Acute blood transfusion reactions in a tertiary care hospital in Pakistan - an initiative towards haemovigilance.

OBJECTIVE: In this study, we report acute blood transfusion reactions at our hospital, compare our analysis with the reported data and identify areas for improvement. BACKGROUND: Haemovigilance programmes have been implemented in many countries, and adverse events associated with blood transfusion are published in their annual reports. Pakistan has no current established programme. MATERIAL AND METHODS: A cross-sectional study was conducted, and all adverse reactions reported to the blood bank from January 2014 to March 2016 were included. An adverse response in the patient, related to administration of blood (within 24 h), was considered an immediate transfusion reaction. RESULTS: During the study period, 20 956 blood components were issued. A total of 32 (0·15%) adverse reactions were documented. Allergic reactions were the most common adverse event observed in 15 (46·8%) of the cases. Febrile non-haemolytic transfusion reaction (FNHTR) was the second most common reaction seen in nine (28%) followed by bacterial contamination in four (12·5%) and acute haemolytic reaction in two (6·2%) of the cases. CONCLUSION: The low incidence indicates underreporting and the need for a formal haemovigilance system. International benchmarking between different medical systems is helpful to identify areas in the transfusion process that have to be changed to improve transfusion safety.

Frequency and reasons of donor deferral prior to blood donation process: a single centre experience.

OBJECTIVE: The aim of the study was to determine the frequency and reasons for donor deferral prior to the blood donation process in our population. BACKGROUND: Transfusion is an irreversible event that carries potential risks as well as benefits to the recipient. Therefore, donor selection prior to blood donation is one of the most important steps in ensuring the safety of blood and blood products. METHODS: A cross-sectional study was carried out at the blood bank department in our hospital from January 2012 to December 2014. All the blood donors who visited our department in the study period were included in this study. RESULTS: A total of 25 901 potential donations were recorded during the study period, comprising 24 309 (93·8%) replacement and 1592 (6·2%) voluntary donations. Females accounted for only 222 (0·9%) of potential donations. Deferral occurred in 3156 (12·2%) of attempts; 280 (1·1%) were permanently deferred, while 2876 (11·1%) were temporarily deferred. The most common reason for permanent deferral was a history of hepatitis B infection (n = 147, 4·7% of all deferrals). Major reasons for temporary donor deferral were low levels of haemoglobin (n = 971, 30·76%), low levels of platelets (n = 611, 19·35%) and previous history of jaundice (n = 192, 6·1%). CONCLUSIONS: This study reported a fairly similar pattern of donor deferrals as in other regional studies. Low haemoglobin levels and a history of hepatitis B infection were the most common factors for temporary and permanent donor deferrals, respectively.

Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations.

Glanzmann thrombasthenia (GT) is an inherited genetic disorder affecting platelets, which is characterized by spontaneous mucocutaneous bleeding and abnormally prolonged bleeding in response to injury or trauma. The underlying defect is failure of platelet aggregation due to qualitative and/or quantitative deficiency of platelet integrin αIIbß3 resulting from molecular genetic defects in either ITGA2B or ITGB3. Here, we examine a Pakistani cohort of 15 patients with clinical symptoms of GT who underwent laboratory and molecular genetic analysis. In patients with a broad range of disease severity and age of presentation, we identified pathogenic mutations in ITGA2B in 11 patients from 8 different families, including 2 novel homozygous mutations and 1 novel heterozygous mutation. Mutations in ITGB3 were identified in 4 patients from 3 families, two of which were novel homozygous truncating mutations. A molecular genetic diagnosis was established in 11 families with GT, including 5 novel mutations extending the spectrum of mutations in this disease within a region of the world where little is known about the incidence of GT. Mutational analysis is a key component of a complete diagnosis of GT and allows appropriate management and screening of other family members to be performed.

Red cell alloimmunisation in regularly transfused beta thalassemia patients in Pakistan.

BACKGROUND: In Pakistan routine blood group typing of thalassemia patients identifies ABO and Rh(D) antigens only. Therefore, other antigen incompatibilities between blood donor and blood recipient may cause alloimmunisation. OBJECTIVE: The aim of this study was to estimate the frequency of alloimmunisation and to evaluate the risk factors associated with its development in beta (ß)-thalassemia patients receiving regular blood transfusions. MATERIALS AND METHODS: In total 162 ß thalassemia patients were included in this study. An extended red cell antigen panel was performed to detect antibodies. Patients received red cell concentrates, which were matched for ABO and Rh(D) antigens. Clinical and laboratory data were collected and analysed to estimate the frequency of alloantibodies and the factors influencing immunisation in patients on regular blood transfusion. RESULTS: The median age of patients was 6·7 (range: 0·5-25) years. A total of 14 (8·6%) patients developed alloantibodies against red cell antigens. The most frequently occurring alloantibodies was anti-E (2·5%), anti-K (1·8%), anti-e (1·2%) and anti-D (0·6%). Five (3·1%) patients developed more than one red blood cell (RBC) alloantibody. Age at first transfusion in alloimmunised patients was 1·22 ± 0·87 years. The frequency of blood transfusion in alloimmunised patients was 23 ± 8·81 days and in those without alloimmunisation was 31·8 ± 16 days (p = 0·02). Logistic regression analysis showed no independent risk factor associated with alloimmunisation. CONCLUSION: The frequency of transfusion was increased in patients who developed alloantibodies. Typing patients and donors to match for Rh and Kell antigens would prevent more than 90% of RBC alloantibodies and reduce the frequency of transfusion in thalassemia patients.

Congenital factor XIII deficiency in Pakistan: characterization of seven families and identification of four novel mutations.

Deficiency of coagulation factor XIII (FXIII) belongs to the rare bleeding disorders and its incidence is higher in populations with consanguineous marriages. The aims of this study were to characterize patients and relatives from seven families with suspected FXIII deficiency from Pakistan and to identify the underlying mutations. As a first indicator of FXIII deficiency, a 5M urea clot solubility test was used. Plasma FXIII A- and B-subunit antigen levels were determined by ELISA. FXIII activity was measured with an incorporation assay. Sequencing of all exons and intron/exon boundaries of F13A was performed, and a novel splice site defect was confirmed by RT-PCR analysis. Genetic analysis revealed six different mutations in the F13A gene. Two splice site mutations were detected, a novel c.1460+1G>A mutation in the first nucleotide of intron 11 and a previously reported c.2045G>A mutation in the last nucleotide of exon 14. Neither of them was expressed at protein level. A novel nonsense mutation in exon 4, c.567T>A, p.Cys188X, was identified, leading in homozygous form to severe FXIII deficiency. Two novel missense mutations were found in exons 8 and 9, c.1040C>A, p.Ala346Asp and c.1126T>C, p.Trp375Arg, and a previously reported missense mutation in exon 10, c.1241C>T, p.Ser413Leu. All patients homozygous for these missense mutations presented with severe FXIII deficiency. We have analysed a cohort of 27 individuals and reported four novel mutations leading to congenital FXIII deficiency.

Genotype and phenotype relationships in 10 Pakistani unrelated patients with inherited factor VII deficiency.

Inherited factor VII (FVII) deficiency is one of the commonest rare bleeding disorders. It is characterized by a wide molecular and clinical heterogeneity and an autosomal recessive pattern of inheritance. Factor VII-deficient patients are still scarcely explored in Pakistan although rare bleeding disorders became quite common as a result of traditional consanguineous marriages. The aim of the study was to give a first insight of F7 gene mutations in Pakistani population. Ten unrelated FVII-deficient patients living in Pakistan were investigated (median FVII:C = 2%; range = 2-37%). A clinical questionnaire was filled out for each patient and direct sequencing was performed on the coding regions, intron/exon boundaries and 5' and 3' untranslated regions of the F7 gene. Nine different mutations (eight missense mutations and one located within the F7 promoter) were identified on the F7 gene. Five of them were novel (p.Cys82Tyr, p.Cys322Ser, p.Leu357Phe, p.Thr410Ala, c-57C>T, the last being predicted to alter the binding site of transcription factor HNF-4). Half of the patients had single mutations in Cys residues involved in disulfide bridges. The p.Cys82Arg mutation was the most frequent in our series. Six of seven patients with FVII:C levels below 10% were homozygous in connection with the high percentage of consanguinity in our series. In addition, we graded the 10 patients according to three previously published classifications for rare bleeding disorders. The use of the bleeding score proposed by Tosetto and co-workers in 2006 appears to well qualify the bleeding tendency in our series.