Fibrin glue in managing intractable gingival bleeding in patients with inherited bleeding disorders-a quasi-experimental pilot study.

This study presents the clinical outcomes of using inhouse prepared fibrin glue for controlling gingival bleeding in patients with inherited bleeding disorders (IBD). The objective of the study was to assess the reduction in transfusion days and improvement in compliance for dental evaluation over a one-year period in a low-to-middle-income country. The quasiexperimental pilot study included 40 IBD patients with gingival bleeding. These were divided into two groups: Group A received fibrin glue (n=20), while Group B did not (n=20). The study compared outcome metrics, including the number of treatment days and blood components transfused, using non-parametric tests with a significance threshold of p<0.05. Results showed that Group A required fewer blood components (n=154) as compared to Group B (n=204) (p<0.001). Patients in Group A with Glanzmann thrombasthenia (GT) had a shorter treatment duration (one day) than those in group B (three days) (p<0.01). In conclusion, the application of fibrin glue effectively managed intractable gingival bleeding in IBD patients.

Burden of ocular abnormalities in patients with beta thalassaemia: a cross-sectional study.

INTRODUCTION: In Pakistan, the reported carrier rate of thalassaemia is estimated to be 5%-8% with 5000 new patients diagnosed every year. Several known systemic complications of beta thalassaemia major have been studied, but no studies are conducted to assess ocular complications among these patients from our population. METHODS: It was a cross-sectional study design conducted at three private and public sector centres in Pakistan. We recruited 203, 11-17 years old children with beta thalassaemia major in our study. Frequency of overall ocular complications such as retinal pigment epithelium degeneration, visual field defects, increased retinal vascular tortuosity, lenticular opacities, anterior segment abnormality, etc among beta thalassaemia patients were verified by an ophthalmologist. RESULTS: On univariate analysis male gender (prevalence ratio (PR): 1.023 (0.903 to 1.160), OGTT levels (PR: 0.99 (0.978 to 1.003) and serum calcium levels (PR: 0.716 (0.616 to 0.936)) were significantly associated with ocular complications. However, on multivariable analysis after adjusting for covariates we observed that the prevalence of ocular complications was 88% higher in males as compared with females. Moreover, with every one unit increase in serum calcium levels the prevalence of ocular complications were decreased by 24%. CONCLUSION: Our study results showed that the frequency of ocular complications in beta thalassaemia children was 22.7%. Male gender was a risk factor for ocular complications among children with beta thalassaemia. However, high calcium levels among these patients were found to be protective for ocular complications.

Bone marrow aplasia in Haemophilia-A with Hepatitis-C and human immunodeficiency virus co-infection: A case report.

Haemophilia A is an inherited bleeding disorder caused due to the deficiency of factor VIII. This case report of a 17-year-old HA boy co-infected by hepatitis C (HCV) and human immunodeficiency virus (HIV) followed by bone marrow aplasia seeks to address the key clinical question of the causality and management of bone marrow aplasia in a resource-constrained setting. Our patient developed pancytopenia which prompted the diagnosis and management of HCV and HIV. Bone marrow biopsy revealed severe aplasia. He was treated with highly active antiretroviral therapy (HAART). Two years later, he developed septic arthritis and haemarthrosis of the elbow and knee joints. He underwent arthrotomy of the knee joint. The patient expired, postoperatively, due to septic shock. This case underlines the need for truly universal access to virally inactivated replacement therapy to prevent complications secondary to infections transmitted by transfusion.

Reduction of cardiac iron overload by optimising iron chelation therapy in transfusion dependent thalassaemia using cardiac T2* MRI: a quality improvement project from Pakistan.

OBJECTIVES: Cardiac T2* MRI (T2*CMR), for accurate estimation of myocardial siderosis, was introduced as part of a QI collaborative to optimise chelation therapy in order to improve cardiac morbidity in transfusion dependent thalassaemia (TDT) patients. We report the impact of this QI initiative from two thalassaemia centres from this collaborative. DESIGN AND SETTING: A key driver based quality initiative was implemented to improve chelation in TDT patients registered at these two centres in Karachi, Pakistan. Protocol optimisation and compliance to treatment through training, communication and feedback were used as the drivers for QI intervention. Preintervention variables (demographics, chelation history, T2*CMR, echocardiography and holters) were collected from January 2015 to December 2016) and compared with variables in the post implementation phase (January to December 2019). A standardised adverse event severity for chelators and its management was devised for safe drug therapy as well as ensuring compliance to the regimen. Preintervention and postintervention variables were compared using non-parametric test. P value<0.05 was statistically significant. RESULTS: 100 patients with TDT, median age 17 (9-34) years, were included. An increase or stabilisation of T2*CMR was documented in 82% patients in the postintervention phase especially in patients with severe myocardial iron overload (5.5 vs 5.3 ms, p <0.01). Significantly fewer patients had abnormal echocardiographic findings (3.5% vs 26%, p <0.05) in the postintervention versus preintervention period. CONCLUSION: This QI initiative improved the chelation therapy leading to improved cardiac status in TDT patients at the participating centres.

Compliance of hand written transfusion requisition form and improvement after online request - a clinical audit.

OBJECTIVE: To assess the compliance of healthcare personnel with regard to sending completely filled transfusion requisition forms. METHODS: The audit was conducted at Aga Khan University Hospital, Karachi, and comprised requisition slips received at the hospital blood bank from September 2014 to February 2015. The British Committee for Standards in Haematology guidelines was used as the standard. Percentage of each variable on the proforma was analsyed. Rating <50% for each form was defined as "needs improvement", 51-99% as "good compliance" and 100% as "excellent compliance". After implementing strategies to increase awareness and the launching of an online transfusion requisition form, a re-audit of physician compliance was done from February to April 2016 and the results were compared with the initial audit.. Data was analysed using SPSS 21. RESULTS: The audit and the re-audit both comprised 1000 transfusion requisition forms each. In the audit, The sum of total scores of all the transfusion requisition forms was 4911, indicating a compliance rate of 46.9%, while the corresponding numbers in the re-audit were 10000 and 100%. CONCLUSIONS: The implementation of online blood transfusion requisition system had a positive impact on compliance rate.

Establishment of a thalassaemia major quality improvement collaborative in Pakistan.

OBJECTIVES: The aim of this study was to establish multidisciplinary care for patients with transfusion-dependent thalassaemia (TDT) by creating a TDT quality improvement (QI) collaborative in a resource-constrained setting. This study presents our initial experience of creating this collaborative, the baseline characteristics of the participants, the proposed QI interventions and the outcome metrics of the collaborative. DESIGN AND SETTING: TDT QI collaborative is a database comprising patients with TDT from four centres in Karachi, Pakistan. Study variables included symptoms of cardiac or endocrine dysfunction, physical examination including anthropometry and Tanner staging, chelation therapy, results of echocardiography, T2* cardiac MRI (CMR) and serum ferritin. The main outcome of this collaborative was improvement in TDT-related morbidity and mortality. Interventions addressing the key drivers of outcome were designed and implemented. RESULTS: At the time of reporting, the total number of patients in this database was 295. Most patients reported cardiac symptoms corresponding to New York Heart Association class 2. Approximately half (52%, n=153) of the patients demonstrated severe myocardial iron overload (T2* <10 ms). Majority of the patients (58%, n=175) were not on adequate chelation therapy. There was no difference in echocardiographic measures of systolic and diastolic left ventricle among the different spectrums of iron overloaded myocardium. CONCLUSION: Using T2* CMR and endocrine testing, we have identified significant burden of iron siderosis in our patients with TDT. Lack of adequate iron load assessment and standardised management was observed. Interventions designed to target these key drivers of outcome are the unique part of this QI-based TDT registry.

Clinical utility of endocrine markers predicting myocardial siderosis in transfusion dependent thalassemia major.

BACKGROUND: Endocrinopathy due to iron overload is the most common morbidity whereas myocardial siderosis causing toxic cardiomyopathy is the leading cause of mortality among patients with transfusion dependent thalassemia major (TDTM). If detected early, this can be treated with aggressive chelation. T2* cardiac magnetic resonance imaging (CMR) guided chelation protocols are now the gold standard but have limited availability in low and middle-income countries. We hypothesized that markers of endocrine dysfunction would correlate with T2* CMR and can be used to predict the severity of myocardial siderosis and guide chelation therapy. METHODOLOGY: We undertook a multicenter retrospective study of 280 patients with TDTM to assess the prevalence of endocrinopathies and the predictive value of a number of individual and composite markers of endocrinopathy with T2* CMR. RESULTS: The prevalence of hypogonadism, stunting, hypoparathyroidism, and hypothyroidism was 82%, 69%, 40%, and 30%, respectively. The sensitivity of hypogonadism and stunting predicting severe myocardial siderosis was 90% and 80%, respectively. CONCLUSION: We conclude that clinical markers of endocrine dysfunction, especially hypogonadism (positive likelihood ratio [LR+] = 1.4, 95% confidence interval [CI] = 1.0-1.9; positive predictive value [PPV] = 77%, 95% CI = 70-82; negative predictive value [NPV] = 57%, 95% CI = 34-77] and stunting (LR+ = 1.3, 95% CI = 1.1-1.6; PPV = 64%, 95% CI = 60-69; NPV = 55%, 95% CI = 45-64) in TDTM can predict severe myocardial siderosis and can potentially guide chelation therapy, especially where access to T2* CMR is limited.

Inherited Bleeding Disorders-Experience of a Not-for-Profit Organization in Pakistan.

Patient registry is a powerful tool for planning health care and setting groundwork for research. This survey reports a detailed registry of inherited bleeding disorders (IBD) and their management at a not-for-profit organization in a developing country to form the basis for planning development and research. We reviewed medical records of patients with IBD from 8 hemophilia treatment centers of Fatimid Foundation located in various cities. Information collected included sociodemographic data, diagnostic tests, severity of hemophilia A and B, number of bleeding episodes per year, site and frequency of hemarthrosis, and seropositivity for viral diseases. We analyzed 1497 patients from November 1, 2015, to April 30, 2016. There were 1296 (87%) males and 201 (13%) females with a mean age of 24.5 (11) years (range, 6 months to 65 years). Hemophilia A constituted the bulk of IBD (848, 57%) followed by von Willebrand disease (172, 11%), hemophilia B (144, 10%), platelet function defect (106, 7%), and rare bleeding disorders (70, 5%). Mucocutaneous bleeding (1144, 76%) and hemarthrosis (1035 patients, 69%) were the main complications. There were 1026 (69%) patients who received only blood components for treatment of any bleeding episode while the remaining 464 (31%) were on combination therapy (blood components and factor concentrate). Seroreactivity for hepatitis C was frequent (28%), while hepatitis B (1%) and human immunodeficiency virus (0.01%) were less commonly seen. This study was an important step toward a patient registry in a hemophilia treatment center in Pakistan. Hemophilia A is the most common bleeding disorder and hepatitis C is the most frequent treatment-related complication.

Anemia in a middle aged female with aortitis: a case report.

BACKGROUND: Idiopathic aortitis is among the most common causes of non-infectious aortitis, which rarely presents with anemia. CASE PRESENTATION: Here we report a case of a 49-year-old muhajir female who presented with shortness of breath and easy fatigability for the past 6 months. Physical examination revealed pallor and a diastolic murmur in the aortic region. Echocardiography showed thickened and calcified aortic and mitral valves, severe aortic regurgitation and dilatation of ascending aorta. She was advised aortic valve replacement and was referred to a haematologist due to concomitant anemia. Complete blood counts revealed haemoglobin: 7.7 gm/dl, mean corpuscular volume (MCV): 78 fl, mean corpuscular haemoglobin (MCH):23 pg, total white cell count: 9.0 × 10(9)/L and platelet count: 227 × 10(9)/L. Erythrocyte sedimentation rate (ESR) was 100 mm/hr. There was suspicion of myelodysplastic syndrome, but could not be confirmed as the patient refused bone marrow and cytogenetic studies. She was given erythropoietin, folic acid and ferrous sulphate. Following relatively prolonged therapy, her haemoglobin level increased to approximately 9.0 gm/dL. She was transfused with packed red cells and underwent aortic valve and ascending aorta replacement. The ascending aorta was dilated and aortic wall markedly thick and irregular. Histopathology of the resected aorta revealed granulomatous aortitis. She was prescribed prednisolone, which resulted in further incremental rise of haemoglobin to 13.1 gm/dL. One month later, she developed complaints of blurred vision in the right eye and was diagnosed with central retinal vein occlusion. She was treated with antiplatelet agents and her vision improved. After 3 months, she was asymptomatic and her haemoglobin level rose to 11.2 gm/dL without hematinic therapy or blood transfusion. She was begun on anticoagulant therapy and remains clinically stable. CONCLUSION: We report a case of idiopathic aortitis with presumed diagnosis of anemia of chronic disease exhibiting a transient response towards steroid therapy post-valvuloplasty.

Response and Adverse Effects of Nilotinib in Imatinib-resistant Chronic Myeloid Leukemia Patients: Data From a Developing Country.

PURPOSE: The purpose of this study was to determine the frequency of major cytogenetic response (MCyR) and adverse events with nilotinib in adults with imatinib-resistant Philadelphia chromosome-positive chronic myeloid leukemia (CML). METHODS: This is a descriptive cross-sectional study conducted at The Aga Khan University Hospital in Karachi from October 17, 2010, to October 17, 2011. A cytogenetic assessment using fluorescent in situ hybridization was performed on peripheral blood before initiation of treatment and 6 months after treatment with nilotinib. The frequency of adverse effects was assessed at 6 months, and the patient overall survival was calculated after 3 years. FINDINGS: This study enrolled 82 imatinib-resistant patients. The mean (SD) patient age was 38.9 (12.2) years. There were 62 patients (75.6%) in chronic phase, 15 patients (18.3%) in accelerated phase, and 5 patients (6%) in blast crisis phase. At 6 months cytogenetic studies were available for 40 (52%) of 77 patients, and MCyR was observed in 31 (77.5%) of 77 patients. The patients in chronic phase had the highest frequency of MCyR (n = 27 [87%] of 31). We observed 6 deaths (7.3%), and the overall survival at 3 years was 92.7%. There was isolated thrombocytopenia in 12 patients (15.6%). The most frequent nonhematologic adverse events were myalgia and headache. IMPLICATIONS: The nilotinib response rates were higher in chronic phase patients, and the most common adverse events were thrombocytopenia, myalgia, and headache.

Quality indicators for critical international normalized ratio measurements in a hemostatic laboratory.

OBJECTIVE: This study aimed at reviewing the quality indicators for reporting critical international normalized ratio (INR) in a coagulation laboratory. DESIGN AND METHODS: This is a retrospective study conducted at Aga Khan University Hospital, hemostatic laboratory from February 2010 till January 2011. Critical INR was defined as ≥5.0. All critical INRs were rechecked and results were communicated to the doctor or patient. Two quality indicators monitored were % of results communicated to the patient/doctor and % of results that remained critical after re-testing. RESULTS: During the study period, a total of 59,980 INRs were reported. Of these 376 or 0.6% were critical. Successful communication of critical results to the doctor or patient was achieved in 275/376 (73.1%). Overall 353 or 94% (343 initial and 10 re-draw) samples had critical INR on repetition. Twenty five patients of the 240 warfarinized patients with critical INR had mild bleeding. No life threatening bleeding was observed in any patient. CONCLUSION: We observed poor communication for notifying critical INR results during the study period. Routine repeat analysis of critical INR did not alter results in majority of samples. The study assisted in improving communication in subsequent years. Further work is needed to establish evidence based upper and lower cutoff of critical INR. Effect of replicate analysis on turnaround time and accuracy of results needs evaluation.

Monitoring and reporting transfusion reactions as a quality indicator - a clinical audit.

BACKGROUND AND OBJECTIVE: This audit was conducted as a part of a quality assurance activity to assess the frequency of receiving completely filled out blood transfusion reaction forms which were accompanied by the required samples. Once this information is known, we will elevate the bar each year to achieve 100% compliance. The sub-aim was to evaluate the frequency of the reported transfusion reactions. MATERIALS AND METHODS: The study was conducted from 1st April 2010 to 30th April 2011. The information was evaluated and the frequency of receiving completely filled blood transfusion reaction forms was assessed. The variables identified were the type of transfusion reaction, the blood component transfused, the health care personnel filling the form, and whether there was legible handwriting and a completely filled form. Transfusion reactions were reported as a percentage of the total number of units transfused. RESULTS: During the study period, 17,880 packed red cells, 13,200 platelets, 13,620 fresh frozen plasma and 2256 cryoprecipitate were transfused and 106 transfusion reactions (0.23%) were reported. Of these, febrile non hemolytic transfusion reaction was the most common (47%), the majority caused by packed red cells. CONCLUSION: Eighty-four percent of the transfusion reaction forms were completely filled as per our criteria. Febrile non hemolytic transfusion reactions were the most common reactions reported.

Leishmania donovani bodies in bone marrow.

KEY CLINICAL MESSAGE: We report a case of a 5-year-old female, resident of Afghanistan, who presented with fever and massive splenomegaly. Bone marrow revealed Leishmania donovani bodies (LD bodies) in macrophages characterized by a kinetoplast and characteristic double dot appearance. She was diagnosed as visceral leishmaniasis which is transmitted by sandflies (Phlebotomus).

Rare cytogenetic abnormalities in acute myeloid leukemia transformed from Fanconi anemia - a case report.

BACKGROUND: Fanconi's anemia (FA) is an inherited bone marrow failure syndrome that carries a higher risk of transformation to acute myeloid leukemia (AML) when compared with general population. AML is the initial presentation in approximately one third of patients. CASE PRESENTATION: A 17 year old male presented to the emergency room with history of high grade fever since two weeks. Examination revealed pallor, short stature and thumb polydactyly. There was no visceromegaly or lymphadenopathy. Complete blood count showed haemoglobin 3.4 gm/dl, MCV 100 fl and MCH 36 pg, white blood cell count 55.9 × 10 E9/L and platelet count 8 × 10E9/L. Peripheral blood smear revealed 26% blast cells. Bone marrow was hypercellular exhibiting infiltration with 21% blast cells. Auer rods were seen in few blast cells. These findings were consistent with acute myelomonocytic leukemia. These blasts cells expressed CD33, CD13, HLA-DR, CD117, CD34 antigens and cytoplasmic myeloperoxidase on immunophenotyping. Bone marrow cytogenetics revealed 46, XY, t (8:21) (q22; q22) [11] / 46, XY, add (2) (q37), t (8; 21) [4] / 46, XY [5]. Molecular studies showed positivity of FLT 3 D835 variant and negativity of NPM 1 and FLT3 ITD (internal tandem domain) mutation. Peripheral blood analysis for chromosomal breakage exhibited tri-radial and complex figures. He received induction chemotherapy with cytarabine and daunorubicin (3 + 7). Day 14 marrow revealed clearance of blast cells. CONCLUSION: The recognition of specific cytogenetic abnormalities present in FA known to predispose to AML is crucial for early haematopoietic stem cell transplant (HSCT) before transformation to leukemia.