Advances in Hematology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. A Preliminary Study of the Suitability of Archival Bone Marrow and Peripheral Blood Smears for Diagnosis of CML Using FISH Mon, 22 Sep 2014 07:08:18 +0000 Background. FISH is a molecular cytogenetic technique enabling rapid detection of genetic abnormalities. Facilities that can run fresh/wet samples for molecular diagnosis and monitoring of neoplastic disorders are not readily available in Ghana and other neighbouring countries. This study aims to demonstrate that interphase FISH can successfully be applied to archival methanol-fixed bone marrow and peripheral blood smear slides transported to a more equipped facility for molecular diagnosis of CML. Methods. Interphase FISH was performed on 22 archival methanol-fixed marrow (BM) and 3 peripheral blood (PB) smear slides obtained at diagnosis. The BM smears included 20 CML and 2 CMML cases diagnosed by morphology; the 3 PB smears were from 3 of the CML patients at the time of diagnosis. Six cases had known BCR-ABL fusion results at diagnosis by RQ-PCR. Full blood count reports at diagnosis were also retrieved. Result. 19 (95%) of the CML marrow smears demonstrated the BCR-ABL translocation. There was a significant correlation between the BCR-ABL transcript detected at diagnosis by RQ-PCR and that retrospectively detected by FISH from the aged BM smears at diagnosis (; ). Conclusion. Archival methanol-fixed marrow and peripheral blood smears can be used to detect the BCR-ABL transcript for CML diagnosis. Alice Charwudzi, Edeghonghon E. Olayemi, Ivy Ekem, Olufunmilayo Olopade, Mariann Coyle, Amma Anima Benneh, and Emmanuel Alote Allotey Copyright © 2014 Alice Charwudzi et al. All rights reserved. Effect of Gender on Coagulation Functions: A Study in Metastatic Colorectal Cancer Patients Treated with Bevacizumab, Irinotecan, 5-Fluorouracil, and Leucovorin Thu, 21 Aug 2014 07:32:50 +0000 Introduction. We designed this study to evaluate how coagulation parameters are changed in metastatic colorectal cancer (mCRC) patients treated with bevacizumab, irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI). Methods. A total of 48 mCRC patients who initially received bevacizumab with FOLFIRI were eligible for this study. Thirty-four patients were analyzed at baseline and on the 4th, 8th, and 12th cycles of chemotherapy. Results. There were 19 male and 15 female patients. Baseline characteristics of the groups were similar, but women had better overall survival than men (14 months versus 12 months, ). D-dimer levels decreased significantly after the 12th cycle compared with baseline in men but not in women. Men and women had increased levels of serum fibrinogen at the early cycles, but these increased fibrinogen levels continued after the 4th cycle of chemotherapy only in women. In addition, serum fibrinogen levels did not significantly change, but aPTT levels decreased in men. Discussion. The major finding of this study is that bevacizumab-FOLFIRI chemotherapy does not promote changes in the coagulation system. If chemotherapy treatment and the possible side effects of FOLFIRI-bevacizumab treatment are well managed, then alterations of the coagulation cascade will not have an impact on overall survival and mortality. Cemil Bilir, Hüseyin Engin, and Yasemin Bakkal Temi Copyright © 2014 Cemil Bilir et al. All rights reserved. Variation of Red Blood Cell Distribution Width and Mean Platelet Volume after Moderate Endurance Exercise Wed, 13 Aug 2014 07:13:13 +0000 Although physical exercise strongly influences several laboratory parameters, data about the hematological changes after medium distance running are scarce. We studied 31 middle-trained athletes (mean training regimen  min/week) who performed a 21.1 km, half-marathon run. Blood samples were collected before the run, at the end, and 3 and 20 hours thereafter. The complete blood count was performed on Advia 2120 and included red blood cell (RBC), reticulocyte, and platelet counts; hemoglobin; mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); reticulocyte haemoglobin content (Ret CHR); RBC distribution width (RDW), mean platelet volume (MPV). No significant variations were observed for MCH and Ret CHR. The RBC, reticulocyte, and hemoglobin values modestly decreased after the run. The MCV significantly increased at the end of running but returned to baseline 3 hours thereafter. The RDW constantly increased, reaching a peak 20 hours after the run. The platelet count and MPV both increased after the run and returned to baseline 3 hours thereafter. These results may have implications for definition of reference ranges and antidoping testing, and may also contribute to explaining the relationship between endurance exercise and mortality, since previous studies reported that RDW and MPV may be significantly associated with cardiovascular disease. Giuseppe Lippi, Gian Luca Salvagno, Elisa Danese, Cantor Tarperi, Gian Cesare Guidi, and Federico Schena Copyright © 2014 Giuseppe Lippi et al. All rights reserved. Hypertransfusion Therapy in Sickle Cell Disease in Nigeria Thu, 07 Aug 2014 10:54:43 +0000 Introduction. Hypertransfusion refers to chronic blood transfusion therapy aimed at ameliorating disease complications in various haemopathies particularly the haemoglobinopathies. In sickle cell disease, hypertransfusion is aimed at maintaining patient’s haemoglobin level at 10 to 11 g/dL using haemoglobin AA blood and its resultant dilutional effect on sickle haemoglobin is sustained by intermittent long-term transfusions. Aim and Objective. This paper highlights hypertransfusion and its privileged position as a secondary measure in prevention and treatment of sickle cell disease, especially in the Nigerian context. Materials and Methods. Relevant literatures were searched on PubMed, Google Scholar and standard texts in haematology and transfusion medicine. Keywords used in the search are hypertransfusion, sickle cell disease, chronic transfusion, and Nigeria. Literatures gathered were reviewed, summarized, and presented in this paper. Result. Immense clinical benefit is associated with hypertransfusion therapy including prevention of stroke and amelioration of severe sickle cell disease especially in transplant ineligible patients. Careful patient selections, appropriate blood component, and prevention of transfusion hazards as well as oversight function of an experienced haematologist are pertinent to a successful hypertransfusion therapy. Conclusion. Improved knowledge of the benefits and practice of hypertransfusion will effectively translate into improved health status even among Nigerian sickle cell disease patients. Ademola Samson Adewoyin and Jude Chike Obieche Copyright © 2014 Ademola Samson Adewoyin and Jude Chike Obieche. All rights reserved. Thalassemia and Hemoglobin E in Southern Thai Blood Donors Mon, 23 Jun 2014 06:56:57 +0000 Thalassemia and hemoglobin E (Hb E) are common in Thailand. Individuals with thalassemia trait usually have a normal hemoglobin concentration or mild anemia. Therefore, thalassemic individuals who have minimum acceptable Hb level may be accepted as blood donors. This study was aimed at determining the frequency of α-thalassemia 1 trait, β-thalassemia trait, and Hb E-related syndromes in Southern Thai blood donors. One hundred and sixteen voluntary blood donors, Southern Thailand origin, were recruited for thalassemia and Hb E screening by red blood cell indices/dichlorophenolindophenol precipitation test. β-Thalassemia and Hb E were then identified by high performance liquid chromatography and 4 common α-thalassemia deletions were characterized by a single tube-multiplex gap-polymerase chain reaction. Overall frequency of hemoglobinopathies was 12.9%, classified as follows: homozygous α-thalassemia 2 (1.7%), heterozygous α-thalassemia 1 (1.7%), heterozygous β-thalassemia without α-thalassemia (0.9%), heterozygous Hb E without α-thalassemia (5.2%), double heterozygotes for Hb E/α-thalassemia 1 (1.7%), homozygous Hb E without α-thalassemia (0.9%), and homozygous Hb E with heterozygous α-thalassemia 2 (0.9%). The usefulness of thalassemia screening is not only for receiving highly effective red blood cells in the recipients but also for encouraging the control and prevention program of thalassemia in blood donors. Manit Nuinoon, Kwanta Kruachan, Warachaya Sengking, Dararat Horpet, and Ubol Sungyuan Copyright © 2014 Manit Nuinoon et al. All rights reserved. Evaluation of Ferric and Ferrous Iron Therapies in Women with Iron Deficiency Anaemia Wed, 11 Jun 2014 10:06:19 +0000 Introduction. Different ferric and ferrous iron preparations can be used as oral iron supplements. Our aim was to compare the effects of oral ferric and ferrous iron therapies in women with iron deficiency anaemia. Methods. The present study included 104 women diagnosed with iron deficiency anaemia after evaluation. In the evaluations performed to detect the aetiology underlying the iron deficiency anaemia, it was found and treated. After the detection of the iron deficiency anaemia aetiology and treatment of the underlying aetiology, the ferric group consisted of 30 patients treated with oral ferric protein succinylate tablets (2 × 40 mg elemental iron/day), and the second group consisted of 34 patients treated with oral ferrous glycine sulphate tablets (2 × 40 mg elemental iron/day) for three months. In all patients, the following laboratory evaluations were performed before beginning treatment and after treatment. Results. The mean haemoglobin and haematocrit increases were 0.95 g/dL and 2.62% in the ferric group, while they were 2.25 g/dL and 5.91% in the ferrous group, respectively. A significant difference was found between the groups regarding the increase in haemoglobin and haematocrit values (). Conclusion. Data are submitted on the good tolerability, higher efficacy, and lower cost of the ferrous preparation used in our study. Ilhami Berber, Halit Diri, Mehmet Ali Erkurt, Ismet Aydogdu, Emin Kaya, and Irfan Kuku Copyright © 2014 Ilhami Berber et al. All rights reserved. Absence of Association between CCR5 rs333 Polymorphism and Childhood Acute Lymphoblastic Leukemia Sun, 13 Apr 2014 16:48:52 +0000 Acute lymphoblastic leukemia (ALL) is a malignant disorder that originates from one single hematopoietic precursor committed to B- or T-cell lineage. Ordinarily, these cells express CCR5 chemokine receptor, which directs the immune response to a cellular pattern and is involved in cancer pathobiology. The genetic rs333 polymorphism of CCR5 (Δ32), results in a diminished receptor expression, thus leading to impaired cell trafficking. The objective of the present study was to investigate the effect of CCR5 chemokine receptor rs333 polymorphism in the pathogenesis of ALL. The genotype distribution was studied in 79 patients and compared with 80 control subjects, in a childhood population of Southern Brazil. Genotyping was performed using DNA samples amplified by polymerase chain reaction with sequence-specific primers (PCR-SSP). The homozygous (Δ32/Δ32) deletion was not observed in any subject involved in the study. Heterozygous genotype was not associated with ALL risk (OR 0.7%; 95% CI 0.21–2.32; ), nor recurrence status of ALL (OR 0.86; 95% CI 0.13–5.48; ). This work demonstrated, for the first time, no significant differences in the frequency of the CCR5/Δ32 genotype between ALL and control groups, indicating no effect of this genetic variant on the ALL susceptibility and recurrence risk. Carlos Eduardo Coral de Oliveira, Marla Karine Amarante, Aparecida de Lourdes Perim, Patricia Midori Murobushi Ozawa, Carlos Hiroki, Glauco Akelinghton Freire Vitiello, Roberta Losi Guembarovski, and Maria Angelica Ehara Watanabe Copyright © 2014 Carlos Eduardo Coral de Oliveira et al. All rights reserved. The Genetic Architecture of Multiple Myeloma Thu, 03 Apr 2014 00:00:00 +0000 Multiple myeloma is a malignant proliferation of monoclonal plasma cells leading to clinical features that include hypercalcaemia, renal dysfunction, anaemia, and bone disease (frequently referred to by the acronym CRAB) which represent evidence of end organ failure. Recent evidence has revealed myeloma to be a highly heterogeneous disease composed of multiple molecularly-defined subtypes each with varying clinicopathological features and disease outcomes. The major division within myeloma is between hyperdiploid and nonhyperdiploid subtypes. In this division, hyperdiploid myeloma is characterised by trisomies of certain odd numbered chromosomes, namely, 3, 5, 7, 9, 11, 15, 19, and 21 whereas nonhyperdiploid myeloma is characterised by translocations of the immunoglobulin heavy chain alleles at chromosome 14q32 with various partner chromosomes, the most important of which being 4, 6, 11, 16, and 20. Hyperdiploid and nonhyperdiploid changes appear to represent early or even initiating mutagenic events that are subsequently followed by secondary aberrations including copy number abnormalities, additional translocations, mutations, and epigenetic modifications which lead to plasma cell immortalisation and disease progression. The following review provides a comprehensive coverage of the genetic and epigenetic events contributing to the initiation and progression of multiple myeloma and where possible these abnormalities have been linked to disease prognosis. Steven M. Prideaux, Emma Conway O'Brien, and Timothy J. Chevassut Copyright © 2014 Steven M. Prideaux et al. All rights reserved. Therapy with Interleukin-22 Alleviates Hepatic Injury and Hemostasis Dysregulation in Rat Model of Acute Liver Failure Tue, 01 Apr 2014 16:21:46 +0000 The therapeutic efficacy of interleukin-22 (IL-22) on liver injury and hematological disturbances was studied in rat model of acute liver failure (ALF) induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS). The following parameters were investigated: (1) survival rate, (2) serum levels of liver function enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), total bilirubin (TBILI), and total albumen (ALB), (3) blood clotting tests (prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level (FIB)) and white blood cells (WBCs), red blood cells (RBCs), and platelet counts, (4) hepatic levels of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2), and (5) liver histopathology. After 48 hours of D-GalN/LPS, the rats exhibited 20% mortality, significant increases in AST, ALT, ALP, TBILI, PT, and aPTT, TNF-α, and COX-2 and significant decreases in FIB, WBCs, and RBCs. By contrast, therapy with IL-22 prevented the lethal effect of D-GalN/LPS by 100% and efficiently alleviated all the biochemical and hematological abnormalities that were observed in ALF untreated group. Furthermore, IL-22 treatment decreased the hepatic contents of TNF-α and COX-2. The histopathological findings also supported the hepatoprotective effect of IL-22. Taken together, therapy with IL-22 can represent a promising therapeutic tool against liver injury and its associated hemostasis disturbances. Tariq Helal Ashour Copyright © 2014 Tariq Helal Ashour. All rights reserved. The Epigenetic Landscape of Acute Myeloid Leukemia Sun, 23 Mar 2014 07:32:16 +0000 Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated. Emma Conway O’Brien, Steven Prideaux, and Timothy Chevassut Copyright © 2014 Emma Conway O’Brien et al. All rights reserved. Results of a Prospective Study of High-Dose or Conventional Anthracycline-Cyclophosphamide Regimen Plus Radiotherapy for Localized Adult Non-Hodgkin’s Primary Bone Lymphoma Sun, 02 Mar 2014 14:07:12 +0000 Background. Primary bone lymphoma (PBL) is a rare entity that has only been reviewed in one prospective and small retrospective studies, from which it is difficult to establish treatment guidelines. We prospectively evaluated high-dose or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL. Patients and Methods. The GOELAMS prospective multicenter study (1986–1998) enrolled adults with localized high-grade PBL according to age and performance status (PS). Patients <60 years received a high-dose CHOP regimen (VCAP) and those ≥60 years a conventional anthracycline-cyclophosphamide regimen (VCEP-bleomycin); all received intrathecal chemotherapy and local radiotherapy. Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7), 39% had poor PS ≥2. With a median follow-up of 8 years, overall survival, event-free survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no significant difference between treatment groups. Poor PS was significantly associated with shorter OS and EFS. Conclusions. Our results confirm the efficacy of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide did not improve the outcome. VCEP-bleomycin is effective and well tolerated for old patients. The intensification must be considered for patients with PS ≥2, a poor prognostic factor. A. Schmidt-Tanguy, R. Houot, S. Lissandre, J. F. Abgrall, P. Casassus, P. Rodon, B. Desablens, J. P. Marolleau, R. Garidi, T. Lamy, M.-P. Moles-Moreau, and G. Damaj Copyright © 2014 A. Schmidt-Tanguy et al. All rights reserved. Influence of the Clinical Status on Stress Reticulocytes, CD 36 and CD 49d of SSFA2 Homozygous Sickle Cell Patients Followed in Abidjan Thu, 27 Feb 2014 07:06:19 +0000 Background and Objectives. Interactions between sickle cells involving CD 49d, CD36, and the vascular endothelium may initiate vasoocclusion leading to acute painful episodes and multiple organ failure. Materials and Methods. We selected 60 SS patients who had never been treated by hydroxyurea. We performed a total blood count. We identified with immunophenotyping by flow cytometry total reticulocytes their distribution according to the degree of maturity (mature, intermediate, very immature) and CD 36+ and CD 49d+ antigens. Stress reticulocytes corresponded to the sum of intermediate and immature cells. Results. Subjects in crisis had more total reticulocytes and very immature reticulocytes than subjects in stationary phase (). During the crisis, total CD 36+ reticulocytes (214 870 ± 107 584/μL versus 148 878 ± 115 024/μL; ) and the very immature CD 36+ reticulocytes (28.9 ± 7.9% versus 23.0 ± 6.4%; ) increased. The clinical status had no impact on CD 49d+ reticulocytes. Conclusion. The rates of stress reticulocytes in general and those expressing CD 49d and CD 36 were very high. The clinical status had an influence on CD 36+ reticulocytes. The expression of adhesion molecules is only one of the parameters involved in sickle cell disease crisis. Duni Sawadogo, Aïssata Tolo-Dilkébié, Mahawa Sangaré, Nelly Aguéhoundé, Hermance Kassi, and Toussaint Latte Copyright © 2014 Duni Sawadogo et al. All rights reserved. Frequency and Prognostic Relevance of FLT3 Mutations in Saudi Acute Myeloid Leukemia Patients Thu, 20 Feb 2014 13:35:49 +0000 The Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that plays a key role in cell survival, proliferation, and differentiation of hematopoietic stem cells. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia (AML). AML patients with FLT3 internal tandem duplication (ITD) mutations have poor cure rates the prognostic significance of point mutations; tyrosine kinase domain (TKD) is still unclear. We analyzed the frequency of FLT3 mutations (ITD and D835) in patients with AML at diagnosis; no sufficient data currently exist regarding FLT3 mutations in Saudi AML patients. This study was aimed at evaluating the frequency of FLT3 mutations in patients with AML and its significance for prognosis. The frequency of FLT3 mutations in our study (18.56%) was lower than many of the reported studies, FLT3-ITD mutations were observed in 14.4%, and FLT3-TKD in 4.1%, of 97 newly diagnosed AML patients (82 adult and 15 pediatric). Our data show significant increase of FLT3 mutations in male more than female (13 male, 5 female). Our results support the view that FLT3-ITD mutation has strong prognostic factor in AML patients and is associated with high rate of relapse, and high leucocytes and blast count at diagnosis and relapse. Ghaleb Elyamany, Mohammad Awad, Kamal Fadalla, Mohamed Albalawi, Mohammad Al Shahrani, and Abdulaziz Al Abdulaaly Copyright © 2014 Ghaleb Elyamany et al. All rights reserved. Procoagulant Phospholipids and Tissue Factor Activity in Cerebrospinal Fluid from Patients with Intracerebral Haemorrhage Mon, 17 Feb 2014 14:02:31 +0000 Brain contains large amounts of tissue factor, the major initiator of the coagulation cascade. Neuronal apoptosis after intracerebral haemorrhage (ICH) leads to the shedding of procoagulant phospholipids (PPLs). The aim of this study was to investigate the generation of PPL, tissue factor activity (TFa), and D-Dimer (D-Di) in the cerebrospinal fluid (CSF) at the acute phase of ICH in comparison with other brain diseases and to examine the relationship between these factors and the outcome of ICH. CSF was collected from 112 patients within 48 hours of hospital admission. Thirty-one patients with no neurological or biochemical abnormalities were used to establish reference range in the CSF (“controls”). Thirty had suffered an ICH, and 51 other neurological diagnoses [12: ventricular drainage following brain surgery, 13: viral meningitis, 15: bacterial meningitis, and 11 a neurodegenerative disease (NDD)]. PPL was measured using a factor Xa-based coagulation assay and TFa by one home test. PPL, D-Di, and TFa were significantly higher () in the CSF of patients with ICH than in controls. TFa levels were significantly () higher in ICH than in patients with meningitides or NDD. Higher levels () of TFa were observed in patients with ICH who died than in survivors. TFa measurement in the CSF of patients with ICH could constitute a new prognostic marker. Patrick Van Dreden, Guy Hue, Jean-François Dreyfus, Barry Woodhams, and Marc Vasse Copyright © 2014 Patrick Van Dreden et al. All rights reserved. The Observation Report of Red Blood Cell Morphology in Thailand Teenager by Using Data Mining Technique Thu, 13 Feb 2014 16:21:00 +0000 It is undeniable that laboratory information is important in healthcare in many ways such as management, planning, and quality improvement. Laboratory diagnosis and laboratory results from each patient are organized from every treatment. These data are useful for retrospective study exploring a relationship between laboratory results and diseases. By doing so, it increases efficiency in diagnosis and quality in laboratory report. Our study will utilize J48 algorithm, a data mining technique to predict abnormality in peripheral blood smear from 1,362 students by using 13 data set of hematological parameters gathered from automated blood cell counter. We found that the decision tree which is created from the algorithm can be used as a practical guideline for RBC morphology prediction by using 4 hematological parameters (MCV, MCH, Hct, and RBC). The average prediction of RBC morphology has true positive, false positive, precision, recall, and accuracy of 0.940, 0.050, 0.945, 0.940, and 0.943, respectively. A newly found paradigm in managing medical laboratory information will be helpful in organizing, researching, and assisting correlation in multiple disciplinary other than medical science which will eventually lead to an improvement in quality of test results and more accurate diagnosis. Sarawut Saichanma, Sucha Chulsomlee, Nonthaya Thangrua, Pornsuri Pongsuchart, and Duangmanee Sanmun Copyright © 2014 Sarawut Saichanma et al. All rights reserved. In Vitro Whole Blood Clot Lysis for Fibrinolytic Activity Study Using D-Dimer and Confocal Microscopy Tue, 11 Feb 2014 00:00:00 +0000 This study aimed to evaluate in vitro whole blood (WB) clot lysis method for the assessment of fibrinolytic activity. Standardized unresected (uncut) retracted WB clot was incubated in pool platelet poor plasma (PPP) for varying incubation times and in streptokinase (SK) at different concentrations. The fibrinolytic activity was assessed by D-dimer (DD), confocal microscopy, and clot weight. DD was measured photometrically by immunoturbidimetric method. There was a significant difference in mean DD levels according to SK concentrations (). The mean according to the SK concentrations of 5, 30, 50, and 100 IU/mL was: , , and  μg/mL. There were no significant changes of clot weight at different SK concentrations. Gradual loss and increased branching of fibrin in both PPP and SK were observed. Quantitation of DD and morphology of fibrin loss as observed by the imaging features are in keeping with fibrinolytic activity. Combination of DD levels and confocal microscopic features was successfully applied to evaluate the in vitro WB clot lysis method described here. Abuzar Elnager, Wan Zaidah Abdullah, Rosline Hassan, Zamzuri Idris, Nadiah Wan Arfah, S. A. Sulaiman, and Zulkifli Mustafa Copyright © 2014 Abuzar Elnager et al. All rights reserved. Plasma and Red Cell Reference Intervals of 5-Methyltetrahydrofolate of Healthy Adults in Whom Biochemical Functional Deficiencies of Folate and Vitamin B12 Had Been Excluded Wed, 15 Jan 2014 15:27:30 +0000 5-Methyltetrahydrofolate (5-MTHF) is the predominant form of folate and a strong determinant of homocysteine concentrations. There is evidence that suboptimal 5-MTHF availability is a risk factor for cardiovascular disease independent of homocysteine. The analysis of folates remains challenging and is almost exclusively limited to the reporting of “total” folate rather than individual molecular forms. The purpose of this study was to establish the reference intervals of 5-MTHF in plasma and red cells of healthy adults who had been prescreened to exclude biochemical evidence of functional deficiency of folate and/or vitamin B12. Functional folate and vitamin B12 status was assessed by respective plasma measurements of homocysteine and methylmalonic acid in 144 healthy volunteers, aged 19–64 years. After the exclusion of 10 individuals, values for 134 subjects were used to establish the upper reference limits for homocysteine (13 μmol/L females and 15 μmol/L males) and methylmalonic acid (430 nmol/L). Subjects with values below these cutoffs were designated as folate and vitamin B12 replete and their plasma and red cell 5-MTHF reference intervals determined, : 6.6–39.9 nmol/L and 223–1041 nmol/L, respectively. The application of these intervals will assist in the evaluation of folate status and facilitate studies to evaluate the relationship of 5-MTHF to disease. Agata Sobczyńska-Malefora, Dominic J. Harrington, Kieran Voong, and Martin J. Shearer Copyright © 2014 Agata Sobczyńska-Malefora et al. All rights reserved. Erratum to “DNMT3A Mutations in Patients with Acute Myeloid Leukemia in South Brazil” Wed, 08 Jan 2014 12:58:46 +0000 Annelise Pezzi, Lauro Moraes, Vanessa Valim, Bruna Amorin, Gabriela Melchiades, Fernanda Oliveira, Maria Aparecida da Silva, Ursula Matte, Maria S. Pombo-de-Oliveira, Rosane Bittencourt, Liane Daudt, and Lucia Silla Copyright © 2014 Annelise Pezzi et al. All rights reserved. Characteristics and Results of the Treatment of Multiple Myeloma in the Subject under the Age of 65 at the University Hospital of Yopougon in Abidjan, Côte d’Ivoire Thu, 26 Dec 2013 07:49:47 +0000 We retrospectively studied 30 cases of multiple myeloma in patients under the age of 65, diagnosed from 1991 to 2005 in the clinical hematology department of the University Hospital of Yopougon that is a hospital incidence of 2.9 cases/year. The age of patients ranged from 34 to 64 years, with a mean age of 49 years and a sex ratio of 1.73. The professional activity was variable with 3% of radiographers and 10% of farmers. Clinically, the dominant sign was bone pain in 83% of cases. Myeloma was secretory in 93% of cases. It was Ig G-type in 86%, kappa-type in 66% of cases. 86% of patients were anemic, 20% had creatinine >20 mg/L, and 10% had serum calcium >120 mg/L. Geodes were found in 80% of cases. 53% were at stage III of DURIE and SALMON. Complications were infectious (33%), renal (20%), and hemorrhagic (7%). Chemotherapy regimens were VAD (10%), VMCP (30%), and VMCP/VBAP (60%) with 47% of partial responses, 33% of stable disease, and 7% of very good quality partial responses. The outcome developed towards death in 37% and causes of death were renal in 46% of cases. The median survival was only 5.1 months. Diebkilé Aïssata Tolo, Duni Sawadogo, Danho Clotaire Nanho, Boidy Kouakou, N’Dogomo Méité, Roméo Ayémou, Paul Kouéhion, Mozart Konan, Yassongui Mamadou Sékongo, Emeraude N’Dhatz, Ismaël Kamara, Alexis Silué, Kouassi Gustave Koffi, and Ibrahima Sanogo Copyright © 2013 Diebkilé Aïssata Tolo et al. All rights reserved. MicroRNAs as Haematopoiesis Regulators Tue, 24 Dec 2013 14:54:45 +0000 The production of different types of blood cells including their formation, development, and differentiation is collectively known as haematopoiesis. Blood cells are divided into three lineages erythriod (erythrocytes), lymphoid (B and T cells), and myeloid (granulocytes, megakaryocytes, and macrophages). Haematopoiesis is a complex process regulated by several mechanisms including microRNAs (miRNAs). miRNAs are small RNAs which regulate the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells. Evidence shows that miRNAs play an important role in haematopoiesis; for example, myeloid and erythroid differentiation is blocked by the overexpression of miR-15a. miR-221, miR-222, and miR-24 inhibit the erythropoiesis, whereas miR-150 plays a role in B and T cell differentiation. miR-146 and miR-10a are downregulated in megakaryopoiesis. Aberrant expression of miRNAs was observed in hematological malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myelomas, and B cell lymphomas. In this review we have focused on discussing the role of miRNA in haematopoiesis. Ram Babu Undi, Ravinder Kandi, and Ravi Kumar Gutti Copyright © 2013 Ram Babu Undi et al. All rights reserved. Approach to Management of Thrombotic Thrombocytopenic Purpura at University of Cincinnati Mon, 16 Dec 2013 14:32:46 +0000 Thrombotic Thrombocytopenic Purpura (TTP) is a rare hematologic emergency, congenital or acquired, characterized by ischemic damage of various organs because of platelet aggregation. It is the common name for adults with microangiopathic hemolytic anemia, thrombocytopenia, with or without neurologic or renal abnormalities, and without another etiology; children without renal failure are also described as TTP. Plasma exchange (PE) is the main stay of treatment in combination with steroids and immunosuppressive therapies. The monoclonal antibody against CD20 Rituximab decreases the production of antibodies from B lymphocytes and it is used for antibodies-mediated diseases including TTP. We present our data on retrospective analysis of rituximab in treatment of TTP at University of Cincinnati in a series of 22 patients from 1997 to 2009. Our results showed that PE with immunosuppressive therapy resulted in decreased duration of PE, relapse rate, and increased duration of remission in patients with TTP. N. Abdel Karim, S. Haider, C. Siegrist, N. Ahmad, A. Zarzour, J. Ying, Z. Yasin, and R. Sacher Copyright © 2013 N. Abdel Karim et al. All rights reserved. Sonoclot Signature Analysis in Patients with Liver Disease and Its Correlation with Conventional Coagulation Studies Wed, 11 Dec 2013 14:34:27 +0000 Introduction. Liver disease patients have complex hemostatic defects leading to a delicate, unstable balance between bleeding and thrombosis. Conventional tests such as PT and APTT are unable to depict these defects completely. Aims. This study aimed at analyzing the abnormal effects of liver disease on sonoclot signature by using sonoclot analyzer (which depicts the entire hemostatic pathway) and assessing the correlations between sonoclot variables and conventional coagulation tests. Material and Methods. Clinical and laboratory data from fifty inpatients of four subgroups of liver disease, including decompensated cirrhosis, chronic hepatitis, cirrhosis with HCC and acute-on-chronic liver failure were analyzed. All patients and controls were subjected to sonoclot analysis and correlated with routine coagulation parameters including platelet count, PT, APTT, fibrinogen, and D-dimer. Results. The sonoclot signatures demonstrated statistically significant abnormalities in patients with liver disease as compared to healthy controls. PT and APTT correlated positively with SONACT ( and <0.0015, resp.) while platelet count and fibrinogen levels depicted significant positive and negative correlations with clot rate and SONACT respectively. Conclusion. Sonoclot analysis may prove to be an efficient tool to assess coagulopathies in liver disease patients. Clot rate could emerge as a potential predictor of hypercoagulability in these patients. Priyanka Saxena, Chhagan Bihari, Archana Rastogi, Savita Agarwal, Lovkesh Anand, and Shiv Kumar Sarin Copyright © 2013 Priyanka Saxena et al. All rights reserved. Clinically Significant Minor Blood Group Antigens amongst North Indian Donor Population Mon, 09 Dec 2013 16:24:32 +0000 Background. Racial differences in blood group antigen distribution are common and may result in striking and interesting findings. These differences in blood group antigen distribution are important due to their influence on the clinical practice of transfusion medicine. Study Design and Methods. This is a prospective study, involving 1000 healthy regular repeat voluntary blood donors associated with the department. The clinically significant minor blood group antigens of these donors were studied. Results. Out of 1000 healthy regular repeat voluntary blood donors, 93% were D positive and 2.8% were K positive. Amongst the Rh antigens, e was the most common (99%), followed by D (93%), C (85.1%), c (62.3%), and E (21.5%). Within the MNS blood group system, antigen frequency was M (88%), N (57.5%), S (57.8%), and s (87.5%). Within the Duffy blood group system, antigen frequency was (87.3%) and (58.3%). Conclusions. This data base will help us to prevent alloimmunisation in young females, pregnant women, and patients who are expected to require repeated transfusions in life by providing them with antigen matched blood. Antigen negative blood can also be made available without delay to already alloimmunized multitransfused patients. Divjot Singh Lamba, Ravneet Kaur, and Sabita Basu Copyright © 2013 Divjot Singh Lamba et al. All rights reserved. Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia Tue, 29 Oct 2013 14:32:06 +0000 Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients. Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients’ series. Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients’ followup was 32 months (range 4–228). Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment ( and , resp.) and overall survival ( and , resp.). They also correlated with β2-microglobulin ( and , resp.), serum albumin ( for summated sFLC), hemoglobin (), abnormal LDH ( and , resp.), Binet stage () and with the presence of beta symptoms ( for summated sFLC). Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters. Katerina Sarris, Dimitrios Maltezas, Efstathios Koulieris, Vassiliki Bartzis, Tatiana Tzenou, Sotirios Sachanas, Eftychia Nikolaou, Anna Efthymiou, Katerina Bitsani, Maria Dimou, Theodoros P. Vassilakopoulos, Marina Siakantaris, Maria K. Angelopoulou, Flora Kontopidou, Panagiotis Tsaftaridis, Nikolitsa Kafasi, Gerasimos A. Pangalis, Panayiotis P. Panayiotidis, Stephen Harding, and Marie-Christine Kyrtsonis Copyright © 2013 Katerina Sarris et al. All rights reserved. Management of Adenovirus in Children after Allogeneic Hematopoietic Stem Cell Transplantation Mon, 28 Oct 2013 14:05:15 +0000 Adenovirus (ADV) can cause significant morbidity and mortality in children following haematopoietic stem cell transplantation (HSCT), with an incidence of up to 27% and notable associated morbidity and mortality. T-cell depleted grafts and severe lymphopenia are major risk factors for the development of adenovirus disease after HSCT. Current antiviral treatments are at best virostatic and may have significant side effects. Adoptive transfer of donor-derived virus-specific T cells has been shown to be an effective strategy for the prevention and treatment of ADV infection after HSCT. Here we review progress in the field and present a pathway for the management of adenovirus in the posttransplant setting. Winnie WY Ip and Waseem Qasim Copyright © 2013 Winnie WY Ip and Waseem Qasim. All rights reserved. Achievement of Therapeutic Goals with Low-Dose Imiglucerase in Gaucher Disease: A Single-Center Experience Mon, 28 Oct 2013 13:30:55 +0000 Gaucher disease, a lysosomal storage disorder, is a multisystem disorder with variable and unpredictable onset and severity. Disease-specific enzyme replacement therapy (ERT) has been shown to reverse or ameliorate disease-specific hepatosplenomegaly and anemia and thrombocytopenia. ERT also impacts bone manifestations, including bone crises, bone pain, and appearance of new osteonecrosis, and improves bone mineral density to varying degrees. The objective of this study was to assess achievement of predefined therapeutic goals based on international registry outcomes for Israeli patients with Gaucher disease receiving imiglucerase for four consecutive years on a low-dose regimen followed in a single center. All data were taken from patient files. The therapeutic goals were taken from standards published in the literature for disease-specific clinical parameters. Among 164 patients at baseline, values for spleen and liver volumes, hemoglobin and platelet counts, and Z-scores for lumbar spine and femoral were significantly different from the goal. After four years ERT, there was a significant improvement () in each of the therapeutic goal parameters from baseline. 15.2% of these patients achieved all hematology-visceral goals. In children, there was achievement of linear growth and puberty. This survey highlights the good overall response in symptomatic patients receiving low-dose ERT with imiglucerase in Israel. Irina Tukan, Irith Hadas-Halpern, Gheona Altarescu, Ayala Abrahamov, Deborah Elstein, and Ari Zimran Copyright © 2013 Irina Tukan et al. All rights reserved. Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog Tue, 01 Oct 2013 09:01:04 +0000 Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by progressive peripheral blood cytopenias associated with ineffective myelopoiesis. They are typically considered neoplasms because of frequent genetic aberrations and patient-limited survival with progression to acute myeloid leukemia (AML) or death related to the consequences of bone marrow failure including infection, hemorrhage, and iron overload. A progression to AML has always been recognized among the myeloproliferative disorders (MPD) but occurs only rarely among those with essential thrombocythemia (ET). Yet, the World Health Organization (WHO) has chosen to apply the designation myeloproliferative neoplasms (MPN), for all MPD but has not similarly recommended that all MDS become the myelodysplastic neoplasms (MDN). This apparent dichotomy may reflect the extremely diverse nature of MDS. Moreover, the term MDS is occasionally inappropriately applied to hematologic disorders associated with acquired morphologic myelodysplastic features which may rather represent potentially reversible hematological responses to immune-mediated factors, nutritional deficiency states, and disordered myelopoietic responses to various pharmaceutical, herbal, or other potentially myelotoxic compounds. We emphasize the clinical settings, and the histopathologic features, of such AMD that should trigger a search for a reversible underlying condition that may be nonneoplastic and not MDS. Ethan A. Natelson and David Pyatt Copyright © 2013 Ethan A. Natelson and David Pyatt. All rights reserved. Imatinib Mesylate Effectiveness in Chronic Myeloid Leukemia with Additional Cytogenetic Abnormalities at Diagnosis among Black Africans Wed, 29 May 2013 16:45:42 +0000 Imatinib mesylate provides good results in the treatment of CML in general. But what about the results of this treatment in CML associated with additional cytogenetic abnormalities at diagnosis among black Africans? For this, we retrospectively studied 27 cases of CML associated with additional cytogenetic abnormalities, diagnosed in the department of clinical hematology of the University Hospital of Yopougon in Côte d'Ivoire, from May 2005 to October 2011. The age of patients ranged from 13 to 68 years, with a mean age of 38 years and a sex ratio of 2. Patients were severely symptomatic with a high Sokal score of 67%. CML in chronic phase accounted for 67%. The prevalence of additional cytogenetic abnormalities was 29.7%. There were variants of the Philadelphia chromosome (18.5%), trisomy 8 (14.8%), complex cytogenetic abnormalities (18.5%), second Philadelphia chromosome (14.8%), and minor cytogenetic abnormalities (44.4%). Complete hematologic remission was achieved in 59%, with 52% of major cytogenetic remission. The outcome was fatal in 37% of patients. Death was related in 40% to hematologic toxicity and in 30% to acutisation. The median survival was 40 months. Tolo Diebkilé Aïssata, Duni Sawadogo, Clotaire Nanho, Boidy Kouakou, N'dogomo Meité, N'Dhatz Emeuraude, Ayémou Roméo, Sekongo Yassongui Mamadou, Paul Kouéhion, Konan Mozart, Gustave Koffi, and Ibrahima Sanogo Copyright © 2013 Tolo Diebkilé Aïssata et al. All rights reserved. Lenalidomide in the Treatment of Lymphoproliferative Disorders and Multiple Myeloma Tue, 16 Apr 2013 14:48:28 +0000 Anna Marina Liberati, Umberto Vitolo, Antonio Palumbo, and Agostino Cortelezzi Copyright © 2013 Anna Marina Liberati et al. All rights reserved. Thrombin-Accelerated Quick Clotting Serum Tubes: An Evaluation with 22 Common Biochemical Analytes Wed, 03 Apr 2013 11:03:08 +0000 Clot activator serum tubes have significantly improved turnaround times for result reporting compared to plain tubes. With increasing workload and service performance expectations confronting clinical laboratories with high-volume testing and with particular emphasis on critical analytes, attention has focussed on preanalytical variables that can be improved. We carried out a field study on the test performance of BD vacutainer rapid serum tubes (RSTs) compared to current institutional issued BD vacutainer serum separator tubes (SSTs) in its test result comparability, clotting time, and stability on serum storage. Data from the study population () of patients attending outpatient clinics and healthy subjects showed that results for renal, liver, lipids, cardiac, thyroid, and prostate biochemical markers were comparable between RSTs and SSTs. Clotting times of the RSTs were verified to be quick with a median time of 2.05 min. Analyte stability on serum storage at 4°C showed no statistically significant deterioration except for bicarbonate, electrolytes, and albumin over a period of 4 days. In conclusion, RSTs offered savings in the time required for the clotting process of serum specimens. This should translate to further trimming of the whole process from blood collection to result reporting without too much sacrifice on test accuracy and performance compared to the current widely used SSTs in most clinical laboratories. Wai-Yoong Ng and Chin-Pin Yeo Copyright © 2013 Wai-Yoong Ng and Chin-Pin Yeo. All rights reserved.