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Objective: To determine the prognostic significance of bone marrow fibrosis grade in predicting the outcome of myeloproliferative neoplasms. Study Design: Prospective longitudinal study. Duration and Place of Study: Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Jun 2021 to May 2022. Methodology: A total of 114 patients with myeloproliferative neoplasms were included. Under aseptic conditions, a bone marrow aspiration and a Trephine biopsy were obtained. Following processing, the samples underwent staining with Hemotoxylin and Eosin and Reticulin. The WHO bone marrow fibrosis grading system was used to grade the fibrosis. Clinical findings and haematological parameters documented at initial diagnosis were compared with one-year interval follow-up counts. Results: Out of a total 114, 72(63.2%) were male and 42(36.8%) were female. Generalised weakness and pallor were documented in 51(44.7%) and 27(23.7%), respectively. While splenomegaly and/or hepatomegaly were detected in 61(53.5%) and 27(23.7%), respectively, 16(14.9%) transformed into other MPNs and 3(2.6%) into acute leukemia. People who had higher levels of MF-2 and MF-3 reticulin fibrosis had the worst prognosis when it came to peripheral blood cytopenias, disease progression, and transformation. Conclusion: Myeloproliferative neoplasms are very different from one another in terms of how they look and behave. As the grade of fibrosis rises, there is a high chance that the disease will progress to myelofibrosis or change into acute leukaemia, both of which are very bad for overall survival.

Objective: To compare the results of High-Performance Liquid Chromatography and Capillary Electrophoresis in the screening of haemoglobinopathies. Study Design: Cross-sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from May 2020 to Nov 2020. Methodology: Ninety(90) newly diagnosed patients with haemoglobinopathies were included. Patients with a history of recent blood transfusion (

Objective: To examine the clinical severity and infarct volume of acute ischemic stroke (AIS) compared to control subjects by comparing the mean platelet volume/platelet count (MPV/PC) ratio. Study Design: Cross-sectional (validation) study. Place and Duration of Study: Acute Stroke Unit, Pak Emirates Military Hospital (PEMH), Rawalpindi, from Jul and Dec 2020. Methodology: This study included 50 consecutive AIS patients (Group-1) and 50 healthy subjects (Group-2). An automated haemanalyser determined MPV and MPV/PC ratios. In addition, a modified Rankin Scale for the severity of AIS and ABC/2 method for infarct volume was used. Results: This study comprised 69 males and 31 females. Statistical analysis showed that MPV and MPV/PC have significantly different mean values between Group-1 and Group-2 at a p-value of 0.001. In addition, according to the Rankin scale, a significant difference of means (p-value

Objective: To determine the frequency and patterns of bone marrow infiltration in non-Hodgkin lymphoma patients. Method: The cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from April to October 2021, and comprised patients of either gender aged 20-80 years who had been diagnosed with non-Hodgkin lymphoma. Following assessment and as per standard protocol, bone marrow aspirate and trephine biopsy were done on all patients from the posterior superior iliac spine, and slides were prepared and assessed. Data was analysed using SPSS 25. Results: Of the 100 patients, 67(67%) were males and 33(33%) were females. The overall mean age was 54.99+12 years, and mean duration of symptoms was 11.7±1.5 months. Diffuse large B-cell lymphoma was the commonest type 43(43%). Infiltration of marrow occurred in 38(38%) patients, with 12(12%) of them being cases of mantle cell lymphoma. The commonest infiltration pattern was diffuse in 17(17%) cases, followed by focal/nodular in 10(10%). Conclusion: Diffuse large B-cell lymphoma was found to be the commonest type of non-Hodgkin lymphoma, and marrow infiltration occurred most frequently in cases of mantle cell lymphoma. Key Words: Bone marrow, Infiltration, Non-Hodgkin lymphoma.

Objective: To compare the marginal integrity of Class-I amalgam and bonded amalgam restorations in maxillary and mandibular molars at seven days, three, six and twelve-months intervals. Study Design: Comparative prospective study. Place and Duration of Study: Department of Operative Dentistry, Armed Forces Institute of Dentistry, Rawalpindi Pakistan,from Jul 2017 to Jul 2018. Methodology: A total number of 114 patients of either gender with an age range of 14-45 years having Class-I cavities in first and second maxillary and mandibular molars on both sides were equally distributed in two groups. Group-A received conventional Amalgam, and Group-B received bonded amalgam restorations. All the fillings were placed and carved using routine instruments used for amalgam restorations, and the restorations were polished after 24 hours. The patients were initially evaluated for marginal ditching around restorations with the help of a dental mirror and explorer at seven days,followed by inspection at 3, 6 and 12 months. Results: Of the 114 participants, all showed excellent marginal integrity at seven-days intervals regardless of the restorative material used. However, marginal integrity deteriorated swiftly with time among those 57(50%) participants who acquired conventional Amalgam. Marginal integrity at 3, 6 and 12-months period was 51(89.5%), 35(61.4%) and 17(29.8%), respectively.Bonded amalgam restorations performed superiorly with 100%, 56(98.2%) and 43(75.4%) successful marginal integrity at 3, 6 and 12-months, respectively. Conclusion: Bonded amalgams can be a better substitute than non-bonded amalgam restorations with superior longevity in marginal integrity. Keywords: Amalgam, Bonded amalgam, Marginal integrity, Micro-leakage, Marginal deterioration, Restoration longevity.

Objective: To evaluate the diagnostic significance of reticulocyte maturity indices in iron deficiency anaemia. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi, from Sep 2019 to Jun 2020. Methodology: A total of 340 children, ages between 1 and 5 years of either gender, were divided into two groups based on haemoglobin and ferritin level. Group A comprised of 203 children with haemoglobin >11 g/dL andferritin level >7 ng/ mL. Group B comprised of 137 children with haemoglobin 0.05) and significant differences were noted in terms of low, medium & high fluorescence ratios in both groups (p

Objective: To determine the magnitude and classification of cases of ambiguous genitalia presenting to our setup. Study Design: Cross-sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Aug 2018 to Feb 2019. Methodology: All the patients with ambiguous genitalia referred for cytogenetic analysis, were included in the study. The patients were subjected to a detailed history and physical examination. The record of radiological investigations was were obtained. Cytogenetic analysis was performed using the conventional G-banding technique. Hormonal testing included 17- hydroxyprogesterone (17-OHP) levels was also performed. Results: Fifty-one cases of ambiguous genitalia were studied. The median age was 15 months. Thirty-three patients (64.7%) had a 46XY karyotype, 17 (33.3%) had a 46XX karyotype while 1 (1.9%) had 45X/46, XY mosaic karyotype. Thirty patients (58.8%) were products of consanguineous marriage. Congenital adrenal hyperplasia was diagnosed in 12 cases (70.5%) of 46 XX karyotype and in 3 cases (9%) of 46XY karyotype. Conclusion: Ambiguous genitalia, currently categorized as disorders of sex development, are not uncommon in our populartion. Increased awareness and early diagnosis are crucial to prevent life threatening complications of congenital adrenal hyperplasia, to determine sex of rearing, and to counsel the parents or patients.

Objectives: To determine the prevalence, clinical manifestations and laboratory findings of Pakistani Glanzmann Thrombasthenia patients and to assess the treatment received by these patients. Materials and Method: This cross-sectional study examined 2542 patients over a period of 10 years who were referred with a suspicion of a platelet function disorder. Clinical details, laboratory parameters and treatment received were noted. Results: Glanzmann thrombasthenia constituted 80.15% of the platelet function disorders. Of these, males were 112 (34.25%) while females were 215 (65.75%). Median age at diagnosis was 9 yrs 2 months (range of 8 months to 26 years) and at first presentation was 4 years 3 months (range of 3 months to 12 years). Consanguinity was observed in 85.32% of the patients. Common clinical features were easy bruisability (85%), epistaxis (78.6%) and gum bleed (56.3%). Mean haemoglobin was 8.6+2.46 g/dl and mean bleeding time was > 15 min. All patients showed no aggregation with collagen, ADP and epinephrine and a normal response to ristocetin on light transmission aggregometry. Conclusion: We have reported a large number of patients of Glanzmann thrombasthenia, a disorder which is not so rare in our population, emphasizing the importance of early diagnosis and appropriate management.

Objective: To determine the frequency of Ten-Eleven-Translocation-2 (TET2) gene mutation in Myeloproliferative Neoplasms (MPNs) and to generate a local data for evaluation of disease behavior in ten-eleven-translocation-2 positive and negative Patients. Study Design: Cross-sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from Apr 2017 to Apr 2018. Methodology: A total of 50 adult myeloproliferative neoplasms patients (>18 years of age), diagnosed according to WHO 2016 diagnostic criteria for myeloproliferative neoplasms were included in the study. Mutational screening for ten-eleven-translocation-2 gene was performed by flourescent in situ hybridization technique using Meta Systems XL-TET2 Deletion probe REF D-5038- 100-OG, LOT 18181, manufactured by Meta-Systems GmbH, Robert-Bosch - Germany. Bone marrow samples were used for Fluorescence in situ hybridization analysis. A total of 500 interphases were examined in each of the specimen. Data was entered and analyzed using SPSS-22. Distinctive demographic, haematological and molecular results are summarized by descriptive statistics. Results: Total 50 cases of myeloproliferative neoplasms (14 CML, 10 PV, 12 essential thrombocythemia (ET) and 14 primary myelofibrosis (PMF) were analyzed. On fluorescent in situ hybridization studies, ten-eleven-translocation-2 mutation was detected in 8 (16%) patients. The mutational frequency among different myeloproliferative neoplasm entities was 4 (28.5%) in chronic myeloid leukemia (CML), 2 (20%) in Polycythemia Vera (PV), 1 (8.3%) in essential thrombocythemia and 1 (7.1%) in primary myelofibrosis respectively. Among the 15 cases, 36 (72%) patients were positive for JAK2V617F mutation while 14 (28%) were positive for BCR-ABL1 mutation. Ten-eleven-translocation-2 mutation observed...................

Objective: To detect ADAMTS-13 deficiency in sepsis patients and its effect on in-hospital morbidity and mortality in adult patients of sepsis. Study Design: Cross sectional study. Place and Duration of Study: Armed Forces Institute of Pathology (AFIP) and Combined Military Hospital (CMH) Rawalpindi, from Apr 2017 to Apr 2018. Methodology: All indoor patients admitted at Combined Military Hospital Rawalpindi and diagnosed as suffering from sepsis at Armed Forces Institute of Pathology according to the guidelines of the Critical Care Society of Medicine Consensus Conference Committee. Forty sepsis patients were recruited for the study. Two groups were formed on the basis of ADAMTS-13 antigen levels, non-deficient and deficient. Basic haematological and clinical parameters were recorded. Levels of ADAMTS-13 antigen were analyzed by using Technozyme kit byenzyme-linked immunosorbent assay (ELISA) and level less than 0.40 IU/ml was taken deficient as defined by manufacturer. Comparison was done between ADAMTS-13 deficient and non-deficient group with regard to clinical and haematological characteristics, ICU stay, hospital admission days and in-hospital mortality. Healthy controls of same age and gender were also observed for ADAMTS-13 antigen level. Results: Among total 40 sepsis patients, thirty two (80%) were males and eight (20%) were females with a mean age of 61 ± 15 years (range: 30-85 years). ADAMTS-13 deficiency (150 x 109/l, mean hospital stay was 10.2 ± 3.6 days and in-hospital mortality was in one (8.3%) patient respectively. ADAMTS-13 antigen level was found sufficient in healthy controls. Conclusion: Majority of the sepsis patients were found ADAMTS-13 deficient. Deficiency exhibit long term hospital admission, thrombocytopenia and increase in hospital mortality. ADAMTS-13 deficiency might play a role in sepsis induced thrombocytopenia and in hospital mortality. More studies are recommended on the subject with larger sample size to evaluate its role in sepsis

Objective: To determine the frequency of clinical features and cytogenetic abnormalities in patients of down syndrome and correlation of cytogenetic abnormalities with clinical features. Study Design: Cross sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from Feb 2017 to Feb 2018. Methodology: Total 163 patients with clinical suspicion of Down syndrome were selected by non-probability convenient sampling and diagnosis was confirmed by conventional cytogenetic analysis using Giemsa trypsin banding technique. Clinical features were assessed and frequency of different cytogenetic abnormalities were noted. Results: Out of total 163 patients, 96 (59%) were male and 67 (41%) were female. Median age of the patients was 11 months. Trisomy 21 was detected in 158 (96.9%), Robertsonian translocation in 4 (2.4%) and mosaicism in 01 (0.6%) patient. The predominant clinical features observed were slaunted with eyes, epicanthic folds, depressed nasal bridge and protruding tongue. Conclusion: Trisomy 21 is the most common cytogenetic abnormality observed in patients of down syndrome.

Objective: To determine the association of various haematological parameters with different species of malarial parasites. Study Design: Cross sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology (AFIP) Rawalpindi, from Sep 2018 to Sep 2019. Methodology: Thick and thin blood smears stained with Leishman stain were examined for the presence of malarial parasites under light microscopy. After the organism was detected by examination of thick blood films, identification of malarial parasite species was carried out using thin blood smears. Basic haematological parameters were evaluated using automated analyzer (Sysmex KX-21). Results: Plasmodium falciparum was identified as the causative organism in 100 (38%) of the malaria cases whereas 100 (62%) of the cases had Plasmodium vivax. A trend towards decreased Hemoglobin, Red Blood Cells, platelet, lymphocyte and eosinophil count was observed in Plasmodium falciparum group as compared to Plasmodium vivax group (p=0.001), whereas, the former showed an increase count of white blood cell, neutrophil and monocyte (p=0.001). Conclusion: Hematological parameters like Hemoglobin, RBC count, WBC count and Platelet count vary significantly with the type of plasmodium species causing malarial infection.

Objective: To determine diagnostic importance of immature granulocyte percentage in patients with infection in early stages in hospital settings. Study Design: Cross sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology (AFIP) Rawalpindi, from Oct 2017 to Oct 2018. Methodology: One hundred patients were inducted who fulfilled the criteria of systemic inflammatory response syndrome (SIRS) and sepsis. Four ml blood from the patients was taken via venepuncture or indwelling catheter in an EDTA tube, White blood cell count (WBC) and immature granulocyte (IG) percentage was analyzed by using Sysmex XN3000 haematology analyzer. Results: The diagnostic accuracy of immature granulocyte percentage in patients with sepsis as compared to white blood cell count was recorded as 67.40%, 82.35%, 94%, 70% and 87.14% for sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate respectively. Conclusion: Immature granulocyte count at 1.0% is a reliable and effective predictor of infection, validating its addition into the diagnostic protocols in the intensive care unit settings

Objective: Detection of MPL and JAK2 exon12 gene mutation in myeloproliferative neoplasms (MPN) in JAK2V617F negative Myeloproliferative Neoplasms. Study Design: Cross sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, from Jun 2017 to Jun 2018. Methodology: Total of 90 newly diagnosed JAK2V617F negative myeloproliferative neoplasms patients were enrolled in the study. Clinico-haematologic features were noted. DNA was extracted from bone marrow samples. Molecular analysis was performed for MPL and JAk2 exon 12 gene by Sanger Sequencing. Results were analyzed by using Genetic Analyzer HITACHI 3130. Results: Out of these 106 patients 86 were males and 20 were females. On mutation analysis of 16 (15%) patients were found positive for JAK2V617F while 90 (84.9%) were JAK2V617F negative. We then studied these 90 JAK2V617F negative myeloproliferative neoplasms patients for other mutations such as MPL gene and JAK2 exon12. On the basis of clinical features, physical examination, Blood complete picture, bone marrow aspiration and trephine biopsy findings 48 (53.3%) were diagnosed as PV, 22 (24.4%) as ET, 20 (22.2%) as PMF. JAK2 exon12 mutation analysis was screened in 48 (54%) patients and remaining 42 (46%) patients, out of which 22 (24.4%) ET patients and 20 (22.2%) were diagnosed as PMF analyzed for MPL gene mutations. Conclusion: We have found that none of these patients carry JAK2 exon12 and MPL gene mutation.

Objective: To detect the calreticulin gene mutation in myeloproliferative neoplasms and its clinicohaematological correlation. Study Design: Cross sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, from Jun 2017 to Jun 2018. Methodology: A cross sectional study was conducted at Department of Haematology, Armed Forces Institute of Pathology from June 2017 to June 2018. A total of 48 newly diagnosed JAK2V617F patients with negative myeloproliferative neoplasma were enrolled in the study. Clinico-haematologic features were noted. DNA was extracted from bone marrow samples. Molecular analysis was performed for Calreticulin gene by Sanger Sequencing. Results were analysed by using Genetic Analyser HITACHI 3130. Results: Of 48 newly diagnosed JAK2V617F negative myeloproliferative neoplasms patients, 38 were male and 10 were females with M:F ratio of 3.8:1. Mean age was 43.5 years (standard deviation ± 15). 9 (18.8%) were diagnosed as polycythemia vera, 21 (43.8%) as Essential thrombocythemia and 18 (37.5%) as having Primary myelofibrosis. CALR mutation was detected in four (8%) of myeloproliferative neoplasms cases. Out of four CALR positive cases, three were diagnosed to have Primary myelofibrosis while only one had a diagnosis of Essential thrombocythemia. Conclusion: We conclude that CALR mutation was an important molecular marker in JAK2V617F negative patients. Primary myelofibrosis shares a high rate of CALR mutation as compared to polycythemia vera and essential thrombocythemia.

Objective: To determine the frequency of NRAS and KRAS mutations in newly diagnosed acute myeloid leukemia patients and correlation with their clinicopathological parameters along with prognostic impact. Study Design: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Haematology, Rawalpindi, from Mar 2017 to Aug 2017. Methodology: A total of 70 acute myeloid leukemia patients were recruited in this study. Each patient was assessed by blood complete picture, bone marrow examination (aspiration and trephine biopsy) and cytochemical staining by sudan black. Flow cytometry was done for immunophenotyping of each patient. Mutation analysis of NRAS and KRAS of exon 1 and exon 2 were performed on Peripheral /bone marrow sample by PCR followed by purification and analysis of gene mutations by Sanger sequencing. Results: Of the seventy patients, five percent were positive for NRAS mutation while no KRAS Mutation was detected in our study. Mean age of our patients was 31.5 with a SD of ± 18.9. Patients presented very high levels of WBC with an average of 83.7 ± 107 years. Regarding clinicopathological parameters all NRAS mutation positive patients and NRAS mutation negative patients there was prominent splenomegaly as well as bleeding from gums but the percentage of splenomegaly and bleeding gums was much greater in NRAS mutation patients as compared to NRAS negative patients. Conclusion: There were limited studies regarding NRAS and KRAS mutations in Pakistan so larger sample size is required to determine frequency along with its prognostic impact.

Objective: To determine the frequency and clinical features of inherited platelet function disorders diagnosed at Armed Forces Institute of Pathology. Study Design: Cross sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from Feb 2017 to Aug 2017. Methodology: All patients with history of bleeding from multiple sites or requiring transfusion were selected. Initial tests performed included complete blood counts, peripheral film and bleeding time. When bleeding time was prolonged, prothrombin time and activated partial thromboplastin time were done to rule out Von Willebrand disease and Fibrinogen deficiency. Results: A total of 172 patients were analyzed during study period.Inherited platelet function disorders were diagnosed in 24 (13.9%) patients, 111 (64.5%) patients had inherited coagulopathies. 3 (1.8%) patients showed inconclusive results while no inherited bleeding disorder was detected in 34 (19.8%) patients. Among platelet function disorders, Glanzmann thrombasthenia was diagnosed in 12 (50%) patients, Bernard soulier syndrome (BSS) in 11 (45.8%) patients and Storage pool disorder in 1 (4.1%) patient. Conclusion: Glanzmann thrombasthenia was the most commonest inherited platelet function disorders. Diagnosis requires platelet aggregation studies.

Objective: To determine the frequency of hyperdiploidy in childhood acute lymphoblastic leukemia (ALL) and its association with remission status after induction therapy. Study Design: Observational study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology (AFIP) and Pediatric Oncology Department Combined Military Hospital (CMH) Rawalpindi, from Apr 2017 to Apr 2018. Patients and Methods: All diagnosed cases of ALL between 1-12 years of age were selected by convenient nonprobability sampling. All other cases of leukemias including patients of acute undifferentiated leukaemia, acute myeloid leukaemia and patients of ALL who did not yield successful cytogenetic culture or those who died during the induction therapy were excluded from the study. Diagnosis of ALL was done on the basis of morphology, cytochemistry, immunophenotyping and cytogenetics. Cytogenetic analysis was done by using conventional Giemsa banding. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN). On the basis of cytogenetics two groups were made one with hyperdiploidy and another without hyperdiploidy. Hyperdiploidy was defined as chromosomes >46. All patients of childhood ALL were treated with ‘UK ALL 2011’ protocol and their remission status was assessed after 1 month of induction therapy by bone marrow examination. Remission status of 2 groups of ALL with and without hyperdiploidy were compared by using chi square test Results: Out of total 80 patients of ALL, 62 (77.5%) yielding successful cytogenetic culture were included in the study. Mean age at diagnosis was 5.6 ± 2.9 years and male to female ratio was 2.4:1. Analytical immunocytometry revealed 58 (93.5%) as B-ALL while 4 (6.55%) were T-ALL. Hyperdiploidy was detected in 19 (30.6%) and t (9:22) (q34:31) in 1 (1.6%). In all other patients no cytogenetic abnormality was detected. Out of 62 patients, Overall complete haematological remission (CHR) was achieved in 47 (75.8%). Out of 19, patients with hyperdiploidy 18 (94.7%) achieved CHR, as compared to other group without hyperdiploidy in which 29 (67.4%) achieved CHR. The difference was statistically significant (p-value 0.021). Conclusion: Remission rate was 94.7% in patients of childhood ALL with hyperdiploidy. Patients with hyperdiploidy achieve higher CHR rate as compared to patients without hyperdiploidy.

Objective: Myelodysplastic syndrome (MDS) is a group of bone marrow diseases that not only have variable morphological presentation and heterogeneous clinical courses but also have a wide range of cytogenetic abnormalities. Clinicohematological parameters have a significant role in diagnosis and along with identification of cytogenetic abnormalities are important for prognostic scoring and risk stratification of patients to plan management and make treatment decisions. This study aimed to determine the clinicohematological characteristics, cytogenetic abnormalities, and risk stratification of newly diagnosed de novo MDS patients. Materials and Methods: This cross-sectional study was conducted in the Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi, from January 2013 to January 2017. Patients were diagnosed on the basis of World Health Organization criteria for MDS, clinicohematological parameters were noted, and cytogenetic analysis was performed. Risk stratification was done using the Revised International Prognostic Scoring System. Results: A total of 178 cases of MDS were analyzed, including 119 males (66.9%) and 59 females (33.1%). The median age was 58 years. The most common presenting feature was anemia in 162 (91%) of the patients. MDS with multilineage dysplasia was the most common diagnosis, seen in 103 (57.9%) patients. A normal karyotype was seen in 95 (53.4%), while 83 (46.6%) showed clonal karyotypic abnormalities at diagnosis. Of these, the common abnormalities found were trisomy 8, complex karyotype, and del 5q. Risk stratification revealed low-risk disease in 73 (41%) patients. Conclusion: Cytogenetic analysis showed the normal karyotype to be the most common while risk stratification revealed a predominance of low-risk disease at the time of presentation.

Background: Glucose 6 phosphate dehydrogenase (G6PD) deficiency is an inherited enzymopathy that is associated with hemolytic anemia. Objective: To evaluate the diagnostic accuracy of G6PD biosensor analyzer used at study site for the quantitative measurement of total G6PD enzyme activity in whole blood using Trinity biotech quantitative assay as gold standard. Study type, settings and duration: This cross-sectional study was conducted in the Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi from April 2018 to September 2018. Methodology: One hundred and thirty seven patients having unexplained hemolytic anemia and suspected to have G6PD deficiency were included in the study using non-probability consecutive sampling technique. Detailed history, including drug history and transfusion history was taken and a complete physical examination was done. Each eligible patient was analyzed by G6PD biosensor analyzer for the quantitative measurement of total G6PD enzyme activity while Trinity biotech quantitative assay was used as gold standard. Results: A total of 137 individuals with unexplained haemolytic anaemia suspected of having G6PD deficiency were enrolled in our study. On statistical analysis, G6PD Biosensor Analyzer was found to be 96.08% (95% CI: 86.54-99.52%) sensitive and 89.53% (95% CI:81.06-95.10%) specific as compared to our gold standard method Trinity Biotech. The positive likelihood ratio was 9.18 (95% CI:4.94-17.08) while the negative likelihood ratio was 0.04 (95% CI:0.01-0.17) with a positive predictive value and a negative predictive value of 84.48% (95% CI: 74.53-91.01%) and 97.47% (95% CI:90.81-99.34%), respectively. The accuracy of our test determined to be 91.97% (95% CI:86.09-95.92%). Conclusion: G6PD Biosensor Analyzer is a rapid and cost-effective method for diagnosis of G6PD deficiency.

Objective: To determine the frequency of additional chromosomal abnormalities in Philadelphia chromosome positive Chronic Myeloid Leukemia (CML) by conventional cytogenetic analysis., Methods: This descriptive cross sectional study was conducted at Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January 2012 to December 2016. A total number of 528 newly diagnosed CML patients were included in the study. The subjects were tested for the presence of Philadelphia (Ph) chromosome and other additional cytogenetic abnormalities by conventional cytogenetic analysis interpreted according to International System of Human Cytogenetic Nomenclature (ISCN) criteria. Molecular analysis for BCR-ABL was also performed for each patient. The additional cytogenetic abnormalities were then classified into major route abnormalities and minor route abnormalities., Results: Out of the 528 newly diagnosed CML patients, 378 (71.6%) were males and 150 (28.4%) were females. The age of patients ranged between 18 to 74 years. Four hundred and ninety-eight (94.3%) patients showed Philadelphia chromosome on karyotyping while 30 (5.7%) were negative for the Philadelphia chromosome. On analysis of these 498 Philadelphia positive patients, additional cytogenetic aberrations were detected in 26 (4.9%) patients. Of these, 7 (1.3%) had major route abnormalities while 19 (3.6%) had minor route abnormalities., Conclusion: The frequency of additional chromosomal abnormalities in our study were not in accordance with previous local and international studies., (Copyright: © Pakistan Journal of Medical Sciences.)

Background & Objectives: Molecular genetic abnormalities have a significant role not only in diagnosis but also in determining the clinical course and prognosis. Nucleophosmin-1 (NPM-1) is associated with good prognosis while internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) confers a poor prognosis. Knowledge of the status of these mutations in AML patients not only guides treatment decisions but also helps in predicting response to frontline induction and consolidation chemotherapy as well as the risk of relapse and overall survival. Our objectives were to determine the prevalence, clinico-haematological features and immunophenotypic characteristics of AML patients with FLT3-ITD and NPM1 mutation and to evaluate the response to induction therapy (CR) and disease free survival (DFS) in this cohort of patients., Methods: Patients diagnosed as AML from March 2015 to March 2017 at Armed Forces Institute of Pathology Rawalpindi were included in the study. Clinico-haematologic and immunophenotypic parameters were noted and molecular analysis for FLT3-ITD and NPM1 mutation was performed. Any correlation with cytogenetics or other molecular markers was also studied. Response to standard induction chemotherapy and disease-free survival were assessed., Results: A total of 108 cases of AML were analyzed. Median age was 35 years and 64.8% were males. The median age of the study group was 35 years. Of these, 70 (64.8%) were males while 38 (35.2%) were females. Twenty-nine (26.9%) patients were NPM1 positive, twelve (11.1%) were FLT3-ITD positive while eight (7.4%) were positive for both mutations. Patients with NPM1 mutations were associated with female gender, higher haemoglobin level and platelet counts while those with FLT3-ITD mutations were predominantly seen in male patients and had significantly higher WBC counts, bone marrow blasts, biopsy cellularity and LDH levels. CR rates of NPM1 positive, FLT3-ITD positive and both mutation positive groups were 72%, 60% and 71%, respectively. The median disease-free survival was significantly lower in the FLT3-ITD positive group (7.1 months) as compared to the NPM1 positive group (16.1 months). The median disease-free survival was 12 months and 11.9 months in the NPM1 positive/FLT3-ITD positive and the NPM1 negative/FLT3-ITD negative groups, respectively., Conclusion: AML patients harbouring NPM1 and FLT3-ITD mutations have distinct clinical and haematological characteristics. NPM1 mutations have a better CR and DFS as compared to FLT3-ITD group.