Aims The majority of haematology laboratories use automated high-performance liquid chromatography (HPLC) as a primary method in the screening of samples for haemoglobin variants and thalassaemia. HPLC detects adducted fractions, such as HbA1C and other peaks of unknown significance. The National Health Service (NHS) Sickle and Thalassaemia Screening Programme does not mandate further assessment of these unknown peaks, but their presence may cause concern or precipitate detailed investigations. Mass spectrometry (MS) is being increasingly used in NHS Laboratories and is an effective method of characterising variant haemoglobins. Method Antenatal blood samples accepted for NHS Sickle and Thalassaemia Screening Programme from 2005 to 2013 were assessed. Those samples with unidentified peaks on HPLC were further analysed by Liquid chromatography tandem MS (LCMSMS). Results 58 493 samples were processed. 966 (1.6%) significant haemoglobinopathies were identified. 68 patients (0.11%) were found to have unidentified peaks on HPLC. α chain variants: two were hyperunstable α variants, Hb Adana and Hb H/Constant Spring. The patient with HbH/Constant Spring required transfusion during pregnancy. Other abnormalities include 24 unstable α chain variants of minimal clinical significance and 17 α chain variants of no clinical significance. The frequency of β chain abnormalities was lower, with 10 patients having an insignificant β chain variant, 4 mildly unstable β chain variants (2 of whom had increased oxygen affinity) and 4 with variants associated with increased oxygen affinity. Conclusions The prevalence of unidentified variants on automated HPLC within our population is 0.1%. LCMSMS is an effective technique to assist in the characterisation of unknown haemoglobin variants. α chain variants of limited clinical significance were the most commonly detected abnormality.
A full blood count was requested on a 2-day-old Pakistani boy. The child had mild anaemia with thalassaemic indices, blood film showed anisocytosis, poikilocytosis, target cells and polychromasia (Table I). High-performance liquid chromatography suggested a three alpha gene deletion with haemoglobin Barts 27·7%, haemoglobin F 44·6% and haemoglobin A 19%. The mother's prenatal test results were normal (Table I). The father's results suggested alpha-thalassaemia trait or silent beta-thalassaemia trait (Table I). No other antenatal testing had been done as the fetus was not felt to be at risk of serious haemoglobinopathy. Further questioning of the mother revealed she had had in vitro fertilization (IVF) using donated ova in another UK city. The donor, from Cyprus, had declared a family history of thalassaemia at the IVF clinic and therefore underwent screening. This was reported as showing possible iron deficiency, and a card was issued stating that she had no significant haemoglobinopathy. Antenatal haemoglobinopathy screening for the biological mother during a previous pregnancy had also been reported as normal. Two further separate screens over a period of years had failed to comment on the significance of thalassaemic indices in the presence of a normal haemoglobin and Hb A2. DNA analysis showed the natural mother to have a Mediterranean α0 deletion (–MED/αα), the father a 3·7-kb α+-thalassaemia deletion (–α3·7/αα) and the baby haemoglobin H disease (–α3·7/–MED). The donated ova from the same woman had also been used in other pregnancies, including a pregnancy using the donated ova and a sperm donor of Asian origin. This sperm donor had not had a haemoglobinopathy screen and had to be recalled. This case highlights common problems in thalassaemia diagnosis, screening and reporting. Although guidelines for the laboratory diagnosis of haemoglobinopathies exist (British Committee for Standards in Haematology, General Haematology, 1998), there is currently no standardized reporting of results. The British Committee for Standards in Haematology (BCSH) guidelines state that screening is equally important in cases where pregnancy is the result of artificial insemination from a donor or in vitro fertilization, yet confidentiality issues mean that this information does not have to be passed on. Screening of both egg and semen donors is also recommended by the Human Fertilization and Embryology Authority, 2001), the British Andrology Society, 199) and the British Fertility Society (2000). Although the majority of populations at risk of α-thalassaemia have α+ deletions, it is recommended that the α0-thalassaemia trait should be detected in prospective parents to predict the occurrence of haemoglobin Barts hydrops fetalis. Mutations causing the α0-thalassaemia trait are found predominantly in south-east Asia, southern China (–SEA/αα, –FIL/αα and –THAI/αα) and the Mediterranean, particularly Cyprus, Turkey and Greece (–MED/αα). DNA analysis should be done in patients from these ethnic groups with a MCH < 25 pg and where β- and δβ-thalassaemia and haemoglobin Lepore have been excluded. In this case, the ethnic origin of the natural mother was not taken into account and the α0-thalassaemia trait therefore not considered. In such cases, it is necessary to add a statement that the ‘α-thalassaemia trait cannot be excluded’ whether iron deficiency is present or not. The National Health Service (NHS) plan is committed to a national, linked antenatal and neonatal screening programme for the haemoglobinopathies (NHS Plan, 2000). We anticipate that this will give clear guidance as to which population groups are to be screened to achieve standardized reporting. These guidelines should include advice regarding the screening of semen and egg donors.
The NHS Plan launched in 2000 advocated a linked antenatal and neonatal screening programme for haemoglobinopathies. Currently screening practices vary widely across the UK and patient sampling is generally performed in a hospital setting. The process is flawed and frequently fails to provide accurate and timely information. In this study we demonstrate that organisational changes can improve the efficiency and quality of screening. The primary care screening process described here has increased partner testing rates and allowed early identification of at risk couples.
Background. Optimal upfront therapy for posttransplant lymphoproliferative disease (PTLD) arising after solid organ transplant remains contentious. Rituximab monotherapy (R-Mono) in unselected patients has shown a lack of durable remissions. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based chemotherapy confers improved response rates, although concerns exist about toxicity. Methods. This multicenter retrospective study reports outcomes for adults with biopsy-proven B-cell PTLD treated initially with R-Mono or Rituximab plus CHOP (R-CHOP). Selection of therapy was made according to physician preference. Results. Among 101 patients, 41 received R-Mono and 60 had R-CHOP. Most (93%) had undergone renal or liver transplantation. R-CHOP showed a trend toward improved complete (53% versus 71%; P = 0.066) and overall (75% versus 90%; P = 0.054) response rates. In the R-Mono group, 13 of 41 (32%) subsequently received chemotherapy, while 25 of 41 (61%) remained progression-free without further therapy. With median follow-up of 47 months, overall survival (OS) was similar for R-Mono and R-CHOP, with 3-year OS of 71% and 63%, respectively ( P = 0.722). Non-PTLD mortality was 3 of 41 (7%) and 4 of 60 (7%) within 12 months of R-Mono or R-CHOP, respectively. The International Prognostic Index was statistically significant, with low- (0–2 points) and high-risk (≥3 points) groups exhibiting 3-year OS of 78% and 54%, respectively ( P = 0.0003). In low-risk PTLD, outcomes were similar between therapies. However, in high-risk disease R-Mono conferred an inferior complete response rate (21% versus 68%; P = 0.006), albeit with no impact on survival. Conclusions. Our data support R-Mono as initial therapy for PTLD arising after renal or liver transplantation. However, upfront R-CHOP may benefit selected high-risk cases in whom rapid attainment of response is desirable.
In homozygous sickle cell disease (SCD), decreased serum Vitamin E is present. Excessive transfusions may lead to iron overload. We hypothesised a relationship between the two and found that Vitamin E type antioxidant capacity was significantly lower in 30 SCD patients than in 30 age- and sex-matched controls (P < 0.001). Antioxidant capacity was lower in 10 transfused patients compared with 20 non-transfused patients (P < 0.001). Transfusional iron overload in SCD may increase the potential for oxidative damage, and low antioxidant capacity may compound this effect.
Until recently management of sickle pain was the province of haematologists. However, a recent National Confidential Enquiry into Patient Outcome and Death report highlighted problems with the management of pain and opioid analgesia in this group and suggested a multiagency approach similar to that used in palliative care.Pain is the most frequent complication of this haemoglobin disorder. Sickle cell disease is very variable with many patients leading full lives with long periods with little or no pain. At the other end of the spectrum there are those who exist in a sea of pain. The mechanisms of sickle pain are poorly understood and evidence for the best treatment modalities sparse. Historically there has been a dearth of clinical trials in sickle cell; however, this is starting to be addressed.In this review we will give a brief overview of the disease and its pathogenesis before examining the epidemiology, management of pain in sickle cell disease. We will also review recent evidence regarding quality of life and discuss the role of opioid hyperalgesia in sickle cell disease.
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