Background: Chronic myeloid leukemia is a form of chronic myeloproliferative disorder described by the presence of specific haematological and cytogenetic markers. It is a very common blood neoplasm that usually requires a basic clinical history, review, and regular blood examination to diagnose. If detected early, it has a high cure rate. Objective: To assess the clinical and laboratory features of chronic phase chronic myeloid leukemia patients. Study Design: Cross-sectional study Place and Duration of Study: Department of Haematology, Liaquat National Hospital and Medical College, Karachi 1st January 2012 to 31st December 2016 Methodology: One hundred and forty four chronic myeloid leukemia patients visited the study site during this period, of which 132 were in the chronic phase and met the eligibility criteria. The patient’s data, including age, gender, clinical and laboratory parameters were obtained. Results: One hundred and fifteen (87.1%) had constitutional symptoms, predominantly fatigue and abdominal discomfort. The clinical presentation displayed splenomegaly among 89.3% of patients with a mean spleen span of 18.9±3.7 cm and massive splenomegaly in 32.5% of patients. Haematological presentation at baseline showed that the mean haemoglobin level of the enrolled patients was 9.6±2.0g/dl, TLC was 167.6±123.3x109/l, and platelet count was 398.7±281.9x109/l. Furthermore, 19.4%of patients were anaemic, and hyperleukocytosis was detected in 24.2%. High LDH, hyperuricemia and elevated serum creatinine were present in 38.6%, 40.9%, and 14.3%, respectively. Conclusion: Unlike the western countries, chronic myeloid leukemiais more prevalent in a very young age group in Pakistan. The chronic myeloid leukemia patients displayed variable clinical and haematological presentation. Constitutional symptoms and splenomegaly were consistent features among the majority of patients. Keywords: Chronic myeloid leukemia, Clinico-hematological, Pakistan

BACKGROUND:Chronic lymphoid leukemia (CLL) is not an uncommon hematological malignancy which primarily affects elderly individuals. It is more common in developed world than in developing countries. The rational of this study was to determine the clinico-hematological profile in Pakistan.MATERIALS AND METHODS:In this prospective cross sectional study, sixty patients with CLL were enrolled from January 2011 to June 2013. Data were analyzed with SPSS version 21.RESULTS:The mean age was 59.0±9.2 years (range 40-82) and the male to female ratio was 2.1:1. Peak age group was 60-70 years (38.3%) and 18.3% were under 50 years old. Major complaints were weakness (51.7%), fever (18.3%) and abdominal discomfort (13.3%). Main clinical findings were splenomegaly (46.6%), lymphadenopathy (36.6%) and pallor (26.7%). Some 16.7% were diagnosed incidentally. The mean hemoglobin was 10.8±2.4 g/dl, with a total leukocyte count of 91.5±87.8x10(9)/l and platelets 197.8±103.2x10(9)/l. Anemia and thrombocytopenia were seen in 26.7% and 21.7% of cases, respectively. High LDH and hyperuricemia were detected in 15% each and elevated serum creatinine was seen in 11.6%. According to Rai staging 11.6% were in stage 0, 13.3% stage 1, 26.7% each for stage II and stage III while 21.7% patients were in stage IV.CONCLUSIONS:CLL in our patients in Pakistan, unlike in the West, is seen in a relatively young population with male predominance. Primarily disease is of B- cell origin and about 2/3 of the patients present at advanced stage.

UNLABELLED:β-thalassemia is the most common genetic disorder worldwide with an increased prevalence around the Mediterranean, Indian subcontinent and in South-East Asia. Various siderotic and non-siderotic complications significantly impact the quality of life. Thalassemic patients are also at risk of zinc deficiency due to diverse causes including desferrioxamine chelation. This study sought to investigate the prevalence of zinc deficiency in beta thalassemia major patients on desferrioxamine for iron chelation.STUDY DESIGN:This was a descriptive, prospective, cross-sectional study over a 6-month period. 63 cases of beta thalassemia major within the age group of 5-15 years on desferrioxamine for at least 1 year, were included. Basic patient demographics such as age, gender and duration of disease were recorded. Serum zinc levels were determined by atomic absorption spectrophotometry.RESULTS:The mean age of patients was 10.84±3.47 (5 to 15) years. There were 35 (55.6%) males and 28(44.4%) females. The prevalence of zinc deficiency (zinc levels>50 µg/dl) was 22.2%. Proportions of deficiency were higher in males with a duration of disease beyond 10 years.CONCLUSIONS:Zinc deficiency is not uncommon in beta thalassemia patients on desferrioxamine. We suggest that zinc levels be regularly monitored in these patients.

BACKGROUND:Chronic lymphoid leukemia (CLL) is the most frequent type of adult leukemia. The Rai and Binet staging systems have been well recognized as standards for assessing the treatment requirements and overall survival in CLL patients. However, there is a need to seek newer prognostic markers to identify stable or progressive forms of CLL that will facilitate risk-adapted treatment strategies. Currently a molecular biomarker ZAP-70 has attracted interest as providing prognostic information in CLL patients. OBJECTIVE:To determine the frequency of ZAP-70 positivity in B-CLL patients at disease presentation. MATERIALS AND METHODS:From January 2011 to September 2014, 89 patients were diagnosed to have chronic lymphoid leukemia. Complete blood count was done on an automated analyzer (Cell Dyne, Abott Architect, USA), while immunophenotyping was conducted for each patient to establish the diagnosis of the disease. ZAP-70 expression was evaluated by flow cytometry. Data were compiled and analyzed by SPSS version 21. RESULTS:Out of the total of 89 B-CLL patients, 62 (69.7%) were male and 27 (30.3%) were females with a male to female ratio of 2:1. The mean age was 57.5±12.1 years. The frequency of ZAP-70 positivity in our B-CLL patients was found to be 13.5%. ZAP- 70 positivity was significantly correlated with stage III disease and high absolute lymphocytic count (P<0.05). No correlation of ZAP-70 could be established with age and gender (p>0.05). CONCLUSIONS:The frequency of ZAP-70 in our patients appears low. It is approximately half that in international data. We would recommend to screen all the newly diagnosed patients with CLL for ZAP-70 protein expression for risk stratification, family counseling and to predict overall survival.

BACKGROUND:Serum 25-hydroxyvitamin D insufficiency is very common in Pakistan and is often related to inferior prognosis in some cancers but limited data exist for hematopoietic malignancies. This study was conducted to determine the vitamin D insufficiency in B-chronic lymphoid leukemia (CLL) cases at the time of presentation and its possible correlation with clinical staging, hematological parameters and biochemical markers.MATERIALS AND METHODS:This descriptive cross sectional study was carried at Liaquat National Hospital from January 2011 to June 2013. Sixty patients with B-chronic lymphoid leukemia were enrolled. Complete blood count, vitamin D levels, serum urea, creatinine, uric acid and LDH levels were assessed. Data were compiled and analyzed using SPSS version 21.RESULTS:Out of 60 patients, 42 (70%) were male and 18 (30%) were female. Mean age was 59.0±9.2 years. The frequency of vitamin D insufficiency was found to be 56.7%. Overall insufficiency was more frequently seen in male gender (40%). Vitamin D insufficiency demonstrated a positive association with low lactate dehydrogenase levels (P=0.005). No links were established with age, clinical stage, hematological and other biochemical markers.CONCLUSIONS:Vitamin D insufficiency is high compared with Western studies. Whether normalization of vitamin D insufficiency in deficient B-CLL patients could improve the clinical outcome or delay disease progression will require further studies.

BACKGROUND:Chronic lymphoid leukemia (CLL) is a malignant hematopoietic disorder, the most common of all adult leukemias with a distinctive immunophenotype. It is well established that CLL patients can have autoimmune complications, amongst them autoimmune hemolytic anemia as the most frequent. This study was carried out to determine the frequency of direct Coombs Test positivity in CLL patients and its possible correlation with Rai staging, hematological parameters and biochemical markers.MATERIALS AND METHODS:This descriptive cross sectional study was carried at Liaquat National Hospital from January 2011 to June 2013. Sixty untreated patients with B- chronic lymphoid leukemia were enrolled. Complete blood count, direct Coombs test, serum urea, creatinine, uric acid and LDH levels were determined. Data were compiled and analyzed using SPSS version 21.RESULTS:Out of 60 patients, 42(70%) were males and 18(30%) were females. Mean age was 59±9.2 years. Male to female ratio was 2.1: 1. The frequency of direct antiglobulin test (DAT) positivity was found to be 23.3%. The monospecific IgG was positive in 11 patients (18.3%); C3d positivity was evident in 1 patient (1.6%) and 2 patients (3.3%) had dual IgG and C3d positivity. The mean hemoglobin was 10.8±2.4gm/ dl. Significantly low mean hemoglobin of 8.3±3.0 gm/dl was seen in Coombs positive patients compared with negative patients having a mean hemoglobin level of 11.7±1.6 gm/dl (P<0.001). DAT positivity also demonstrated a positive association with advanced Rai stage III disease (P<0.01). No associations were noted with age, gender and biochemical markers.CONCLUSIONS:Direct Coombs test positivity in CLL in our patients, unlike in Western studies, appears relatively high, indicating significant autoimmune hemolytic anemia and advanced Rai stage in our setting. DAT positivity can be considered as a surrogative marker for advanced clinical disease.

β-thalassemia is an autosomal hemoglobinopathy with inconsistent universal distribution. Among patients with thalassemia diverse non-siderotic complications distinctly influence the attribute of life, including zinc deficiency due to varied etiologies. The objective of the present study was to determine zinc levels in patients with β-thalassemia major and its correlation with maternal characteristics, hematological parameters, liver enzymes, serum ferritin, duration of chelation and number of transfusions among Pakistani patients. Patients and Methods: Seventy-five β-thalassemia major patients on desferrioxamine were enrolled from August 2010 to July 2012. CBC, liver function tests, serum ferritin, HbsAg and Anti-HCV were evaluated. Zinc level was measured using atomic absorption spectrophotometer. Results: The mean age of patients was 10.57±3.5 years. Forty one (54.7%) and 34(45.3%) patients were males and females respectively. The frequency of zinc deficiency was 24%. We established positive correlation between zinc deficiency and longer duration of chelation (P<0.001) and also with anemia (P<0.001). No correlation could be established with other parameters. Conclusion: Our study revealed that hypozincemia is not unusual in β-thalassemic patients on desferrioxamine. We propose zinc levels should be regularly measured primarily in anemic patients with long duration of chelation.

Introduction: Serum fasting lipid profile has been studied in various clinical spectrum of β-thalassemia syndrome. Premature cardiac impairment in thalassemia major (TM) appears primarily due to iron accumulation and oxidative injury; however it might be a sequel of abnormal lipoprotein concentrations. Recent studies revealed impaired lipid profile and atherosclerosis in TM as an emerging complication in patients with prolonged survival. As these children are at risk of premature atherosclerosis, sub clinical atherosclerosis probably begins early in their life might evolve into coronary heart diseases in later life. The rational of this prospective cross sectional study is to analyze the serum fasting lipid profile in cardiovascular disease free thalassemia major patients and to establish any correlation with age, gender, hematological parameters, liver enzymes and serum ferritin. Method: The study group comprises of thirty six patients with β-thalassemia major, who were enrolled from March 2012 to March 2014. Fasting blood lipid levels (total lipid, cholesterol, triglycerides, HDL and LDL-cholesterol), liver function test and serum ferritin were measured in all study participants on Hitachi 912 through photometric assay (for lipid profile and liver function test) and by immunoturbidity methodology for serumferritin. Hematological parameters were determined by Cell Dyne Ruby (Abbot, Architect, USA). Patients were stratified in two groups, age ≤ 15 years and >15 years, to determine the possible lipid profile distinction in relation to increasing age. Results: Of the 36 patients, 17 were males (15.5±5.9 years) and 19 were females (10.1±4.5 years) with the mean age of 12.69±5.85 (range 5-24) years. Mean hemoglobin was 7.4±1.9gm/dl with the hematocrit of 23.1±5.7% while serum ferritin was markedly elevated 4699.7±3089ng/ml. The mean total lipid, cholesterol and triglycerides levels were 494.7 ± 114.5, 90.3 ±23.9 and 150.5±95.1 mg/dl respectively. High triglycerides were detected in 36.1%. While HDL cholesterol and LDL cholesterol were markedly low 17.7±9.2 and 42.3±22.0 mg/dl respectively. The mean total cholesterol to HDL ratio was significantly elevated, 6.21± 3.06 (normal <5.0). In addition, total-cholesterol to HDL-cholesterol ratios were increased irrespective of gender, that is 6.0±2.0 and 6.4± 3.8 in males and females respectively (P=0.6). Data analysis revealed that 22.2% females and 13.8% males had high triglyceride levels (P=0.05). No statistically significant difference was noted in two stratified age groups in respect to lipid profile (table-1). We established positive correlation of elevated total bilirubin with cholesterol, HDL and LDL cholesterol (P 8gm/dl (P<0.05). Low HDL cholesterol was correlated positively with LDL cholesterol levels. While no significant correlation of serum lipid could be established with age, gender, high ferritins and with liver enzymes. Conclusion: Our study revealed that lipid profile impairment is not unusual in β-thalassemia major patients irrespective of age. Considerable deficiency of high density cholesterol and significantly high total-cholesterol to HDL-cholesterol ratio may strongly be associated with occurrence of coronary heart disease in later life. We propose that lipid profile should be regularly done in these patients particularly those with hemoglobin > 8gm/dl and high total bilirubin levels. Whilst total to HDL ratio, underlines as a significant diagnostic marker for future cardiac events in these patients. Keywords: β-thalassemia major, triglyceride, HDL-cholesterol, LDL-cholesterol. | Parameters | Age ≤15 years n= 24 | Age >15 years n= 12 | P- value | | --------------------------- | ---------------------------- | ---------------------------- | ---------------- | | Total lipid | 515.7± 121.1 | 452.9 ±90.6 | 0.1 * | | Cholesterol | 95.0±17.6 | 80.9±32.1 | 0.09 * | | Serum triglyceride | 168.1 ± 109.7 | 115.2± 40.1 | 0.1 * | | HDL cholesterol | 19.4±10.2 | 14.4± 5.9 | 0.1 * | | LDL cholesterol | 43.1±19.9 | 40.9±26.6 | 0.7 * | | Cholesterol ratio | 6.3± 3.4 | 6.0 ±2.1 | 0.8 * | Table 1: Comparative analysis of serum lipid profile in relation to age *Not significant Disclosures No relevant conflicts of interest to declare.

Objective: Many studies have reported an association between chronic immune thrombocytopenia and Helicobactor pylori infection. Significant improvement in platelet count is seen after eradication therapy. We looked for the frequency of H. pylori infection in immune thrombocytopenia and clinico-hematological features. Material and Method: A prospective case-control study was conducted from January 2009 to December 2011. One hundred and ten chronic immune thrombocytopenic patients and 40 control subjects were enrolled. H. pylori infection was documented by H. pylori stool antigen enzyme immunoassay method. Results: H. pylori infection in immune thrombocytopenic patients was seen in 45 cases (40.9%) and in 24 (60%) controls; not significant statistically. No significant differences were seen in H. pylori positive and negative patients with respect to maternal characteristics and clinical features except for mean platelet count, which was lower in H. pylori negative group (P = 0.035). Conclusion: Unlike many related studies, we found no significant difference between the frequencies of cases versus controls. Degree of thrombocytopenia appears more marked in H pylori negative patients.

Introduction Hypercoagulopathy and thromboembolic manifestations are being increasing acknowledged in transfusion dependent thalassemics; both intermedia and major. Studies in preceding decade have shown that hemostatic alterations including natural anticoagulant deficiency obligate thalassemic for thromboembolism. The aim of our study is to determine the status of natural anticoagulants and their association with thromboembolism during follow up. Method This is a prospective case-control study, during which 40 cases and 30 controls were registered between Jan 2009 to Dec 2009. Complete blood count, protein C, protein S, antithrombin, serum ferritin, liver function test; HbsAg and Anti HCV were determined. Patients were followed till 30th June 2012 for thromboembolic disease. Data was entered and analyzed using SPSS version 17. The results were expressed as mean ± SD for quantitative variables and qualitative variables are presented as frequency & percentages. Student‘t’ test was applied for the comparison of means. We also computed spearman correlation at 5% level of significance to identify relationship between the deficiency of natural anticoagulants with maternal characteristics, hematological parameters and biochemical markers. Chi- square test was applied for correlation of prothrombotic markers with hepatitis B & C. Results The mean age of patients and control was 12.30±5.5 and 13.39±4.5 years respectively. There were 21 males and 19 females in patient group. The mean protein C, protein S and antithrombin in patients and control were 58.25±22.5 versus 110.67±22.60 ( P <0.001), 67.90±19.58 versus 98.70±21.54 and 89.73±18.09 versus 104.0±10.98 ( P <0.001) respectively. Protein C was exceedingly deficient in 65% followed by protein S & antithrombin in 35% and 20% respectively. Protein S deficiency revealed positive correlation with protein C deficiency and hemoglobin ≤ 8 gm% was correlated with antithrombin deficiency( P <0.05). No positive correlation of prothrombotic markers were established with others parameters evaluated. Till June 2012, 7 patients were lost to follow up and 2 died owing to cardiac failure. Of the 31 patients in regular follow up none has experienced thromboembolism both clinically and radiologically. Conclusion Decremented prothrombotic markers, primarily protein C, are implicated in elevated thrombotic risk in TM patients. However we did not encounter thromboembolism in our patients during follow up. We recommend prothrombotic screening and prophylactic anticoagulation in high risk group: bed bound splenectomized, cardiopulmonary complications and post operative. Disclosures: No relevant conflicts of interest to declare.