therefore, to optimize clinical management, haemostatic evaluation after severe PPH is recommended.
- Published
- 2019
19. Determinants of health-related quality of life in the postpartum period after obstetric complications
- Author
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A.J. Gerard Jansen, Marie-Louise Essink-Bot, Ben W.J. Mol, Babette W. Prick, Dick J. van Rhenen, Kim E. Boers, Corine M. Koopmans, Sicco A. Scherjon, Johannes J. Duvekot, Mariëlle G. van Pampus, Denise Bijlenga, Reproductive Origins of Adult Health and Disease (ROAHD), Obstetrics & Gynecology, Amsterdam Public Health, Public and occupational health, and Obstetrics and Gynaecology
- Subjects
Adult ,Gestational hypertension ,medicine.medical_specialty ,IMPACT ,Health-related quality of life ,Birth weight ,Population ,TERM ,law.invention ,Young Adult ,DELIVERY ,HEMORRHAGE ,Obstetric labor complications ,Randomized controlled trial ,law ,medicine ,Humans ,education ,reproductive and urinary physiology ,Pregnancy ,education.field_of_study ,Cesarean Section ,Obstetrics ,Vaginal delivery ,business.industry ,WOMEN ,Obstetrics and Gynecology ,Postpartum period ,medicine.disease ,BIRTH-WEIGHT ,humanities ,Obstetric labor complication ,PREECLAMPSIA ,PREGNANCY ,Socioeconomic Factors ,Pregnancy complications ,Reproductive Medicine ,INCONTINENCE ,Quality of Life ,Regression Analysis ,Female ,TRIAL ,business - Abstract
Objective: To determine the influence of socio-demographic, clinical parameters and obstetric complications on postpartum health-related quality of life (HRQoL).Study design: We used data of three randomized controlled trials to investigate HRQoL determinants in women after an obstetric complication. The DIGITAT and HYPITAT trials compared induction of labor and expectant management in women with intra-uterine growth restriction (IUGR) and hypertensive disorders. The WOMB trial randomized anemic women after postpartum hemorrhage to red blood cell transfusion or expectant management. The HRQoL-measure Short-Form36 was completed at six weeks postpartum. Multivariable analyses were used to identify which parameters affected the Short-Form36 physical component score (PCS) and mental component score (MCS).Results: HRQoL analyses included 1391 women (60%) of the 2310 trial participants. HYPITAT and DIGITAT participants had significantly lower MCS than WOMB participants. In multivariable analysis, PCS after elective and emergency cesarean section was 5-6 points lower than after vaginal delivery. Gestational hypertension, neonatal admission and delivery in an academic hospital had a small negative effect on PCS. No effect was found for randomization status, maternal age, BMI, country of birth, education, parity, induction of labor, analgesics, birth weight, perineal laceration, delivery of placenta, postpartum hemorrhage, congenital anomaly, urinary tract infection, thromboembolic event or endometritis. MCS was influenced only mildly by these parameters.Conclusions: IUGR and hypertensive disorders lead to lower HRQoL scores postpartum than PPH. In a heterogeneous obstetric population, only mode of delivery by cesarean section has a profound, negative impact, on physical HRQoL (PCS). No profound impacts on MCS were detected. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2015
20. Psychometric evaluation of health-related quality of life measures in women after different types of delivery
- Author
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A.J. Gerard Jansen, Dick J. van Rhenen, Johannes J. Duvekot, Marie-Louise Essink-Bot, Public Health, Obstetrics & Gynecology, Hematology, and Public and occupational health
- Subjects
Adult ,Longitudinal study ,medicine.medical_specialty ,Psychometrics ,Personality Inventory ,Test validity ,Cronbach's alpha ,Quality of life ,Medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Fatigue ,business.industry ,Vaginal delivery ,Cesarean Section ,Postpartum Period ,Discriminant validity ,Construct validity ,Delivery, Obstetric ,Psychiatry and Mental health ,Clinical Psychology ,Elective Surgical Procedures ,Physical therapy ,Hemoglobinometry ,Quality of Life ,Female ,Emergencies ,business ,Attitude to Health - Abstract
OBJECTIVE: We examined the psychometric properties of three internationally established measures for health-related quality of life (HRQoL) in women after vaginal delivery (VD), elective cesarean section (CS), and emergency CS and the relationship of HRQoL scores with blood loss after delivery. METHODS: This is a prospective longitudinal study. One hundred forty-one consecutive patients (71 after VD, 36 after elective CS, and 34 after emergency CS) were enrolled in two university hospitals and one general hospital from June 2003 to March 2004. Women completed the Multidimensional Fatigue Inventory (MFI) and the EQ-5D classification of own health between 12 and 24 h after VD or between 24 and 48 h after CS. Subsequent assessments, additionally including the Short Form 36 (SF-36), were made 1, 3, and 6 weeks after delivery. We analyzed feasibility (response, completion time, reported difficulties, item nonresponse), reliability (Cronbach's alpha), discriminative validity between groups by type of delivery, and responsiveness over time (Wilcoxon's signed rank tests and effect sizes). RESULTS: The MFI, SF-36, and EQ-5D proved to be highly feasible and reliable (alpha>.7 for all scales of MFI and SF-36). The measures were able to discriminate between groups by mode of delivery and to detect moderate recovery in physical and small recovery in mental status over time in the first 6 weeks after delivery. The suboptimal total questionnaire response of 60% after 6 weeks was attributable to low response among women of non-Dutch ethnic origin. The significant correlation between Hb level and mean physical HRQoL scores found at T=0 disappeared 1 week postpartum. CONCLUSION: The combination of MFI, SF-36, and EQ-5D showed good psychometric performance and is a good choice to measure HRQoL after delivery in scientific studies. Development of a shorter set is needed for use in routine clinical practice
- Published
- 2007
21. New insights into fatigue and health-related quality of life after delivery
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Marie-Louise Essink-Bot, Dick J. van Rhenen, Johannes J. Duvekot, Veronique H.M. Karsdorp, Wim C. J. Hop, Erik A M Beckers, Eric A.P. Steegers, Sicco A. Scherjon, A.J. Gerard Jansen, Obstetrics & Gynecology, Epidemiology, Public Health, Hematology, and Public and occupational health
- Subjects
Adult ,medicine.medical_specialty ,Anemia ,Cohort Studies ,Hemoglobins ,Quality of life ,Pregnancy ,Surveys and Questionnaires ,Humans ,Medicine ,Childbirth ,Prospective Studies ,Prospective cohort study ,Fatigue ,Anemia, Iron-Deficiency ,Vaginal delivery ,business.industry ,Obstetrics and Gynecology ,Puerperal Disorders ,General Medicine ,Delivery, Obstetric ,medicine.disease ,humanities ,Clinical trial ,Quality of Life ,Physical therapy ,Female ,business ,Cohort study - Abstract
Background. A delivery has a major impact on the health-related quality of life (HRQoL) of the new mother, especially on fatigue. A common complication during delivery that might have a relationship with maternal morbidity is blood loss. The objectives were to investigate fatigue and HRQoL in women after vaginal delivery (VD), elective caesarean section (CS) and emergency CS, and its relationship with postpartum hemoglobin (Hb) levels during the first 6 weeks postpartum. Methods. Some 141 patients (71 after VD, 36 after elective CS and 34 after emergency CS) completed the HRQoL questionnaires MFI and EQ-5D between 12 and 24 h after VD and 24-48 h after CS (t=0). At 1, 3 and 6 weeks postpartum these questionnaires were repeated, together with the SF36. Results. Patients after VD had higher mean physical HRQoL scores than after CS. The average period to reach full physical recovery was 3 weeks after VD, 6 weeks after elective CS, and >6 weeks after emergency CS. Mean mental HRQoL scores of the study groups were similar or even better compared to reference values. The significant correlation between Hb level and mean physical HRQoL scores found at t=0 had disappeared at 1 week postpartum. Conclusions. Results of this study provided insights into the natural course of fatigue and HRQoL postpartum. Important differences in fatigue and HRQoL scores were observed between the 3 modes of delivery. These HRQoL measures can be used in future clinical trials to assess the effects of interventions postpartum.
- Published
- 2007
22. P44. The effect of hypertensive disorders in pregnancy on quality of life post partum
- Author
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Eric A.P. Steegers, Ivette Meester, A.J. Gerard Jansen, Johannes J. Duvekot, Gerhard H. Visser, and Ingrid A. Brussé
- Subjects
Pregnancy ,medicine.medical_specialty ,Quality of life (healthcare) ,Obstetrics ,business.industry ,Internal Medicine ,medicine ,Obstetrics and Gynecology ,medicine.disease ,business ,Post partum - Published
- 2015
23. Platelets Can Phagocytose Influenza Virus Which May Contribute to the Occurrence of Thrombocytopenia during Influenza Infection
- Author
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Hui Zhi Low, Debbie van Riel, A.J. Gerard Jansen, Erhard van der Vries, Albert D. M. E. Osterhaus, and Judith M. A. van den Brand
- Subjects
0301 basic medicine ,Oseltamivir ,Immunology ,Orthomyxoviridae ,030204 cardiovascular system & hematology ,Biology ,medicine.disease_cause ,Biochemistry ,Virus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Influenza A virus ,Platelet ,virus diseases ,Cell Biology ,Hematology ,biology.organism_classification ,Virology ,Influenza A virus subtype H5N1 ,Sialic acid ,030104 developmental biology ,chemistry ,Viral load - Abstract
Thrombocytopenia is a common and sometimes life-threatening symptom in patients with influenza, which indicates that platelets may play a significant role during virus infection. However, the mechanisms underlying influenza associated thrombocytopenia are still unclear to date. In this study, the relationship between platelets and influenza infection was studied in vivo and in vitro. In the period 2009-2012 we randomly measured viral load and platelet count in laboratory-confirmed influenza patients (A/H1N1 subtype; n=85) presented at the emergency department of Erasmus MC. In a cross-sectional study we found, after excluding patients with HIV infection, chemotherapy treatment and immediate referral to the ICU, that a high viral load was significantly correlated with a low platelet count at presentation (n=36; Spearman correlation coefficient 0.341; P=0.042). To study this relationship further we inoculated ferrets (n=120) with an H3N2 (n=30), pandemic H1N1 (n=30), or H5N1 influenza A virus (n=30) and measured platelet counts in six ferrets per time point at day 0, 1, 2, 3 and 4 after infection. Thrombocytopenia was seen at day 3 in all ferrets compared to the control animals (n=30). The decrease in platelet counts was significant in the H5N1 infected ferrets (p Finally, we studied the interaction between platelets and influenza viruses by electron microscopy. In a platelet suspension incubated for 1 minute with influenza virus we observed platelets with virus containing vacuoles, suggesting that the platelets had rapidly phagocytosed the viruses. Characteristics of these platelets incubated with influenza virus were measured including membrane expression of the GPIb-IX-V complex, CD62P, and surface glycans sialic acid and GlcNac using flowcytometry and functional capacity employing aggregometry using collagen, thrombin and ADP as agonists. However, no effect was seen in expression of GPIba and GPIX, P-selectin expression and surface expression of sialic acid and GlcNAc after incubation with influenza virus. Also no effect was seen on functional capacity of these platelets. Our study shows that influenza virus is significantly correlated with a lower platelet count. Phagocytosis of influenza virus by platelets may play an important role in the occurrence of thrombocytopenia during influenza infection and may be a mechanism of virus clearance during infection. Disclosures Osterhaus: Viroclinics Biosciences: Other: chief scientific officer and hold certificates of shares.
- Published
- 2016
24. Well being of obstetric patients on minimal blood transfusions (WOMB trial)
- Author
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Anneke Kwee, Martina Porath, Babette W. Prick, Aren J. van Loon, D.N. Papatsonis, Godfried C.H. Metz, Nico W.E. Schuitemaker, Kim E. Boers, Bettina M.C. Akerboom, Marcel van Alphen, Marc E. A. Spaanderman, Joris A. M. van der Post, N. Peters, A.J. Gerard Jansen, R.H. Stigter, Ben W.J. Mol, H.A. Bremer, Eric A. P. Steegers, Frans J.M.E. Roumen, Marie-Louise Essink-Bot, Hubertina C.J. Scheepers, Kitty W.M. Bloemenkamp, Carin A. Uyl-de Groot, D. H. Schippers, Wim C. J. Hop, Dick J. van Rhenen, Johannes J. Duvekot, Robbert J.P. Rijnders, Amsterdam Public Health, Public and occupational health, Amsterdam Reproduction & Development (AR&D), Obstetrics and Gynaecology, and Obstetrics & Gynecology
- Subjects
medicine.medical_specialty ,Blood transfusion ,Anemia ,medicine.medical_treatment ,Population ,lcsh:Gynecology and obstetrics ,Study Protocol ,Clinical Protocols ,Pregnancy ,Obstetrics and Gynaecology ,Pelvic inflammatory disease ,medicine ,Humans ,education ,Intensive care medicine ,Misoprostol ,lcsh:RG1-991 ,Netherlands ,education.field_of_study ,business.industry ,Postpartum Hemorrhage ,Obstetrics and Gynecology ,Retrospective cohort study ,medicine.disease ,Surgery ,Clinical research ,Research Design ,Practice Guidelines as Topic ,Quality of Life ,Female ,business ,Erythrocyte Transfusion ,medicine.drug - Abstract
Background Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands. Methods/Design The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs. The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%). Discussion This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs. Trial registration ClinicalTrials.gov NCT00335023, Nederlands Trial Register NTR335
- Published
- 2010
25. 64: RBC transfusion leads to an improvement of physical fatigue in women with acute postpartum anemia: the WOMB study (NCT00335023)
- Author
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Martina Porath, Anneke Kwee, Aren J. van Loon, Johannes J. Duvekot, Frans J.M.E. Roumen, Dimitri N.M. Papatsonis, D. H. Schippers, R.H. Stigter, Kim E. Boers, Robbert J.P. Rijnders, Henk A. Bremer, Godfried C.H. Metz, Babette W. Prick, A.J. Gerard Jansen, Marc E. A. Spaanderman, Carin A. Uyl-de Groot, Nico W.E. Schuitemaker, Ben W.J. Mol, Bettina M.C. Akerboom, Wim C. J. Hop, Joris A. M. van der Post, Marcel van Alphen, Dick J. van Rhenen, Eric A.P. Steegers, Marie-Louise Essink-Bot, Hubertina C.J. Scheepers, and Kitty W.M. Bloemenkamp
- Subjects
Rbc transfusion ,medicine.medical_specialty ,Physical Fatigue ,business.industry ,Anemia ,Emergency medicine ,Physical therapy ,Obstetrics and Gynecology ,Medicine ,business ,medicine.disease - Published
- 2012
26. Thrombopoietin-Receptor Agonists for Immune Thrombocytopenia
- Author
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Reinout M. Swart, Peter A. W. te Boekhorst, and A.J. Gerard Jansen
- Subjects
Thrombopoietin Receptor Agonists ,business.industry ,Recombinant Fusion Proteins ,food and beverages ,Receptors, Fc ,General Medicine ,Benzoates ,Thrombocytopenia ,Immune thrombocytopenia ,Autoimmune Diseases ,Hydrazines ,Thrombopoietin ,hemic and lymphatic diseases ,Immunology ,Humans ,Pyrazoles ,Medicine ,Female ,business ,Receptors, Thrombopoietin - Abstract
To the Editor: In response to the review by Imbach and Crowther (Aug. 25 issue)1 of thrombopoietin-receptor agonists for primary immune thrombocytopenia: we would like to draw attention to the fact...
- Published
- 2011
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