British Committee For Standards In Haematology Research Articles

Second Line Systemic Treatments Including Extracorporeal Photopheresis Among Patients with Chronic Graft Versus Host Disease (cGVHD) in the United States, 2009-2016

Introduction: Extracorporeal photopheresis (ECP) is a cell-based immunomodulatory therapeutic procedure approved by the FDA for cutaneous T-cell lymphoma (CTCL) among individuals who have not been responsive to other forms of treatment in the United States (US). As clinical evidence accumulated over the years, Centers for Medicare & Medicaid Services (CMS) issued several Medicare National Coverage Decisions (NCDs) for coverage of ECP in patients with acute cardiac allograft rejection or chronic graft versus host disease (cGVHD), who are, refractory to standard immunosuppressive drug treatment. In contrast, per British Committee for Standards in Haematology (BCSH) guidelines on treatment of cGVHD, ECP is recommended as the first option over other 2nd-line systemic treatments including rapamycin (mTOR) inhibitors, pentostatin, rituximab, and imatinib. The objective of this analysis was to describe real-world use of ECP in patients with cGVHD in the US between 2009 and 2016.Methods: A retrospective analysis was conducted using the Truven Health MarketScan® Commercial and Medicare Supplemental claims databases (2009-2016). Adult (≥18 years) cGVHD patients receiving 2nd-line systemic treatments, with continuous health plan enrolment 3 months prior to first cGVHD diagnosis (i.e., baseline period) and 6 months following the initiation of 2nd-line systemic treatment were included. Patient demographic and clinical characteristics were summarized by type of 2nd-line systemic treatment (ECP vs. non-ECP). In addition, treatment patterns including the time from cGVHD diagnosis to initiation of 2nd-line systemic treatment, duration of ECP treatment (ie, time from initiation to end of ECP treatment), and ECP use (proportion of patients receiving ECP treatment among those receiving 1 of the 5 2nd-line systemic treatments) by year were reported. Annual per person all-cause cost for cGVHD patients for emergency room (ER) visits, office visits, and inpatient visits incurred after receiving 2nd-line systemic treatment (ie, the follow-up period) were also reported.Results: Of the 3086 adult cGVHD patients, 663 (21.5% of patients with cGVHD) patients had ≥2 claims for 2nd-line systemic treatments, of which 464 met the continuous enrollment criterion and were included in the study (mean age=49.7 years; 60.1% males). The most commonly reported underlying conditions at baseline were bone marrow transplant (268 [57.8%]), stem cell transplant (280 [60.4%]) and CTCL (25 [5.4%]). The average time from first cGVHD diagnosis to initiation of 2nd-line systemic treatment was 5.4 months. Among patients receiving 2nd-line systemic treatments, 210 (45.3%) received ECP treatment for an average duration of 11.1 months. ECP and non-ECP patients were similar in terms of demographic and clinical characteristics, with organ transplant as the most common underlying condition during the baseline period. As the number of cGVHD patients increased from 16 in 2009 to 100 in 2016, ECP use increased from 31.3% in 2009 to 54.0% in 2016. The total annual all-cause per patient cost was $190,148, including $4619 for ER visits, $8,673 for office visits, and $176,856 for hospitalizations during the follow-up period.Conclusions: Results from the latest US commercial administrative claims data pointed to an increase rate of cGVHD between 2009 and 2016. Of the 464 study patients with cGVHD, 2nd-line systemic treatment was initiated 5.4 months following the first diagnosis of cGVHD. As the number of cGVHD patients increased the rate of ECP use increased over time as well. During the study period, ECP was used by 45.3% of study patients with average duration of 11.1 months. In addition, high economic burden was reported among cGVHD patients receiving 2nd-line systemic treatments. DisclosuresJoshi:Pharmerit International: Employment; Mallinckrodt Pharmaceuticals: Research Funding. Luo:Mallinckrodt Pharmacueticals: Research Funding; Pharmerit International: Employment. Huang:Mallinckrodt Pharmaceuticals: Employment. Mitri:Mallinckrodt: Employment. Lovelace:Mallinckrodt Pharmaceuticals: Employment. Pham:University of California, School of Pharmacy: Employment; Mallinckrodt Pharmaceuticals: Employment. Gao:Mallinckrodt Pharmaceuticals: Consultancy, Employment.

The Utility of Hereditary Thrombophilia Testing Among Hospitalized Patients: A Single Center Experience

Background: Hereditarythrombophilias (HT) are a group of inherited diseases that predispose to venous thromboembolism (VTE). It can increase the risk of VTE by 3 to 20-fold compared to general population. HT are common and present in 7% of the population. Testing for HT is routine but knowing when to order the tests and how to interpret the results can be challenging. In the United Kingdom, it is estimated that 30,000 tests are done each year to screen for HT with an annual cost of 15,000,000 Euros. This led the British Committee For Standards in Haematology (BCSH) to release guidelines in 2010 that recommends against testing patients at the time of acute venous thrombosis as it will not influence the initial treatment. In the United States there are no clear guidelines regarding testing for HT. We performed a retrospective study to look at the utilization of HT tests among hospitalized patients. This study attempts to address the clinical utility of these tests and concurrent costs to the health care system.Methods: This is a retrospective study. We reviewed 2402 patient charts with at least one HT test ordered between 2/2016-1/2018 in St Luke's Health Care System records in Kansas City, MO. The following HT tests were included: Activated protein C resistance, antiphospholipid panel, antithrombin III level, factor V Leiden mutation, factor VIII level, homocysteine level, protein C level, protein S level, and prothrombin 20210 mutation. Only patients who had testing done during hospitalization were included. Positive actionable tests were analyzed to determine the clinical benefit of ordering the tests. A positive actionable test was defined as a positive test that changed the anticoagulation intensity, type or duration. Patients with history of previous thromboembolic disease, ongoing medical condition requiring life-long anticoagulation (such as atrial fibrillation), or unprovoked thromboembolic disease were considered non actionable. We also documented the total number of positive tests, ordering providers, and total cost related to ordering these tests (total cost of tests+ cost of hematology consult after an abnormal test).Results: A total of 2402 patients were reviewed. 954 patients were included with a mean age of 54 years. 397 (41.6%) were ordered for venous thromboembolism (VTE) (Deep vein thrombosis, pulmonary embolism or both). Among the included patients, 634 had at least one positive test (Table-1). Only 89 positive tests were actionable (14% of the positive tests and 9.3% of the total ordered tests). There was a statistically significant association between increasing age and having both a positive test result (P-value 0.006), and an actionable test (P-value 0.046). The chance of having actionable tests was more if the test was done in an inpatient setting rather that in the emergency room (OR 0.361, CI 95% (0.177-0.737)). The total cost of ordering these tests was estimated to be $551,218.1 and the cost of subsequent hematology consults was $15,367 leading to total cost of $566,585 during our study period.Conclusion: Inpatient testing for thrombophilia is associated with increased health care cost and did not change management in many situations. The decision of ordering these tests should be based on a clinical risk assessment. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prophylaxis and treatment of venous thromboembolism in cancer patients: a systemic review and critical appraisal of clinical practice guidelines

: Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer and many organizations have published guidelines to help clinicians in prophylaxis and treatment with VTE in cancer patients. However, the quality of different guidelines remains unclear. In this study, we aimed to explore score and provide a whole picture of the current guidelines. Clinical guidelines and consensus statements in English to July 2017 were searched using MEDLINE via PubMed, EMBASE and some websites of guideline organizations. The guidelines containing recommendations on the prophylaxis and treatment with VTE in cancer patients were included. Three reviewers appraised the quality of the included guidelines by using Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Six domains with 23 items were appraised and standardized averages were calculated as the final scores in every domain. Of 2,335 citations identified, 13 guidelines were included in this study. Associazione Italiana di Oncologia Medica (AIOM), British Committee for Standards in Haematology (BCSH) and French national guideline were regard as “recommended for use with some modification” while the others were “strongly recommended for use in practice”. Most included guidelines scored high in domain 1 (scope and purpose) and domain 2 (stakeholder involvement), but scored poorly in domain 5 (applicability). The recommendations were consistent in general among the included guidelines. Low molecular weight heparin (LMWH) was the major choice for the prophylaxis and treatment but the duration for the long-term treatment for VTE was controversy and the guidelines with high quality tended to recommend 3 months. Apart from the BCSH guidelines, direct acting oral anticoagulants (DOACs) were not recommended on prophylaxis or treatment. The guidelines on VTE in cancer patients were of relative high quality. More effort is needed to decrease the gap between the practice and guideline. DOACs seem to be potential candidate when clinicians are reluctant to use LMWH, but more researches must be performed.

Prophylaxis and treatment of venous thromboembolism in cancer patients: a systemic review and critical appraisal of clinical practice guidelines

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer and many organizations have published guidelines to help clinicians in prophylaxis and treatment with VTE in cancer patients. However, the quality of different guidelines remains unclear. In this study, we aimed to explore score and provide a whole picture of the current guidelines. Clinical guidelines and consensus statements in English to July 2017 were searched using MEDLINE via PubMed, EMBASE and some websites of guideline organizations. The guidelines containing recommendations on the prophylaxis and treatment with VTE in cancer patients were included. Three reviewers appraised the quality of the included guidelines by using Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Six domains with 23 items were appraised and standardized averages were calculated as the final scores in every domain. Of 2,335 citations identified, 13 guidelines were included in this study. Associazione Italiana di Oncologia Medica (AIOM), British Committee for Standards in Haematology (BCSH) and French national guideline were regard as “recommended for use with some modification” while the others were “strongly recommended for use in practice”. Most included guidelines scored high in domain 1 (scope and purpose) and domain 2 (stakeholder involvement), but scored poorly in domain 5 (applicability). The recommendations were consistent in general among the included guidelines. Low molecular weight heparin (LMWH) was the major choice for the prophylaxis and treatment but the duration for the long-term treatment for VTE was controversy and the guidelines with high quality tended to recommend 3 months. Apart from the BCSH guidelines, direct acting oral anticoagulants (DOACs) were not recommended on prophylaxis or treatment. The guidelines on VTE in cancer patients were of relative high quality. More effort is needed to decrease the gap between the practice and guideline. DOACs seem to be potential candidate when clinicians are reluctant to use LMWH, but more researches must be performed.

Clinical usefulness of the dilute Russell viper venom time test for patients taking warfarin

Warfarin use often causes false-positive results in the dilute Russell viper venom time test (DRVVT). Thus, three sets of guidelines-those presented by the International Society on Haemostasis and Thrombosis (ISTH), the British Committee for Standards in Haematology (BCSH), and the Clinical and Laboratory Standards Institute (CLSI)-are advocated. We evaluated the clinical usefulness of the testing methods recommended in these three guidelines using laboratory samples. Of the 242 samples from patients using warfarin, 38 were positive for lupus anticoagulant (LA). After adding normal pooled plasma (NPP) as recommended in the ISTH, BCSH, and CLSI guidelines, the number of samples testing positive for LA decreased to 13, 18, and 19, respectively. The number of samples with inconsistent results between the activated partial thromboplastin time and mixing test, and the DRVVT following the ISTH, BCSH, and CLSI guidelines were four of 205 (1.9%), 15 of 242 (6.2%), and 17 of 242 (7.0%), respectively. In patients with an international normalized ratio (INR)≥3.0, 11 of 37 (29.7%) and 12 of 37 (32.4%) samples showed inconsistent results according to the BCSH and CLSI guidelines, respectively. The accuracy of the DRVVT result may thus decrease in markedly anticoagulated patients.

Guideline for the investigation and management of eosinophilia.

The guideline group was selected to be representative of UK-based medical experts with an interest in myeloproliferative neoplasms and eosinophilia. PubMed and EMBASE were searched systematically for publications in English until August 2015 using the key words eosinophilia, hypereosinophilia, eosinophilic leukaemia and HES. The writing group produced the draft guideline which was subsequently revised by consensus by members of the General Haematology and Haemato-oncology Task Forces of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of UK haematologists and representatives from the Nordic MPN Study Group, the British Committee for Standards in Haematology (BCSH) and the British Society for Haematology (BSH) Committee and comments were incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found in Table I. The objective of this guideline is to provide healthcare professionals with clear guidance on the investigation and management of eosinophilia.

DIC: an update on diagnosis and treatment.

Disseminated intravascular coagulation (DIC) was considered to be a fatal disease. However, it has recently been suggested that very early DIC protects the host against microthrombosis and infection localization. Therefore, early treatment of DIC may be contraindicated in patients with sepsis. These factors suggest that the diagnosis and treatment of DIC will gain further importance. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG2016), which include details regarding the management of DIC, have been recently published. Differences in recommendations for DIC treatment, such as antithrombin and recombinant human thrombomodulin, between J-SSCG2016 and other guidelines, including the Japanese Society on Thrombosis and Hemostasis (JSTH), British Committee for Standards in Haematology (BCST), Italian Society for Thrombosis and Haemostasis (SISET), and International Society on Thrombosis and Haemostasis (ISTH) have been discussed. Furthermore, differences in the diagnostic criteria for DIC between the Japanese Ministry of Health, Labor and Welfare, ISTH overt, ISTH non-overt, Japanese Association for Acute Medicine, and JSTH have been discussed.

English

BACKGROUND Entry of foetal erythrocytes into maternal circulation before or during delivery is referred as Foetomaternal Haemorrhage (FMH). An Rh-D negative women when exposed to the cells of an Rh-D positive foetus, produces anti-D antibodies that causes complications like foetal anaemia, hydrops foetalis and neonatal jaundice. The Kleihauer-Betke test is a quantitative test, which uses the concept of differential resistance to acid by foetal and adult haemoglobin. As the potential risk factors can be determined by placental morphology and provide information on pregnancy outcome, they may provide information on incidence and amount of FMH also.The objective of this study is to determine the relationship between placental parameters (weight and diameter) and the incidence as well as severity of Foetomaternal Haemorrhage (FMH). The secondary aim was to correlate FMH with maternal factors and neonatal anaemia.MATERIALS AND METHODS A total of 333 women who delivered in the hospital after 28 weeks of gestation were enrolled for the study. Maternal blood (2 mL) was collected in EDTA bottle after the delivery of the baby. Samples were sent to Blood Bank. FMH was quantified by Kleihauer-Betke’s test. The foetomaternal haemorrhage is calculated as: Number of foetal cells per high power field/Number of maternal cells per high power field x 2400.1 FMH > 2 mL was considered positive for FMH as per BSCH (British Committee for Standards in Haematology) guidelines.2 Placental parameters like weight (after trimming cord at 5 mm from the insertion point and clearing membranes, clots) and diameter were measured. A cut-off of 500 gms for placental weight and 22 cm for placental diameter was taken.3,4,5 Actual birth weight and neonatal Haemoglobin (Hb) was noted.BSCH = British Committee for Standards in Haematology.RESULTS Out of 333 subjects 48 (14.4%) were positive for FMH (Group 1) and 285 (85.6%) were negative for FMH (Group 2). The mean placental weight (508.54 ± 80.34 gm) and the mean placental diameter (19.92 ± 3.99 cm) were significantly more in patients having positive FMH when compared to those with negative FMH. (P value = 0.0005 for placental weight and p = 0.005 for placental diameter). When placental weight was ≥ 500 gm more subjects were significantly positive for FMH (25.6%) compared to when that was less than 500 gm (7%) (P value = 0.00). When the placental weight was between 600 and 699 gm, the odds of having FMH was 13.43 times more. When the placental diameter was ≥ 22 cm, the incidence of positive FMH was significantly more (33.9%) compared to when that was 2 mL both mean placental weight (508.54 ± 80.34 gm) and diameter (19.92 ± 4.00 cm) were significantly higher when compared to lesser FMH. (P value 0.00 for both weight and diameter). Incidence of positive FMH was significantly more in maternal risk factors such as GDM, preeclampsia, placenta previa. The odd of having positive FMH was 16.45 times more in the presence of placenta previa. There was a mild negative correlation coefficient existed between the neonatal haemoglobin and amount of FMH, which was statistically significant (p value = 0.000). That means although neonatal anaemia was not found in the babies in our study, there was a trend of having lower haemoglobin with higher FMH.CONCLUSION With the findings of present study, it was concluded that bigger the placenta in terms of weight and diameter more is the foetomaternal haemorrhage. Foetomaternal haemorrhage is associated with maternal complications such as multifoetal gestation, GDM, preeclampsia and a diagnostic test for FMH should be considered in such cases to detect neonatal anaemia at the earliest possible and to decide on adequate dose of anti-D to clear the foetal cells from maternal circulation.

Guidelines on transfusion for fetuses, neonates and older children.

Guidelines on transfusion for fetuses, neonates and older children.

Effective implementation of a patient blood management programme for platelets

To implement a patient blood management (PBM) programme in platelet transfusion. To improve the appropriate use of blood components, reduce wastage and generate savings. PBM is a multidisciplinary, evidence-based approach to optimising the care of patients who need blood transfusion and to use blood products appropriately. Strategies for PBM ensure that patients receive the best possible treatment with the transfusion of components when indicated, at the same time avoiding or reducing unnecessary transfusions. Typically, PBM initiatives have addressed the use of red cells. PBM initiatives in platelets (PBM-P) are an important aspect of Transfusion Medicine. We present data from an initiative for PBM-platelets (PBM-P) comprising a service improvement programme through the role of a 'platelet co-ordinator' (PBM-Pc) to optimise the use of platelets in a large complex tertiary care hospital in a National Health Service (NHS) setting. Analysis at 18 months of the role showed sustained improvement in compliance with quality standards defined by British Committee for Standards in Haematology (BCSH) guidelines and significant financial savings due to improved use and reduced wastage. The appropriate use of platelets increased by 17, 23 and 18% in the prophylactic, pre-procedure and peri-procedure categories, respectively. Importantly, despite concurrent increases of patient activity, platelet issues and cost reduced by 21% over the period of analysis. Our model has been efficacious in delivering the effective stewardship of platelets and can be successfully implemented in NHS.

Audit of compliance with the British Committee for Standards in Haematology (BCSH) revised guidelines for the diagnosis and assessment of treatment response of hairy cell leukemia in University Hospital Galway.

Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferative disorder. The object of the present audit was to assess whether the investigation and management of HCL in University College Hospital Galway (UCHG) complies with the British Committee for Standards in Haematology (BCSH) guidelines. Following a review of the records in our Haematology Department, 18 cases of HCL were identified between January 2006 and October 2014. Blood film examination had been performed in all cases. Flow cytometry of liquid material had been undertaken in 89% (n=16) of cases, of which only 31% (n=5) included all four hairy cell panel markers (CD11c, CD25, CD103, CD123). Although all initial trephine biopsies included CD20, none analyzed DBA44. Only 65% (n=11) of treated patients had a post-treatment bone marrow biopsy preformed. This audit highlights areas of improvement in the diagnosis and management of HCL in UCHG, which do not currently adhere to the BCSH recommendations.

Recommendations for the electronic pre-transfusion check at the bedside.

The current risk of acquiring viral transmission through blood components is very small1. Thus, serious non-infectious hazards of transfusion have emerged as the most common complications2. The risk of non-infectious complications, including risks related to hospital-based steps in transfusion care, is at least 100 times greater than the risk of acquiring human immunodeficiency virus or hepatitis C virus infection through blood components3. One of the most frequent causes of transfusion-associated morbidity or mortality is mistransfusion, when the wrong blood is transfused to the wrong patient. Mistransfusion is the final outcome of one or more procedural errors or technical failures in the transfusion process, starting with the decision to transfuse a patient and ending with the actual administration of blood components3. In particular, ABO-incompatible transfusions attributable to incorrect identification of the patient or the blood unit are among the most serious transfusion hazards3–5. The Japan Society of Transfusion Medicine and Cell Therapy (JSTMCT) conducted nationwide surveys in Japan regarding ABO-incompatible blood transfusions (1st survey: January 1995–December 1999; 2nd survey: January 2000–December 2004). They found that the main cause of ABO-incompatible transfusion was identification error between the patient and blood unit6. These two surveys reported 9 and 8 “preventable” fatalities, respectively. Mislabelled and wrongly collected patient samples (wrong blood in tube [WBIT]) can also initiate a chain of events leading to mistransfusion3. Thus, correct patient identification at the time of sample collection and administration of blood components is critical. The Serious Hazards of Transfusion (SHOT) scheme in England showed that approximately 70% of incorrect blood component transfused (IBCT) errors take place in clinical areas, with the most frequent error being failure of the final patient identification checking procedure at the bedside; the frequency of IBCT events was calculated as 7 per 100,000 components7. However, the true incidence of mistransfusion seems to be even higher due to a failure to recognise many of the errors, and because complete data on transfusion episodes are not available. Thus, the pre-transfusion checking procedure at the bedside is the most critical step to prevent mistransfusion, and represents the final opportunity to prevent blood component misuse. However, a large observational audit revealed a failure to perform the final bedside checking procedure8, in which the practice compliance of healthcare workers for identification and vital sign monitoring of patients receiving blood transfusions were substandard in many hospitals. Machine-readable identification technology, especially a bar code-based electronic identification system (EIS), is ideally suited for pre-transfusion checking procedures and has been reported to significantly improve transfusion practice9–15. The British Committee for Standards in Haematology (BCSH) Guidelines for the Use of Information Technology (IT) in blood transfusion laboratories were recently up-dated16, providing mainly guidance on the operational use of laboratory information management systems (LIMS). Thus, to our knowledge, there are no available recommendations addressing the issues regarding the pre-transfusion check procedures at the bedside employing an EIS. The JSTMCT Task Force proposed the original draft of recommendations for the electronic pre-transfusion check procedures at the bedside and raised public awareness regarding the draft of recommendations on the home page of the JSTMCT17. The draft of the current recommendations developed by the Task Force adopted the opinions were submitted without major changes to the description. The objective of this study was to establish recommendations for the electronic pre-transfusion checking procedures at the bedside, appropriate for clinical situations, where a bar code-based EIS is used.

Clinical Impact of Bone Marrow Morphology for the Diagnosis of Essential Thrombocythemia: Comparison Between the British Standards (BCSH) and the WHO Criteria

Background Accurate diagnosis of essential thrombocythemia (ET) continues to be a challenging issue for both hematopathologists and clinicians. Diagnosis is usually performed by applying either the 2014 British Committee for Standards in Haematology (BCSH) guidelines or the 2008 World Health Organization (WHO) criteria. While the WHO classification requires bone marrow morphology (BM) as a major criterion, the BCSH guidelines allow diagnosis also based solely on clinical symptoms and is more focused on exclusion of the other subtypes of myeloproliferative neoplasia (MPN). However, prefibrotic/early stages of primary myelofibrosis (prePMF) may also present with thrombocytosis, while failing to meet the diagnostic signs and symptoms characterizing overt PMF. Moreover, a small fraction of polycythemia vera (PV) patients may present with low hemoglobin and hematocrit levels, but a platelet count in keeping with BCSH- and WHO-defined ET, thus mimicking phenotypically ET at onset (masked PV). Clinical outcome in prePMF patients is considerably worse than in ET patients, while treatment strategies are likely to change for prePMF patients with the use of interferon-alpha or JAK1/2-inhibitors.Aims The aim of this study was to investigate the prognostic relevance of BM morphology for ET diagnosis as underscored by the WHO classification versus the first set of the BCSH criteria that do not include BM evaluation.Methods A clinic-pathological database including 450 MPN patients was created by clinicians and hematopathologists from a major Austrian center. Treatment-naive BM biopsies were centrally re-reviewed by three of the authors, who were completely blinded to initial data (except for age and gender). Follow-up data, including clinical course and mutation status, were analyzed after the completion of the histopathology review. For purpose of this study we selected two cohorts of ET patients presenting with a sustained platelet count > 450x10^9/L: (1) 209 ET patients in accordance with the diagnostic requirements of the BCSH (A1-A3) that included no BM biopsy examination. (2) 152 patients in strict agreement with the diagnostic guidelines of the WHO including BM biopsy evaluation as major criterion. Both cohorts were compared and analyzed to regarding their presenting clinico-pathological data, driver mutation status, and follow-up. Diagnosis of post-ET myelofibrosis or progression into overt myelofibrosis with myeloid metaplasia was made according to previously published criteria.Results Following the BCSH criteria, 209 patients were diagnosed as ET. When reclassifying those cases according to the WHO criteria including BM morphology examination, 80 (38.3%) patients were diagnosed as prePMF and 14 (6.7%) as PV and two were diagnosed as PMF (0.9%). Comparison of clinical features of BCSH-ET and WHO-ET revealed significant differences in LDH levels and palpable splenomegaly at diagnosis. Fibrosis-free survival was significantly shorter in BCSH-ETs (Fig. 1A) as was overall survival (Fig. 1B). When reclassifying the BCSH cohort according to WHO criteria, progression-free and overall survival were significantly shorter in WHO-confirmed prePMF (Fig. 1C and 1D).Summary/Conclusion The striking differences in outcome are certainly linked with the entry of many prePMF cases in the BCSH-confirmed cohort. The inclusion of these cases, as well as cases with masked PV demonstrates, that BCSH criteria A1-3 may lead clinicians to refrain from performing BM biopsy in patients with elevated thrombocyte counts, which impairs accurate diagnosis with subsequent inadequate management and inferior prognosis. Our results highlight the central role of BM biopsy to achieve accurate diagnosis and differentiation of ET and prePMF. [Display omitted] DisclosuresGisslinger:Geron: Consultancy; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi Aventis: Consultancy; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen Cilag: Honoraria, Speakers Bureau.

Guidelines for the diagnosis and management of adult aplastic anaemia.

Sally B. Killick (Writing Group Chair), Nick Bown, Jamie Cavenagh, Inderjeet Dokal, Theodora Foukaneli, Peter Hillmen, Robin Ireland, Austin Kulasekararaj, Ghulam Mufti, John A Snowden, Sujith Samarasinghe, Anna Wood (BCSH Task Force Member), Judith C.W. Marsh on behalf of the British Society for Standards in Haematology. The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, Northern Genetics Service, Newcastle upon Tyne, St Bartholomew’s Hospital, Barts Health NHS Trust, London, Barts and The London School of Medicine and Dentistry, Queen Mary University of London and Barts Health NHS Trust, London, Addenbrooks Hospital, University of Cambridge, Cambridge, Leeds Teaching Hospitals, Leeds, Kings College Hospital NHS Foundation Trust, London, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield Great Ormond Street Hospital for Children NHS Foundation Trust, London, West Hertfordshire NHS Trust, Watford.

Carol Briggs (1958-2015).

After studying at Portsmouth Polytechnic, she started her career as a biomedical scientist at St Mary's Hospital as a research technician and then undertook standard haematology laboratory training at Chelsea and Westminster Hospital in central London. I first met her at a UK Haematology Laboratory meeting in Guernsey, one of the Channel Islands, in the early 1990s. We discussed how general basic skills in worldwide laboratory practice were declining and the lack of training facilities for scientists wishing to continue to investigate novel instrumentation and in-house assay development. After returning from this meeting, we established, at University College London Hospital (UCLH) in conjunction with University College London (UCL), a laboratory haematology evaluation centre, with initial support from several instrument manufacturers, and were able to offer Carol a position as a full-time research fellow to establish such a unit. Support was also obtained from the Department of Health, Medical Devices Agency to approve newly released haematology instrumentation, independent of commercial company bias, using a predetermined reporting format. Carol started working in the evaluation unit in 1997 and continued in this role for the next 17 years until her untimely death earlier this year. During this time, she published more than 50 publications in prime review journals, along with numerous guideline documents, review papers and book chapters on various subjects in laboratory haematology. Her most important work was in the development of the immature platelet fraction (IPF) or reticulated platelet parameter on the XE and then XN Sysmex analysers, and the initial development work on the XN analyser series between 2008 and 2011. In addition to her ground-breaking laboratory work, she was invited and then served on several national and international haematology standardization committees and evidence-based guideline groups. These included the general haematology working party of the British Committee for Standards in Haematology (BCSH), membership of the United Kingdom National External Quality Assessment Service (UKNEQAS) advisory group and internationally as Scientific Secretary of the International Committee of Standardisation in Haematology (ICSH) and recently as a Board Member of the International Society of Laboratory Haematology (ISLH). She has proudly served as an Associate Editor for the International Journal of Laboratory Hematology (IJLH) for the past few years and frequently helped numerous authors to correct and rewrite their papers in a form acceptable for publication. One of her proudest achievements was to be invited to write and edit a chapter on blood cell counters for the last two editions of the oldest standard haematology text, ‘Dacie and Lewis Practical Haematology’. Despite all these achievements, she resisted several invitations to work for large global haematology instrument manufacturers in senior positions, but was committed to continue expertly supervising and training young scientists and clinicians in laboratory practice. Carol will be sadly missed from the world of laboratory haematology internationally and leaves many friends and her husband, Roger, who will all miss her incisive wit, charm and inventiveness in laboratory automation. Already firm offers have been received to recognize her skills and foresight, with an annual international award from the Sysmex Corporation and possibly associated standardization bodies. Her presence as a thoughtful mind and innovator in her chosen subject is now unfortunately a great premature loss to the scientific, haematological world as a whole.

Guideline on aspects of cancer-related venous thrombosis.

The guideline was drafted by a writing group identified by the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology (BCSH). All the authors are consultants in haematology in the UK. A search was performed of PubMed and Embase using the term 'cancer' combined with 'thrombosis', 'treatment', 'prophylaxis' and 'clinical presentation'. The search covered articles published up until December 2014. Only human studies were included and articles not written in English were excluded. References in recent reviews were also examined. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the BCSH and the BCSH executive. The guideline was then reviewed by the sounding board of the British Society for Haematology (BSH). This comprises 50 or more members of the BSH who have reviewed the guidance and commented on thecontent and application to the UK setting. The 'GRADE' system was used to quote levels and grades of evidence, details of which can be found at: http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMENDATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the prevention and management of venous thromboembolism (VTE) in patients with cancer and to advise on an approach to screening for cancer in patients with unprovoked VTE in whom cancer was not initially suspected based on clinical grounds.

Masked polycythaemia vera: presenting features, response to treatment and clinical outcomes.

Masked polycythaemia vera (PV) has been proposed as a new entity with poorer outcome than overt PV. In this study, the initial clinical and laboratory characteristics, response to treatment and outcome of masked and overt PV were compared using red cell mass and haemoglobin or haematocrit levels for the distinction between both entities. Sixty-eight of 151 PV patients (45%) were classified as masked PV according to World Health Organisation diagnostic criteria, whereas 16 (11%) were classified as masked PV using the British Committee for Standards in Haematology (BCSH). In comparison with overt PV, a higher platelet count and a lower JAK2V617F allele burden at diagnosis were observed in masked PV. Patients with masked PV needed lower phlebotomies and responded faster to hydroxcarbamide than those with overt PV. Complete haematological response was more frequently achieved in masked than in overt PV (79% vs. 58%, P = 0.001). There were no significant differences in the duration of haematological response, the rate of resistance or intolerance to hydroxycarbamide and the probability of molecular response according to type of PV (masked vs. overt). Overall survival, rate of thrombosis and major bleeding, and probability of transformation was superimposable among patients with masked and overt PV.

Guideline on the management of acute chest syndrome in sickle cell disease.

1. Department of Haematology, Guy’s and St Thomas’ NHS Foundation Trust 2. Lane Fox Respiratory Unit, St Thomas’ Hospital, Guy’s and St Thomas’ NHS Foundation Trust 3. Department of Haematology, North Middlesex Hospital 4. Department of Paediatric Haematology, Bristol Royal Hospital for Children 5. Department of Haematological Medicine, King’s College Hospital 6. Department of Haematology, Whittington Hospital

Usefulness of BCSH Criteria for Diagnosing Japanese Polycythemia Vera

Objectives: The WorldHealth Organization (WHO) classification (2008) is wid ely usedto d iagnose polycythemia vera (PV). However, some patients clinically suspected of PV may not be definitely diagnosed because they do not have a high hemoglobin (Hb) level, one of the main andessential d iagnostic criteria, or because of the lack of or unfilledminor criteria such as bone marrow biopsy, endogenous erythroid colonies, and serum erythropoietin. The British Committee for Standards in Haematology (BCSH) employed hematocrit (Ht), but not Hb, as an indicator in the PV diagnostic guidelines. Furthermore, if the presence of the JAK2 gene mutation is demonstrated, PV can be diagnosed with Ht only by BCSH. Therefore, we evaluated the usefulness of BCSH criteria for diagnosing PV in Japanese patients. Methods: We determinedhematological andclinical differences in 99 patients who met the BCSH criteria (Group A) and69 PV patients who met the WHO criteria (Group B). Results: All patients in Group B also met the BCSH criteria. Thirty patients in Group A (43%) did not fulfill the WHO criteria. No significant differences were observedin white bloodcell andplatelet counts, serum erythropoietin levels, the JAK2V617F allele burd en, or the risk of thrombosis andtransformation into myelofibrosis between Groups A andB. Conclusions: PV cases diagnosedby the BCSH criteria showedthe same clinical picture as those diagnosedby the WHO criteria. In view of actual clinical settings, the diagnostic criteria of BCSH criteria may be useful for the diagnosis of PV in Japanese patients.

The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology.

The guideline group was selected to be representative of UKbased medical experts. MEDLINE and EMBASE were searched systematically for publications in English from 2002 using the key word Willebrand. The writing group produced the draft guideline, which was subsequently reviewed by the A United Kingdom Haemophilia Centre Doctors Organization (UKHCDO) advisory committee, a British Committee for Standards in Haematology (BCSH) sounding board of approximately 50 UK haematologists, and the BCSH executive; comments were incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found in at http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_ GRADES_OF_RECOMMENDATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with von Willebrand disease.