Frequency of TP53 Mutation in B-Cell Chronic Lymphocytic Leukaemia and its Association with Lymphocyte Doubling Time.

OBJECTIVE: To determine the frequency of TP53 mutation at diagnosis of B-cell Chronic Lymphocytic Leukaemia (B-CLL) in Pakistani patients, and to investigate whether lymphocyte doubling time (LDT) of less than 1 year could be used as a surrogate marker for TP53 mutation. STUDY DESIGN: A cross-sectional descriptive study. Place and Duration of the Study: Department of Haematology, Liaquat National Hospital, from January 2020 to December 2022. METHODOLOGY: Patients diagnosed with B-CLL based on the criteria set by International Workshop on Chronic Lymphocytic Leukaemia were included in the study. Clinico-haematological parameters were recorded, and TP53 mutation analysis was performed by fluorescence in situ hybridisation. Patients were followed every 3-6 months after diagnosis with the recent complete blood count (CBC) reports to record CBC parameters and calculate LDT. RESULTS: A total of 128 B-CLL cases were evaluated, with a mean age of 62 years. Among these cases, 10 patients (7.8%) tested positive for TP53 mutation, while 118 patients (92.2%) tested negative. During the follow-up period, 26 patients were lost to follow-up, with only one patient from the TP53 positive group. In the TP53 positive group, 55.6% (n=5/9) patients had an LDT of less than 1 year, indicating aggressive disease compared to 30.1% (n=28/93) patients in the negative group (p <0.1). CONCLUSION: TP53 mutations may be associated with shorter LDT, indicating aggressive disease. Further research is needed to fully comprehend the relationship between TP53 mutation and LDT in B-CLL. KEY WORDS: TP53 mutation, B-Cell chronic lymphocytic leukaemia (B-CLL), Lymphocyte doubling time (LDT).

Effectiveness of Using Nucleic Acid Amplification Test to Screen Blood Donors for Hepatitis B, Hepatitis C, and HIV: A Tertiary Care Hospital Experience From Pakistan.

Background Ensuring blood safety is the primary goal of transfusion medicine. Despite extensive serological tests and strict safety measures, the risk of transfusion-transmitted infections (TTIs) still exists. As applied to blood screening, Nucleic Acid Amplification Test (NAT) offers much higher sensitivity for detecting viral infections. It is, however, currently available to a handful of centers due to the high cost. This study aims to establish the Effectiveness of NAT by assessing the NAT yield and residual risk of transmission of Hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV with and without NAT testing. Material and method This prospective cross-sectional study recruited blood donors from January 2020 to November 2022. All donors underwent routine serologic screening. Only serologically negative donors were tested for HBV, HCV, and HIV by NAT. The NAT yield and residual risk (RR) per million donors were computed for viral infections in seronegative blood donors and calculated using the incidence/window period model. Result A total of 59708 donors were included during the study period. The overall prevalence of TTI's were: For HCV 1.7% (n = 1018), HBV 1.5% (n = 918), HIV 0.07% (n = 47), Syphilis 1.2% (n = 758) and malaria 0.3% (n = 218). Out of 57759 seronegative donors, thirty-four NAT-reactive samples were identified, with 3 cases of HCV, 31 cases of HBV, and Nil HIV cases. NAT yield of HBV was 1 in 1863 with an RR of 8.6 per million, followed by HCV with a NAT yield of 1 in 19253 and RR of 0.8 per million donations. NAT testing reduced RR for HBV by 48.9% and HCV by 94.5%. Conclusion Our study showed that NAT detected 34 out of 57759 cases initially missed by serological tests. The study suggests that the parallel use of serology and NAT screening of donated blood would be beneficial.

Marked Acanthocytosis Associated With Klipple Trenaunay Syndrom.

Klipple-Trenaunay syndrome (KTS) is an extremely rare congenital vascular disorder with poorly defined incidence and prevalence. We report a case of a patient who presented after road traffic accident with primary complaints of poor wound healing and persistent bleeding from wound site. Discernible presence of arteriovenous malformation and skin hypertrophy since birth lead to the diagnosis of Klipple-Trenaunay syndrome (KTS). There was an incidental finding of acanthocytosis on peripheral film of blood which remained elevated even after clinical improvement of the patient. This case report highlights a close association of marked acanthocytosis of red blood cells and Klipple-Trenaunay syndrome.

Frequency Of Raised Serum Lactate Dehydrogenase In Patients With Jak2 Positive Polycythaemia Vera.

BACKGROUND: Serum Lactate Dehydrogenase (LDH) is an easily available bio marker used to determine prognosis in various Myeloproliferative Neoplasms (MPN). Its utility in Polycythaemia Vera (PV) is yet to be accessed. The purpose of this study was to determine the frequency of raised serum LDH in patients with JAK2 V617F positive PV patients and its clinic-pathological association. METHODS: A cross-sectional study using non probability consecutive sampling was conducted at our institute from July 2018 to June 2019. Adult patients of either gender, newly diagnosed with JAK-2 V617F positive PV were included. Patients' demographics, clinical characteristics and baseline CBC and LDH levels were analysed. Stratification was done with regards to age, gender, diabetes mellitus, hypertension, splenomegaly and thrombosis to see the effect of these modifiers on patients with raised LDH by using Chi Square test. p-value≤0.05 was considered as significant. RESULTS: Forty patients were inducted in the study with male to female ratio of 2:1. Twenty-two (55%) patients had raised LDH levels and showed significant association with diabetes mellitus (p=0.001), splenomegaly (p=0.001) and thrombosis (p=0.018). CONCLUSIONS: This study observed raised LDH levels in almost half of JAK2 V617F positive PV patient. It warrants a larger scale study and suggests the value of plasma LDH to be used as a future prognostic marker in PV.

Frequency of Zygosity in Jak-2 Positive Patients with Polycythemia Vera-Pakistan's Perspective.

BACKGROUND: Estimation of JAK2V617F mutational load in Polycythemia Vera (PV) helps to determine the severity of the disease phenotype, the risk of thrombotic events, progression to post-PV myelofibrosis and survival. Amplification Refractory Mutation Screening (ARMS) PCR or Allele Specific (AS) PCR is a simple easy method with a reasonable sensitivity for screening of zygosity.The purpose of this study was to see the frequency of disease burden and phenotypic characteristics in Pakistani patients diagnosed with JAK2V617F mutation positive PV. MATERIALS AND METHODS: A cross-sectional study using non probability consecutive sampling was conducted at Hematology Department, Liaquat National Hospital Karachi from October 2018 to July 2019.Adult newly diagnosed JAK2V617F positive PV patients of either gender were included. Patients' demographics, clinical characteristics and baseline CBC were noted. JAK2V617F zygosity was qualitatively analyzed by ARMS-PCR technique. Age and gender were stratified to see to see the result of qualitative and quantitative effect modifiers on these patients using Chi Square and fisher exact test as appropriate while mean comparison was done by independent t-test and one way ANOVAtest. P value of ≤0.05 was considered as significant. RESULTS: Fifty one patients were included in the study with an average age of 59.60±14.29years.90.2% of patients had hypertension.All patients tested positive for heterozygous state. Significant association of gender was found with smoking (p=0.001) while age was significantly linked with hypertension (p-0.033). CONCLUSION: JAK2V617F positive PV patients are mainly heterozygous males showing significant association with smoking and hypertension. ARMS-PCR is a robust technique to determine zygosity which can be used for screening purposes.
.

Paediatric case of prolonged COVID-19 manifesting as PMIS-TS and atypical Kawasaki.

The COVID-19 pandemic has created an unprecedented disease burden worldwide, affecting patients of all ages. Recently, there has been a rise in a new inflammatory condition termed paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). We are yet to understand significant risk factors, disease progression and prognosis in children affected. We describe a case of a 9-year-old boy who tested positive concurrently for the SARS-CoV-2 virus 4 weeks apart. He presented with a 2-day history of fever, abdominal pain, headache and diarrhoea. Initial investigations supported PMIS-TS and he went on to develop atypical Kawasaki disease. With no results to differentiate between his positive results, we question whether he remained positive throughout or recovered with reactivation of the virus. There are reports of reactivation in adults but none in children. There are also no reports of children remaining positive for such a prolonged period, which raises public health concerns.

Outcome of heat stroke patients referred to a tertiary hospital in Pakistan: a retrospective study.

BACKGROUND: Climate change has heightened the threat of heat stroke in previously temperate zones. AIMS: This study aimed to assess the outcome of patients in relation to mortality and the role of effect modifiers among heatstroke patients presenting to a tertiary care hospital in Karachi during June 2015. METHODS: A retrospective observational study was conducted on heatstroke patients 20-27 June 2015 at the Emergency Room(ER) of a private hospital in Karachi, Pakistan. Patients' demographic data, disease severity, presentation and outcomes were determined. Statistical data was reported as numbers, percentages and mean ± SD. RESULTS: In total, 315 patients reported to ER; 76.6% patients survived, 23% expired. Males were 55% and 60% patients were fully mobile. Hypertension was the most frequent concurrent disorder. Fever documented in 79.4% and CNS derangement in 73.3% patients were the top most presenting features. Fever and disease severity were found to exert significant impact on disease outcome. Mortality rate dropped from 26 June onwards from 24.35% to 15.9% by using evaporative cooling technique combined with air conduction and maintaining room temperature at 22-24°C. CONCLUSIONS: Poor outcome during heatstroke can be minimized by advance planning and timely intervention in lowand middle-income countries.

Reactive Blood Donor Notification; Their Responses And Perceptions: Experience From Southern Pakistan.

BACKGROUND: Donor notification of reactive status is important to prevent the spread of disease. Response of reactive donors to seek confirmation and treatment is a direct reflection of their knowledge and attitudes towards transfusion transmittable infections. METHODS: A cross sectional observational study was conducted from August 2014 to July 2015 at the blood bank of a tertiary care hospital, Karachi, Pakistan. Reactive donors' notification and responses were noted with reasons of failure. A cross-sectional analytical survey with non-probability purposive sampling was done on 350 potential consenting blood donors using a pre-tested questionnaire to assess their knowledge and attitude about disease awareness, transmission routes, financial implications and disease sensitization. RESULTS: Out of 16660 donations, 5.57% were rejected on positive screening tests. Repeat donors (69.5%) with primary to secondary qualifications constituted the bulk of reactive donors. Donor notification rate were 54.25% whereas 28.68% donors responded to blood bank in person. The survey showed limited awareness about transfusion transmitted infections. Respondents who were ignorant of disease spread through blood transfusion comprised of 48%. 96.6% donors did not know the financial impact of treatment and 69.7% were unable to afford it. Moreover, 94.9% donors were not protected against hepatitis B. Participants with secondary education had significantly less odds of being adequately knowledgeable (OR=0.372, 95% CI: 0.203-0.681, p-value <0.01) but more likely to have a positive attitude. CONCLUSIONS: There is need for structured pre-donation counselling to sensitize donors about transfusion related diseases in resource limited countries where treatment costs are high and out of reach for most donors..

Multiple complications in sickle cell anaemia.

Sickle Cell Disease (SCD) is a structural haemoglobinopathy which is extremely diverse in its presentation regarding disease severity and organ involved. The homozygous form if poorly managed gives rise to numerous life threatening conditions which are otherwise avoidable. Here we report the case of a male adolescent with homozygous SCD who presented with haemolytic anaemia, massive ascites, hepatomegaly and multiple fractures secondary to severe malnourishment associated with the disease.

Hemophagocytic Lymphohistiocytosis in an Adult: A Rapidly Progressive Disease with Grave Outcome.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal syndrome seen primarily in children. It is characterized by pathologic systemic hyper inflammation which in adults is easily overlooked due to non-specific clinical features. Most of the data available are on paedriatic population, making the diagnosis of HLH in adults challenging for the clinician. Here we report a case of HLH in a 48-year male who presented with pyrexia of unknown origin for 2 months but remained undiagnosed despite extensive workup. Due to a high index of suspicion, re-evaluation of bone marrow biopsy was done which showed hemophagocytosis, earlier reported as normal. It led to specific investigations, needed for establishing the diagnostic criteria of HLH. Even though chemotherapy was initiated, the patient did not survive. The aggressive nature of this disease makes it crucial for the physician to be aware of its signs and symptoms for the early diagnosis and immediate introduction of adequate treatment.

Prospective Audit of Blood Donor Selection Process in a Tertiary Care Hospital of a Developing Country.

OBJECTIVE: The aim of this study was to emphasize the significance of internal audits of the blood donor selection process and documentation in a resource-limited country by assessing compliance with the established protocols, and to identify weak areas in the process. MATERIALS AND METHODS: This audit reviewed the donor selection process at the blood bank of Liaquat National Hospital & Medical College, Karachi, over a 6-month period. Seven variables selected as performance indicators were graded as very good (%90-100%), good (80%-89%), satisfactory (70%-79%), or unacceptable (<70%). Blood bank staff was asked for feedback and suggestions. RESULTS: Documentation of donor demographics was not within the acceptable range (documentation rates of 65.14%), donor status records were satisfactory (77.64%), and donor physical exam records were graded as good (86.34%). Five performance indicators were graded as very good (90%-100%). CONCLUSION: The audit proved productive in identifying major causes of irregularities in documentation and in making valuable suggestions for their rectification.