Bushra Moiz

Estimating window period blood donations for human immunodeficiency virus Type 1, hepatitis C virus, and hepatitis B virus by nucleic acid amplification testing in Southern Pakistan.

Recently, strategic planning was initiated by the National Blood Transfusion Services Pakistan to improve its blood bank facilities. Emphasis has been placed on appropriate screening of blood products. Located in the southern region, Aga Khan University Hospital is a 700‐bed tertiary care academic institute with comprehensive blood banking. Screening of blood donors has been based on verbal screening and serologic testing to date. Additionally, the need of implementing nucleic acid testing (NAT) was considered in 2011 because of an upsurge in hepatitis epidemiology. The aim of this study was to analyze the efficacy of this additional donor screening program and to evaluate the impact of NAT on the yield and residual risk of transfusion‐transmissible viral infections.

Retrospective review of pediatric patients with acute lymphoblastic leukemia: A single center experience

OBJECTIVEnWe reviewed the clinical details and treatment outcome of children with newly diagnosed acute lymphoblastic leukemia (ALL) to determine the significance of already established prognostic factors in our patients.nnnSETTINGnA tertiary care hospital in Karachi, Pakistan.nnnSTUDY DESIGNnThis is a retrospective study.nnnMATERIALS AND METHODSnChildren diagnosed with ALL were evaluated over a period of 17 years (January 1, 1989 to December 31, 2006). Data was collected by reviewing the medical records of the patients and the prognostic factors analyzed by us include age, gender, white blood cell count, central nervous system and mediastinal involvement at presentation, morphology and immunophenotype of the blast cells, and response to induction therapy.nnnRESULTSnThere were 46 patients diagnosed during the study period and on regular follow-up. Forty five (97.8%) of these were in complete remission after 28 days of induction therapy. Thirty patients (65.2%) were alive and doing well at the time of study. Of these 30 patients, 26 (86.6%) remained relapse free while only four (13.3%) had relapsed. The remaining 16 patients (34.7%) did not survive including 11 (68.7%) who had a relapse. Only significant variables in terms of prognosis were age and ALL phenotype with a P value 0.04 and 0.03 respectively.nnnCONCLUSIONnWe found that ALL is a frequent childhood hematological malignancy in our setting and is more prevalent in males and children less than ten years of age. Age and leukemia phenotype emerged as the important prognostic factors in pediatric ALL in our patients.

Neonatal hyperbilirubinemia in infants with G6PD c.563C > T Variant.

BackgroundThere is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T.MethodsThis was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing.ResultsG6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3u2009±u20090.2 U/gHb vs. 14.0u2009±u20094.5 U/gHb, pu2009<u20090.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8u2009±u20095.4 mg/dl vs. 13.8u2009±u20094.6 mg/dl, pu2009=u20090.008) which peaked earlier after birth (mean ± 1SD 2.9u2009±u20091.6 vs. 4.3u2009±u20092.3 days, pu2009=u20090.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups.ConclusionsWe concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity.

Feasibility of pediatric plasma apheresis in intensive care settings.

Therapeutic plasma apheresis or exchange (TPE) in the pediatric population is technically challenging. Moreover, there is generally an apprehension in using TPE in children compared to adults. Recently, usage of TPE has evolved and is now being used in heterogenous clinical conditions. Its usefulness is classified by the American Society for Apheresis (ASFA) into various categories ranging from I to IV. The objective of this paper was to review the procedure in context of clinical indications, complications and outcomes in children. For this purpose, we retrospectively reviewed all TPE procedures performed on inpatients of 3 to 16 years of age during a 6‐year period (2007–2012). A total of 130 procedures were performed on 28 patients (M : F ratio of 1:1) with median age (range) of 8.8 (4–16) years. All procedures were done using the continuous cell‐separator centrifugal method. Due to organ dysfunctions, the majority of procedures (Nu2009=u200926 of 28 or 92% patients) were performed in the pediatric intensive care unit. Twenty‐three, four and one patient belonged to ASFA categories I, II and III, respectively. The most common indications were neurological disorders (Nu2009=u200913 or 46.4%), comprised of Guillain–Barré syndrome (Nu2009=u200910) and myasthenia gravis (Nu2009=u20093). Hematological disorders (Nu2009=u200910 or 35.7%) including thrombotic thrombocytopenic purpura‐hemolytic uremic syndrome were a close second. Complete recovery was seen in 23 patients (84%). Trivial adverse effects were observed in 18/130 (13.8%) procedures. Major complications including cardiac arrest, hypotension and transfusion‐related acute lung injury were observed in 5/130 or 3.8% of procedures. However, there was no procedure‐related death though five patients died during treatment due to underlying pathology. In conclusion, TPE is a safe and effective option in sick children for appropriate indications. An experienced staff with sound procedural skills is imperative for successful therapy.

Hemoglobin E syndromes in Pakistani population

BackgroundHemoglobin E is an important hemoglobin variant with a worldwide distribution. A number of hemoglobinopathies have been reported from Pakistan. However a comprehensive description of hemoglobin E syndromes for the country was never made. This study aimed to describe various hemoglobin E disorders based on hematological parameters and chromatography. The sub-aim was to characterize hemoglobin E at molecular level.MethodsThis was a hospital based study conducted prospectively for a period of one year extending from January 1 to December 31, 2008. EDTA blood samples were analyzed for completed blood counts and hemoglobin variants through automated hematology analyzer and Bio-Rad beta thalassaemia short program respectively. Six samples were randomly selected to characterize HbE at molecular level through RFLP-PCR utilizing MnlI restriction enzyme.ResultsDuring the study period, 11403 chromatograms were analyzed and Hb E was detected in 41 (or 0.36%) samples. Different hemoglobin E syndromes identified were HbEA (n = 20 or 49%), HbE/β-thalassemia (n = 14 or 34%), HbEE (n = 6 or 15%) and HbE/HbS (n = 1 or 2%). Compound heterozygosity for HbE and beta thalassaemia was found to be the most severely affected phenotype. RFLP-PCR utilizing MnlI successfully characterized HbE at molecular level in six randomly selected samples.ConclusionsVarious HbE phenotypes are prevalent in Pakistan with HbEA and HbE/β thalassaemia representing the most common syndromes. Chromatography cannot only successfully identify hemoglobin E but also assist in further characterization into its phenotype including compound heterozygosity. Definitive diagnosis of HbE can easily be achieved through RFLP-PCR.

Root cause analysis of non-infectious transfusion complications and the lessons learnt

BACKGROUNDnTransfusion of blood and blood products can be associated with hazards which may be at times fatal. Timely reporting of transfusion reactions is imperative for root cause analysis and their prevention in future.nnnMETHODSnWe retrospectively reviewed the transfusion reactions at our institution during last seven years. The data was retrieved from our computerized blood bank information system and by reviewing the medical charts of patients. The frequency of adverse effects, implicated products, wrong blood transfusion and its outcome were observed.nnnRESULTS AND CONCLUSIONSnDuring study period (2006-2012), a total of 393,662 blood or blood products were transfused. There were 458 adverse events with an estimated rate of 1.16 per 1000 blood products administered. During 2011-2012, 121 transfusion reactions were reported of 119,921 transfused units. The most common adverse effects were allergic reactions (70 episodes of 121 or 57.8%) followed by febrile non hemolytic transfusion reactions or FNHTR (43 events of 121 or 35.5%). Transfusion associated dyspnea, circulatory overload and transfusion associated lung injury were less frequent. During the study period, 142,066 red cell units were transfused with nine recognized ABO-mismatch transfusions and two fatalities. The computed incidence of ABO-mismatch transfusion was 1 in 15,785 with a mortality rate of 1 in 71,033 units transfused. Etiology included: errors in final bed side check (n=5), blood bank clerical errors (n=3) and mislabeled tube (n=1). A review of these cases prompted hospital transfusion committee for re-enforcing policies and protocols to minimize accidental ABO incompatible transfusions. We concluded that urticaria and FNHTR are the most frequent transfusion reactions in our setting. ABO mismatched blood transfusions are rare but preventable errors and result mainly from clerical imprecisions.

Risk of maternal alloimmunization in Southern Pakistan – A study in a cohort of 1000 pregnant women

BACKGROUNDnHaemolytic disease of the fetus and the newborn [HDFN] is caused by incompatibility of maternal and fetal erythrocytes. Red blood cell alloimmunization is a well-known cause of HDFN. Due to heterogeneity of populations, the spectrum of alloimmunization varies around the world. This study aimed to determine the frequency of alloimmunization in pregnant women and to determine the risk of HDFN in our population.nnnSTUDY DESIGN AND METHODSnThis was a descriptive study conducted at Aga Khan University Hospital Karachi. Blood type and red cell antibody screening was determined on every pregnant woman at her first antenatal visit. Red cell antibody identification was performed on positive screening results.nnnRESULTSnA total of 1000 pregnant females including 633 (63.3%) multigravida were studied. Blood type B was predominant (nu2009=u2009374 or 37.4%) and D negative was observed in 136 women (13.6%). No red cell antibody was detected in 982 females (98.2%). 20 red cell antibodies were detected in 18 women (1.8%). The incidence of non-anti-D was 16/1000 [1.6%] in all pregnant females. The non-anti-D alloantibodies included anti-M (nu2009=u20093; 15%), anti-Lewis(a) (nu2009=u20093; 15%), anti C ( nu2009=u20091; 5%), anti-E (nu2009=u20091; 5%), anti-e (nu2009=u20091; 5%), anti-Lewis(b) (nu2009=u20091; 5%) and nonspecific antibodies (nu2009=u20096; 30%). The incidence of anti-D was 4/136 or 2.9% in D negative blood type. After excluding prior sensitization due to blood transfusions, risk remained was 2.2%. Antibodies of clinical significance were identified in 9 (0.9%) females.nnnCONCLUSIONSnIn our cohort, frequency of red cell alloimmunization during pregnancy was 1. 8% out of which 0.9% were clinically significant antibodies posing a risk for HDFN. Despite prenatal and post natal prophylaxis, risk of sensitization with D antigen in D negative women was high at 2.2%. We recommend that all pregnant women should be screened for irregular antibodies irrespective of the rhesus type.

Implementation of Maximum Surgical Blood Ordering Schedule and an Improvement in Transfusion Practices of Surgeons subsequent to Intervention

Over ordering of blood is a common practice for elective surgeries in many developing countries. Over a decade back, our institution—The Aga Khan University, Pakistan noticed that surgeons were making unnecessary arrangement of red cells. This was reflected in their undesirably high cross-matched to transfusion (CT) ratios. A clinical audit conducted in 1998–2000 confirmed this. This prompted the institution for designing a maximum surgical blood ordering schedule (MSBOS) in 2000 based on the retrospective usage of blood in various elective surgeries. This study aimed at observing the impact of implementation of MSBOS on surgeons’ transfusion practices by comparing pre and post intervention cross-matched to transfused ratio in selected elective surgeries. For this purpose, we conducted a clinical audit from 2009 to 2010 and data was retrieved for quantity of red cells units arranged and transfused in the peri-operative period. C:T ratio was computed and compared with those in 2000. Identification of patients and physicians were kept confidential. Baseline C:T ratios for C-section, TURP, total knee replacement, laparoscopic cholecystectomy and CABG were 32, 22, 11.42, 23 and 4.77 respectively. In 2009–2010, red cells were transfused in 86 of 1,224 C-sections (7xa0%), 599 of 727 CABG (82xa0%), 10 of 324 TURP (3xa0%),16 of 890 laparoscopic cholecystectomy (1.7xa0%) and 14 of 85 total knee replacement (16.4xa0%) The C:T ratio in these surgeries was between 0 and 1. Implementation of MSBOS and efforts of BUC showed a significant impact in transfusion practices of surgeons with marked reduction in the utilization of blood and the C:T ratio. We recommend that regular audits should be conducted in every institution to improve the quality of services, encourage team work and ensure high standards.

Use of ISTH bleeding assessment tool to predict inherited platelet dysfunction in resource constrained settings

Abstract Background: The International Society of Thrombosis & Hemostasis (ISTH) bleeding assessment tool (ISTH-BAT) is used to record bleeding symptoms in patients with possible bleeding disorders. Aim: To investigate the utility of the ISTH-BAT in predicting platelet dysfunction in individuals with suspected inherited platelet function disorders. Method: Individuals with clinical evidence of bleeding and suspected inherited platelet function disorder and healthy volunteers were included in the study. The ISTH-BAT questionnaire was applied prior to light transmission aggregometry (LTA). Results: A total of 261 participants were included (100 healthy volunteers, and 161 with suspected inherited platelet function disorders). The ISTH-BAT score in participants with suspected inherited platelet function disorders (median 2; interquartile range [IQR] 5–1) was significantly higher than in healthy volunteers (median 0; IQR 2–0). There was also a significant difference between participants with suspected inherited platelet function disorders with a platelet defect detected by LTA (median 4; IQR 8–3) and those with normal platelet function (median 2; IQR 3–1) (pu2009<u20090.001). The ISTH-BAT score was associated with a demonstrable platelet defect on platelet function testing (area under the receiver operating characteristic curveu2009=u20090.8 [95% confidence interval 0.72–0.87, pu2009=u2009<u20090.001] and odds ratio 3.25 [95% confidence interval 2.13–4.37, pu2009=u2009< 0.001]). Conclusion: The ISTH-BAT is a useful tool for documenting bleeding symptoms and the score obtained is also predictive of the presence of a platelet defect on LTA in patients with suspected inherited platelet dysfunction.

Transfusion transmitted dengue: One donor infects two patients

Dengue virus can be transmitted via blood transfusion. We report an interesting case where two surgical patients developed possible transfusion transmitted dengue when transfused blood components of the same donor. Dengue remains a threat to blood supply especially in endemic region.