Cascade screening for beta-thalassemia in Pakistan: development, feasibility and acceptability of a decision support intervention for relatives.

The government-funded 'Punjab Thalassaemia Prevention Project' (PTPP) in Pakistan includes cascade screening for biological relatives of children with beta-Thalassaemia Major (ß-TM). However, there is low uptake of cascade screening. This paper presents the (i) development of a paper-based 'decision support intervention for relatives' (DeSIRe) to enable PTPP Field Officers to facilitate informed decision making about carrier testing, and (ii) assessment of the feasibility and acceptability of the DeSIRe. The intervention was developed using the International Patient Decision Aids Standards quality criteria and Ottawa Decision Support Framework. Twelve focus groups were conducted (September and October 2020) to explore the views of healthcare professionals (HCPs) and relatives of children with ß-TM, in six cities. The focus groups were attended by 117 participants (60 HCPs and 57 relatives). Thematic analysis showed that the DeSIRe was considered acceptable for supporting relatives to make informed decisions about cascade screening, and potentially feasible for use in clinical practice. Suggestions for changing some words, the structure and adding information about how carrier testing relates to consanguineous marriages will enable further development of the DeSIRe. Participants generally welcomed the DeSIRe; however, they highlighted the perceived need to use more directive language, hence showed a cultural preference for directive genetic counselling. The findings highlight challenges for researchers using western theories, frameworks, policies and clinical guidelines to develop decision support interventions for implementation more globally. Future research is needed to evaluate the use of the DeSIRe in routine practice and whether it enables relatives to make informed decisions.

Modulatory effect of single nucleotide polymorphism in Xmn1, BCL11A and HBS1L-MYB loci on foetal haemoglobin levels in ß-thalassemia major and Intermedia patients.

OBJECTIVE: To evaluate the influence of certain genetic modifiers on foetal haemoglobin levels in thalassemia major and thalassemia intermedia. METHODS: The cohort study was conducted from November 2018 to August 2019, at Department of Haematology, University of Health Sciences, Lahore and comprised beta thalassemia intermedia and thalassemia major patients who were referred by various healthcare facilities across Punjab, Pakistan. Foetal haemoglobin was quantified by high performance liquid chromatography. Primary mutation analysis and single nucleotide polymorphisms were done by amplification refractory mutation system-based polymerase chain reaction. Data was analysed using SPSS 20. RESULTS: Of the 116 patients, 52(45%) had beta thalassemia intermedia and 64(55%) had thalassemia major. Foetal haemoglobin levels were primarily influenced by alleles of the HBG2 (rs7482144) and BCL11A (rs766432) genes, but single nucleotide polymorphism of HBS1L-MYB (rs9399137) had no significant role (p>0.05). The rs7482144 single nucleotide polymorphism explained 8.3% of the variation in the foetal haemoglobin levels, while 5% of trait variation was explained by rs766432. CONCLUSIONS: There was found a clear association between foetal haemoglobin level and single nucleotide polymorphisms in HBG2 (rs7482144) and BCL11A (rs766432) genes. This correlation was additive and was seen both in thalassemia major and thalassemia intermedia cohorts.

Six-year experience of prenatal diagnosis for beta thalassemia in twin pregnancies and selective foetal reduction - A case series.

A retrospective study was conducted for prenatal diagnosis and selective foetal reduction, which included 41 beta thalassemia carrier couples with twin pregnancy. Chorionic villi sampling was carried out at 12-14 weeks of gestation. Thirty-three couples presented with dizygotic while eight had monozygotic twins. Molecular analysis for beta thalassemia revealed similar results in both the twins in 27 cases, while different results were obtained in 14 cases. Selective foetal reduction was offered to couples with discordant results. One miscarriage occurred due to the procedure. The results of prenatal molecular analysis were confirmed by postnatal molecular analysis. This series of trans-abdominal Chorionic villi sampling in twin pregnancies with the option of selective foetal reduction of the affected foetus was found to be useful as well as acceptable by the at-risk couples.