Publications by authors named "Helen Enright"

36 Publications

Vaccine-induced immune thrombotic thrombocytopenia (VITT) - a novel clinico-pathological entity with heterogeneous clinical presentations.

Br J Haematol 2021 Jun 22. Epub 2021 Jun 22.

National Coagulation Centre, St. James's Hospital, Dublin, Ireland.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel entity that emerged in March 2021 following reports of unusual thrombosis after ChAdOx1 nCoV-19, (AstraZeneca) vaccination. Following the recognition of this syndrome, multiple consensus guidelines have been released to risk stratify patients presenting with possible symptoms after ChAdOx1 nCoV-19 vaccination. All guidelines rapidly identify VITT in patients with the complete triad of thrombocytopenia, thrombosis and elevated D-dimers after ChAdOx1 nCoV-19 vaccination. However, with earlier recognition of the associated symptoms, the clinical manifestations are likely to be more heterogeneous and represent an evolving spectrum of disease. In this setting, current guidelines may lack the sensitivity to detect early cases of VITT and risk missed or delayed diagnoses. The broad clinical phenotype and challenges associated with diagnosis of VITT are highlighted in our present case series of four patients with confirmed VITT. Dependent on the guidance used, each patient could have been classified as a low probability of VITT at presentation. The present study highlights the issues associated with the recognition of VITT, the limitations of current guidance and the need for heightened clinical vigilance as our understanding of the pathophysiology of this novel condition evolves.
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http://dx.doi.org/10.1111/bjh.17613DOI Listing
June 2021

Posttransplant Lymphoproliferative Disorder After Solid Organ Transplant: A Heterogeneous, Aggressive Disorder.

Clin Lymphoma Myeloma Leuk 2021 May 24. Epub 2021 May 24.

Department of Haematology, St Vincent's University Hospital, Elm Park, Dublin, Ireland.

Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplant. We identified 40 patients diagnosed with PTLD between 2009 and 2020 and analyzed their presentation, treatment strategies, and outcomes. Median age at diagnosis was 52.5 years (range 21.3 to 79). Median duration of immunosuppression was 95 months (range 4 to 292). Diffuse large B cell lymphoma (n = 16, 40%) and Burkitt lymphoma (n = 6, 15%) were the most common histological subtypes. First-line therapy varied. The median number of treatment lines was 1 (range 0 to 4). Sixteen patients (40%) achieved complete response after first-line therapy. Nineteen patients (47.5%) relapsed or progressed and received salvage therapy; 45% were alive at the end of the study period (median survival 52 months; range 1 to 266; 95% confidence interval 0 to 104). Causes of death included lymphoma-related (45.5%), therapy-related (27.3%), and other (27.3%). Five (22.7%) died within 3 months of diagnosis. Pearson's r test identified disease stage (P = .045) and proliferation index (P = .005) as negative predictors of response to frontline therapy. Bone marrow involvement (P = .033) and increased age (P = .018) were significant predictors of survival. Early mortality and poor response to frontline therapy are common, outlining the need for improved treatment strategies.
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http://dx.doi.org/10.1016/j.clml.2021.05.009DOI Listing
May 2021

AZD1222 vaccine-related coagulopathy and thrombocytopenia without thrombosis in a young female.

Br J Haematol 2021 Aug 25;194(3):553-556. Epub 2021 May 25.

Department of Haematology, Tallaght University Hospital, Dublin, Ireland.

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http://dx.doi.org/10.1111/bjh.17530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239588PMC
August 2021

Can absolute basophilia distinguish e1a2 BCR-ABL1 chronic myeloid leukemia from chronic myelomonocytic leukemia?

Blood Cells Mol Dis 2021 03 19;87:102521. Epub 2020 Nov 19.

Department of Haematology, Tallaght University Hospital, Dublin, Ireland.

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http://dx.doi.org/10.1016/j.bcmd.2020.102521DOI Listing
March 2021

Argatroban for therapeutic anticoagulation for heparin resistance associated with Covid-19 infection.

J Thromb Thrombolysis 2021 Jan 24;51(1):243-245. Epub 2020 Aug 24.

Department of Haematology, Tallaght University Hospital, Tallaght, D24 NR0A, Ireland.

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http://dx.doi.org/10.1007/s11239-020-02251-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443371PMC
January 2021

Structuring ward rounds to enhance education.

Clin Teach 2020 06 26;17(3):286-291. Epub 2019 Aug 26.

Department of Paediatrics, The University of Melbourne, Melbourne, Australia.

Background: Ward rounds are a fundamental part of hospital culture and teaching on rounds has a long tradition. Yet evidence points towards increasing difficulties in delivering ward round education in complex heath care settings. Drawing on the literature and gaps identified in our own hospital setting we hypothesised that a tool for structuring ward rounds could improve the educational experience on rounds without adding a time burden to already busy consultants.

Methods: We used a developmental evaluation approach to develop a framework and evaluate a tool for improving ward round education. The ward round framework STIC (Set, Target, Inspect and Close) and ward round tool was developed through an iterative process of reviewing and piloting in a clinical department and was evaluated against Moore's outcome levels drawing on quantitative and qualitative data. Surveys of consultants were used to quantify uptake, acceptability and usefulness of the ward round tool. Focus groups of trainee doctors evaluated their experience of ward round education.

Results: The majority of consultants used the ward round tool and found it accessible, and useful to enhance education, without extending ward round time. Trainee doctors had seen the ward round tool in use and reflected that it provided structure, focused their learning opportunities, gave clarity to the agenda and provided closure. Unintended benefits were seen for enhanced team work.

Conclusions: We present a structured framework STIC and tool for ward rounds that incorporates education, which is acceptable to consultants and is perceived to enhance education for trainees and to strengthen team work. Understanding our framework STIC and our ward round tool's applicability in other settings, scalability and impact and the perspective of patients, would be valuable extensions of this work. We present a structured framework STIC and tool for ward rounds that incorporates education, which is acceptable to consultants and is perceived to enhance education for trainees and to strengthen team work.
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http://dx.doi.org/10.1111/tct.13086DOI Listing
June 2020

Myeloid sarcoma: deciphering a rare cause of cardiac compromise.

Br J Haematol 2019 07 9;186(2):203. Epub 2019 May 9.

Department of Haematology, St James's Hospital, Dublin, Ireland.

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http://dx.doi.org/10.1111/bjh.15945DOI Listing
July 2019

Genome instability is a consequence of transcription deficiency in patients with bone marrow failure harboring biallelic variants.

Proc Natl Acad Sci U S A 2018 07 9;115(30):7777-7782. Epub 2018 Jul 9.

Genomics and Child Health, Blizard Institute, Queen Mary University of London, E1 2AT London, United Kingdom.

Biallelic variants in the ERCC excision repair 6 like 2 gene () are known to cause bone marrow failure (BMF) due to defects in DNA repair and mitochondrial function. Here, we report on eight cases of BMF from five families harboring biallelic variants in , two of whom present with myelodysplasia. We confirm that ERCC6L2 patients' lymphoblastoid cell lines (LCLs) are hypersensitive to DNA-damaging agents that specifically activate the transcription coupled nucleotide excision repair (TCNER) pathway. Interestingly, patients' LCLs are also hypersensitive to transcription inhibitors that interfere with RNA polymerase II (RNA Pol II) and display an abnormal delay in transcription recovery. Using affinity-based mass spectrometry we found that ERCC6L2 interacts with DNA-dependent protein kinase (DNA-PK), a regulatory component of the RNA Pol II transcription complex. Chromatin immunoprecipitation PCR studies revealed ERCC6L2 occupancy on gene bodies along with RNA Pol II and DNA-PK. Patients' LCLs fail to terminate transcript elongation accurately upon DNA damage and display a significant increase in nuclear DNA-RNA hybrids (R loops). Collectively, we conclude that ERCC6L2 is involved in regulating RNA Pol II-mediated transcription via its interaction with DNA-PK to resolve R loops and minimize transcription-associated genome instability. The inherited BMF syndrome caused by biallelic variants in can be considered as a primary transcription deficiency rather than a DNA repair defect.
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http://dx.doi.org/10.1073/pnas.1803275115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064997PMC
July 2018

Opening the black box: An observational study of teaching and learning interactions for paediatrics trainees on consultant ward rounds.

J Paediatr Child Health 2018 09 22;54(9):1011-1015. Epub 2018 May 22.

Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

Aim: Ward rounds are complex activities in which education must be balanced against service. Limited evidence exists regarding how to optimise ward round education. In order to improve the educational experience, we aimed to understand the teaching and learning interactions on ward rounds with a particular focus on the experience of paediatric trainees.

Methods: We conducted an initial quantitative survey as a needs assessment regarding learning and teaching in clinical settings using a structured survey of 21 trainees. This was followed by an observational study using focused ethnography of 20 consultant ward rounds in a general medical department of tertiary paediatric hospital. We used a structured observation form to document ward round characteristics and educational interactions. Data were analysed using inductive content analysis to understand key influences on teaching and learning interactions.

Results: Trainees reported a discrepancy between the actual educational value of ward rounds (mean rating 2.7/5) and what they desired (mean 4.3/5). Ward round ethnography revealed examples of excellent education and practice alongside missed opportunities. Explicit education on rounds was dominated by technical content with little focus on other aspects of professionalism. Major influences on educational interactions were the ward round model - consultant-as-expert versus learner-centred - and the hidden curriculum.

Conclusion: There are many examples of excellence in ward round education, yet there remains substantial scope to better harness the education potential of rounds. This requires us to challenge assumptions, enable feedback and reflection and make learning explicit - while putting the learner at the centre of educational opportunities.
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http://dx.doi.org/10.1111/jpc.14056DOI Listing
September 2018

False-negative mutation in a suspected myeloproliferative neoplasm: identification, resolution and corrective action.

J Clin Pathol 2018 05 20;71(5):473-474. Epub 2018 Feb 20.

Cancer Molecular Diagnostics, St. James Hospital, Dublin, Ireland.

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http://dx.doi.org/10.1136/jclinpath-2018-205029DOI Listing
May 2018

Population pharmacokinetics of total and unbound teicoplanin concentrations and dosing simulations in patients with haematological malignancy.

J Antimicrob Chemother 2018 04;73(4):995-1003

University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.

Objectives: To develop a pharmacokinetic model describing total and unbound teicoplanin concentrations in patients with haematological malignancy and to perform Monte Carlo simulations to evaluate target attainment of unbound trough concentrations with various dose regimens.

Methods: This was a hospital-based clinical trial (EudraCT 2013-004535-72). The dosing regimen was 600/800 mg q12h for three doses then 600/800 mg daily. Serial total and unbound teicoplanin concentrations were collected. Maximum protein binding was estimated from serum albumin concentration. Population pharmacokinetic analyses and Monte Carlo simulations were conducted using Pmetrics®. Target total and unbound trough concentrations were ≥20 and ≥1.5 mg/L, respectively.

Results: Thirty adult patients were recruited with a mean (SD) bodyweight of 69.1 (15.8) kg, a mean (SD) CLCR of 72 (41) mL/min and a median (IQR) serum albumin concentration of 29 (4) g/L. A three-compartment complex binding pharmacokinetic model best described the concentration-time data. Total and unbound teicoplanin concentrations were related by serum albumin concentration and a dissociation constant. CLCR and bodyweight were supported as covariates for CL and volume of the central compartment, respectively. Dosing simulations showed that high CLCR was associated with reduced probability of achieving target total and unbound trough concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound trough concentrations. A method to estimate the unbound teicoplanin concentration from the measured total concentration at different serum albumin concentration was demonstrated.

Conclusions: Standard teicoplanin dosing regimens should be used with caution in patients with haematological malignancy. Bodyweight, CLCR and serum albumin concentration are important considerations for appropriate dosing.
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http://dx.doi.org/10.1093/jac/dkx473DOI Listing
April 2018

Risk adjusted therapy in chronic lymphocytic leukemia: a phase II cancer trials Ireland (CTRIAL-IE [ICORG 07-01]) study of fludarabine, cyclophosphamide, and rituximab therapy evaluating response adapted, abbreviated frontline therapy with FCR in non-del(17p) CLL.

Leuk Lymphoma 2018 06 19;59(6):1338-1347. Epub 2017 Sep 19.

a Department of Haematology , St. James's Hospital and Trinity College Dublin , Dublin , Ireland.

Minimal residual disease negative complete response (MRD-negative CR) provides an early marker for time to treatment failure (TTF) in CLL treated with fludarabine, cyclophosphamide, and rituximab (FCR). MRD was assessed after four FCR cycles (FCR4); MRD-negative CR patients discontinued treatment. Fifty-two patients (35M; 17F) were enrolled. Eighteen (18/52; 34.6%) patients reached MRD-negative CR after FCR4 and 29/52 (55.8%) were MRD-negative CR at end of treatment (EOT). Median TTF was 71.1 months (95% CI 61.3-84.1 months), with median overall survival not reached. Mutated immunoglobulin heavy chain gene rearrangements (IGHV) were associated with early MRD-negative remissions, translating into prolonged TTF. Unmutated-IGHV, mutated-SF3B1 and mutated-NOTCH1 were associated with shortened TTF. No TTF difference was observed between patients in MRD-negative CR after four versus six cycles (82.2 versus 85.3 months, p = .6306). Abbreviated FCR therapy is effective for patients achieving early MRD-negative remissions. Interim MRD assessment assists in personalizing therapy and reducing chemotherapy-associated toxicity.
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http://dx.doi.org/10.1080/10428194.2017.1376746DOI Listing
June 2018

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy.

Antimicrob Agents Chemother 2017 06 24;61(6). Epub 2017 May 24.

Tallaght Hospital, Dublin, Ireland.

The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h ( < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.).
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http://dx.doi.org/10.1128/AAC.02466-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444128PMC
June 2017

A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience.

Hematology 2017 Jul 15;22(6):341-346. Epub 2017 Feb 15.

a Department of Haematology , Tallaght Hospital , Dublin , Ireland.

Objectives: To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre.

Methods: Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival.

Results: 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count <5% at diagnosis, previous haematological disorder, lower risk IPSS-R and a normal karyotype. Four out of five patients who received intensive therapy/transplant remain alive with median OS of 14 months. Median OS of Azacitidine-treated group was 11 months.

Discussion: t-MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.
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http://dx.doi.org/10.1080/10245332.2017.1286539DOI Listing
July 2017

Immune thrombocytopenia purpura associated with multiple myeloma.

Ann Hematol 2016 Aug 13;95(8):1371-2. Epub 2016 May 13.

Haematology Department, Adelaide and Meath incorporating the National Children's Hospital (AMNCH), Tallaght, Dublin 24, Ireland.

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http://dx.doi.org/10.1007/s00277-016-2694-yDOI Listing
August 2016

Teicoplanin use in adult patients with haematological malignancy: Exploring relationships between dose, trough concentrations, efficacy and nephrotoxicity.

Int J Antimicrob Agents 2015 Oct 2;46(4):406-12. Epub 2015 Jul 2.

Department of Haematology, Tallaght Hospital, Dublin 24, Ireland.

In 2010, our hospital introduced a higher target teicoplanin trough concentration of ≥20 mg/L by Day 3 for haematological malignancy patients. This study aimed to explore whether target trough concentrations were achieved, to identify factors associated with trough concentrations attained, and to assess clinical efficacy with teicoplanin treatments and nephrotoxicity. This was a retrospective, single-centre, cohort study of 172 teicoplanin treatments in 104 adults with haematological malignancy. Mixed-effects regression was used to evaluate factors affecting trough concentrations, and logistic regression was used to assess the relationship between trough concentrations and treatment outcomes. Nephrotoxicity was assessed using the RIFLE criteria. Considerable variability in trough concentrations was observed, with trough concentrations ≥20 mg/L rarely achieved early in therapy. A mixed-effects regression model explaining 52% of the variation in trough concentrations was developed. Dose and day of therapy were positively associated with trough concentration, whilst estimated renal function and, interestingly, acute myeloid leukaemia diagnosis were negatively associated (P<0.05). Results suggested a positive relationship between trough concentration and the likelihood of a favourable outcome for coagulase-negative staphylococcal central line-associated bloodstream infections. Elucidation of a specific target concentration requires further investigation. Teicoplanin was well tolerated renally. Findings suggest a risk of underexposure if conventional teicoplanin doses are used in haematological malignancy patients. Given the variability in trough concentrations observed, the identified factors affecting trough concentrations attained and the suggested link with clinical outcome, individualised initial dosing followed by therapeutic drug monitoring is recommended to ensure early adequate exposure in this vulnerable patient group.
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http://dx.doi.org/10.1016/j.ijantimicag.2015.05.019DOI Listing
October 2015

A 5-day: the favourable way?

Ann Hematol 2014 Sep 9;93(9):1619-20. Epub 2014 Jan 9.

Department of Haematology, Beaumont Hospital, Beaumont Road, Dublin, 9, Ireland,

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http://dx.doi.org/10.1007/s00277-013-2005-9DOI Listing
September 2014

A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia.

Br J Haematol 2013 Oct 2;163(1):118-22. Epub 2013 Aug 2.

Department of Haematology, University Hospital Limerick, Limerick, Ireland; Department of Haematology, Tallaght Hospital (AMNCH), Dublin, Ireland.

This retrospective analysis assessed the response, safety and duration of response to standard dose rituximab 375 mg/m(2) weekly for four weeks as therapy for patients with primary or secondary warm autoimmune haemolytic anaemia (WAIHA), who had failed initial treatment. Thirty-four patients received rituximab for WAIHA in seven centres in the Republic of Ireland. The overall response rate was 70·6% (24/34) with 26·5% (9/34) achieving a complete response (CR). The time to response was 1 month post-initiation of rituximab in 87·5% (21/24) and 3 months in 12·5% (3/24) of patients. The median duration of follow-up was 36 months (range 6-90 months). Of the patients who responded, 50% (12/24) relapsed during follow up with a median time to next treatment of 16·5 months (range 6-60 months). Three patients were re-treated with rituximab 375 mg/m2 weekly for four weeks at relapse and responded. There was a single episode of neutropenic sepsis. Rituximab is an effective and safe treatment for WAIHA but a significant number of patients will relapse in the first two years post treatment. Re-treatment was effective in a small number of patients, suggesting that intermittent pulse treatment or maintenance treatment may improve long-term response.
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http://dx.doi.org/10.1111/bjh.12486DOI Listing
October 2013

Successful Use of Alternative Anticoagulants in the Management of Heparin-induced Thrombocytopenia with Thrombotic Complications: Report of 5 cases and review of literature.

Sultan Qaboos Univ Med J 2011 Aug 15;11(3):391-8. Epub 2011 Aug 15.

Department of Haematology, Sultan Qaboos University Hospital, Muscat, Oman;

Heparin is one of the most frequently used anticoagulants. It is easy to use, but can be associated with life-threatening side effects. One of these is heparin-induced thrombocytopenia syndrome (HITS), which develops in about 3-5% of patients exposed to heparin and is associated with thrombosis in 1% of cases. We report here the successful treatment of five patients with HITS who were treated with alternative anticoagulants namely danaparoid or hirudin. The median time between their exposure to heparin and onset of symptoms and or signs was 10.2 days (range 7-14 days). Platelet counts decreased to a mean of 38.4 x 10(9) /l (12-82 x 10(9)/l). All five patients had evidence of thrombosis; four patients had clinical and radiological evidence of pulmonary emboli, one patient had confirmed deep vein thrombosis (DVT) and one patient had extensive skin necrosis of the thighs and abdomen. Platelet aggregation test were positive in two patients, inconclusive in one patient and negative in two patients. Two patients were anticoagulated with danaparoid and three with hirudin until their platelet counts returned to normal between 4 and 14 days (average 6 days) following the recognition of the syndrome. Our patients had significant morbidity, but no mortality. Immediate withdrawal of heparin is of paramount importance and introduction of alternative anticoagulant is necessary in the presence of thrombosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210050PMC
August 2011

Image of the month. Pericardial varices secondary to superior vena cava obstruction.

J Thorac Oncol 2010 Jan;5(1):142-3

Department of Radiology, Adelaide and Meath Incorporating National Children's Hospital, Tallaght, Dublin, Ireland.

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http://dx.doi.org/10.1097/JTO.0b013e3181c2fca2DOI Listing
January 2010

Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients.

Br J Haematol 2008 Sep 28;142(6):925-33. Epub 2008 Jun 28.

CRUK Institute for Cancer Studies, University of Birmingham, Birmingham, UK.

Ataxia Telangiectasia (A-T) patients have biallelic inactivation of the ATM gene and exhibit a 200-fold-increased frequency of lymphoid tumours. ATM mutations have been found in a number of adult lymphoid malignancies but there is no data on the occurrence of ATM mutations in multiple myeloma tumours. The purpose of our work was to investigate the occurrence of ATM mutations in multiple myeloma and to this end we screened 45 sporadic cases for ATM mutations using denaturing high-performance liquid chromatography analysis and DNA sequencing. Pathogenic ATM mutations were identified in 2/45 of the myelomas compared with a published estimate of ATM mutant allele frequency in the UK population of 2/521 (P = 0.033). One was the missense mutation 7181C>T which was then modelled in an expression system and the S2394L protein shown to have no ATM kinase activity. The second myeloma had the pathogenic ATM splice site mutation IVS40-1G>C leading to loss of exon 41. We also report a 48-year-old ataxia telangiectasia patient who developed multiple myeloma. Taken together our study suggests that ATM mutation may play a role in the pathogenesis of a subset of multiple myelomas.
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http://dx.doi.org/10.1111/j.1365-2141.2008.07281.xDOI Listing
September 2008

Chronic leukemias.

Dis Mon 2008 Apr;54(4):242-55

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http://dx.doi.org/10.1016/j.disamonth.2007.12.005DOI Listing
April 2008
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