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   2015| July-September  | Volume 40 | Issue 3  
    Online since September 8, 2015

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How to approach drug-induced agranulocytosis in ICU
Seema Mahant, Piyu Deo Mahant, Upasana Shobhane
July-September 2015, 40(3):109-112
Many drugs can cause agranulocytosis and neutropenia by bone marrow suppression. Drug-induced agranulocytosis (DIA) is a relatively rare, but life-threatening disorder that frequently occurs as an adverse reaction to drugs. The overall incidence of DIA ranges from 2.4 to 15.4 cases/million patients exposed to drugs per year. DIA remains a serious adverse event because of the occurrence of severe sepsis with severe deep infections (such as pneumonia), septicemia, and septic shock in around two thirds of patients. In this setting, older age (>65 years), septicemia or shock, metabolic disorders such as renal failure, and a neutrophil count below 0.1×10 9 /l are poor prognostic factors. The severity of neutropenia (<0.1×10 9 /l) and its duration (>10 days) may also impact negatively on the outcome. Commonly used drugs such as antibiotics (b-lactam and cotrimoxazole), antiplatelet agents (ticlopidine), antithyroid drugs, sulfasalazine, neuroleptics (clozapine), antiepileptic agents (carbamazepine), nonsteroidal anti-inflammatory agents, and dipyrone are the most common causes of neutropenia and agranulocytosis. Recent investigations suggest that there are at least three mechanisms by which it can be produced, namely, differences in drug pharmacokinetics, abnormal sensitivity of myeloid precursors, and adverse immune responses to drug administration. Genetic factors are important and could act by any of the above mechanism. In management, use of hematopoietic growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, reduced mortality rate from 21.5 to 5%. Now a days, physicians use many drugs to increased life expectancy, as well as the development of new agents, should be aware of this complication and its management.
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Prevalence and significance of hepatitis B core antibodies among hepatitis B surface antigen-negative Egyptian polytransfused adult patients
Tamer A Elbedewy, Nashwa M Noreldin, Sarah A Hamam
July-September 2015, 40(3):143-147
Background/aims Blood transfusion is a well-established line of therapy associated with risk of infection transmission. Occult hepatitis B virus (HBV) infection is defined as the presence of HBV-DNA in the serum and/or the liver in the absence of hepatitis B surface antigen (HBsAg). Combined screening of HBsAg and hepatitis B core antibody (anti-HBc) can virtually eradicate blood-transmitted HBV. The aim of this study was to evaluate the presence of anti-HBc among Egyptian polytransfused adult patients and to determine the presence or absence of HBV-DNA in the serum samples of HBsAg-negative, anti-HBc-positive polytransfused adult patients using the polymerized chain reaction (PCR) method to assess the magnitude of occult HBV infection in these patients. Patients and methods This cross-sectional study included 79 polytransfused patients negative for HBsAg, HBsAb, and anti-hepatitis C virus. Patients were investigated for anti-HBc and samples of anti-HBc-positive patients were tested for HBV-DNA using real-time PCR. Results Among the 79 HBsAg-negative sera, anti-HBc was detected in 12 of 79 (15.19%) cases. All anti-HBc-positive sera were anti-HBs-negative. HBV-DNA was detected in five of 12 (41.67%) cases. Occult HBV infection was present in 6.33% of patients. Conclusion The overall prevalence of occult HBV in adult Egyptian polytransfused patients on regular blood transfusion is 6.33%.
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Evaluation of CD69 expression as a prognosticator in chronic lymphocytic leukemia
Emad A Abd El-hadi, Yasmin N El-Sakhawy, Amany A Osman
July-September 2015, 40(3):113-120
Introduction Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the western world. It is a malignancy of mature B cells involving the blood, bone marrow (BM), and lymphoid tissues, and its cells arise from polyclonal expansion of CD5+ B lymphocytes transformed into a monoclonal population by mutational agents. CD69 is an integral membrane protein belonging to the lectin family. It is expressed after activation in all BM-derived cells except erythrocytes. CLL exhibits features of activated and antigen-experienced B lymphocytes and CD69 overexpression. CD69 is significantly correlated with poor clinical and biological prognostic factors, and this supports its introduction into routine laboratory assessment and, possibly, in a prognostic scoring system for CLL after an adequate standardization process. Objective The aim of this study was to detect CD69 expression in newly diagnosed patients with CLL by flow cytometry and correlate it with clinical and laboratory parameters to evaluate it as a prognostic factor. Patients and methods This study was conducted on 40 B-CLL patients who attended Ain Shams University Hospitals over 1 year. All patients were subjected to full medical history and clinical examination, RAI staging according to disease burden and the degree of BM involvement, abdominal ultrasonography, complete blood count with examination of peripheral blood smears, BM aspiration with morphological examination, and immunophenotyping of BM or whole peripheral blood applying monoclonal antibodies CD20, CD79b, FMC7, serum IgM, CD5/CD19, CD10, CD103, CD123, CD23, and CD38, and κ and λ light chains and CD69 expression. Results In the current study all of the studied B-CLL patients expressed CD69. Among the 40 studied patients 23 had high CD69 expression (group I) and 17 had low CD69 expression (group II). A highly significant elevation in group I patients compared with group II patients was found (P = 0.000). A highly significant reduction in hemoglobin (Hb) level (P = 0.001), elevation in lactate dehydrogenase concentration (P = 0.006), elevation in RAI staging, and elevation in CD38 expression (P = 0.005) were observed in group I. A highly significant negative correlation was found between CD69% and Hb level (P = 0.008) and platelet count (P = 0.009). A highly significant positive correlation was found between CD69% and hepatomegaly (P = 0.008) and RAI stage (P = 0.008) and significant positive correlation was found between CD69% and CD38% expression (P = 0.012). An association study was conducted between CD69% expression and all the standard prognostic factors in B-CLL patients. There was a highly significant association between CD69% expression and presence of hepatomegaly (P = 0.002) and a significant association between CD69% expression and presence of splenomegaly (P = 0.028) and low Hb levels (P = 0.013). Conclusion Several clinical and biological variables have been reported to predict the outcome of CLL patients, such as advanced patient age, male sex, higher absolute lymphocyte count, greater extent of lymphadenopathy, and raised serum β2-microglobulin levels, all of which are associated with inferior prognosis. In the current study all of the studied B-CLL patients expressed CD69. CLL patients were divided into two subsets with significantly different prognosis: those with high CD69 (group I) (≥30%) and those with low CD69 (group II) (<30%) expression; both were compared with respect to the different studied parameters. There was highly significant elevation of CD69 in group I compared with group II. There was a highly significant reduction in Hb level and elevation in lactate dehydrogenase concentration in group I patients in comparison with group II patients. A highly significant relation was found between the two groups with respect to RAI staging: an advanced RAI stage was found among group I patients in comparison with group II patients. The current study evaluated CD69 as a prognosticator and studied the significant association of its high expression with the standard prognostic factors, notably splenomegaly (P = 0.028) and hepatomegaly (P = 0.002), low Hb level, low platelet count, and advanced RAI stage. CD69 expression is associated with both immunoglobulin variable heavy chain mutation status and survival. It is recommended to perform a larger prospective study on CD69 expression in B-CLL patients, studying its relation to overall survival and progression-free survival and its re-evaluation during the course of treatment as we recommend assessment of this marker by flow cytometry among independent prognostic markers in B-CLL.
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Factor XIII deficiency: the first case reported from Nepal
Bishesh S Poudyal, Gentle S Shrestha
July-September 2015, 40(3):148-149
The initial hemostatic plug is not sufficient to prevent blood loss unless it is stabilized by the action of plasma factor XIII. Congenital or acquired factor XIII deficiency must be considered when a patient has a major bleeding disorder and all of the initial screening laboratory tests are normal, including prothrombin time, activated partial thromboplastin time, platelet count, and bleeding time. Here we report the case of a child with congenital factor XIII deficiency, who presented with bleeding from umbilical stump and spontaneous hematoma in the left buttock.
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The SALL4 gene in acute leukemias
Hasnaa A Abo-Elwafa, Shereen P Aziz, Maged M Salah, Osamah B Sedek
July-September 2015, 40(3):121-129
Background The SALL gene family is involved in normal development as well as tumor genesis. SALL4 is essential for the maintenance of the pluripotent and the self-renewal properties of embryonic stem cells. Patients and methods It was conducted from the period of April 2008 to June 2012 on 40 patients with acute leukemia (group I), 20 patients who had nonmalignant hematologic disease (group II), and 20 healthy individuals (group III). They were subjected to laboratory investigations including a complete blood picture, RT-PCR for the detection of the SALL4 gene, for group I bone marrow aspiration biopsy, cytochemical studies, and immunophenotyping of either peripheral blood or bone marrow samples to diagnose and classify the hematologic malignancy. Results SALL4 mRNA was expressed in 50% of the acute myeloid leukemia (AML) cases and was undetectable in 50% of the cases. Whereas it was expressed in only 20% of acute lymphoblastic leukemia (ALL), it was undetectable in 80% of ALL. SALL4 mRNA was undetectable in all cases of immune thrombocytopenic purpura (group II) (0%). SALL4 mRNA was undetectable in all samples of the control group (group III) (0%). There was no significant difference between the expression level of CD markers and SALL4 in AML cases, whereas there was a significant elevation of the CD10 expression level in SALL4-positive ALL cases (P < 0.05). There was a significant reduction in the RBC count and the hematocrite (Hct) and platelet level in SALL4-positive ALL cases (P < 0.05), and there was a statistically significant reduction in the platelet count in SALL4-positive AML cases. Conclusion SALL4 mRNA expression was higher in cases of AML (50%), compared with ALL cases (20%). There was no SALL4 mRNA expression detected in all cases of immune thrombocytopenic purpura patients and in normal control individuals.
  2,182 147 -
Plasmablastic lymphoma developing in thyroid: a rare entity in an immunocompetent individual
Faiq Ahmed, Manasi C Mundada, Sudha S Murthy, Senthil J Rajappa
July-September 2015, 40(3):150-152
A case of plasmablastic lymphoma that has not been described previously in the thyroid is presented with its clinicopathological features and the diagnostic difficulties encountered. A detailed histopathology in conjunction with immunohistochemistry is recommended for appropriate diagnosis and management in the setting of HIV-negative status. Dealing with a case presenting primarily as a thyroid mass can be challenging in the scenario of a CD20-negative immunoprofile.
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CD44 as a diagnostic and prognostic marker in Egyptian patients with non-Hodgkin lymphoma
AA Hasnaa, AE Mohamed, HS Eman, MA Hanaa
July-September 2015, 40(3):130-137
Background CD44 is an adhesion molecule that plays a role in lymphocyte homing; it is a multifunctional cell surface molecule involved in cell proliferation, angiogenesis, presentation of cytokines, chemokines, and growth factors. Patients and methods This study was carried out on 50 newly diagnosed non-Hodgkin lymphoma patients (33 men and 17 women) and 20 healthy controls; the patients were divided into two groups: group I included 20 patients with stage I, II, and III non-Hodgkin lymphoma and group II included 30 patients with stage IV non-Hodgkin lymphoma. They ranged in age from 38 to 75 years; all patients were subjected to a clinical examination, a complete blood count, bone marrow aspiration, and immunophnotyping using monoclonal for CD44 in addition to a routine panel of different chronic lymphoproliferative disorders (CD19, CD5, CD10, CD20, CD22, CD23, SIgM, CD38, CD79b, FMC7, CD103, CD123, κ, and λ light chains). Results CD19, CD20, CD22, CD23, κ/CD19, CD5/CD19, CD10, CD123, and CD103 expression levels showed no statistically significant differences between group I and group II, using the Mann-Whitney U-test, whereas other investigations showed significant differences; these differences were highly significant in terms of gated cell count, CD79b, SIgM, FMC7, λ/CD19, and CD44 expression levels. There was a positive correlation with significant differences between CD44 and FMC7, lymphocytic count, and LDH, a positive correlation with significant differences between CD44 and gated cell count and SIgM, and a highly statistically significant correlation between CD44 and λ/CD19, FMC7, lymphocytic count, and platelet count. Sixty percent of CD44-positive patients in group II had lymph node enlargement compared with only 15% of CD44-positive patients in group I. Conclusion Strong CD44 expression appears to be a powerful prognostic indicator in adult non-Hodgkin's lymphoma, with no difference between male and female patients. It is associated with standard poor prognostic markers such as bone marrow infiltration.
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Protein Z serum levels as a risk factor for acute ischemic stroke in patients with systemic lupus erythematosus: a comparison with diabetic cases
Alyaa A El-Sherbeny, Emad A Abd El-Hadi, Maram M Maher, Hanan M EL-Saadny, Doaa A El-Aidy, Mona Gameel, Magdy A Abd El-Aziz
July-September 2015, 40(3):138-142
Introduction A number of clinical studies that explored the role of protein Z in coronary heart disease, ischemic stroke, and deep vein thrombosis patients have been published. Particularly in ischemic stroke, patients or at least subgroups of patients with low levels (in the convalescent phase of stroke) or high levels (in the acute phase of stroke) of protein Z have been associated with increased risk of stroke. Aim of the work This cross-sectional study aimed to investigate the role of protein Z in patients with systemic lupus erythematosus (SLE) and/or diabetes mellitus (DM) to determine the association between protein Z serum concentration and acute ischemic stroke in these patients. Patients and methods The study was carried out on selected 40 stroke patients divided into 20 patients with SLE and 20 without SLE, who were further divided equally into diabetic and nondiabetic patients. Assessment included demographic data (age, height, weight, and BMI), clinical examination, laboratory investigations including complete blood count, erythrocyte sedimentation rate, HbA1c, lipid profile, protein Z level, MRI-brain, and extracranial carotid duplex ultrasound. Results As regards protein Z levels, it was 4.4 ± 0.6 μg/ml in group I (DM+SLE), 3.0 ± 0.8 μg/ml in group II (SLE + no DM), 2.6 ± 0.8 μg/dl in group III (no SLE, no DM), and 1.1 ± 0.6 μg/dl in group IV (no SLE + DM), which demonstrated a significant difference between the four groups, with the highest protein Z serum level in group I. Conclusion Our study demonstrated an independent association between increasing blood levels of protein Z in SLE rather than in DM patients and an increased risk for ischemic stroke. However, it remains unclear whether elevated protein Z concentrations are a cause or a consequence of ischemic stroke.
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