British Committee Research Articles

Neutrality challenged in a cold war conflict: Switzerland, the International Committee of the Red Cross, and the Angolan War

The Swiss government’s actions in Angola in the 1970s highlight its aim to improve the credibility of its neutrality policy in Southern Africa, which was greatly challenged in the global Cold War context. Drawing on Swiss, US, British, and International Committee of the Red Cross archival sources, this paper argues that the Swiss authorities’ participation in the relief mission of the ICRC during the Angolan War permitted them to benefit from this organisation’s good image. Switzerland’s early recognition of the People’s Republic of Angola was closely coordinated with European political leaders and underlines the country’s increased independence from Washington during Détente.

Therapeutic Challenges in the Management of Acute Pulmonary Embolism in a Cancer Patient with Chemotherapy-induced Thrombocytopenia.

This case demonstrates the therapeutic challenges encountered when managing an acute pulmonary embolism in a cancer patient with thrombocytopenia. A 64-year-old man with a history of lung cancer receiving chemotherapy was admitted to Walsall Manor Hospital with haemodynamic instability consistent with a pulmonary embolism, proven on computed tomographic pulmonary angiogram. His platelet count was noted to be 35×109/l (chemotherapy-induced thrombocytopenia). After discussions, he was deemed not suitable for thrombolysis based on risk versus benefits. The patient was initially transfused one adult dose of platelets and treated with half the therapeutic dose of low molecular weight heparin (LMWH). The same management plan was followed until the platelet count exceeded 50×109/l, after which the patient was established on the full therapeutic dose of LMWH. Clinically, the patient improved and was discharged. Three months after discharge, follow-up revealed sustained clinical improvement while the patient continued to be on the full therapeutic dose of LMWH with a stable platelet count.LEARNING POINTSCancer patients have a three-fold higher risk of venous thromboembolism compared with non-cancer patients, but also a higher risk of bleeding, hence neoplasm is considered an absolute contraindication to thrombolysis by the European Society of Cardiologists.The management of an acute pulmonary embolism in cancer patients with thrombocytopenia is still debated. However, a few recognised medical societies and expert opinions have established recommendations on this specific area, such as the British Committee for Standards in Haematology, the American Society of Clinical Oncology and the International Society of Thrombosis and Haemostasis.Expert opinion agrees on: giving the full therapeutic dose of low molecular weight heparin (LMWH) if the platelet count is above 50×109/l; if it drops below 50×109/l, halving the dose of LMWH with or without platelet transfusion until the platelet count improves above 50×109/l; and when the platelet count is below 20–30×109/l, withholding anticoagulation and considering the insertion of an inferior vena cava filter.

Defibrotide: An Oligonucleotide for Sinusoidal Obstruction Syndrome.

To review the efficacy and safety of defibrotide as well as its pharmacology, mechanism of action, pharmacokinetics (PK), drug-drug interactions, dosing, cost considerations, and place in therapy. A PubMed search was performed through August 2017 using the terms defibrotide, oligonucleotide, hepatic veno-occlusive disease (VOD), sinusoidal obstruction syndrome (SOS), and hematopoietic cell transplantation (HCT). Other data sources were from references of identified studies, review articles, and conference abstracts plus manufacturer product labeling and website, the Food and Drug Administration website, and clinicaltrials.gov. English-language trials that examined defibrotide's pharmacodynamics, mechanism, PK, efficacy, safety, dosing, and cost-effectiveness were included. Trials have confirmed the safety and efficacy of defibrotide for treatment of VOD/SOS in adult and pediatric HCT patients, with complete response rates and day +100 overall survival rates ranging from 25.5% to 76% and 35% to 64%, respectively. The British Committee for Standards in Haematology/British Society for Blood and Marrow Transplantation Guidelines recommend defibrotide prophylaxis in pediatric and adult HCT patients with risk factors for VOD/SOS; however, its prophylactic use in the United States is controversial. Although there are efficacy data to support this strategy, cost-effectiveness data have not shown it to be cost-effective. Defibrotide has manageable toxicities, with low rates of grade 3 to 4 adverse effects. Defibrotide is the first medication approved in the United States for the treatment of adults and children with hepatic VOD/SOS, with renal or pulmonary dysfunction following HCT. Data evaluating defibrotide for VOD/SOS prevention are conflicting and have not shown cost-effectiveness.

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.

Interleukin-6 and Interleukin-8 Levels Correlate With the Severity of Aplastic Anemia in Children.

The aim of this study was to evaluate the levels of interleukin (IL)-6 and IL-8 in patients with aplastic anemia and its correlation with severity of the disease. IL-6 and IL-8 levels were measured in 40 patients with aplastic anemia in the age group of 4 to 14 years. A total of 40 healthy children served as controls. Quantitative estimation of IL-6 and IL-8 was performed using a solid-phase sandwich ELISA kit. Results were presented as IL-6 and IL-8 concentrations in pg/mL. Patients received immunosuppressive therapy per the British Committee for Standards in Haematology Guidelines 2009. Mean age of the patients was 9.78±2.74 years. IL-6 level of patients was elevated compared with controls (193.48±352.3 vs. 4.58±3.39; P<0.001). IL-8 levels were also significantly elevated in patients compared with controls (15.58±18.0 vs. 1.85±0.95; P<0.001). IL levels were also assessed in relation to severity of the disease. Levels were the highest in patients with very severe aplastic anemia (724.33±519.42), followed by severe aplastic anemia (80.51±66.28 pg/mL), and non-severe aplastic anemia (6.01±1.89). Differences were statistically significant. A similar trend was also observed for IL-8 levels, where the levels were 41.02±24.23, 11.34±8.0, and 1.67±0.71 for very severe aplastic anemia, severe aplastic anemia, and non-severe aplastic anemia, respectively. The differences were again statistically significant. IL levels were also correlated with the treatment outcome. Responders had lower levels compared with nonresponders, but the difference was not statistically significant (186.36±322.45 vs. 198.74±368.10). Levels of ILs decreased in responders, but were not comparable with that of controls 6 months after therapy. High levels of IL-6 and IL-8 were observed in children with aplastic anemia. Increased levels showed correlation with disease severity and therefore appear to play an important role in aplastic anemia. However, levels had no significant correlation with the treatment outcome.

Cost-Effectiveness of Defibrotide in the Prophylaxis of Veno-Occlusive Disease after Pediatric Allogeneic Stem Cell Transplantation

Veno-occlusive disease (VOD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prophylactic use of defibrotide (DF) might further reduce VOD rates but has no impact on the incidence of severe VOD or VOD-associated mortality. We investigated the cost-effectiveness of prophylactic DF according to the British Committee for Standards in Haematology/British Society for Blood and Marrow Transplantation guidelines in 348 children who underwent transplantation between 2001 and 2014 in our hospital, 138 of whom were at risk for VOD. The VOD incidence was 7.4% for the total cohort. Patients at risk had a higher incidence of VOD compared with patients without risk factors (15.2% versus 2.4%, P < .0001). VOD occurred more often in patients after busulfan-based myeloablative conditioning than in patients after total body irradiation (11.2% versus 3.5%, P = .001). Donor types or the transplantation-related mortality (TRM) risk score did not correlate with VOD incidence. In 81% of patients who responded to therapeutic DF, VOD resolved completely. Overall VOD-associated mortality was .3% for the complete cohort, 3.7% for patients diagnosed with VOD, and 20% for patients with severe VOD. Neither the cumulative incidence of TRM (19% ± 8% versus 17% ± 2%, P = .706) nor the median length of hospitalization differed between patients with VOD and patients without. The median costs per HSCT in patients with VOD were about one-third higher than the overall median costs per transplantation at our institution. The calculated total costs of prophylactic DF treatment for 138 patients at risk was almost 6 times as high as the incremental costs for patients with VOD. We conclude that prophylactic DF for children at risk for VOD is not cost-effective with respect to TRM and length of hospital stay.

Janus kinase 2 negative polycythemia vera

Abstract Background A Janus kinase 2 (JAK2) mutation polycythemia vera (PV) is a common manifestation of stem cell disorder. However, available data on the clinical and treatment response of JAK2-negative PV patients are limited. Objectives We report the case and clinical course of a patient with PV and left hemiparesis who was JAK2V617-negative. Methods We conducted a literature review and compared our patient with previously published reports of JAK2-negative patients with P V. Results Our patient presented with hemiparesis without a previous history of hematological disease. He was diagnosed with PV based on the British Committee for Standards in Haematology guidelines 2007. He underwent only phlebotomy with subsequent improvement of his neurological condition. He was discharged with therapeutic phlebotomy for one and a half months. Conclusions Although this rare condition required complex diagnostic criteria, the patient achieved good clinical outcome with therapeutic phlebotomy alone.

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.

Determination in vivo viability of a transfused platelet product by corrected count increment and percentage platelet response.

IntroductionFor many years, platelet concentrates have been used for the prevention as well as treatment of bleeding disorders, especially in those patients with haematological problems involving platelet disorders as well as refractoriness, In addition, platelet concentrates (PCs) have been widely used to support patients undergoing bone marrow transplantation or who are receiving myelotoxic treatments. The aim of this study was to determine the quality of platelet concentrates by assessing platelet counts, volume, pH changes, swirling, residue of the red blood cells and white blood cell counts. Assess the in vivo viability of a transfused platelet product using the corrected count increment (CCI) and the percentage platelets response (PPR). This descriptive analysis study was done in Kenyatta National Hospital Blood Transfusion Unit between July 2016 and December 2016.MethodsThe in vitro Platelets concentrates quality was accurately determined and assessed using certain parameters. Platelet concentrates in ethylene diamine tetra acetic acid (EDTA) was used for analysis using Cell-Dyn 3700 analyser. The volume of PCs used was an average of 2mls of PCs, the pH was measured using digitalised Hanna edge pH kit. Agitation was done using Helmer agitator and centrifugation was done using Roto silenta 630 RS centrifuge. The in vivo viability of a transfused product was determined using corrected count increment (CCI) and percentage recovery (PR) between 1 and 20-hour after transfusion. Pre and post-transfused whole blood in EDTA collected from the recipients was analysed to access the functional platelets in the circulation. Data analysis was done using SPSS.ResultsA total of 384 platelet concentrates were analysed and used in transfusion. The majority 96, (40%) were O Rhesus D+ and the least being AB Rhesus D-at (1%).Centrifugation, separation and agitation was done according to standard procedure (n=384). Only (246 (65%) of the concentrates were found fit for use out of a total of (n=384) leaving 138 (35%) which did not meet the KNH/KNBTS criteria. The minimum specifications for platelet count are 5.5 x (109). The duration of 3 days of storage on average, the WBC count (109) was Mean ± SD 4.50 ± 3.50. Using the Hanna edge pH kit the pH Mean was ±SD 7.18 ± 8.82 and the used Volume (Mls) was at 55 ± 15. The concentrate was issued within 3 days of processing. After transfusion, the percentage platelet response (PPR) was 72% in male recipients at 1-hour and 30% at 20-hours while 69% in female recipients at 1-hour and 25% at 20-hours. The invivo viability of platelet product had a corrected count increment (CCI) of 75% ≥ 7500 at 1-hour and CCI of18% ≥ 30% at 20-hours in male recipients. In the same study, the female recipients had a CCI of 80% ≥ 7500 at 1-hour and a CCI of 25% ≥ 30% at 20-hours.ConclusionThe findings on platelets concentrates quality 65% met platelets transfusion criteria while 35% did not. On preparation of platelets concentrates there was high counts of white blood cells 4.5±3.5×109than recommended counts by Kenya National Blood Transfusion Services < 0.83×109. Both percentage platelet response (PPR) and corrected count increment (CCI) were very low at 20 hours compared to British committee for standards haematology criteria for successful increment of platelet products (PPR ≥ 30% and CCI ≥ 7500). Apheresis platelets transfusion can be introduced at KNH and use of leukoreduction performed on the platelet concentrates which are prepared within the Hospital. With such rate of refractoriness, additional tests to confirm the real cause of unviability of platelets in the patients need to be performed. Recipients should be done evaluation of the pattern of refractoriness followed by HLA compatibility testing. In addition, if there is a high, compatible cross-matched, selected apheresis platelet concentrate pint should be transfused. This unviability was due to recipients with either immune-mediated refractoriness or non-immune mediated refractoriness.

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.

Laboratory Diagnosis of the Lupus Anticoagulant

OBJECTIVE: This review describes consensus guidelines and laboratory methods for diagnosing a lupus anticoagulant (LAC). BACKGROUND: A prolonged APTT due to the presence of a LAC is a frequent finding in the clinical laboratory in patients referred for preadmission testing. Accurate detection of the LAC can often be very challenging for the laboratory. While no single assay is specific for diagnosing a LAC, there is a combination of assays that can be used to improve laboratory diagnosis. METHOD: This review describes several assays used to detect a LAC; reviews consensus guidelines that influence the choice of assays by laboratories; and associated preanalytical variables that may lead to a missed diagnosis. CONCLUSION: A thorough understanding of the principles involved in LAC testing and preanalytical variables may lead to a more accurate diagnosis of the LAC. ABBREVIATIONS:aB2GPI - anti-B2 glycoprotein I, aCL - anti-cardiolipin, APLAs - antiphospholipid antibodies, BCSH - British Committee for Standards in Haematology, CLSI - Clinical and Laboratory Standards Institute, DOAC - direct oral anticoagulant, dRVVT - dilute Russell9s viper venom time, ISTH-SSC - International Society for Thrombosis and Haemostasis – Scientific Standardization Committee, LAC - lupus anticoagulant, VKA - vitamin K antagonist, SCT - silica clotting time.

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.

Further evidence of the limitations of Activated Partial Thromboplastin Time to monitor Argatroban

Further evidence of the limitations of Activated Partial Thromboplastin Time to monitor Argatroban

Британский комитет по изучению внешней политики и Английская школа международных отношений

Британский комитет по изучению внешней политики и Английская школа международных отношений

The evaluation of the audit of Fresh-Frozen Plasma (FFP) usage in emergency department

ObjectivesIn our study, the aim is to evaluate the use of Fresh-Frozen Plasma (FFP) in our emergency department and to assess its audit for transfusion. MethodsAll the patients aged 18 and over who received FFP transfusion in the emergency department between March 1, 2013 and March 1, 2016 were included into the study. The audit of FFP use was evaluated by according to ‘British Committee for Standards in Hematology Guideline-2004’. ResultsTotal 141 patients were identified to receive FFP transfusion in our emergency department. When the audit of FFP use was evaluated, 59.6% of all the practices were regarded as improper use. We identified that while the rate of improper use was 40.2% in patients with bleeding, it rose to 90.7% in patients without active bleeding or in those who used FFP with the aim of bleeding prophylaxis. ConclusionWe have determined that FFP transfusions were conducted with improper indications at high rate in our emergency department. Preparing an up-to-date transfusion guideline for the practices in emergency departments in our country and training and supervising the medical staff at regular intervals may help prevent the shortcomings in FFP practices.

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.

Британский комитет Индийского национального конгресса: цели, задачи, итоги деятельности

Британский комитет Индийского национального конгресса: цели, задачи, итоги деятельности

WHINNEY AND WATERHOUSE'S GOVERNMENT ASSIGNMENT 1887–1888: A STUDY OF ITS SIGNIFICANCE

The episode narrated in this paper is situated in late-Victorian Britain when leading chartered accountants, Frederick Whinney and Edwin Waterhouse, were engaged by a British parliamentary committee to examine the costing and accountability practices of the government's military manufacturing establishments (GMMEs). The contributions of this study to accounting's historiography are two-fold. First, the significance of Whinney and Waterhouse's appointment for the status of chartered accountants in late-Victorian Britain is assessed. Second, Whinney and Waterhouse's criticisms of existing accounting routines are examined and evaluated as is the impact of their findings on the subsequent course of accounting practices within GMMEs.

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.