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British Journal of Haematology Aug 2019Post-transfusion hyperhaemolysis syndrome (PTHS) is a rare life-threatening transfusion complication reported mainly in sickle cell patients. Its pathogenesis is poorly...
Post-transfusion hyperhaemolysis syndrome (PTHS) is a rare life-threatening transfusion complication reported mainly in sickle cell patients. Its pathogenesis is poorly understood. Antibody-mediated haemolysis and bystander effect have been proposed as putative mechanisms, but in half of cases, red cell antibodies are undetectable, and PTHS develops despite transfusion of cross-matched compatible RBC. An alternate hypothesis proposes activated macrophages as the main drivers of red cell destruction through direct phagocytosis. We report the histopathological findings of two patients with PTHS showing extensive macrophage expansion and erythrophagocytosis, supportive of macrophage activation driving PTHS. This supports a possible role for novel therapies that target macrophage activation.
Topics: Adult; Anemia, Sickle Cell; Hemolysis; Humans; Macrophage Activation; Male; Transfusion Reaction
PubMed: 31020643
DOI: 10.1111/bjh.15925 -
BMC Health Services Research Nov 2019Young people's experiences of healthcare as they move into adult services can have a major impact on their health, and the transition period for young people with sickle...
BACKGROUND
Young people's experiences of healthcare as they move into adult services can have a major impact on their health, and the transition period for young people with sickle cell disease (SCD) needs improvement. In this study, we explore how young people with SCD experience healthcare during this period of transition.
METHODS
We conducted a co-produced longitudinal qualitative study, including 80 interviews in 2016-2017 with young people with SCD aged 13-21 (mean age 16.6) across two cities in England. We recruited 48 participants (30 female, 18 male): 27 interviews were one-off, and 53 were repeated 2-3 times over approximately 18 months. We used an inductive analytical approach, combining elements of Grounded Theory and thematic analysis.
RESULTS
Participants reported significant problems with the care they received in A&E during painful episodes, and in hospital wards as inpatients during unplanned healthcare. They experienced delays in being given pain relief and their basic care needs were not always met. Participants said that non-specialist healthcare staff did not seem to know enough about SCD and when they tried to work with staff to improve care, staff often seemed not prepared to listen to them or act on what they said. Participants said they felt out of place in adult wards and uncomfortable with the differences in adult compared with paediatric wards. Because of their experiences, they tried to avoid being admitted to hospital, attempting to manage their painful episodes at home and accessing unplanned hospital care only as a last resort. By contrast, they did not report having problems within SCD specialist services during planned, routine care.
CONCLUSIONS
Our study underscores the need for improvements to make services youth-friendly and youth-responsive, including training staff in SCD-specific care, compassionate care and communication skills that will help them elicit and act on young people's voices to ensure they are involved in shaping their own healthcare. If young people are prevented from using transition skills (self-management, self-advocacy), or treated by staff who they worry do not have enough medical competency in their condition, they may well lose their trust in services, potentially compromising their own health.
Topics: Adolescent; Anemia, Sickle Cell; Emergency Medical Services; Empathy; England; Female; Hospitalization; Humans; Interviews as Topic; Longitudinal Studies; Male; Pain; Pain Management; Professional-Patient Relations; Qualitative Research; Quality of Health Care; Transition to Adult Care; Young Adult
PubMed: 31752858
DOI: 10.1186/s12913-019-4726-5 -
Health and Quality of Life Outcomes Apr 2019The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) has been shown to be a reliable and valid questionnaire measuring health-related quality...
BACKGROUND
The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) has been shown to be a reliable and valid questionnaire measuring health-related quality of life (HRQoL) in the US sickle cell disease (SCD) population. The study objective was to test the validity and reliability of the ASCQ-Me for use in the UK.
METHODS
The US ASCQ-Me, Hospital Anxiety and Depression Scale (HADS), self-reported symptoms, and Medical Outcome Survey Short Form 36 (SF-36) were administered to 173 patients with SCD. Clinical severity was assessed by the number of painful episodes indicated by hospital admissions.
RESULTS
The results showed that the item banks of the UK ASCQ-Me had good internal consistency. Anxiety and depression were strongly correlated with the emotional, and social item banks of the UK ASCQ-Me, with moderate correlations between the UK ASCQ-Me item banks and SF-36 components suggesting convergent validity. A confirmatory factor analysis confirmed the conceptual framework of the scale as being the same as the US ASCQ-Me, indicating construct validity. Known groups validity was found, with the ASCQ-Me being able to differentiate by SCD severity groups.
CONCLUSION
The analysis of the sample shows evidence of both validity and reliability of the ASCQ-Me for use in the UK SCD population.
Topics: Adult; Anemia, Sickle Cell; Anxiety; Depression; Factor Analysis, Statistical; Female; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Psychometrics; Quality of Life; Reproducibility of Results; Severity of Illness Index; United Kingdom
PubMed: 31036017
DOI: 10.1186/s12955-019-1136-7 -
British Journal of Haematology Nov 2001A quantitative polymerase chain reaction (Q-PCR) method based on the TaqMan technology has been devised for the prenatal diagnosis of homozygous alpha*-thalassaemia...
A quantitative polymerase chain reaction (Q-PCR) method based on the TaqMan technology has been devised for the prenatal diagnosis of homozygous alpha*-thalassaemia (south-east Asian type deletion). Primers and TaqMan probes were designed to specifically amplify an alpha*-thal chromosomal fragment or a normal alpha-chromosomal fragment. Variations in input target DNA in individual sample wells were normalized by the simultaneous amplification of a beta-actin gene fragment and results expressed as a ratio to that of beta-actin. There was no overlap of the data between the homozygous alpha*-thal, alpha*-thal and normal subjects. Up to 5% maternal DNA (alpha*-thal) contamination did not affect the specificity of the result. In 31 prenatal diagnoses, the result using Q-PCR compared favourably with the gold standard of Southern hybridization of alpha-genes.
Topics: Actins; Female; Homozygote; Humans; Hydrops Fetalis; Polymerase Chain Reaction; Pregnancy; Prenatal Diagnosis; alpha-Thalassemia
PubMed: 11703333
DOI: 10.1046/j.1365-2141.2001.03112.x -
British Journal of Haematology Jan 2019Ticagrelor is an antiplatelet agent for adults with coronary artery disease. The inhibition of platelet activation may decrease the frequency of vaso-occlusion crisis... (Randomized Controlled Trial)
Randomized Controlled Trial
Ticagrelor is an antiplatelet agent for adults with coronary artery disease. The inhibition of platelet activation may decrease the frequency of vaso-occlusion crisis (VOC) in sickle cell disease (SCD). The HESTIA2 study (NCT02482298) randomised 87 adults with SCD (aged 18-30 years) 1:1:1 to twice-daily ticagrelor 10, 45 mg or placebo for 12 weeks. Numerical decreases from baseline in mean proportion of days with patient-reported pain (primary endpoint) were seen in all three groups, as well as in pain intensity and analgesic use, with no significant differences between placebo and ticagrelor treatment groups. Plasma ticagrelor concentrations and platelet inhibition increased with dose. Adverse events were distributed evenly across groups and two non-major bleeding events occurred per group. Ticagrelor was well tolerated with a low bleeding risk, but no effect on diary-reported pain was detected. Potential effects on frequency of VOCs will need to be evaluated in a larger and longer study.
Topics: Adolescent; Adult; Analgesics; Anemia, Sickle Cell; Female; Humans; Male; Pain; Platelet Aggregation Inhibitors; Ticagrelor; Young Adult
PubMed: 30443999
DOI: 10.1111/bjh.15646 -
Journal of Medical Genetics Dec 1974An investigation was undertaken to find the incidence of α-thalassaemia in Egypt. Blood was collected from the umbilical cords of 550 newborns and from 630 adults from...
An investigation was undertaken to find the incidence of α-thalassaemia in Egypt. Blood was collected from the umbilical cords of 550 newborns and from 630 adults from central hospitals in Cairo that drain patients from all over Egypt. Starch gel electrophoreses at both pH 8·6 and 7·0, and brilliant cresyl blue incubation revealed the absence of haemoglobins Barts and H in the blood specimens examined.
Topics: Adult; Arabia; Blood; Egypt; Electrophoresis, Starch Gel; Ethnicity; Female; Hemoglobin H; Hemoglobins, Abnormal; Humans; Infant, Newborn; Male; Thalassemia; Umbilical Cord
PubMed: 4443982
DOI: 10.1136/jmg.11.4.335 -
The Medical Journal of Malaysia Dec 2011Detection and quantification of Hb subtypes of human blood is integral to presumptive identification of thalassaemias. It has been used in neonatal screening of...
Detection and quantification of Hb subtypes of human blood is integral to presumptive identification of thalassaemias. It has been used in neonatal screening of thalassaemia and Hb variants. The use of discarded red blood cells following processing of the cord blood for stem cells provides readily available diagnostic material for thalassaemia screening. In this study, we determined the range of Hb subtypes in 195 consecutive cord blood samples collected for cord blood banking. The 'cord blood samples' analysed were those of the remaining red blood cells after the cord blood was processed for stem cell storage. Quantification of Hb subtypes by high performance liquid chromatography (HPLC) was done on BioRad Variant II Hb testing system. Only 73 (36.5%) of the samples could be analyzed neat without dilution. With a 1:300 dilution with wash solution the acceptable area as recommended by the manufacturer for reading of a C-gram within the 1 to 3 million ranges were achieved in all. Eighteen (9%) 12 showed classical Hb Barts (y4) prerun peaks were confirmed by Sebia Hydrasys automated Hb gel electrophoresis and quantified by Sebia Capillarys 2 capillary electrophoresis. Only 1 (0.5%) was presumptively identified with HbH disease. Due to the limited number of samples no beta-thalassaemia major, Hb E beta-thalassaemia and Hb Barts hydrops fetalis were found. The HPLC assay was possible at a cost US$ 5 per sample and a turnover time of 10 samples per hour without technical difficulties. This study reports an effective and valuable protocol for thalassaemia screening in red blood cells which would otherwise be discarded during cord blood processing. Cord blood with severe and intermediate forms of thalassaemia can be preselected and not stored.
Topics: Chromatography, High Pressure Liquid; Electrophoresis; Erythrocytes; Feasibility Studies; Fetal Blood; Humans; Infant, Newborn; Neonatal Screening; Thalassemia
PubMed: 22390095
DOI: No ID Found -
Blood Jun 1994The clinical diversity of thalassemia depends on interaction of diverse genetic defects. We have characterized a severe form of alpha thalassemia caused by coinheritance...
The clinical diversity of thalassemia depends on interaction of diverse genetic defects. We have characterized a severe form of alpha thalassemia caused by coinheritance of a rare alpha-globin gene deletion and a nondeletional defect in a southern Italian family. The proband, a 7-year-old girl, exhibited an abnormal hemoglobin electrophoresis pattern with hemoglobin H and hemoglobin Barts, indicating inheritance of H and hemoglobin Barts, indicating inheritance of a severe form of alpha thalassemia. Southern blot analysis of DNA showed normal as well as aberrant alpha-globin gene fragments indicating heterozygosity for a deletional form of alpha thalassemia in the proband and her mother. The coinheritance of a nondeletional form of alpha thalassemia (alpha alpha T) was suspected because of the severity of the proband's phenotype and the presence of normal alpha-globin gene fragments in the father. Selective polymerase chain reaction of the paternal alpha 1- and alpha 2-globin genes in the proband followed by DNA sequence analysis showed an AATAAA to AATGAA mutation in the polyadenylation signal sequence of the alpha 2-globin gene. Genomic DNA mapping and sequence analysis of a unique polymerase chain reaction product generated across the deletion breakpoint of the maternal allele showed a 5,201-bp deletion extending from 870 nucleotides 5' of the alpha 2-globin gene to nucleotide +519 in the alpha 1-globin gene. This deletion is similar to that previously suggested by blotting studies in a Greek family (Pressley et al, Nucleic Acids Res 8:4889, 1980) and removes the entire alpha 2-globin gene and a portion of the 5' end of the alpha 1-globin gene. Sequence characterization of the resultant aberrant truncated alpha 1-globin gene from the proband showed a 27 nucleotide duplication corresponding to the 3' end of the alpha-globin gene IVS-2 region separated by the insertion of a tetranucleotide (GGTT), suggesting that this deletion is caused by an illegitimate recombination event.
Topics: Base Sequence; Child; Female; Gene Deletion; Globins; Humans; Male; Molecular Sequence Data; Mutation; Poly A; Polymerase Chain Reaction; Recombination, Genetic; Restriction Mapping; alpha-Thalassemia
PubMed: 8193372
DOI: No ID Found -
Bone Marrow Transplantation Oct 2019Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and...
Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to rise with 45,418 HCT in 41,100 patients [(17,155 allogeneic (42%) and 23,945 autologous (58%)] reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning.
Topics: Female; Hematopoietic Stem Cell Transplantation; History, 21st Century; Humans; Male; Neoplasms; Surveys and Questionnaires; Transplantation Conditioning; Transplantation, Homologous
PubMed: 30728439
DOI: 10.1038/s41409-019-0465-9 -
Blood Dec 2011Cervical internal carotid artery (cICA) occlusion is a recognized cause of acute ischemic stroke (AIS) in sickle cell disease (SCD), but the associated clinical and... (Clinical Trial)
Clinical Trial
Cervical internal carotid artery (cICA) occlusion is a recognized cause of acute ischemic stroke (AIS) in sickle cell disease (SCD), but the associated clinical and radiologic features are not well described. We reviewed data on cervical magnetic resonance angiography (cMRA) performed prospectively in 67 patients (55 children) for indications including transcranial Doppler (TCD) abnormalities, AIS, or previous AIS. cICA lesions were seen in 10 (15%) patients, including 4 of 7 patients presenting with AIS, and appear to have been missed on first presentation in 4 of 10 patients with previous AIS. Radiologic features in 7 patients were consistent with dissection. In 2 patients, there was strong clinical and radiologic evidence for thromboembolic AIS, and this was also considered possible in 4 other patients. Three of the 4 AIS patients were anticoagulated acutely, and the nontreated patient had recurrent, probably thromboembolic, AIS. TCD findings were variable, but in 4 patients there were high velocities in the cerebral vessels contralateral to the cICA stenosis. We suggest that all patients with AIS should have cMRA during acute evaluation to identify cICA occlusions that may require anticoagulation. Routine screening of children with SCD should also include evaluation of neck vessels by carotid Doppler followed by cMRA if a cervical vascular lesion is suspected.
Topics: Acute Disease; Adolescent; Adult; Anemia, Sickle Cell; Anticoagulants; Carotid Artery Thrombosis; Carotid Stenosis; Cervical Vertebrae; Child; Child, Preschool; Female; Humans; Imaging, Three-Dimensional; Magnetic Resonance Angiography; Male; Neck; Prospective Studies; Stroke; Young Adult
PubMed: 21885600
DOI: 10.1182/blood-2011-03-337915