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.

Validation of MASCC Score for Risk Stratification in Patients of Hematological Disorders with Febrile Neutropenia.

OBJECTIVES: The purpose of this study is to evaluate the association of MASCC score (Multinational Association for Supportive Care in Cancer Score) in patients with febrile neutropenia (as resultant treatment of hematological disorders) for risk assessment of morbidity and mortality. PATIENTS AND METHODS: Patients presenting with Febrile Neutropenia from November 2011 till December 2013 were enrolled in the study. Initially all patients were hospitalized and their MASCC score was calculated, however those with high risk stayed in hospital till full ANC recovery while low risk group was discharged earlier and keenly followed as out-patient while being on prophylactic oral antibiotics. The MASCC risk-index score was calculated and patients with risk score >21 were regarded as low-risk while <21 were labeled as high-risk. RESULTS: On the basis of 226 febrile neutropenia patient 132(58.4 %) were categorized as low risk while 94(41.5 %) as high risk patients according to MASCC risk index score. In low risk group 123(93 %) had uncomplicated infection while 9(7 %) had complicated infections. There was no mortality documented in low risk group while eight patients died in high risk group. CONCLUSION: In this study we correctly predicted outcome of 123(93 %) low risk group patients. The study had positive predictive value of 93 % with both sensitivity and specificity of 65 and 75 % respectively. The MASCC risk score is a valuable tool in determining the outcome in patients with febrile neutropenia.

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.

Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies.

INTRODUCTION: A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. AIM: Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. METHODS: A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed. RESULTS: In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 µg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 µg kg(-1) (divided as three doses). CONCLUSION: Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies.

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.

Clinical and Microbiological Profile of Pathogens in Febrile Neutropenia in Hematological Malignancies: A Single Center Prospective Analysis.

Background. Febrile neutropenia is the consequence of treatment of hematological disorders. The first-line empirical treatment should cover the prevalent microorganism of the institute. The aim of study was to establish the effectiveness of current practices used at the institution and to review the culture sensitivity pattern of isolated microorganisms. Patients and Methods. Data was recorded and analyzed prospectively for 226 hospitalized patients of febrile neutropenia from January 2011 till December 2013. Results. Out of 226 cases, 173 were males and 53 were females. Clinically documented infections were 104 (46.01%) and microbiologically documented infections were 80 (35.39%), while 42 (18.58%) had pyrexia of undetermined origin. Gram negative infections accounted for 68 (85%) and Escherichia coli was the commonest isolate. Gram positive microorganisms were isolated in 12 (15%) cases and most common was Staphylococcus aureus. First-line empirical treatment with piperacillin/tazobactam and amikacin showed response in 184 patients (85.9%) till 72 hours. Conclusion. There is marked decline in infections due to Gram positive microorganisms; however, Gram negative infections are still of great concern and need further surveillance. In this study the antibiogram has shown its sensitivity for empirical antibiotic therapy used; hence, it supports continuation of the same practice.

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.

Response of first-line antibiotic therapy in patients with febrile neutropenia during treatment of hematological disorders.

Patients with hematological disorders develop febrile neutropenia (FN); most of these events remain undetermined in origin. We performed a prospective study to determine the microbiological characteristics of infections and their response to the first-line antibiotic therapy in FN. The study was conducted at National Institute of Blood Disease and Bone Marrow Transplant. Two-hundred episodes of FN were assessed for the bacterial growth, antimicrobial susceptibility pattern and response to the first-line treatment of FN. All patients were given Ceftazidime and Amikacin Bosch Pharmaceutical (Pvt. Ltd), as first-line antibiotic in FN. Out of 200 episodes we had 108 clinically and microbiologically documented infections. The isolated frequencies for gram negative and gram positive organisms were n = 52 and 49 (48 and 45 %) respectively. Among gram negative micro-organisms, Escherichia coli (E. coli) was isolated in 15 (28.8 %), Klebsiella pneumonae in 4 (7.6 %) and Pseudomonas aeruginosa in 10 (19.2 %) were in highest frequencies. Methicillin sensitive staphylococci emerged as the frequently isolated gram-positive bacteria. Eight-one episodes (45.3 %) responded to the first-line treatment and death reported in 20 cases (10 %). Our study showed almost equal trend of gram positive and gram negative bacteria isolated from patients suffering from neutropenic fever. Empirical use of Ceftazidime and Amikacin as first-line antibiotics was able to cover the infection only in 45.3 % of episodes suffering from FN.

Sharing a driver's context with a caller via continuous audio cues to increase awareness about driver state.

In an experiment using a driving simulator we investigated whether sharing information of a driver's context with a remote caller via continuous audio cues can make callers more aware of the driving situation. Increased awareness could potentially help in making the conversation less distracting. Prior research has shown that although sharing context using video can create such beneficial effects, it also has some practical disadvantages. It is an open question whether other modalities might also provide sufficient context for a caller. In particular, the effects of sharing audio, a cheaper, more salient, and perhaps more practical alternative than video, are not well understood. We investigated sharing context using direct cues in the form of realistic driving sounds (e.g., car honks, sirens) and indirect cues in the form of elevated heartbeats. Sound sharing affected the caller's perception of the driver's busyness. However, this had at most a modest effect on conversation and driving performance. An implication of these results is that although sharing sounds can increase a caller's awareness of changes in the driver's busyness, they need more training or information on how to leverage such context information to reduce disruption to driving. Limitations and implications are discussed.

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.

Special issues related to hematopoietic SCT in the Eastern Mediterranean region and the first regional activity report.

Although several centers are now performing allogeneic hematopoietic SCT (HSCT) in the Eastern Mediterranean (EM) region, the availability is still limited. Special issues including compatible donor availability and potential for alternative donor programs are discussed. In comparison to Europe and North America, differences in patterns of diseases and pre-HSCT general status, particularly for patients with BM failure, are described. Other differences including high sero-positivity for CMV, hepatitis B and C infection, and specific observations about GVHD and its relation to genetically homogeneous communities are also discussed. We report that a total of 17 HSCT programs (performing five or more HSCTs annually) exist in 9 countries of the EM region. Only six programs are currently reporting to European Group for Blood and Marrow Transplantation or Center for International Blood and Marrow Transplantation Research. A total of 7617 HSCTs have been performed by these programs including 5701 allogeneic HSCTs. The area has low-HSCT team density (1.56 teams per 10 million inhabitants vs 14.43 in Europe) and very low-HSCT team distribution (0.27 teams per 10 000 sq km area vs <1-6 teams in Europe). Gross national income per capita had no clear association with low-HSCT activity. Much improvement in infrastructure and formation of an EM regional HSCT registry are needed.

Liver dysfunction in pregnancy: an important cause of maternal and perinatal morbidity and mortality in Pakistan.

The objective of this study was to evaluate the maternal and perinatal outcome of women with liver dysfunction during pregnancy. The study involved a prospective observational study design and was carried out at the Dow University of Health Sciences and Civil Hospital Karachi, Pakistan. A total of 800 women, who delivered during the study period from January 2006 to September 2006, constituted the study population. Pregnant women with liver dysfunction underwent evaluation for the aetiology of their liver dysfunction, including screening for hepatitis E. Thirty-five women were identified with liver dysfunction. Fourteen (40%) presented in the second trimester and 21 (60%) presented in the third trimester. Twenty-two of the 35 women (63%) had isolated acute hepatitis E; five (14%) had HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome; two (6%) had intrahepatic cholestasis of pregnancy (IHCP), two had acute fatty liver of pregnancy (AFLP) and two women had hepatitis A. A specific diagnosis was not reached in two women who died prior to delivery. In women with hepatitis E, the mean values of bilirubin and alanine transaminase were 12 mg/dL and 675 U/L, respectively. Abnormal coagulation parameters were present in 20 (57%) of the women and in 18 of 22 (82%) with hepatitis E. Fulminant hepatic failure (FHF) was seen in four patients. Seven women (20%) underwent caesarean section, 26 (74%) delivered vaginally and two women died undelivered. There were six maternal deaths in the study population; two were due to hepatitis E, one each from HELLP and AFLP, and two remained undiagnosed. The overall perinatal mortality within the group was 43%. Hepatitis E was the most common cause of FHF and maternal death in pregnant women with liver dysfunction.

Febrile neutropenia in paediatric peripheral blood stem cell transplantation, in -vitro sensitivity data and clinical response to empirical antibiotic therapy.

OBJECTIVE: To find the in-vitro sensitivity data and clinical response in order to determine the changes required in empiric antibiotic therapy for management of febrile neutropenia in paediatric patients undergoing peripheral blood stem cell transplantation. DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Paediatric bone marrow transplant unit at Bismillah Taqee Institute of Health Sciences and Blood Disease Center from September 1999 to May 2004. PATIENTS AND METHODS: All patients were treated according to institutional protocol for febrile neutropenia. Empirical antibiotics include Ceftriaxone and Amikacin. In non-responders, changes made included Imipenem and Amikacin, Piperacillin Tazobactum/Tiecoplanin or Vancomycin/Cloxacilin/Ceftazidime. In non-responders, amphotaracin was added until recovery. RESULTS: Out of 52 patients, 5 did not develop any fever; in the remaining 47 patients there were 57 episodes of febrile neutropenia. The mean days of febrile episodes were 4.71 (range 3-8). Fever of unknown origin (FUO) occurred in 31 (54.3%) episodes. Microbiologically documented infection (MDI) occurred in 17 (29.8%) episodes of fever. Clinically documented infection (CDI) occurred in 9 (15.7%) episodes. Gram-negative organisms were isolated in 10 while gram-positive organisms in 7. Klebseilla, S. aureus were the most common isolates. Empirical therapy was effective in 12 of the 33 (36%) episodes. Out of 28, 26 (92%) responded to Imipenem/Amikacin as second line therapy while those who received any other second line combination, only 11 out of 22 (50%) showed response. Systemic Amphotericin was used in 4 patients, 2 responded. Infection related mortality rate was 4%. CONCLUSION: Gram-negative infections predominated, Imipenem/ Amikacin found to be most effective therapy while a low mortality rate is recorded in our setting suggesting good infection control.

In-vivo purging with the anti-CD20 antibody rituximab along with standard allogeneic peripheral blood stem cell transplantation (PBSCT) for relapsed childhood pre-B acute lymphoblastic leukaemia (ALL).

This case report describes the use of Rituximab for in vivo purging (by intravenous infusion) in a 12 years old boy with second remission of pre-B ALL. It was followed by conditioning therapy consisted of Busulphan and Cyclophosphamide. rh-G-CSF primed stem cells from an HLA identical sibling donor were infused. Standard graft versus host disease prophylaxis was given. He engrafted within two weeks. He did not develop acute graft versus host disease (aGvHD) but localized chronic GvHD developed. He had been on regular follow-up at CMH, Rawalpindi and is in complete remission 13 months post-PBSCT with no evidence of chronic GvHD at present.