Frequency of peripheral blood count abnormalities in patients with chronic active hepatitis C

Liver disease causes a greater range of hematological changes than does disease in any other organ. Viral hepatitis and its sequel are the important hepatic disorders. Hepatitis C virus [HCV] is considered to be the main etiological factor for chronic liver disease. Present study was done to determine the frequency of peripheral blood count abnormalities in chronic active hepatitis [CAH] caused by Hepatitis C virus [HCV]. It was a cross sectional study which was conducted in Department of Haematology, Shaikh Zayed Hospital Lahore from June to December 2010. In this study the frequency of anemia was found to be 41.3%, neutropenia 16.6% and thrombocytopenia 22.6% in CAH caused by HCV. Patients who develop hematological abnormalities during treatment need hematological growth factor support so that treatment could be continued without hindrance

Aetiological factors, diagnosis and treatment of disseminated intravascular coagulation - a study in a tertiary care hospital

Disseminated intravascular coagulation is a syndrome, characterized by a systemic activation of the blood coagulation system. It results in the generation and deposition of fibrin, leading to microvascular thrombi in various organs contributes to the development of multi organ failure. It is always secondary to or associated with an underlying disorder.1,2 The objectives of this study were to: describe the clinicopathological pattern of DIC, to find out the associated factors for DIC, and enlist different diagnostic tests and follow the therapeutic outcome and prognosis. It is a case series study. The study was carried out at Shaikh Zayed Hospital Lahore which is 750 bedded facility affiliated with FPGMI. Sociodemographic data like name, age, sex, address was collected. The history of the present illness was noticed with regard to severity of symptoms like fever, bleeding, cough, dyspnoea and altered consciousness. Patients were investigated for complete blood counts like Hb%, Platelet count, D-dimer, FDPs levels and fibrinogen level. Association factors for DIC were also noticed. In this study the most frequent association factor was found to be sepsis. Bleeding manifestations present in 90% of the patients, cough in 63.3% of the subjects. Patients with hypotension and altered consciousness were found to have a bad prognosis. Those treated with heparin infusion were not found to have a significant improvement in their clinical outcome. DIC is an important acquired coagulation abnormality most frequently associated with sepsis requiring vigorous treatment with blood products and anticoagulants

Clinico-haematological characteristics in Pakistani patients of primary myelodysplastic syndrome according to world health organization classification

To assess the applicability of WHO classification on a cohort of Pakistani myelodysplastic syndrome [MDS] patients, and determine their epidemiological and clinico-pathological features. Case series. Haematology Department, Shaikh Zayed Hospital, Lahore, from April 2004 to March 2006. Forty six patients of primary MDS diagnosed by World Health Organization [WHO] criteria were included in the study by nonprobability purposive sampling. The cohort was classified accordingly and the epidemiological, clinical and haematological parametres were assessed. Descriptive statistics were used to describe the data. Forty six patients [28 males and 18 females] of primary MDS were included in the study. The mean age was 46.21 years. According to the WHO classification, 12 cases of refractory anaemia, 24 cases of refractory cytopenia with multi lineage dysplasia, 1 case of refractory cytopenia with multi lineage dysplasia and ring sideroblasts, 3 cases of MDS unclassified and 3 cases each of refractory anaemia with excess of blasts I and II were diagnosed. Symptomatic anaemia was seen in 37 cases and pancytopenia was documented in 33 cases. Dyserythropoiesis affected 41 cases. Grade III reticulosis was seen in 7 cases. ALIP was present in 13 cases. MDS presented at a young age. Refractory cytopenia with multi lineage dysplasia was the dominant disease category. Further studies are suggested for identifying the cytogenetic abnormalities and del 5q- category

Clinicopathological analysis of myelodysplastic syndrome according to French-American-British classification

To evaluate the age of onset, gender ratio, clinical presentation of Myelodysplastic syndrome patients, and to classify these patients according to French-American-British classification on the basis of morphological features in blood and bone marrow. Case series. The department of Haematolgoy, Shaikh Zayed Hospital, Lahore, from April 2007 to March, 2007. Fifty patients of primary Myelodysplastic syndrome [MDS] were studied. The patients were classified according to French-American-British [FAB] criteria and the epidemiological, clinical and haematological features of MDS patients were evaluated. Descriptive statistics were used to describe data. There were 31 males and 19 females. The mean age was 41 years. According to FAB classification, 39 cases of retractory anaemia, 1 case of retractory anaemia with ring sideroblast, 6 cases of retractory anaemia with excess of blasts and 4 cases of refractory anaemia with excess of blasts in transformation were identified. The commonest complaint was easy fatiguablity affecting 41 cases [82%]. Anaemia was the most common finding seen in 47 patients [94%]. Pancytopenia was seen in 33 cases [66%]. Dyserythropoeisis was present in 42 [84%], dysmyelopoeisis was seen in 21 [42%] and morphologically abnormal megakaryocytes were identified in 29 [58%] of the bone marrow aspirates. Grade-III reticulosis was seen in 9 bone marrow trephine biopsies. Abnormla localization of immature precursors [ALIP] were present in 18 cases. MDS was more frequent in young males, Refractory anaemia constituted a major chunk of the disease entity

Clinico hematologic features of immune thrombocytopenic purpura and its association with autoimmune disorders

Immune thrombocytopenic purpura [ITP] is a clinical syndrome in which a decreased number of circulating platelets [thrombocytopaenia] manifests as a bleeding tendency, easy bruising [purpura], or extravasation of blood from capillaries into skin and mucous membranes [petechiae]. Present study was done to observe the clinico-haematological features of ITP in Adults and to analyse the association of autoimmune disorders with ITP in Pakistani patients. It was a cross-sectional descriptive study conducted at Shaikh Zayed Hospital, Lahore, from 1st January 2006 to 30[th] June 2007. The study included 44 adult patients of both genders diagnosed as having ITP according to WHO guidelines. Bone marrow biopsy was carried out in all patients and other causes of thrombocytopaenia were carefully excluded. Antinuclear antibodies, rheumatoid factor, HBs Ag, anti HCV, HIV were also done. The data was analysed by SPSS version 10. Results showed peak incidence in third decade with female to male ratio of 3.1:. Bleeding and bruising were common symptoms of ITP. Seven [15.9%] of 44 patients had serological evidence of systemic autoimmune disorders, i.e., SLE or RA. Platelet count was significantly lower in SLE patients than in entire cohort. It was concluded that adult ITP is predominantly seen in young females, presents with bleeding from more than 2 sites and may be associated with autoimmune disorders at the time of diagnosis

Hyper eosinophilic syndrome; a case series

Hyper eosinophilic syndrome [HES] is a subset of idiopathic eosinophilia that fulfils the criteria of a persistent [>6 months] increase in absolute eosinophil count [AEC] [>1.5x10[9]/l] associated with target organ damage. Recently it was classified into myeloproliferative and lymphoid variants. Present study is aimed to study the clinico morphological features and variants of HES and their response to various therapeutic modalities. In Pakistani population. It is a case series conducted at Haematology department, Shaikh Zayed hospital, Lahore during 4 years from Jan 2005 to Dec 2008. This study included 8 adult patients of HES diagnosed on history, clinical features and elevated absolute eosinophil count [AEC]. Seven of 8 patients were of lymphoid-HES and 1 was of myeloproliferative-HES. M: F ratio is 7:1, mean age of presentation was 37 years in lymphoid- HES and 69 years in myeloproliferative -HES. Presenting features were fatigue, weight loss, fever, SOB, paraesthesia and skin rash. Mean AEC in l-HES was 16109/l and in myeloproliferative- HES was 22.7x109/l. Organ damage was seen in cardiovascular, gastrointestinal [GIT], respiratory and nervous systems. All of the lymphoid-HES responded to steroids. In conclusion, early diagnosis and targeted therapy improve outcome in HES

Idiopathic hyper-eosinophilic syndrome [IHES] presenting with peripheral neuropathy: a case report

A 40 years old man presented with excruitiating pain and numbness in all 4 extremities and pain cpigastrium. After thorough investigations he was diagnosed as a case of idiopathic hypereosinophilic syndrome [IHES] and successfully treated with oral prednisolone, following which the patient is doing well. This case is being reported as IHES presenting with peripheral neuropathy is rarely seen

Thrombotic thrombocytopenic purpura, at a tertiary care centre in lahore, Pakistan

Thrombotic thrombocytopenic purpura is a syndrome, characterized by microangiopathic hae-molytic anaemia, thrombocytopaenia, neurological symptoms, renal disease and fever. Commonly considered rare, but actually it is one of the most under diagnosed disorders. This study was aimed at evaluating the clinical features, course, prognostic factors and treatment outcome in 17 patients diagnosed as having thrombotic thrombocytopaenic purpura [TTP]. It was a cross-sectional descriptive study at Shaikh Zayed Hospital Lahore. This study includes patients diagnosed as having TTP by the department of haematology from January 2005 to December 2007. Eight of 17 patients were treated with plasma exchange. Six of these 8 patients survived. Plasma infusions were performed in 9 patiejits, 5 of them recovered. Overall 65% patients recovered and mortality was 35%

Hairy cell leukemia: a case report

We report a case of a middle aged male diagnosed as Hairy cell leukemia. Clinicohematologic features were fever, weight loss, splenomegaly, anemia and thrombocytopenia. Bone marrow and spleen were infilterated by Hairy cells. An unusual feature was high TLC with large number of Hairy cells resembling superficially Hairy cell Variant. But the Flow cytometric analysis confirmed that immunophenotype was that of classic Hairy cell leukemia. Patient responded to Cladarabine therapy and had an uneventful recovery

Molecular screening for G6PD gene mutations in children with glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase [G6PD] deficiency is a heterogeneous enzyme abnormality with a high frequency among people of African, Mediterranean and Southeast Asian origins. In almost every group studied in the Middle East, only three to four different G6PD mutations were detected. Among these, the G6PD Mediterranean mutation [563C -> T] was by far the most common. Apart from this mutation, little is known about the genetic heterogeneity of G6PD deficiency in Egypt. To screen for G6PD gene mutations in a group of Egyptian children with G6PD-deficiency who were previously screened for the Mediterranean [563C -> T] mutation. This work was conducted on twenty-one unrelated Egyptian children [17 males and 4 females] presenting with G6PD deficiency previously screened for the G6PD Mediterranean mutation [563C -> T]. Carefully-preserved DNA of patients refrigerated at -20°C and DNA of 21 age-matched normal subjects extracted from blood leukocytes by saltingout technique were screened for mutations in the G6PD gene by PCR-single strand conformation polymorphism [SSCP] analysis followed by DNA sequencing. In addition to the G6PD Mediterranean mutation 563C -> T previously identified by PCR-RFLP analysis in 6/21 male patients [28.6%], a further of 2 different mutations; G6PD A- mutation and G6PD Chatham were observed in 2/21 [9.5%] and 1/21 [4.8%] patients respectively. Twelve patients [57.1%] remained uncharacterized at the genetic level, a normal African G6PD A genotype was detected in one patient of them. Patients with G6PD Mediterranean mutation were more susceptible to hemolysis than were patients with G6PD A- and G6PD Chatham mutations. The lower prevalence of G6PD Mediterranean mutation in our patients and the finding of three different mutations in a relatively small number of G6PD-deficient subjects reflect the considerable genetic heterogeneity of G6PD deficiency of the Egyptian population

study of chemokine receptor "CCXCR4" expression as an indicator for significant extramedullary organ infiltration in childhood acute lymphoblastic leukemia

CXCR4 is a G-protein linked seven transmembrane spanning chemokine receptor that binds stromal cell-derived factor-1 [SDF-1]. CXCR4 plays a crucial role in the survival and trafficking of leukemia cells. Childhood acute lymphoblastic leukemia [ALL] is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potent mechanism in the trafficking of leukemia cells is in the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells and its ligand stromal cell-derived factor-1 [SDF-1], produced by stromal cells in bone marrow and extramedullary organs. To evaluate the predictive value of high expression of CXCR4 receptor for extramedullary organ infiltration in childhood ALL. The study was conducted on 32 patients with newly diagnosed ALL and 15 healthy children as a control. The 32 studied patients were 18 males [56.3%] and 14 females [43.8%], age ranged from 1.7 years to 17 years, with a mean value of 6.18 +/- 4.38 years. Significant extramedullary organ infiltration was found in 8 patients [25%]. Flowcytometric analysis was used to measure CXCR4 expression on bone marrow lymphoblasts in ALL patients, and on normal peripheral blood lymphocytes in control subjects. CXCR4 expression was statistically significantly higher [p<0.001] in patients compared with control group CXCR4 expression with extramedullary organ infiltration [mean: 56.47 +/- 20.54], when compared with patients without significant extramedullary organ infiltration [mean: 20.58 +/- 7.42]. High expression of CXCR4 receptor has a predictive value for extramedullary organ infiltration in childhood ALL. Pharmacological agents affecting CXCR4 may have a potential therapeutic effect in the management and outcome of the disease

study of some genetic ameliorating factors in beta thalassemia

There are over 150 mutations affecting the beta globin gene that can lead to an altered expression of the gene and a decrease [beta [0]] or an absence [beta [+]] of beta globin production. The genes can be inherited in a homozygous or a heterozygous fashion. The result of inheritance of these genes can be diverse, ranging from beta thalassemia trait with no hematological disease to thalassemia major requiring repeated blood transfusions. There are co-inherited variables that can also influence the expression of this inheritance. Alpha gene deletion or the inheritance of the G gamma Xmn-1 gene sequence [C-T variation] at position -158 upstream of the G [gamma]-globin gene which is detectable by the restriction enzyme XmnI, are among these variables. The aim of this study is to clarify the effect of the above two variables as ameliorating factors in homozy-gous/double heterozygous beta thalassemia among a group of Egyptian thalassemic children. Thirty two cases of beta thalassemia were screened for common Mediterranean mutations [IVS1-110, 1-6,1-1, 11-745, codon 39, -87] alpha-gene deletions, and presence of G gamma Xmn-1 polymorphic site. As regards allele frequency, IVSI-6 showed the highest incidence [40.6%] followed by IVSI-110 [18.75%], IVSII-745 [12.5%], -87[9.37%], IVSI-1[3.12%] and codon 39 [0%]. 7 cases [21.87%] were uncharacterized as regards to the 6 screened mutations. The co-inheritance of a-thalassemia was found in 5 cases out of 32 cases [15.63%] and DNA polymorphism at -158 [C-T] of the gamma globin gene was demonstrated in 2/32 cases [6.25%]. Both variables ameliorated the severity of the disease either in the form of decreased frequency of blood transfusion or delay in age of presentation or an amelioration of clinical severity of a known severe allele

Correction of Aberrant pre mRNA splicing using antisense oligonucleotides in B thalassemia patients with known IVS-I,nt 110 mutation

1VS In l 110 mutation is the most common mutation in Egyptian thalassemics. The mutation causes aberrant splicing ofpre-mRNA resulting in labile RNA causing deficient B-globin chain synthesis. Antisense oligonucleotide strategy is one of the more simple technique in gene therapy. Using oligonucleotides covering the aberrant splice site gives chance for normal splicing and correction of the anomaly at the RNA level. Blocking of aberrant splicing at IVS 1nt 110 site of B-globin pre-mRNA using antisense oligonucleotides results in subsequent restoration of normal mRNA production in B-thalasseamia patients with IVS 1nt 110 mutation This study involved 10 patients with known IVS IntllO mutation; 6 homozygous and 4 heterozygous patients peripheral blood mononuclear cells were separated and duplicate liquid culture systems were set using erythropoietin and stem cell factor with and without antisense oligonucleotides [20 micro. mol/ml]. Correction of aberrant splicing was evaluated by estimation of total hemoglobin, hemoglobin F, and a reverse transcriptase polymerase chain reaction followed by agar gel electrophoresis was used to amplify and detect both aberrant mRNA and normal mRNA in duplicate samples. Five cases [50%] showed correction after antisense oligonucleotide treatment, two cases showed the appearance of normal mRNA band with absence of aberrant band and in 3 cases an increased ratio of normal mRNA band to aberrant band was found [from 2:1 to 3:1 in two cases and from 2:1 to 4:1 in the third case]. The 5 corrected cases showed significant increase in total Hb which varied between 4 to 6 folds increase. Antisense oligonucleotide treatment corrects splicing ofpre-mRNA leading to appropriate expression of B-globin mRNA which may pave the way for treatment of thalassaemia.

Chronic constipation in Egyptian infants and children: some common etiologies

Constipation is a common complaint heard in clinical Pediatrics. In most children, constipation is functional that is without objective evidence of a pathological condition. The aim of the present work was to identify some of the different etiologies of chronic constipation and to investigate the possible relation between constipation and cow milk allergy [CMA]. 30 consecutive infants and children with chronic constipation, attending the outpatient clinic of Cairo University Children Hospital, were studied. Beside the careful history taking and clinical examination, children were subjected to different investigations to diagnose the possible etiology of chronic constipation. In addition, diagnosis of CMA was done by challenge test to CM and blood tests including blood eosinophilic count, total serum IgE and specific IgE to cow milk proteins [ELISA technique]. Out of the 30 studied cases, the etiology of constipation was dietetic in 60%, CMA in 26.7%, Hirshsprung disease [HD] in 10%, and psychological constipation in only one patient [3.3%]. The diagnosis of dietetic constipation and CMA were significantly more common than HD [P = 0.0001]. The mean age and age of onset were not significantly different between the 3 groups. No sex predilection for the prevalence of constipation was found in different age groups [<12 months and >/= 12 months] [P = 0.7]. Most of patients were 6 months of age while CMA-related constipation was more common in patients

Identification of five common Alpha-thalassaemia genotypes among a group of Egyptian neonates by single tube PCR

The alpha thalassaemias are common genetic disorders that arise from reduced synthesis of the alpha globin chains. At present, large scale carrier screening and clinically valuable antenatal detection programs have not been established for the congenital disorder alpha thalassaemia. This study was conducted on 410 umbilical cord blood samples to detect the relative frequency and differentiate between the five common alpha thalassaemia deletional forms, regardless of the break points, among a group of Egyptian neonates using a single tube multiplex-PCR assay. The method proved to be simple, easy and fast as the number of alpha genes present in the subjects were directly determined by the number and intensity of the alpha l and alpha 2 bands normalized with that of beta actin [serving as an internal control]. A complete blood picture was done for all samples. Among the DNA samples tested, ten cases were discarded due to failure of amplification. Our results showed that 38 samples [9.5%] were identified as carriers of alpha thalassaemia or suffering from Hb H disease. The percentage of the different genotypes detected was: 4.5% alpha thalassaemia 2 heterozygous [-alpha/ alpha alpha], 3% alpha thalassaemia 2 homozygous [-alpha /-alpha], 1.75% alpha thalassaemia 1 heterozygous [--/alpha alpha] and 0.25% Hb H disease [--/-alpha]. No cases of Hb B art's hydrops fetalis were detected. On comparing the hematological profile of the normal subjects with that of those with gene deletions it was found that alpha thalassaemia carriers had significantly lower Hb levels, Hct%, MCH and MCHC while the MCV did not differ markedly. No statistically significant difference was found between the various genotypes detected regarding their blood indices. From this we can not rely upon blood indices only for detection of alpha thalassaemia and we highlight the importance of molecular diagnosis using this simple single tube PCR assay in diagnosis of alpha thalassaemia carriers

Protein C, protein S, antithrombin lll and factor V leiden [Q506] mutation in veno-occlusive disease in Egyptian children

Thickening of the subintimai zone of the central vein and sublobular venules leads to decreased venous outflow, increased resistance and severe hemodynamic changes characteristic of veno-occlusive disease [VOD]. The role of the coagulation pathways in the pathophysiology of VOD is an area of controversy. This work aimed at evaluation of the presence of protein C, protein S, antithrombin III deficiency and the presence of factor V Leiden in children having VOD. This cross-sectional study included 20 children suffering from veno-occlusive disease and 20 age and sex matched clinically free infants as a control group. They underwent protein C, protein S, antithrombin III assays. Molecular study of factor V mutation [mutation Q506] detection was carried out. The results proved that protein C deficiency was present in 14 children [70%], and antithrombin III in 2 children [10%]. Protein 8 deficiency was not encountered in our studied group. Two children were heterozygous for the mutation Q506. The 2 children with heterozygous factor V Leiden mutation had protein C deficiency. The percutaneous liver biopsies revealed central vein obstruction in 11 children [55%], extensive fibrosis in one and cirrhosis in one. The biopsy findings did not correlate with the clinical stage [P=0.47] or duration of disease [P=0.49]. None of these changes was encountered in the control group

Conclusion: We report the presence of protein C and antithrombin III deficiency and heterozygous Factor V Leiden [Q506] mutation in children with VOD. We support that thrombophilia is a host susceptibility factor and not the etiology of VOD

Infiltration of bone marrow in solid tumours

In this study a total of 51 patients were selected with established malignant disorders. The frequency of metastatic involvement of the bone marrow was determined by obtaining concurrent bilateral aspiration and biopsy from posterior iliac spine. Routine investigations [hemoglobin, total and differential leucocyte count platelets and ESR] were performed in all cases. Specific investigations included bilateral bone marrow biopsies and trephines. In these tumors, breast, prostate and lung most commonly metastasized to marrow in adults, whereas neuroblastoma was most common in pediatric age group. It is suggested that the aspirate and biopsy were found complementary in the diagnosis of bone marrow metastases

Elevated levels of interleukin 18 in children with acute and chronic liver disease: further evidence of T cell-mediated liver injury

IL-18, derived from macrophages and kupffer cells, is the central pro-inflammatory cytokine leading to experimental liver failure. The objective of this study was to evaluate IL-18 in sera of infants and children suffering from acute hepatitis, chronic hepatitis and cirrhosis and to define its role as a predictive factor for chronicity of liver disease. Eighteen children suffering from acute viral hepatitis, 26 from chronic hepatitis and 15 suffering from cirrhosis were included in this study. They were attendants of the Hepatology Clinic of the New Children's Hospital, Cairo University. Twenty-three age and sex matched, clinically free infants and children, were also included as a control group. All studied infants and children, and the control group underwent quantitative determination of IL-18 in serum by ELISA. The mean IL-18 was found to be statistically significantly lower among the control group compared to the others. The mean IL-18 values were 38.65 +/- 15.46, 510.27 +/- 757, 305.03 +/- 647 and 257.86 +/- 395 pg/ml for the healthy control, acute hepatitis, chronic hepatitis and cirrhosis groups respectively. IL-18 level was not found to be predictive of pathology or etiology [P=0.067]. No correlation was found between IL-18 level and total bilirubin [P=0.70], direct bilirubin [P=0.79], ALT [P=0.29], AST [P=0.48] or alkaline phosphatase [P=0.222]. Higher levels of IL-18 were encountered in those children having more severe AIH. High IL-18 was present in children having various liver diseases. This supports the view that hepatocytes destruction is in part immune mediated. Immune modulation remains a potential future perspective for liver disease intervention