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3. Evaluating the clinical validity of genes related to hemostasis and thrombosis using the Clinical Genome Resource gene curation framework

Author

Ross, Justyne E., Mohan, Shruthi, Zhang, Jing, Sullivan, Mia J., Bury, Loredana, Lee, Kristy, Futchi, Isabella, Frantz, Annabelle, McDougal, Dara, Perez Botero, Juliana, Cattaneo, Marco, Cooper, Nichola, Downes, Kate, Gresele, Paolo, Keenan, Catriona, Lee, Alfred I., Megy, Karyn, Morange, Pierre-Emmanuel, Morgan, Neil V., Schulze, Harald, Zimowski, Karen, Freson, Kathleen, and Lambert, Michele P.

Published
2024
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4. The role of CD8+ T-cell clones in immune thrombocytopenia

Author

Malik, Amna, Sayed, Anwar A., Han, Panpan, Tan, Michelle M. H., Watt, Eleanor, Constantinescu-Bercu, Adela, Cocker, Alexander T. H., Khoder, Ahmad, Saputil, Rocel C., Thorley, Emma, Teklemichael, Ariam, Ding, Yunchuan, Hart, Alice C. J., Zhang, Haiyu, Mitchell, Wayne A., Imami, Nesrina, Crawley, James T. B., Salles-Crawley, Isabelle I., Bussel, James B., Zehnder, James L., Adams, Stuart, Zhang, Bing M., and Cooper, Nichola

Published
2023
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8. Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19

Author

Maher, Allison K., Burnham, Katie L., Jones, Emma M., Tan, Michelle M. H., Saputil, Rocel C., Baillon, Laury, Selck, Claudia, Giang, Nicolas, Argüello, Rafael, Pillay, Clio, Thorley, Emma, Short, Charlotte-Eve, Quinlan, Rachael, Barclay, Wendy S., Cooper, Nichola, Taylor, Graham P., Davenport, Emma E., and Dominguez-Villar, Margarita

Published
2022
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9. Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA)

Author

Rosas, Ivan O., Bräu, Norbert, Waters, Michael, Go, Ronaldo C., Malhotra, Atul, Hunter, Bradley D., Bhagani, Sanjay, Skiest, Daniel, Savic, Sinisa, Douglas, Ivor S., Garcia-Diaz, Julia, Aziz, Mariam S., Cooper, Nichola, Youngstein, Taryn, Sorbo, Lorenzo Del, Zerda, David J. De La, Ustianowski, Andrew, Gracian, Antonio Cubillo, Blyth, Kevin G., Carratalà, Jordi, François, Bruno, Benfield, Thomas, Haslem, Derrick, Bonfanti, Paolo, van der Leest, Cor H., Rohatgi, Nidhi, Wiese, Lothar, Luyt, Charles Edouard, Bauer, Rebecca N., Cai, Fang, Lee, Ivan T., Matharu, Balpreet, Metcalf, Louis, Wildum, Steffen, Graham, Emily, Tsai, Larry, and Bao, Min

Published
2022
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11. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells

Author

Chauss, Daniel, Freiwald, Tilo, McGregor, Reuben, Yan, Bingyu, Wang, Luopin, Nova-Lamperti, Estefania, Kumar, Dhaneshwar, Zhang, Zonghao, Teague, Heather, West, Erin E., Vannella, Kevin M., Ramos-Benitez, Marcos J., Bibby, Jack, Kelly, Audrey, Malik, Amna, Freeman, Alexandra F., Schwartz, Daniella M., Portilla, Didier, Chertow, Daniel S., John, Susan, Lavender, Paul, Kemper, Claudia, Lombardi, Giovanna, Mehta, Nehal N., Cooper, Nichola, Lionakis, Michail S., Laurence, Arian, Kazemian, Majid, and Afzali, Behdad

Published
2022
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17. Real‐world use of thrombopoietin receptor agonists for the management of immune thrombocytopenia in adult patients in the United Kingdom: Results from the TRAIT study.

Author

Cooper, Nichola, Scully, Marie, Percy, Charles, Nicolson, Phillip L. R., Lowe, Gillian, Bagot, Catherine N., Thachil, Jecko, Grech, Henri, Nokes, Tim, Hill, Quentin A., Bradbury, Charlotte, Talks, Kate, Dutt, Tina, Evans, Gillian, Pavord, Sue, Wexler, Sarah, Charania, Asad, Collington, Sarah J., Ervin, Andrew, and Ramscar, Nicholas

Subjects
*THROMBOPOIETIN receptor agonists, *IDIOPATHIC thrombocytopenic purpura, *PLATELET count, *ROMIPLOSTIM, *ELTROMBOPAG
Abstract

Summary: Few studies have reported the real‐world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO‐RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO‐RA. A platelet count ≥30 × 109/L was achieved in 89% of patients with the first TPO‐RA treatments, while 68% achieved a platelet count ≥100 × 109/L. Treatment‐free response (TFR; platelet count ≥30 × 109/L, 3 months after discontinuing treatment) was achieved by 18% of the total patients. Overall, 61 patients (23%) switched TPO‐RAs, most of whom achieved platelet counts ≥30 × 109/L with the second TPO‐RA (23/25 who switched from eltrombopag to romiplostim [92%]; 28/36 who switched from romiplostim to eltrombopag [78%]). TFR was associated with secondary ITP, early TPO‐RA initiation after diagnosis, the presence of comorbidity and no prior splenectomy or treatment with steroids or mycophenolate mofetil. Both TPO‐RAs had similar efficacy and safety profiles to those reported in clinical studies. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Multi-arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate COVID-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial

Author

Vergis, Nikhil, Phillips, Rachel, Cornelius, Victoria, Katsarou, Alexia, Youngstein, Taryn, Cook, Lucy, Willicombe, Michelle, Pilay, Clio, Shturova, Tina, Almonte, Melanie, Charania, Asad, Turner, Richard, Kon, Onn Min, Cooke, Graham, Thursz, Mark, Cherlin, Svetlana, Wason, James, Milojkovic, Dragana, Innes, Andew J., and Cooper, Nichola

Published
2021
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20. Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders

Author

Downes, Kate, Megy, Karyn, Duarte, Daniel, Vries, Minka, Gebhart, Johanna, Hofer, Stefanie, Shamardina, Olga, Deevi, Sri V.V., Stephens, Jonathan, Mapeta, Rutendo, Tuna, Salih, Al Hasso, Namir, Besser, Martin W., Cooper, Nichola, Daugherty, Louise, Gleadall, Nick, Greene, Daniel, Haimel, Matthias, Martin, Howard, Papadia, Sofia, Revel-Vilk, Shoshana, Sivapalaratnam, Suthesh, Symington, Emily, Thomas, Will, Thys, Chantal, Tolios, Alexander, Penkett, Christopher J., Ouwehand, Willem H., Abbs, Stephen, Laffan, Michael A., Turro, Ernest, Simeoni, Ilenia, Mumford, Andrew D., Henskens, Yvonne M.C., Pabinger, Ingrid, Gomez, Keith, and Freson, Kathleen

Published
2019
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21. Updated international consensus report on the investigation and management of primary immune thrombocytopenia

Author

Provan, Drew, Arnold, Donald M., Bussel, James B., Chong, Beng H., Cooper, Nichola, Gernsheimer, Terry, Ghanima, Waleed, Godeau, Bertrand, González-López, Tomás José, Grainger, John, Hou, Ming, Kruse, Caroline, McDonald, Vickie, Michel, Marc, Newland, Adrian C., Pavord, Sue, Rodeghiero, Francesco, Scully, Marie, Tomiyama, Yoshiaki, Wong, Raymond S., Zaja, Francesco, and Kuter, David J.

Published
2019
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22. The role of Protein Kinase Cα in the skin and cutaneous wound healing

Author

Cooper, Nichola, Hardman, Matthew, and Travis, Mark

Subjects
617.1, Desmosome, Wound healing, Collagen, Extracellular matrix
Abstract

Chronic wounds represent a severe socio-economic burden and a key area of unmet clinical need. PKCα is ubiquitous in the skin, particularly the epidermis and functions in numerous pathways that are fundamental to wound repair. By utilising a global PKCα-/- mouse we have identified PKCα-regulated processes both in unwounded skin and during wound healing. PKCα-/- mice display considerably delayed wound healing with a dramatic reduction in re-epithelialisation. By analysing the ultrastructure of the epidermis, I have shown that this delay directly correlates with a failure of wound edge desmosomes to switch to a their adhesive properties. A major risk factor for the development of chronic wounds is age. Crucially, this delay in modulating cell adhesion is conserved in human chronic wounds and aged murine skin. Furthermore, manipulation of PKCα using an inducible bitransgenic mouse containing epidermal specific constitutively active PKCα can accelerate the modulation of desmosome adhesion and subsequently improve re-epithelialisation. Global gene expression analysis of PKCα-/- skin and wounds revealed further defects. Upon wounding, we observed a failure to correctly regulate expression of key collagen and Wnt signalling genes that are essential for correct and timely wound healing. Finally, intrinsic gene expression changes were identified in the skin of PKCα-/- mice, specifically a downregulation of multiple extracellular matrix genes. Of note was the downregulation of small leucine-rich proteoglycans which led to alterations to dermal collagen structure and skin tensile strength. These changes render the PKCα-/- skin susceptible to breaking and wound development. To conclude, we have identified multiple roles for PKCα intrinsically in the skin and also during cutaneous wound healing. Importantly, these intrinsic changes appear to predispose PKCα-/- skin to the development of cutaneous wounds and altered wound-specific processes that manifest in a delayed healing phenotype.

Published
2014

24. Human retinoic acid–regulated CD161+ regulatory T cells support wound repair in intestinal mucosa

Author

Povoleri, Giovanni A. M., Nova-Lamperti, Estefania, Scottà, Cristiano, Fanelli, Giorgia, Chen, Yun-Ching, Becker, Pablo D., Boardman, Dominic, Costantini, Benedetta, Romano, Marco, Pavlidis, Polychronis, McGregor, Reuben, Pantazi, Eirini, Chauss, Daniel, Sun, Hong-Wei, Shih, Han-Yu, Cousins, David J., Cooper, Nichola, Powell, Nick, Kemper, Claudia, Pirooznia, Mehdi, Laurence, Arian, Kordasti, Shahram, Kazemian, Majid, Lombardi, Giovanna, and Afzali, Behdad

Published
2018
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27. Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura

Author

Alwan, Ferras, Vendramin, Chiara, Vanhoorelbeke, Karen, Langley, Katy, McDonald, Vickie, Austin, Steve, Clark, Amanda, Lester, William, Gooding, Richard, Biss, Tina, Dutt, Tina, Cooper, Nichola, Chapman, Oliver, Cranfield, Tanya, Douglas, Kenny, Watson, H.G., van Veen, J.J., Sibson, Keith, Thomas, William, Manson, Lynn, Hill, Quentin A., Benjamin, Sylvia, Ellis, Debra, Westwood, John-Paul, Thomas, Mari, and Scully, Marie

Published
2017
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29. Safety and efficacy of SARS‐CoV‐2 vaccination in patients with immune thrombocytopenia: A two‐centre review.

Author

Stefani, Sara, Buti, Noora, Hart, Alice C. J., Paul, Deena, Rizvi, Naghma, Ragoonanan, Vashti, Vladescu, Camelia, Szydlo, Richard, Ademokun, Christine, Jansen, A. J. Gerard, and Cooper, Nichola

Subjects
IDIOPATHIC thrombocytopenic purpura, SARS-CoV-2, VACCINATION, ANTIBODY formation, PATIENT safety
Abstract

Summary: Multiple studies have reported immune thrombocytopenia (ITP) relapse following SARS‐CoV‐2 vaccination, however baseline ITP relapse rate and antibody response to vaccination are not known. Patients with ITP who received at least one of the first three SARS‐CoV‐2 vaccination doses were included in the study. One hundred and twenty‐four patients met the inclusion criteria. Relapse rate was 4.2% following a first vaccine dose, 9.1% after a second and 2.9% after a third; baseline relapse rate was 7.6%. Ninety‐four per cent of patients who received three vaccine doses developed a clinical antibody response. SARS‐CoV‐2 vaccination appears to be safe and effective in patients with ITP. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Recent advances in understanding spleen tyrosine kinase (SYK) in human biology and disease, with a focus on fostamatinib.

Author

Cooper, Nichola, Ghanima, Waleed, Hill, Quentin A., Nicolson, Phillip L. R., Markovtsov, Vadim, and Kessler, Craig

Subjects
*PROTEIN-tyrosine kinases, *HUMAN biology, *AUTOIMMUNE diseases, *AUTOIMMUNE hemolytic anemia, *SPLEEN, *THERAPEUTICS, *IDIOPATHIC thrombocytopenic purpura
Abstract

Spleen tyrosine kinase (SYK) is an important regulatory molecule of signal transduction pathways involved in the pathogenesis of autoimmune diseases such as immune thrombocytopenia (ITP), and the SYK-signaling pathway has emerged as a potential target for the treatment of numerous diseases. The aim of this narrative review is to summarize the biological properties of SYK and its involvement in disease pathways, provide an update on SYK inhibitors in the treatment of ITP, and consider other potential applications. Fostamatinib, the only licensed SYK inhibitor to date, produces clinical response in ITP patients, including those who are refractory to other treatments. It appears to reduce the risk of thrombotic events and may therefore be a drug to consider for patients with an increased thrombotic risk. Encouraging results have also been obtained in the treatment of warm autoimmune hemolytic anemia. Several other SYK inhibitors have entered clinical trials for a range of indications, reflecting the ability of these drugs to affect multiple signaling pathways. SYK inhibitors have the potential to target several aspects of COVID-19 pathogenesis including thrombosis, without affecting normal hemostasis, and data from the first study of fostamatinib in COVID-19 are encouraging. It is hoped that ongoing trials in autoimmune indications other than ITP, as well as in hematological malignancies and other disorders, confirm the promise of SYK inhibitors. [ABSTRACT FROM AUTHOR]

Published
2023
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32. European Delphi panel to build consensus on tapering and discontinuing thrombopoietin receptor agonists in immune thrombocytopenia.

Author

Barlassina, Adele, José González-López, Tomás, Cooper, Nichola, and Zaja, Francesco

Subjects
THROMBOPOIETIN receptor agonists, IDIOPATHIC thrombocytopenic purpura, LITERATURE reviews, MEDICAL personnel, DELPHI method
Abstract

To establish pan-European consensus on tapering and discontinuing thrombopoietin receptor agonists (TPO-RAs) in patients with immune thrombocytopenia (ITP), we applied a three-step Delphi technique consisting of a one-to-one interview round and two online survey rounds. Three healthcare professionals (HCPs) from Italy, Spain, and the United Kingdom formed the Steering Committee (SC), which advised on study design, panelist selection, and survey development. A literature review also informed the development of the consensus statements. Likert scales were used to collect quantitative data on panelists' level of agreement. Twelve hematologists representing nine European countries assessed 121 statements spanning three categories: (1) patient selection; (2) tapering and discontinuation strategies; (3) post-discontinuation management. Consensus was reached on approximately half of the statements in each category (32.2%; 44.6%; 66%). Panelists agreed on patients' main selection criteria, patients' involvement in decision-making, tapering strategies, and follow-up criteria. Areas not reaching consensus were risk factors and predictors of successful discontinuation, monitoring intervals, and rates of successful discontinuation or relapse. This lack of consensus signals knowledge and practice gaps among European countries and suggests the need for the development of clinical practice guidelines that outline a pan-European, evidence-based approach to tapering and discontinuing TPO-RAs. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Could machine learning revolutionize how we treat immune thrombocytopenia?

Author

Ghanima, Waleed and Cooper, Nichola

Subjects
*THROMBOPOIETIN receptor agonists, *IDIOPATHIC thrombocytopenic purpura, *MACHINE learning, *CORTICOSTEROIDS, *RITUXIMAB
Abstract

The absence of reliable biomarkers in immune thrombocytopenia (ITP) complicates treatment choice, necessitating a trial‐and‐error approach. Machine learning (ML) holds promise for transforming ITP treatment by analysing complex data to identify predictive factors, as demonstrated by Xu et al.'s study which developed ML‐based models to predict responses to corticosteroids, rituximab and thrombopoietin receptor agonists. However, these models require external validation before can be adopted in clinical practice. Commentary on: Xu et al. A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopenia. Br J Haematol 2024; 205:1108‐1120. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD

Author

Khoder, Ahmad, Sarvaria, Anushruti, Alsuliman, Abdullah, Chew, Claude, Sekine, Takuya, Cooper, Nichola, Mielke, Stephan, de Lavallade, Hugues, Muftuoglu, Muharrem, Fernandez Curbelo, Irina, Liu, Enli, Muraro, Paolo A., Alousi, Amin, Stringaris, Kate, Parmar, Simrit, Shah, Nina, Shaim, Hila, Yvon, Eric, Molldrem, Jeffrey, Rouce, Rayne, Champlin, Richard, McNiece, Ian, Mauri, Claudia, Shpall, Elizabeth J., and Rezvani, Katayoun

Published
2014
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36. A HaemSTAR-led, UK-wide 'flash-mob’ audit of ­intravenous immunoglobulin use in immune ­thrombocytopenia

Author

Nicolson, Phillip, Perry, Rita, Fisher, Amelia, Scott, Gemma, Magill, Laura, Chan-Lam, Dominique, Thorpe, Alice, Macheta, Mac, Carter-Brzezinski, Luke, Ackroyd, Sam, Katumba, Alvin, Bradbury, Charlotte, Jen, Sheila, Camillieri, Marquita, Besser, Martin, Bull, Tom, Leighton, Katherine, Ayalew, Yezenash, Willan, John, Watson, Edmund, Oshinyemi, Pamela, Upadhye, Yogesh, Pickard, Keir, Swart-Rimmer, Imogen, Knott, Chloe, Chown, Sally, Crolla, Francesca, Quinn, Daire, McLeod-Kennedy, Lindsay, Oun, Hajer, McDermott, Christopher, Walker, Mairi, Mullally, Ryan, Herlihy, Naoimh, Shah, Gulnaz, Doyle, Andrew, Robinson, Susan, Sayar, Zara, Pryor, Rebecca, Peet, Chris, Shenouda, Amir, Venkatadasari, Indrani, Cartier, Jorge, Akay, Melek, Tsitsikas, Dimitris, Sivapalaratnam, Suthesh, Cooper, Nichola, Lentaigne, Claire, Bailey, Chris, Xu, Dan Mei, Janum, Sine, Mohan, Arunodaya, Kimberger, Katja, Kgologolo, Maipelo, Sevillano, Belen, Hanina, Sophie, Danga, Akila, Mustafa, Chira, Wilding, Charlotte, Trikha, Roochi, Wang, Han, Crossette-Thambiah, Cristina, Hastings, Andrew, Sreedhara, Sree, Wright, David, Batey, Laura, Atkin, Abigail, Davis, Sarah, Jaafar, Sarah, Ejaz, Ayesha, Biss, Tina, Swieton, Jennifer, Noh, Mohd Sharin Mohd, Gibson, Holly, Freeman, Tanya, Badaguma, Upekha, Kreze, Olivia, Kirkpatrick, Suriya, Suntharalingam, Surenthini, Kmonicek, Miroslab, Joffe, Michael, Halperin, Dan, Desborough, Michael, Rampotas, Alexandros, Dhillon, Elissa, Greaves, Paul, Blacker, Edward, Aiken, Laura, Boot, Jesca, Prasannan, Nithya, Kerr, Jonathan, Martin, Abi, Wexler, Sarah, Burney, Claire, Melly, Michelle, Nolan, Regina, Hipkins, Rupert, Kaddam, Israa, Elmoamly, Shereef, Darlow, Jennifer, Plews, Dianne, Shrubsole, Caroline, Loizou, Eleana, Garth, Louise, Peter, Hina, Wolf, Julia, Walia, Shivali, MacDonald, Vickie, Zaidi, Abbas, Dunk, Robert, Miah, Haroon, Miah, Atiqa, Tucker, David, Skinner, Thomas, Cakmak, Seda, Cakmak, Ipek, Hussein, Hayder, Buka, Richard, Wilson, Lydia, Talbot, Georgina, Qureshi, Hafiz, Wharin, Sarah, Dillon, Anna, Bailiff, Benjamin, McIlroy, Graham, Murray, Duncan, Seymour, Frances, Graham, Jane, Harrison, Samuel, Salhan, Beena, Sharpe, David, Thomas, Wayne, McCulloch, Rory, Crosbie, Nicola, Lowe, Gillian, and Hill, Quentin

Published
2019
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38. GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Author

Dixon, Peter H., Levine, Adam P., Cebola, Inês, Chan, Melanie M. Y., Amin, Aliya S., Aich, Anshul, Mozere, Monika, Maude, Hannah, Mitchell, Alice L., Zhang, Jun, Adlard, Julian, Ahmed, Munaza, Aitman, Tim, Alachkar, Hana, Allsup, David, Almeida-King, Jeff, Ancliff, Philip, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Ashford, Sofie, Astle, William, Attwood, Anthony, Babbs, Chris, Bakchoul, Tamam, Bariana, Tadbir, Barwell, Julian, Bennett, David, Bentley, David, Bierzynska, Agnieszka, Biss, Tina, Bleda, Marta, Bogaard, Harm, Bourne, Christian, Boyce, Sara, Bradley, John, Breen, Gerome, Brennan, Paul, Brewer, Carole, Brown, Matthew, Browning, Michael, Buchan, Rachel, Buckland, Matthew, Bueser, Teofila, Burns, Siobhan, Burren, Oliver, Calleja, Paul, Carr-White, Gerald, Carss, Keren, Casey, Ruth, Caulfield, Mark, Chambers, John, Chambers, Jennifer, Cheng, Floria, Chinnery, Patrick F., Christian, Martin, Church, Colin, Brod, Naomi Clements, Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor, Collins, Janine, Collins, Peter, Colombo, Camilla, Condliffe, Robin, Cook, Stuart, Cook, Terry, Cooper, Nichola, Corris, Paul, Crisp-Hihn, Abigail, Curry, Nicola, Danesino, Cesare, Daniels, Matthew, Daugherty, Louise, Davis, John, Deevi, Sri V. V., Dent, Timothy, Dewhurst, Eleanor, Dixon, Peter, Downes, Kate, Drazyk, Anna, Drewe, Elizabeth, Dutt, Tina, Edgar, David, Edwards, Karen, Egner, William, Erber, Wendy, Erwood, Marie, Estiu, Maria C., Evans, Gillian, Evans, Dafydd Gareth, Everington, Tamara, Eyries, Mélanie, Favier, Remi, Fletcher, Debra, Fox, James, Frary, Amy, French, Courtney, Freson, Kathleen, Frontini, Mattia, Gale, Daniel, Gall, Henning, Geoghegan, Claire, Gerighty, Terry, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, Simon, Gilmour, Kimberley, Girerd, Barbara, Goddard, Sarah, Gomez, Keith, Gordins, Pavels, Gosal, David, Gräf, Stefan, Grassi, Luigi, Greene, Daniel, Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip, Grigoriadou, Sofia, Grocock, Russell, Grozeva, Detelina, Hackett, Scott, Hadinnapola, Charaka, Hague, William, Haimel, Matthias, Hall, Matthew, Hanson, Helen, Harkness, Kirsty, Harper, Andrew, Harris, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Henderson, Alex, Hoffmann, Jonathan, Horvath, Rita, Houweling, Arjan, Howard, Luke, Hu, Fengyuan, Hudson, Gavin, Hughes, Joseph, Huissoon, Aarnoud, Humbert, Marc, Humphray, Sean, Hunter, Sarah, Hurles, Matthew, Izatt, Louise, James, Roger, Johnson, Sally, Jolles, Stephen, Jolley, Jennifer, Jurkute, Neringa, Kasanicki, Mary, Kazkaz, Hanadi, Kazmi, Rashid, Kelleher, Peter, Kiely, David, Kingston, Nathalie, Klima, Robert, Kostadima, Myrto, Kovacs, Gabor, Koziell, Ania, Kreuzhuber, Roman, Kuijpers, Taco, Kumar, Ajith, Kumararatne, Dinakantha, Kuria, Manju, Laffa, Michael, Lalloo, Fiona, Lamber, Michele, Alle, Hana Lango, Lawrie, Allan, Layton, Mark, Lentaigne, Claire, Levine, Adam, Linger, Rachel, Longhurst, Hilary, Louka, Eleni, Ross, Robert MacKenzie, Madan, Bella, Maher, Eamonn, Maimaris, Jesmeen, Mangles, Sarah, Mapeta, Rutendo, Marchbank, Kevin, Marks, Stephen, Markus, Hugh S., Marshall, Andrew, Martin, Jennifer, Mathias, Mary, Matthews, Emma, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark, Meacham, Stuart, Mead, Adam, Megy, Karyn, Mehta, Sarju, Michaelides, Michel, Millar, Carolyn, Moledina, Shahin, Montani, David, Moor, Tony, Morrell, Nicholas, Muir, Keith, Mumford, Andrew, Newnham, Michael, O'Sullivan, Jennifer, Obaji, Samya, Okoli, Steven, Olschewski, Andrea, Olschewski, Horst, Ong, Kai Ren, Ormondroy, Elizabeth, Ouwehan, Willem, Papadi, Sofia, Park, Soo-Mi, Parry, David, Paterson, Joan, Peacock, Andrew, Peden, John, Peerlinck, Kathelijne, Penkett, Christopher, Pepke-Zaba, Joanna, Petersen, Romina, Pyle, Angela, Rankin, Stuart, Rao, Anupama, Raymond, F. Lucy, Rayner-Matthew, Paula, Rees, Christine, Rendon, Augusto, Renton, Tara, Rice, Andrew, Richardson, Sylvia, Richter, Alex, Roberts, Irene, Roughley, Catherine, Roy, Noemi, Sadeghi-Alavijeh, Omid, Saleem, Moin, Samani, Nilesh, Sanchis-Juan, Alba, Sargur, Ravishankar, Satchell, Simon, Savic, Sinisa, Scelsi, Laura, Schulman, Sol, Scully, Marie, Searle, Claire, Seeger, Werner, Sewell, Carrock, Seyres, Denis, Shapiro, Susie, Sharmardina, Olga, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simeoni, Ilenia, Simpson, Michael, Sivapalaratnam, Suthesh, Skytte, Anne-Bine, Smith, Katherine, Smith, Kenneth G. C., Snape, Katie, Soubrier, Florent, Staines, Simon, Staples, Emily, Stark, Hannah, Stephens, Jonathan, Stirrups, Kathleen, Stock, Sophie, Suntharalingam, Jay, Swietlik, Emilia, Tait, R. Campbell, Talks, Kate, Tan, Rhea, Thaventhiran, James, Themistocleous, Andreas, Thomas, Moira, Thomson, Kate, Thrasher, Adrian, Thys, Chantal, Tischkowitz, Marc, Titterton, Catherine, Toh, Cheng-Hock, Toshner, Mark, Traylor, Matthew, Treacy, Carmen, Trembath, Richard, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Vale, Tom, Van Geet, Chris, Van Zuydam, Natalie, Vazquez-Lopez, Marta, von Ziegenweidt, Julie, Noordegraaf, Anton Vonk, Waisfisz, Quintin, Walker, Suellen, Ware, James, Watkins, Hugh, Watt, Christopher, Webster, Andrew, Wei, Wei, Welch, Steven, Wessels, Julie, Westbury, Sarah, Westwood, John-Paul, Wharton, John, Whitehorn, Deborah, Whitworth, James, Wilkins, Martin R., Wong, Edwin, Wood, Nicholas, Wood, Yvette, Woods, Geoff, Woodward, Emma, Wort, Stephen, Worth, Austen, Yates, Katherine, Yong, Patrick, Young, Tim, Yu, Ping, Yu-Wai-Man, Patrick, Ambrose, J. C., Arumugam, P., Bevers, R., Bleda, M., Boardman-Pretty, F., Boustred, C. R., Brittain, H., Brown, M. A., Caulfield, M. J., Chan, G. C., Fowler, T., Giess, A., Hamblin, A., Henderson, S., Hubbard, T. J. P., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Kousathanas, A., Lahnstein, L., Leigh, S. E. A., Leong, I. U. S., Lopez, F. J., Maleady-Crowe, F., McEntagart, M., Minneci, F., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A. C., O'Donovan, P., Odhams, C. A., Patch, C., Perez-Gil, D., Pereira, M. B., Pullinger, J., Rahim, T., Rendon, A., Rogers, T., Savage, K., Sawant, K., Scott, R. H., Siddiq, A., Sieghart, A., Smith, S. C., Sosinsky, A., Stuckey, A., Tanguy, M., Taylor Tavares, A. L., Thomas, E. R. A., Thompson, S. R., Tucci, A., Welland, M. J., Williams, E., Witkowska, K., Wood, S. M., Chambers, Jenny, Syngelaki, Argyro, Donnelly, Jennifer, Cooley, Sharon, Geary, Michael, Nicolaides, Kypros, Thorsell, Malin, Hague, William M., Estiu, Maria Cecilia, Marschall, Hanns-Ulrich, Gale, Daniel P., Williamson, Catherine, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, ACS - Atherosclerosis & ischemic syndromes, Pediatrics, Foundation for the National Institutes of Health (FNIH), The Academy of Medical Sciences, British Heart Foundation, Imperial College Healthcare NHS Trust- BRC Funding, Paediatric Infectious Diseases / Rheumatology / Immunology, and ARD - Amsterdam Reproduction and Development

Subjects
VARIANT, LOCI, INTEGRATIVE ANALYSIS, General Physics and Astronomy, Cholestasis, Intrahepatic, TRIGLYCERIDE LEVELS, DISEASE, General Biochemistry, Genetics and Molecular Biology, Bile Acids and Salts, Pregnancy, Humans, MUTATION, Science & Technology, Multidisciplinary, Genomics England Research Consortium Collaborators, Infant, Newborn, NIHR BioResource, General Chemistry, GLUCOCORTICOID-RECEPTOR, Multidisciplinary Sciences, ALKALINE SPHINGOMYELINASE, Pregnancy Complications, INSIGHTS, Science & Technology - Other Topics, Premature Birth, Female, FASTING GLUCOSE, Genome-Wide Association Study
Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility. ispartof: NATURE COMMUNICATIONS vol:13 issue:1 ispartof: location:England status: published

Published
2022

43. Retrospective, Observational, Multicenter Study Assessing the Thrombopoietin Receptor Agonist (TPO-RA) Romiplostim and Other Treatments for Patients with Newly Diagnosed or Persistent Primary Immune Thrombocytopenia (ITP) in Routine Clinical Practice in the United Kingdom (UK)

Author

McDonald, Vickie, Bradbury, Charlotte, Talks, Kate, Lowe, Gillian, Pavord, Sue, Evans, Gillian, Andiappan, Manoharan, Sandschafer, Darcie, De Sousa Barbosa, Vitor Jose, Stephens, Lorraine, and Cooper, Nichola

Published
2022
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44. Tyrosine kinase inhibitors impair B-cell immune responses in CML through off-target inhibition of kinases important for cell signaling

Author

de Lavallade, Hugues, Khoder, Ahmad, Hart, Melanie, Sarvaria, Anushruti, Sekine, Takuya, Alsuliman, Abdullah, Mielke, Stephan, Bazeos, Alexandra, Stringaris, Kate, Ali, Sara, Milojkovic, Dragana, Foroni, Letizia, Chaidos, Aristeidis, Cooper, Nichola, Gabriel, Ian, Apperley, Jane, Belsey, Sarah, Flanagan, Robert J., Goldman, John, Shpall, Elizabeth J., Kelleher, Peter, Marin, David, and Rezvani, Katayoun

Published
2013
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45. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group

Author

Rodeghiero, Francesco, Michel, Marc, Gernsheimer, Terry, Ruggeri, Marco, Blanchette, Victor, Bussel, James B., Cines, Douglas B., Cooper, Nichola, Godeau, Bertrand, Greinacher, Andreas, Imbach, Paul, Khellaf, Mehdi, Klaassen, Robert J., Kühne, Thomas, Liebman, Howard, Mazzucconi, Maria Gabriella, Newland, Adrian, Pabinger, Ingrid, Tosetto, Alberto, and Stasi, Roberto

Published
2013
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46. Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Author

Hadinnapola, Charaka, Bleda, Marta, Haimel, Matthias, Screaton, Nicholas, Swift, Andrew, Dorfmüller, Peter, Preston, Stephen D., Southwood, Mark, Hernandez-Sanchez, Jules, Martin, Jennifer, Treacy, Carmen, Yates, Katherine, Bogaard, Harm, Church, Colin, Coghlan, Gerry, Condliffe, Robin, Corris, Paul A., Gibbs, Simon, Girerd, Barbara, Holden, Simon, Humbert, Marc, Kiely, David G., Lawrie, Allan, Machado, Rajiv, MacKenzie Ross, Robert, Moledina, Shahin, Montani, David, Newnham, Michael, Peacock, Andrew, Pepke-Zaba, Joanna, Rayner-Matthews, Paula, Shamardina, Olga, Soubrier, Florent, Southgate, Laura, Suntharalingam, Jay, Toshner, Mark, Trembath, Richard, Noordegraaf, Anton Vonk, Wilkins, Martin R., Wort, Stephen J., Wharton, John, Gräf, Stefan, Morrell, Nicholas W., Aitman, Timothy, Bennett, David, Caulfield, Mark, Chinnery, Patrick, Gale, Daniel, Koziell, Ania, Kuijpers, Taco W, Laffan, Michael A, Maher, Eamonn, Markus, Hugh S, Ouwehand, Willem H, Perry, David, Raymond, F Lucy, Roberts, Irene, Smith, Kenneth, Thrasher, Adrian, Watkins, Hugh, Williamson, Catherine, Woods, Geoffrey, Ashford, Sofie, Bradley, John R, Fletcher, Debra, Hammerton, Tracey, James, Roger, Kingston, Nathalie, Ouwehand, Willem H, Penkett, Christopher J, Raymond, F Lucy, Stirrups, Kathleen, Veltman, Marijke, Young, Tim, Ashford, Sofie, Brown, Matthew, Clements-Brod, Naomi, Davis, John, Dewhurst, Eleanor, Erwood, Marie, Frary, Amy, Linger, Rachel, Papadia, Sofia, Rehnstrom, Karola, Stark, Hannah, Allsup, David, Austin, Steve, Bakchoul, Tamam, Bariana, Tadbir K, Bolton-Maggs, Paula, Chalmers, Elizabeth, Collins, Peter, Erber, Wendy N, Everington, Tamara, Favier, Remi, Freson, Kathleen, Furie, Bruce, Gattens, Michael, Gomez, Keith, Greene, Daniel, Greinacher, Andreas, Hart, Daniel, Heemskerk, Johan WM, Henskens, Yvonne, Kazmi, Rashid, Keeling, David, Kelly, Anne M, Laffan, Michael A, Lambert, Michele P, Lentaigne, Claire, Liesner, Ri, Mangles, Sarah, Mathias, Mary, Millar, Carolyn M, Mumford, Andrew, Nurden, Paquita, Ouwehand, Willem H, Papadia, Sofia, Payne, Jeanette, Pasi, John, Perry, David J, Peerlinck, Kathelijne, Richards, Michael, Rondina, Matthew, Roughley, Catherine, Schulman, Sol, Schulze, Harald, Scully, Marie, Sivapalaratnam, Suthesh, Tait, R Campbell, Talks, Kate, Thachil, Jecko, Turro, Ernest, Toh, Cheng-Hock, Van Geet, Chris, De Vries, Minka, Warner, Timothy Q, Westbury, Sarah, Furnell, Abigail, Mapeta, Rutendo, Simeoni, Ilenia, Staines, Simon, Stephens, Jonathan, Stirrups, Kathleen, Whitehorn, Deborah, Watt, Christopher, Attwood, Antony, Daugherty, Louise, Deevi, Sri VV, Halmagyi, Csaba, Hu, Fengyuan, James, Roger, Matser, Vera, Meacham, Stuart, Megy, Karyn, Penkett, Christopher J, Stirrups, Kathleen, Titterton, Catherine, Tuna, Salih, Yu, Ping, von Ziegenweldt, Julie, Astle, William, Carss, Keren, Greene, Daniel, Lango-Allen, Hana, Turro, Ernest, Astle, William, Greene, Daniel, Richardson, Sylvia, Turro, Ernest, Calleja, Paul, Rankin, Stuart, Turek, Wojciech, Bryson, Christine, Anderson, Julie, Fletcher, Debra, McJannet, Coleen, Stock, Sophie, Young, Tim, Wassmer, Evangeline, Sohal, Aman, Santra, Saikat, Vogt, Julie, Chitre, Manali, Krishnakumar, Deepa, Ambegaonkar, Gautum, Maw, Anna, Armstrong, Ruth, Park, Soo-Mi, Mehta, Sarju, Paterson, Joan, Carmichael, Jenny, Allen, Louise, Hensiek, Anke, Firth, Helen, Stein, Penelope, Deegan, Patrick, Doffinger, Rainer, Parker, Alasdair, Bitner-Glindzicz, Maria, Scott, Richard, Hurst, Jane, Rosser, Elisabeth, Lees, Melissa, Clement, Emma, Henderson, Robert, Thompson, Dorothy, Gardham, Alice, Gissen, Paul, Josifova, Dragana, Thomas, Ellen, Patch, Chris, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Canham, Natalie, Wakeling, Emma, Holder, Susan, Ghali, Neeti, Brady, Angie, Clowes, Virginia, MacLaren, Robert, Webster, Andrew, Moore, Anthony, Arno, Gavin, Michaelides, Michel, Rankin, Julia, Kurian, Manju, Murphy, Elaine, Carss, Keren, Sanchis-Juan, Alba, Erwood, Marie, Dewhurst, Eleanor, Grozeva, Detelina, Raymond, F Lucy, Reid, Evan, Woods, Geoff, Tischkowitz, Marc, Sandford, Richard, Ali, Sonia, Creaser-Myers, Amanda, Cookson, Victoria, DaCosta, Rosa, Dormand, Natalie, Ghataorhe, Pavandeep K, Greenhalgh, Alan, Huis in’t Veld, Anna, Kennedy, Fiona, Mackenzie Ross, Rob, Masati, Larahmie, Meehan, Sharon, Othman, Shokri, Pollock, Val, Polwarth, Gary, Rhodes, Christopher J, Rue-Albrecht, Kevin, Schotte, Gwen, Shipley, Debbie, Tan, Yvonne, Wanjiku, Ivy, Wort, John, Smith, Kenneth, Kuijpers, Taco, Thrasher, Adrian, Thaventhiran, James, Brown, Matthew, Lango Allen, Hana, Simeoni, Ilenia, Staples, Emily, Samarghitean, Crina, Alachkar, Hana, Antrobus, Richard, Arumugakani, Gururaj, Bacchelli, Chiara, Baxendale, Helen, Bethune, Claire, Bibi, Shahnaz, Booth, Claire, Browning, Michael, Burns, Siobhan, Chandra, Anita, Cooper, Nichola, Davies, Sophie, Devlin, Lisa, Doffinger, Rainer, Drewe, Elizabeth, Edgar, David, Egner, William, Ghurye, Rohit, Gilmour, Kimberley, Goddard, Sarah, Gordins, Pavel, Grigoriadou, Sofia, Hackett, Scott, Hague, Rosie, Hayman, Grant, Herwadkar, Archana, Huissoon, Aarnoud, Jolles, Stephen, Kelleher, Peter, Kumararatne, Dinakantha, Lear, Sara, Longhurst, Hilary, Lorenzo, Lorena, Maimaris, Jesmeen, Manson, Ania, McDermott, Elizabeth, Murng, Sai, Nejentsev, Sergey, Noorani, Sadia, Oksenhendler, Eric, Ponsford, Mark, Qasim, Waseem, Quinti, Isabella, Richter, Alex, Sargur, Ravishankar, Savic, Sinisa, Seneviratne, Suranjith, Sewell, Carrock, Stauss, Hans, Thomas, Moira, Welch, Steve, Willcocks, Lisa, Yeatman, Nigel, and Yong, Patrick

Published
2017
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48. The effect of TRV027 on coagulation in COVID-19: A pilot randomized, placebo-controlled trial.

Author

Robbins, Alexander J., Che Bakri, Nur Amalina, Toke-Bjolgerud, Edward, Edwards, Aaron, Vikraman, Asha, Michalsky, Cathy, Fossler, Michael, Lemm, Nana-Marie, Medhipour, Savviz, Budd, William, Gravani, Athanasia, Hurley, Lisa, Kapil, Vikas, Jackson, Aimee, Lonsdale, Dagan, Latham, Victoria, Laffan, Michael, Chapman, Neil, Cooper, Nichola, and Szydlo, Richard

Subjects
ANGIOTENSIN converting enzyme, COVID-19, EXPERIMENTAL medicine, BLOOD coagulation, BAYESIAN analysis, ANGIOTENSIN II, CYCLOSERINE
Abstract

COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer a predictor of adverse outcome. The precise mechanism of this coagulopathy remains unclear; one hypothesis is that loss of angiotensin-converting enzyme 2 activity during viral endocytosis leads to pro-inflammatory angiotensin-II accumulation, loss of angiotensin-1-7 and subsequent vascular endothelial activation. We undertook a double-blind randomized, placebo-controlled experimental medicine study to assess the effect of TRV027, a synthetic angiotensin-1-7 analogue on D-dimer in 30 patients admitted to hospital with COVID-19. The study showed a similar rate of adverse events in TRV027 and control groups. There was a numerical decrease in D-dimer in the TRV027 group and increase in D-dimer in the placebo group; however, this did not reach statistical significance (P = .15). A Bayesian analysis demonstrated that there was a 92% probability that this change represented a true drug effect. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Rozrolimupab, a mixture of 25 recombinant human monoclonal RhD antibodies, in the treatment of primary immune thrombocytopenia

Author

Robak, Tadeusz, Windyga, Jerzy, Trelinski, Jacek, von Depka Prondzinski, Mario, Giagounidis, Aristoteles, Doyen, Chantal, Janssens, Ann, Álvarez-Román, María Teresa, Jarque, Isidro, Loscertales, Javier, Rus, Gloria Pérez, Hellmann, Andrzej, Jêdrzejczak, Wiesław Wiktor, Kuliczkowski, Kazimierz, Golubovic, Lana M., Celeketic, Dusica, Cucuianu, Andrei, Gheorghita, Emanuil, Lazaroiu, Mihaela, Shpilberg, Ofer, Attias, Dina, Karyagina, Elena, Svetlana, Kalinina, Vilchevska, Kateryna, Cooper, Nichola, Talks, Kate, Prabhu, Mukhyaprana, Sripada, Prasad, Bharadwaj, T.P.R., Næsted, Henrik, Skartved, Niels J.Ø., Frandsen, Torben P., Flensburg, Mimi F., Andersen, Peter S., and Petersen, Jørgen

Published
2012
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