31 results on '"Bagot, Catherine"'
Search Results
2. Long-term risk of relapse in immune-mediated thrombotic thrombocytopenic purpura and the role of anti-CD20 therapy
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Doyle, Andrew J., Stubbs, Matthew J., Dutt, Tina, Lester, Will, Thomas, Will, van Veen, Joost, Hermans, Joannes, Cranfield, Tanya, Hill, Quentin A., Clark, Amanda, Bagot, Catherine, Austin, Steven, Westwood, John-Paul, Thomas, Mari, and Scully, Marie
- Abstract
Disease relapse is recognized as a risk in immune-mediated thrombotic thrombocytopenic purpura (iTTP) after treatment of the acute presenting episode. Identification of patients at risk of relapse and its patterns are yet to be clearly established. We reviewed patients with iTTP having had >3 years of follow-up over 10 years in the United Kingdom to identify patient characteristics for relapse, assess relapse rates and patterns, and response to anti-CD20 therapy in those with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) relapses (ADAMTS13 activity of <20% without thrombocytopenia). We identified 443 patients demonstrating relapse rates of 40% at 5-year follow-up. At 10-year follow-up, no difference in relapse was observed irrespective of whether rituximab was used at acute presentation (P = .39). Black Caribbean ethnicity increased the risk of disease relapse in the British population. There was a distinct population of patients (6%) that relapsed early with subsequent frequent relapses occurring on average within 2 years (average time to relapse in subgroup, 1.7 years). Overall, nearly 60% of relapses described were ADAMTS13 relapses, with subsequent treatment reducing the risk of progression to clinical relapses. We demonstrate that iTTP diagnosed in the latter part of the study period had lower rates of clinical relapses (22.6% vs 11.1%, P = .0004) with the advent of regular monitoring and preemptive rituximab. In ADAMTS13 relapses, 96% responded to anti-CD20 therapy, achieving ADAMTS13 activity of >20%. Anti-CD20 therapy was demonstrated to be an effective long-term treatment regardless of relapse pattern and there was no loss of this treatment response after subsequent treatment episodes.
- Published
- 2023
- Full Text
- View/download PDF
3. The suboptimal fibrinolytic response in COVID‐19 is dictated by high PAI‐1
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Whyte, Claire S., Simpson, Megan, Morrow, Gael B., Wallace, Carol A., Mentzer, Alexander J., Knight, Julian C., Shapiro, Susan, Curry, Nicola, Bagot, Catherine N., Watson, Henry, Cooper, Jamie G., and Mutch, Nicola J.
- Abstract
Severe COVID‐19 disease is associated with thrombotic complications and extensive fibrin deposition. This study investigates whether the hemostatic complications in COVID‐19 disease arise due to dysregulation of the fibrinolytic system. This prospective study analyzed fibrinolytic profiles of 113 patients hospitalized with COVID‐19 disease with 24 patients with non‐COVID‐19 respiratory infection and healthy controls. Antigens were quantified by Ella system or ELISA, clot lysis by turbidimetric assay, and plasminogen activator inhibitor‐1 (PAI‐1)/plasmin activity using chromogenic substrates. Clot structure was visualized by confocal microscopy. PAI‐1 and its cofactor, vitronectin, are significantly elevated in patients with COVID‐19 disease compared with those with non‐COVID‐19 respiratory infection and healthy control groups. Thrombin activatable fibrinolysis inhibitor and tissue plasminogen activator were elevated in patients with COVID‐19 disease relative to healthy controls. PAI‐1 and tissue plasminogen activator (tPA) were associated with more severe COVID‐19 disease severity. Clots formed from COVID‐19 plasma demonstrate an altered fibrin network, with attenuated fiber length and increased branching. Functional studies reveal that plasmin generation and clot lysis were markedly attenuated in COVID‐19 disease, while PAI‐1 activity was elevated. Clot lysis time significantly correlated with PAI‐1 levels. Stratification of COVID‐19 samples according to PAI‐1 levels reveals significantly faster lysis when using the PAI‐1 resistant (tPA) variant, tenecteplase, over alteplase lysis. This study shows that the suboptimal fibrinolytic response in COVID‐19 disease is directly attributable to elevated levels of PAI‐1, which attenuate plasmin generation. These data highlight the important prognostic potential of PAI‐1 and the possibility of using pre‐existing drugs, such as tenecteplase, to treat COVID‐19 disease and potentially other respiratory diseases.
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- 2022
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4. The suboptimal fibrinolytic response in COVID‐19 is dictated by high PAI‐1
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Whyte, Claire S., Simpson, Megan, Morrow, Gael B., Wallace, Carol A., Mentzer, Alexander J., Knight, Julian C., Shapiro, Susan, Curry, Nicola, Bagot, Catherine N., Watson, Henry, Cooper, Jamie G., and Mutch, Nicola J.
- Abstract
Severe COVID‐19 disease is associated with thrombotic complications and extensive fibrin deposition. This study investigates whether the hemostatic complications in COVID‐19 disease arise due to dysregulation of the fibrinolytic system.
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- 2022
- Full Text
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5. The bleeding phenotype in people with nonsevere hemophilia
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Kloosterman, Fabienne R., Zwagemaker, Anne-Fleur, Bagot, Catherine N., Beckers, Erik A. M., Castaman, Giancarlo, Cnossen, Marjon H., Collins, Peter W., Hay, Charles, Hof, Michel, Laros-van Gorkom, Britta, Leebeek, Frank W. G., Male, Christoph, Meijer, Karina, Pabinger, Ingrid, Shapiro, Susan, Coppens, Michiel, Fijnvandraat, Karin, and Gouw, Samantha C.
- Abstract
Detailed information on the onset, frequency, and severity of bleeding in nonsevere hemophilia is limited. We aimed to assess the bleeding phenotype of persons with nonsevere hemophilia and to analyze the association between baseline factor VIII/IX (FVIII/IX) levels and the joint bleeding rate. In the DYNAMO (Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B) study, an international multicenter cohort, we included males with nonsevere hemophilia (FVIII/IX, 0.02-0.35 IU/mL) aged 12 to 55 years. Information on age at first treated (joint) bleed, annual bleeding rates (ABRs), and annual joint bleeding rates (AJBRs) was collected from the medical files. The association between baseline FVIII/IX levels and the joint bleeding rate was assessed by using a frailty model for recurrent events. In total, 304 persons (70 with moderate hemophilia and 234 with mild hemophilia) were included. The median age was 38 years (interquartile range [IQR], 25-49 years), and the median baseline FVIII/IX level was 0.12 IU/mL (IQR, 0.05-0.21 IU/mL). In total, 245 (81%) persons had experienced at least 1 bleed, and 156 (51%) had experienced at least 1 joint bleed. The median age at first bleed and first joint bleed was 8 and 10 years, respectively. The median ABR and AJBR was 0.2 (IQR, 0.1-0.5) and 0.0 (IQR, 0.0-0.2). From baseline FVIII/IX levels 0.02 to 0.05 IU/mL to >0.25 IU/mL, the median ABR decreased from 0.6 (IQR, 0.2-1.4) to 0.1 (IQR, 0.0-0.2) and the AJBR from 0.2 (IQR, 0.0-0.4) to 0.0 (IQR, 0.0-0.0). Baseline FVIII/IX was inversely associated with the joint bleeding rate (P < .001). Low bleeding rates were observed in persons with nonsevere hemophilia. However, one-half of all adolescents and adults had experienced a joint bleed.
- Published
- 2022
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6. The bleeding phenotype in people with nonsevere hemophilia
- Author
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Kloosterman, Fabienne R., Zwagemaker, Anne-Fleur, Bagot, Catherine N., Beckers, Erik A.M., Castaman, Giancarlo, Cnossen, Marjon H., Collins, Peter W., Hay, Charles, Hof, Michel, Laros-van Gorkom, Britta, Leebeek, Frank W.G., Male, Christoph, Meijer, Karina, Pabinger, Ingrid, Shapiro, Susan, Coppens, Michiel, Fijnvandraat, Karin, and Gouw, Samantha C.
- Abstract
Detailed information on the onset, frequency, and severity of bleeding in nonsevere hemophilia is limited. We aimed to assess the bleeding phenotype of persons with nonsevere hemophilia and to analyze the association between baseline factor VIII/IX (FVIII/IX) levels and the joint bleeding rate. In the DYNAMO (Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B) study, an international multicenter cohort, we included males with nonsevere hemophilia (FVIII/IX, 0.02-0.35 IU/mL) aged 12 to 55 years. Information on age at first treated (joint) bleed, annual bleeding rates (ABRs), and annual joint bleeding rates (AJBRs) was collected from the medical files. The association between baseline FVIII/IX levels and the joint bleeding rate was assessed by using a frailty model for recurrent events. In total, 304 persons (70 with moderate hemophilia and 234 with mild hemophilia) were included. The median age was 38 years (interquartile range [IQR], 25-49 years), and the median baseline FVIII/IX level was 0.12 IU/mL (IQR, 0.05-0.21 IU/mL). In total, 245 (81%) persons had experienced at least 1 bleed, and 156 (51%) had experienced at least 1 joint bleed. The median age at first bleed and first joint bleed was 8 and 10 years, respectively. The median ABR and AJBR was 0.2 (IQR, 0.1-0.5) and 0.0 (IQR, 0.0-0.2). From baseline FVIII/IX levels 0.02 to 0.05 IU/mL to >0.25 IU/mL, the median ABR decreased from 0.6 (IQR, 0.2-1.4) to 0.1 (IQR, 0.0-0.2) and the AJBR from 0.2 (IQR, 0.0-0.4) to 0.0 (IQR, 0.0-0.0). Baseline FVIII/IX was inversely associated with the joint bleeding rate (P< .001). Low bleeding rates were observed in persons with nonsevere hemophilia. However, one-half of all adolescents and adults had experienced a joint bleed.
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- 2022
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7. A multisystem, cardio-renal investigation of post-COVID-19 illness
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Morrow, Andrew J., Sykes, Robert, McIntosh, Alasdair, Kamdar, Anna, Bagot, Catherine, Bayes, Hannah K., Blyth, Kevin G., Briscoe, Michael, Bulluck, Heerajnarain, Carrick, David, Church, Colin, Corcoran, David, Findlay, Iain, Gibson, Vivienne B., Gillespie, Lynsey, Grieve, Douglas, Hall Barrientos, Pauline, Ho, Antonia, Lang, Ninian N., Lennie, Vera, Lowe, David J., Macfarlane, Peter W., Mark, Patrick B., Mayne, Kaitlin J., McConnachie, Alex, McGeoch, Ross, McGinley, Christopher, McKee, Connor, Nordin, Sabrina, Payne, Alexander, Rankin, Alastair J., Robertson, Keith E., Roditi, Giles, Ryan, Nicola, Sattar, Naveed, Allwood-Spiers, Sarah, Stobo, David, Touyz, Rhian M., Veldtman, Gruschen, Watkins, Stuart, Weeden, Sarah, Weir, Robin A., Welsh, Paul, Wereski, Ryan, Mangion, Kenneth, and Berry, Colin
- Abstract
Deep clinical phenotyping at 28–60 days post-discharge of patients who had been hospitalized with COVID-19 and subsequent long-term follow-up with electronic health records reveal evidence of persistent cardio-renal involvement.
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- 2022
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8. Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran—Results of the phase 1 inhibitor cohort
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Pasi, K. John, Lissitchkov, Toshko, Mamonov, Vasily, Mant, Tim, Timofeeva, Margarita, Bagot, Catherine, Chowdary, Pratima, Georgiev, Pencho, Gercheva‐Kyuchukova, Liana, Madigan, Kate, Nguyen, Huy, Yu, Qifeng, Mei, Baisong, Benson, Craig C., and Ragni, Margaret V.
- Abstract
Fitusiran, an investigational small interfering RNA therapy, reduces antithrombin production to rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. To evaluate the safety and efficacy of fitusiran treatment for people with moderate/severe hemophilia A or B with inhibitors. In this open‐label phase 1, part D study, 17 males with hemophilia A or B with inhibitors received three once‐monthly subcutaneous injections of fitusiran 50 mg (n= 6) or 80 mg (n= 11); followed for up to 112 days. Endpoints included safety (primary), pharmacokinetics/pharmacodynamics (secondary), annualized bleeding rate, and patient‐reported outcomes (exploratory). The most common adverse event was injection site erythema (n= 8). No thrombotic events were reported. At nadir, mean (standard error of the mean [SEM]) antithrombin activity decreased from baseline by 82.0% (2.2) and 87.4% (0.7) in the 50 mg and 80 mg groups, respectively. Antithrombin reduction was associated with increased thrombin generation. 11/17 (64.7%) participants had no bleeds during the observation period (mean [standard deviation] 69.4 [16.3] days). Mean (SEM) changes from baseline in Haemophilia Quality of Life Questionnaire for Adults total (−9.2 [2.9]) and physical health (−12.3 [3.9]) domain scores suggested clinically meaningful improvement. Monthly fitusiran was generally well tolerated, lowered antithrombin levels from baseline, and resulted in improved thrombin generation. These preliminary results suggest that monthly fitusiran treatment may reduce bleeding episodes and improve quality of life in participants with hemophilia A or B with inhibitors.
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- 2021
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9. Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran—Results of the phase 1 inhibitor cohort
- Author
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Pasi, K. John, Lissitchkov, Toshko, Mamonov, Vasily, Mant, Tim, Timofeeva, Margarita, Bagot, Catherine, Chowdary, Pratima, Georgiev, Pencho, Gercheva‐Kyuchukova, Liana, Madigan, Kate, Van Nguyen, Huy, Yu, Qifeng, Mei, Baisong, Benson, Craig C., and Ragni, Margaret V.
- Abstract
Fitusiran, an investigational small interfering RNA therapy, reduces antithrombin production to rebalance hemostasis in people with hemophilia A or B, with or without inhibitors.
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- 2021
- Full Text
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10. Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial
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Kenet, Gili, Nolan, Beatrice, Zulfikar, Bulent, Antmen, Bulent, Kampmann, Peter, Matsushita, Tadashi, You, Chur-Woo, Vilchevska, Kateryna, Bagot, Catherine N., Sharif, Azizan, Peyvandi, Flora, Young, Guy, Negrier, Claude, Chi, Jiarui, Kittner, Barbara, Sussebach, Christian, Shammas, Fadi, Mei, Baisong, Andersson, Shauna, and Kavakli, Kaan
- Abstract
•Fitusiran prophylaxis provided consistent protection against bleeding vs prior BPA/CFC prophylaxis in PwHA/B, with or without inhibitors.•Fitusiran was well tolerated, and reported adverse events were consistent with previously identified risks of fitusiran.
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- 2024
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11. History of the West of Scotland Haemophilia Centre, Glasgow, 1950–2019
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Lowe, Gordon, Walker, Isobel, Gibson, Brenda, Tait, Campbell, and Bagot, Catherine
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Over 70 years, the West of Scotland Haemophilia Centre in the UK has played a leading role in research, education and training. Its staff studied the natural history of haemophilias, their complications, and their treatment complications, pioneered the use of fibrinolytic inhibitors to reduce the risk of receiving a blood transfusion and developed national audit. Collaborations across Scotland with other haemophilia centres and the Scottish National Blood Transfusion Service progressed self-sufficiency in NHS-produced factor concentrates, heat treatments to prevent HIV and hepatitis transmission, and finally, replacement of human by recombinant factor concentrates.
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- 2020
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12. Fibrinogenolysis and fibrinolysis in Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT)
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Simpson, Megan, Narwal, Anuj, West, Eric, Martin, Jill, Bagot, Catherine N., Page, Andrew R., Watson, Henry G., Whyte, Claire S., and Mutch, Nicola J.
- Abstract
Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterised by thrombosis, anti-platelet factor 4 (PF4) antibodies, thrombocytopenia, high D-dimer and hypofibrinogenemia.
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- 2023
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13. Helen Cotton
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Bagot, Catherine, Ariaratnam, Mala, Ahmad, Zahida, and Webb, Liz
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- 2023
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14. Long-term risk of relapse in immune-mediated thrombotic thrombocytopenic purpura and the role of anti-CD20 therapy
- Author
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Doyle, Andrew J., Stubbs, Matthew J., Dutt, Tina, Lester, Will, Thomas, Will, van Veen, Joost, Hermans, Joannes, Cranfield, Tanya, Hill, Quentin A., Clark, Amanda, Bagot, Catherine, Austin, Steven, Westwood, John-Paul, Thomas, Mari, and Scully, Marie
- Abstract
Disease relapse is recognized as a risk in immune-mediated thrombotic thrombocytopenic purpura (iTTP) after treatment of the acute presenting episode. Identification of patients at risk of relapse and its patterns are yet to be clearly established. We reviewed patients with iTTP having had >3 years of follow-up over 10 years in the United Kingdom to identify patient characteristics for relapse, assess relapse rates and patterns, and response to anti-CD20 therapy in those with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) relapses (ADAMTS13 activity of <20% without thrombocytopenia). We identified 443 patients demonstrating relapse rates of 40% at 5-year follow-up. At 10-year follow-up, no difference in relapse was observed irrespective of whether rituximab was used at acute presentation (P = .39). Black Caribbean ethnicity increased the risk of disease relapse in the British population. There was a distinct population of patients (6%) that relapsed early with subsequent frequent relapses occurring on average within 2 years (average time to relapse in subgroup, 1.7 years). Overall, nearly 60% of relapses described were ADAMTS13 relapses, with subsequent treatment reducing the risk of progression to clinical relapses. We demonstrate that iTTP diagnosed in the latter part of the study period had lower rates of clinical relapses (22.6% vs 11.1%, P = .0004) with the advent of regular monitoring and preemptive rituximab. In ADAMTS13 relapses, 96% responded to anti-CD20 therapy, achieving ADAMTS13 activity of >20%. Anti-CD20 therapy was demonstrated to be an effective long-term treatment regardless of relapse pattern and there was no loss of this treatment response after subsequent treatment episodes.
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- 2022
- Full Text
- View/download PDF
15. Deep vein thrombosis: diagnosis, prevention and treatment
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Bagot, Catherine and Tait, Campbell
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Deep vein thrombosis can lead to significant morbidity and has well‐recognised risk factors. The authors describe the signs and symptoms and current recommended approaches to diagnosis, prevention and treatment. Copyright © 2012 Wiley Interface Ltd
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- 2012
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16. Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia a or B without Inhibitors (ATLAS-A/B)
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Srivastava, Alok, Rangarajan, Savita, Kavakli, Kaan, Klamroth, Robert, Kenet, Gili, Khoo, Liane, You, Chur-Woo, Xu, Weiqun, Malan, Niel, Frenzel, Laurent, Bagot, Catherine N., Stasyshyn, Oleksandra, Chang, Chia-Yau, Poloskey, Stacey, Andersson, Shauna, Qiu, Zhiying, Mei, Baisong, and Pipe, Steven W.
- Abstract
Srivastava: Roche: Other: Advisory Board, Research Funding; Novo Nordisk: Other: Advisory Board, Research Funding; Sanofi: Other: Advisory Board, Research Funding; Pfizer: Other: Advisory Board, Research Funding; Takeda: Other: Advisory Board, Research Funding; Bayer Healthcare: Other: Grant Review & Awards Committee. Rangarajan: Sanofi: Other: Advisory Board; Pfizer: Other: Advisory Board; Reliance Life Sciences: Consultancy; Takeda: Other: Advisory Board, Conference Support, Speakers Bureau. Kavakli: Pfizer, Bayer, Takeda, Roche, Novo Nordisk: Honoraria; Pfizer, Bayer, Roche, Novo Nordisk, Takeda: Speakers Bureau; Roche, Bayer, Pfizer, Novo Nordisk, Takeda: Membership on an entity's Board of Directors or advisory committees. Klamroth: Bayer, Leo: Research Funding; Bayer, Biotest, Biomarin, BMS, CSL B
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- 2021
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17. Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia a or B withoutInhibitors (ATLAS-A/B)
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Srivastava, Alok, Rangarajan, Savita, Kavakli, Kaan, Klamroth, Robert, Kenet, Gili, Khoo, Liane, You, Chur-Woo, Xu, Weiqun, Malan, Niel, Frenzel, Laurent, Bagot, Catherine N., Stasyshyn, Oleksandra, Chang, Chia-Yau, Poloskey, Stacey, Andersson, Shauna, Qiu, Zhiying, Mei, Baisong, and Pipe, Steven W.
- Abstract
Background
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- 2021
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18. Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation
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Bagot, Catherine N., Kliman, Harvey J., and Taylor, Hugh S.
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Hoxa10 is a homeobox gene that is expressed both during the embryogenesis of the genitourinary tract and in the adult reproductive tract. Maternal Hoxa10 expression is necessary for endometrial receptivity to blastocyst implantation. The mechanism by which Hoxa10 induces endometrial development to a state of receptivity is unknown as HOXA10-deficient endometrium appears histologically normal. We altered the expression of Hoxa10 in the uterus of cycling adult female mice and examined the uterus at the time of implantation by transmission electron microscopy for alterations in epithelial morphology. Pinopods are projections on the surface of the uterine endometrial epithelial cells that develop transiently at the time of endometrial receptivity. Blocking Hoxa10 expression by transfection of Hoxa10 antisense into the cycling mouse uterus before implantation dramatically decreased pinopod number. Constitutively expressing Hoxa10 in the uterus just before the normal time of pinopod formation resulted in increased pinopod number. Therefore, Hoxa10 is necessary for pinopod development. Hox genes have been implicated in both the regulation of cellular proliferation and the determination of developmental fate. Hoxa10 exemplifies this dual role in the uterus by regulating both endometrial stromal cell proliferation and epithelial cell morphogenesis. Taken together, these results demonstrate that maternal Hoxa10 has an essential role in pinopod development and this function of Hoxa10 likely contributes to endometrial receptivity for the purpose of blastocyst implantation. © 2001 Wiley-Liss, Inc.
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- 2001
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19. Endometrium. HOX gene expression is altered in the endometrium of women with endometriosis
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Taylor, Hugh S., Bagot, Catherine, Kardana, Andrew, Olive, David, and Arici, Aydin
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HOXA10 and HOXA11 are homeobox genes that function as transcription factors essential to embryonic development. We have recently described a role for each of these two genes in regulating endometrial development in the adult during the course of a menstrual cycle. Both Hoxa10 and Hoxa11 are essential for implantation in the mouse and appear to play a similar role in women. To investigate the role of HOX genes in the endometrium of women with endometriosis, quantitative Northern blot analysis was performed on the endometrium of 40 normal cycling controls and 40 patients with documented endometriosis. Patients with endometriosis failed to show the expected mid-luteal rise in HOX gene expression as demonstrated in the controls. Aberrant HOX gene expression suggests that altered development of the endometrium at the molecular level may contribute to the aetiology of infertility in patients with endometriosis.
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- 1999
20. A Multicentre Randomised Trial of First Line Treatment Pathways for Newly Diagnosed Immune Thrombocytopenia: Standard Steroid Treatment Versus Combined Steroid and Mycophenolate. the Flight Trial
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Bradbury, Charlotte A, Greenwood, Rosemary, Pell, Julie, Breheny, Katie, Kandiyali, Rebecca, Ingram, Jenny, Thomas, Ian, Bagot, Catherine, Hill, Quentin, Collaborators, HaemSTAR, and Cooper, Nichola
- Abstract
No relevant conflicts of interest to declare.Mycophenolate is unlicensed for ITP treatment
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- 2020
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21. A Multicentre Randomised Trial of First Line Treatment Pathways for Newly Diagnosed Immune Thrombocytopenia: Standard Steroid Treatment Versus Combined Steroid and Mycophenolate. the Flight Trial
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Bradbury, Charlotte A, Greenwood, Rosemary, Pell, Julie, Breheny, Katie, Kandiyali, Rebecca, Ingram, Jenny, Thomas, Ian, Bagot, Catherine, Hill, Quentin, Collaborators, HaemSTAR, and Cooper, Nichola
- Abstract
BACKGROUND
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- 2020
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22. Extrinsic venous compression: A sufficient explanation for venous thromboembolism due to massive fibroids?
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Barsam, Sarah, Bagot, Catherine, Patel, Raj, Sidhu, Paul S., Davies, Anthony, and Arya, Roopen
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- 2006
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23. Real World Use of Thrombopoietin-Receptor Agonists in the Management of Immune Thrombocytopenia in the United Kingdom: Results from the TRAIT Study
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Cooper, Nichola, Provan, Andrew, Scully, Marie, Grech, Henri, Bagot, Catherine, Hill, Quentin A, Nokes, Tim, Ramscar, Nicholas, and Saunders, Luke
- Abstract
Cooper: Amgen, Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Provan:Amgen, Novartis: Honoraria, Research Funding. Scully:Novartis: Honoraria, Other: Member of Advisory Board, Speakers Bureau. Grech:Novartis: Other: sponsorship for scientific meetings. Bagot:Amgen, Novartis: Speakers Bureau. Hill:Novartis: Honoraria; Novartis: Honoraria. Nokes:Bayer, MSD, Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ramscar:Novartis: Employment. Saunders:pH associates: Employment.
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- 2018
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24. Real World Use of Thrombopoietin-Receptor Agonists in the Management of Immune Thrombocytopenia in the United Kingdom: Results from the TRAIT Study
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Cooper, Nichola, Provan, Andrew, Scully, Marie, Grech, Henri, Bagot, Catherine, Hill, Quentin A, Nokes, Tim, Ramscar, Nicholas, and Saunders, Luke
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- 2018
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25. Perioperative myocardial infarction in a patient receiving low-dose prothrombin complex concentrates
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Bagot, Catherine N., Cregg, Roman, Patel, Raj K., Shariff, Amina, and Arya, Roopen
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- 2007
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26. Low Dose Prothrombin Complex Concentrates Reverse Oral Anticoagulation with Minimal Complications.
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Bagot, Catherine N., Kothari, Jaimal, Patel, Raj K., and Arya, Roopen
- Abstract
Prothrombin complex concentrate (PCC) is widely used for the reversal of warfarin in the context of life threatening haemorrhage or emergency surgery. For these indications, it is considered superior to fresh frozen plasma (FFP), in terms of viral safety, efficacy and speed of administration. Dosage of PCCs for coumarin reversal (30–50IU/kg) is based on that required for patients with haemophilia B. This dose is frequently associated with thrombosis, particularly in the presence of liver disease. Factors underlying the prothrombotic potential of PCCs include the activation of clotting factors during the manufacturing process, coexisting co morbidities in the patient and repeated administration leading to clotting factor accumulation in vivo. The risk of thrombosis has led to a reluctance to administer PCCs, despite proven efficacy, in patients with arterial or venous thromboembolism, sepsis and liver disease. Recent work suggests that PCCs can effectively reverse anticoagulation when administered in much lower doses. We collected data on 38 patients (mean age 70 years) who received Beriplex (Aventis Behring) to reverse anticoagulation either for life threatening haemorrhage or emergency surgery. Patients were receiving warfarin for atrial fibrillation (50%), recurrent thromboembolic disease (18.5%) and mechanical heart valves (13%). 52.5% received Beriplex following haemorrhage, 26.5% to correct the INR prior to emergency surgery and 2.5% for an excessively elevated INR. 87.6% received 500IU Beriplex with the remainder receiving 1000IU. Of 38 patients, 18 out of 29 received Vitamin K. Mean INR fell significantly (p<0.01) following Beriplex administration (mean INR pre-Beriplex 4.8, post-Beriplex 1.8). 81% had an INR <2 following Beriplex. Of patients with an INR <8 receiving one vial, 64% corrected their INR to <1.4 (96% patients had an INR <2). 59% of patients had additional risk factors including ischaemic heart disease, recurrent thromboembolism, sepsis or abnormal liver function. No patients had thrombotic complications. Three had evidence of DIC following administration of Beriplex, all in association with sepsis and no patient experienced bleeding complications at the time of surgery. Bleeding was well controlled in those experiencing life threatening haemorrhage except in two patients, who presented with massive intracranial bleeds. This data indicates that PCCs should be considered in all patients on warfarin who require urgent anticoagulation reversal, at a dose of 500IU only. PCCs at a fixed low dose appear to correct anticoagulation effectively based on both clinical and laboratory parameters, without the need for repeated administration. Importantly, PCCs at this lower dose were not associated with thromboembolic events. Low dose PCCs therefore provide patients with a safe and effective antidote to warfarin.
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- 2006
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27. Extrinsic Venous Compression May Not Be a Sufficient Explanation for Venous Thromboembolism Due to Massive Fibroids.
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Barsam, Sarah, Bagot, Catherine N., Patel, Raj K., Sidhu, Paul S., Davies, Anthony, and Arya, Roopen
- Abstract
The relationship between uterine leiomyomata (fibroids) and venous thromboembolism (VTE) is poorly characterised. Fibroids are smooth muscle cell tumours of the uterus; occuring in approximately 40% of women of reproductive age, they are twice as prevalent in women from African compared to Caucasian origin. It is assumed that massive leiomyomata (palpable beyond the level of the umbilicus) cause deep vein thrombosis as a consequence of a direct compressive effect on pelvic veins but this explanation may be insufficient. Other hypotheses for the thrombogenic nature of leiomyomata include the abnormal expression of type 1 basic FGF receptor, increased expression of thrombospondin 1 and nitrogen oxide synthase, abnormal oestrogen regulation and fibroid-induced polycythaemia. We describe the cases of seven women (mean age 41 yrs, range 29–46yrs) with VTE presumed secondary to massive fibroids. The majority of women (86%) were of African or Carribbean origin. Massive uterine leiomyomata were demonstrated in each patient by transvaginal ultrasound scanning. All cases had objectively confirmed (duplex ultrasound) symptomatic DVT, and two had CT-confirmed symptomatic pulmonary embolism (PE) at presentation. Direct venous compression by massive fibroids was demonstrated in only one case using magnetic resonance imaging (MRI)(case 1). Interestingly the two cases with left sided proximal DVT (cases 2 and 5) revealed right-sided lateral and posterior uterine wall fibroids. Data on known acquired risk factors for VTE was recorded for each patient. Thrombophilia screening was performed in all cases at least four weeks following cessation of anticoagulation. Venous compression alone failed to explain six of the cases, where fibroids were not positionally related to the site of DVT. Of these, only one had significant additional risk factors for VTE (case 3). Whereas extrinsic compression of the pelvic veins may contribute to venous stasis and DVT formation in some cases, our findings suggest that it is unlikely that this is the only pathogenic mechanism. In conclusion, we suggest that the occurrence of VTE in women with massive fibroids is unlikely to be due solely to mechanical compression of the pelvic veins. It is possible that biological growth factors produced by the leiomyomata may trigger VTE formation and that oestrogen may have an independent growth promoting effect on both VTE and leiomyomata. Further research is required to characterise the prothrombotic state in these women. Patient Characteristics Ethnicity Site DVT D-dimer(mcg/l) Thrombophilia Risk Factors Fibroid Site Fibroid Size (mm) 1 Caribbean Left Proximal 1563 No No Left lateral wall 147 × 134 × 102 2 Caribbean Left Proximal 481 No No Posterior and right lateral wall and fundus 99 × 94 × 79 3 Caucasian Left Distal 969 Yes Flight, Previous DVT Posterior wall and fundus 89 × 77 4 African Right Proximal/PE 1883 No No Posterior wall 350 × 300 × 250 5 African Left Proximal 6152 No No Posterior and right lateral wall 136 × 124 × 124 6 African Right Proximal/PE N/A No No Multiple, widespread 60 × 58 × 73 7 Caribbean Right Proximal 2503 No No Right lateral wall 130×116
- Published
- 2006
- Full Text
- View/download PDF
28. Extrinsic Venous Compression May Not Be a Sufficient Explanation for Venous Thromboembolism Due to Massive Fibroids.
- Author
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Barsam, Sarah, Bagot, Catherine N., Patel, Raj K., Sidhu, Paul S., Davies, Anthony, and Arya, Roopen
- Abstract
The relationship between uterine leiomyomata (fibroids) and venous thromboembolism (VTE) is poorly characterised. Fibroids are smooth muscle cell tumours of the uterus; occuring in approximately 40% of women of reproductive age, they are twice as prevalent in women from African compared to Caucasian origin. It is assumed that massive leiomyomata (palpable beyond the level of the umbilicus) cause deep vein thrombosis as a consequence of a direct compressive effect on pelvic veins but this explanation may be insufficient. Other hypotheses for the thrombogenic nature of leiomyomata include the abnormal expression of type 1 basic FGF receptor, increased expression of thrombospondin 1 and nitrogen oxide synthase, abnormal oestrogen regulation and fibroid-induced polycythaemia. We describe the cases of seven women (mean age 41 yrs, range 29–46yrs) with VTE presumed secondary to massive fibroids. The majority of women (86%) were of African or Carribbean origin. Massive uterine leiomyomata were demonstrated in each patient by transvaginal ultrasound scanning. All cases had objectively confirmed (duplex ultrasound) symptomatic DVT, and two had CT-confirmed symptomatic pulmonary embolism (PE) at presentation. Direct venous compression by massive fibroids was demonstrated in only one case using magnetic resonance imaging (MRI)(case 1).
- Published
- 2006
- Full Text
- View/download PDF
29. Low Dose Prothrombin Complex Concentrates Reverse Oral Anticoagulation with Minimal Complications.
- Author
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Bagot, Catherine N., Kothari, Jaimal, Patel, Raj K., and Arya, Roopen
- Abstract
Prothrombin complex concentrate (PCC) is widely used for the reversal of warfarin in the context of life threatening haemorrhage or emergency surgery. For these indications, it is considered superior to fresh frozen plasma (FFP), in terms of viral safety, efficacy and speed of administration. Dosage of PCCs for coumarin reversal (30–50IU/kg) is based on that required for patients with haemophilia B. This dose is frequently associated with thrombosis, particularly in the presence of liver disease. Factors underlying the prothrombotic potential of PCCs include the activation of clotting factors during the manufacturing process, coexisting co morbidities in the patient and repeated administration leading to clotting factor accumulation in vivo. The risk of thrombosis has led to a reluctance to administer PCCs, despite proven efficacy, in patients with arterial or venous thromboembolism, sepsis and liver disease. Recent work suggests that PCCs can effectively reverse anticoagulation when administered in much lower doses. We collected data on 38 patients (mean age 70 years) who received Beriplex (Aventis Behring) to reverse anticoagulation either for life threatening haemorrhage or emergency surgery. Patients were receiving warfarin for atrial fibrillation (50%), recurrent thromboembolic disease (18.5%) and mechanical heart valves (13%). 52.5% received Beriplex following haemorrhage, 26.5% to correct the INR prior to emergency surgery and 2.5% for an excessively elevated INR. 87.6% received 500IU Beriplex with the remainder receiving 1000IU. Of 38 patients, 18 out of 29 received Vitamin K. Mean INR fell significantly (p<0.01) following Beriplex administration (mean INR pre-Beriplex 4.8, post-Beriplex 1.8). 81% had an INR <2 following Beriplex. Of patients with an INR <8 receiving one vial, 64% corrected their INR to <1.4 (96% patients had an INR <2). 59% of patients had additional risk factors including ischaemic heart disease, recurrent thromboembolism, sepsis or abnormal liver function. No patients had thrombotic complications. Three had evidence of DIC following administration of Beriplex, all in association with sepsis and no patient experienced bleeding complications at the time of surgery. Bleeding was well controlled in those experiencing life threatening haemorrhage except in two patients, who presented with massive intracranial bleeds. This data indicates that PCCs should be considered in all patients on warfarin who require urgent anticoagulation reversal, at a dose of 500IU only. PCCs at a fixed low dose appear to correct anticoagulation effectively based on both clinical and laboratory parameters, without the need for repeated administration. Importantly, PCCs at this lower dose were not associated with thromboembolic events. Low dose PCCs therefore provide patients with a safe and effective antidote to warfarin.
- Published
- 2006
- Full Text
- View/download PDF
30. The Outcome of Lymphoproliferative Disorder in Liver Transplant Recipients May Correlate with Age at Diagnosis and the Use of Chemotherapy: A Single Centre Report.
- Author
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Bagot, Catherine N., Kulasekararaj, Austin, Ramalingam, Sandeep, Heaton, Nigel, O’Grady, John, Hadzic, Dino, Portmann, Bernard, Rela, Mohamed, Salisbury, Jon, Devereux, Steven, Mufti, Ghulam J., and Pagliuca, Antonio
- Abstract
Post transplant lymphoproliferative disorder (PTLD) occurs with an incidence of 1.7–3.3% and 5.6–13% in adults and children respectively. Mortality remains high with rates of 40–70%; approximately double that of other high grade lymphoproliferative disorders. To date, no preventative or therapeutic regimen has been shown to have an overall survival advantage. We examined the clinical and histological features of 31 adults and children diagnosed with PTLD following liver transplantation in a single centre to determine which factors might influence clinical outcome. Patient records were reviewed from the database of cases at King’s College Hospital from 1988–2005 including both children and adults. 60 cases were identified and in 31 cases, relevant data could be obtained. This gave an incidence of PTLD of 1.7% and 2.7% in adults and children respectively. 10 of the 31 cases were children. Most children had an original diagnosis of extra hepatic biliary atresia; the adults had a broad range of primary liver disease. At the time of diagnosis of PTLD, the mean age was 34 years (1.5–64). The mean onset of PTLD from the time of liver transplantation was 50 months (3–156). Approximately equal numbers of patients were on either 1, 2 or 3 forms of immunosuppression when diagnosed. 12 patients presented with extranodal disease and 13 with Stage 4 disease. In 18 patients the IPI could be assessed, with 14 having an IPI of 2 or more. The histological diagnosis in 20 patients was high grade B cell lymphoma, 1 high grade T cell, 1 TNK cell, 1 Hodgkins, 1 low grade B cell, 1 mixed cell, 1 B cell, 1 high grade, 1 plasmacytoid variant and in 3 cases the histological diagnosis was unknown. The tissue affected by lymphoproliferative disease was positive for EBV in 22 cases and 6 patients (all aged <15) were positive for EBV DNA in the serum at diagnosis. Only one adult was tested and found to be negative. All patients were treated with immunoreduction with 18 receiving chemotherapy. 14 patients also received antivirals. 6 patients were treated with immunoreduction alone. Cytotoxic T lymphocytes were used in 2 cases. Chemotherapy used included CHOP, CHOPR and Rituximab alone. 16 patients had a complete response, 2 a partial response and 9 no response. In 4 patients the outcome was unknown. The median follow up was 12.5 months (1–166). Overall survival was 40.36% with median survival at 1 year being 59%. Using univariate analysis, favourable outcome was associated with age <15 at diagnosis (p=0.04) and treatment with chemotherapy (p<0.01). Overall survival in those patients developing PTLD>1 year post transplant was 52.6% compared to 25% in those developing PTLD<1 year post transplant (p=0.28). 1 patient treated with immunoreduction alone survived. Longer term remissions appear to be achieved in younger patients, those who present later following liver transplantation and in whom chemotherapy is used. The amount of immunosuppression, EBV positivity of tissue and stage of disease at presentation do not appear to influence outcome. IPI scores are high in many patients although it remains unclear whether these are applicable to PTLD.
- Published
- 2005
- Full Text
- View/download PDF
31. The Outcome of Lymphoproliferative Disorder in Liver Transplant Recipients May Correlate with Age at Diagnosis and the Use of Chemotherapy: A Single Centre Report.
- Author
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Bagot, Catherine N., Kulasekararaj, Austin, Ramalingam, Sandeep, Heaton, Nigel, O'Grady, John, Hadzic, Dino, Portmann, Bernard, Rela, Mohamed, Salisbury, Jon, Devereux, Steven, Mufti, Ghulam J., and Pagliuca, Antonio
- Abstract
Post transplant lymphoproliferative disorder (PTLD) occurs with an incidence of 1.7–3.3% and 5.6–13% in adults and children respectively. Mortality remains high with rates of 40–70%; approximately double that of other high grade lymphoproliferative disorders. To date, no preventative or therapeutic regimen has been shown to have an overall survival advantage. We examined the clinical and histological features of 31 adults and children diagnosed with PTLD following liver transplantation in a single centre to determine which factors might influence clinical outcome. Patient records were reviewed from the database of cases at King's College Hospital from 1988–2005 including both children and adults. 60 cases were identified and in 31 cases, relevant data could be obtained. This gave an incidence of PTLD of 1.7% and 2.7% in adults and children respectively. 10 of the 31 cases were children. Most children had an original diagnosis of extra hepatic biliary atresia; the adults had a broad range of primary liver disease. At the time of diagnosis of PTLD, the mean age was 34 years (1.5–64). The mean onset of PTLD from the time of liver transplantation was 50 months (3–156). Approximately equal numbers of patients were on either 1, 2 or 3 forms of immunosuppression when diagnosed. 12 patients presented with extranodal disease and 13 with Stage 4 disease. In 18 patients the IPI could be assessed, with 14 having an IPI of 2 or more. The histological diagnosis in 20 patients was high grade B cell lymphoma, 1 high grade T cell, 1 TNK cell, 1 Hodgkins, 1 low grade B cell, 1 mixed cell, 1 B cell, 1 high grade, 1 plasmacytoid variant and in 3 cases the histological diagnosis was unknown. The tissue affected by lymphoproliferative disease was positive for EBV in 22 cases and 6 patients (all aged <15) were positive for EBV DNA in the serum at diagnosis. Only one adult was tested and found to be negative. All patients were treated with immunoreduction with 18 receiving chemotherapy. 14 patients also received antivirals. 6 patients were treated with immunoreduction alone. Cytotoxic T lymphocytes were used in 2 cases. Chemotherapy used included CHOP, CHOPR and Rituximab alone. 16 patients had a complete response, 2 a partial response and 9 no response. In 4 patients the outcome was unknown. The median follow up was 12.5 months (1–166). Overall survival was 40.36% with median survival at 1 year being 59%. Using univariate analysis, favourable outcome was associated with age <15 at diagnosis (p=0.04) and treatment with chemotherapy (p<0.01). Overall survival in those patients developing PTLD>1 year post transplant was 52.6% compared to 25% in those developing PTLD<1 year post transplant (p=0.28). 1 patient treated with immunoreduction alone survived. Longer term remissions appear to be achieved in younger patients, those who present later following liver transplantation and in whom chemotherapy is used. The amount of immunosuppression, EBV positivity of tissue and stage of disease at presentation do not appear to influence outcome. IPI scores are high in many patients although it remains unclear whether these are applicable to PTLD.
- Published
- 2005
- Full Text
- View/download PDF
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