Advances in Hematology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Impaired Fibrinolysis in Angiographically Documented Coronary Artery Disease Mon, 23 Feb 2015 12:03:43 +0000 Impaired fibrinolysis may predispose to coronary artery disease (CAD). Hypofibrinolysis due to high levels of plasminogen activator inhibitor-1 (PAI-1) has been reported in CAD. A novel regulator of fibrinolytic activity, thrombin activatable fibrinolysis inhibitor (TAFI), has attracted attention in recent years. It acts by blocking the formation of a ternary complex of plasminogen, fibrin, and tissue plasminogen activator (t-PA). Previously ambiguous results regarding TAFI levels have been reported in CAD. We measured plasma levels of PAI-1 and TAFI antigen in 123 patients with age ranging from 40 to 65 years who had been submitted to coronary angiography and assessed the association of these markers with the extent of stenosis in three groups: angiographically normal artery (NAn), mild to moderate atheromatosis (MA), and severe atheromatosis (SA). Plasma levels of PAI-1 were increased in patients with severe atheromatosis compared to mild/moderate atheromatosis or to normal patients (66.60, 40.50, and 34.90 ng/mL, resp.; P < 0.001). For TAFI no difference was found between different groups. When patients were grouped in only two groups based on clinical cut-off point for intervention (stenosis less than or above 70%) we found increased plasma levels for PAI-1 (37.55 and 66.60 ng/mL, resp.; P < 0.001) and decreased plasma levels for TAFI (5.20 and 4.53 μg/mL, resp.; P = 0.04) in patients with stenosis above 70%. No difference was found in PAI-1 or TAFI levels comparing the number of affected vessels. Conclusion. As evidenced by a raised level of PAI-1 antigen, one can suggest an impaired fibrinolysis in stable CAD, although no correlation with the number of affected vessels was found. Curiously, a decreased plasma level of total TAFI levels was observed in patients with stenosis above 70%. Further studies measuring functional TAFI are required in order to elucidate its association with the extent of degree of atheromatosis. Adriano Basques Fernandes, Luciana Moreira Lima, Marinez Oliveira Sousa, Vicente de Paulo Coelho Toledo, Rashid Saeed Kazmi, Bashir Abdulgader Lwaleed, and Maria das Graças Carvalho Copyright © 2015 Adriano Basques Fernandes et al. All rights reserved. RhD Specific Antibodies Are Not Detectable in HLA-DRB1 Mice Challenged with Human RhD Positive Erythrocytes Wed, 31 Dec 2014 11:57:31 +0000 The ability to study the immune response to the RhD antigen in the prevention of hemolytic disease of the fetus and newborn has been hampered by the lack of a mouse model of RhD immunization. However, the ability of transgenic mice expressing human HLA DRB1 to respond to immunization with purified RhD has allowed this question to be revisited. In this work we aimed at inducing anti-RhD antibodies by administering human RhD+ RBCs to mice transgenic for the human HLA DRB1 as well as to several standard inbred and outbred laboratory strains including C57BL/6, DBA1/J, CFW(SW), CD1(ICR), and NSA(CF-1). DRB1 mice were additionally immunized with putative extracellular immunogenic RhD peptides. DRB1 mice immunized with RhD+ erythrocytes developed an erythrocyte-reactive antibody response. Antibodies specific for RhD could not however be detected by flow cytometry. Despite this, DRB1 mice were capable of recognizing immunogenic sequences of Rh as injection with Rh peptides induced antibodies reactive with RhD sequences, consistent with the presence of B cell repertoires capable of recognizing RhD. We conclude that while HLA DRB1 transgenic mice may have the capability of responding to immunogenic sequences within RhD, an immune response to human RBC expressing RhD is not directly observed. Lidice Bernardo, Gregory A. Denomme, Kunjlata Shah, and Alan H. Lazarus Copyright © 2014 Lidice Bernardo et al. All rights reserved. H. pylori May Not Be Associated with Iron Deficiency Anemia in Patients with Normal Gastrointestinal Tract Endoscopy Results Wed, 31 Dec 2014 00:10:37 +0000 Background. The aim of this study was to investigate the association between iron deficiency anemia and H. pylori in patients with normal gastrointestinal tract endoscopy results. Materials and Methods. A total of 117 male patients with normal gastrointestinal tract endoscopy results were included in this retrospective study. The study and control groups included 69 and 48 patients with and without iron deficiency anemia, respectively. The prevalence of H. pylori, the number of RBCs, and the levels of HGB, HTC, MCV, iron, and ferritin were calculated and compared. Results. There was no statistically significant difference found between the groups according to the prevalence of H. pylori (65.2% versus 64.6%, ). Additionally, the levels of RBCs, HGB, HTC, MCV, iron, and ferritin in the patients in the study group were lower than those in the control group (). Finally, there was no association between iron deficiency anemia and H. pylori (OR 1.02, Cl 95% 0.47–2.22, and ). Conclusion. H. pylori is not associated with iron deficiency anemia in male patients with normal gastrointestinal tract endoscopy results. Tayyibe Saler, Şakir Özgür Keşkek, Sibel Kırk, Süleyman Ahbab, and Gülay Ortoğlu Copyright © 2014 Tayyibe Saler et al. All rights reserved. Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction Sun, 14 Dec 2014 12:34:27 +0000 Persistent polyclonal B cell lymphocytosis (PPBL) is a rare disorder, diagnosed primarily in adult female smokers and characterized by an expansion of CD19+CD27+IgM+ memory B cells, by the presence of binucleated lymphocytes, and by a moderate elevation of serum IgM. The clinical course is usually benign, but it is not known whether or not PPBL might be part of a process leading to the emergence of a malignant proliferative disorder. In this study we sought to investigate the functional response of B cells from patients with PPBL by use of an optimal memory B cell culture model based on the CD40-CD154 interaction. We found that the proliferation of PPBL B cells was almost as important as that of B cells from normal controls, resulting in high immunoglobulin secretion with in vitro isotypic switching. We conclude that the CD40-CD154 activation pathway is functional in the memory B cell population of PPBL patients, suggesting that the disorder may be due to either a dysfunction of other cells in the microenvironment or a possible defect in another B cell activation pathway. Emmanuelle Dugas-Bourdages, Sonia Néron, Annie Roy, André Darveau, and Robert Delage Copyright © 2014 Emmanuelle Dugas-Bourdages et al. All rights reserved. Aromatic Amines Exert Contrasting Effects on the Anticoagulant Effect of Acetaldehyde upon APTT Mon, 08 Dec 2014 00:10:09 +0000 The pharmacological effects of amphetamine, procaine, procainamide, DOPA, isoproterenol, and atenolol upon activated partial thromboplastin time in the absence and presence of acetaldehyde have been investigated. In the absence of acetaldehyde, amphetamine and isoproterenol exhibit a procoagulant effect upon activated partial thromboplastin time, whereas atenolol and procaine display anticoagulant effects upon activated partial thromboplastin time. DOPA and procainamide do not alter activated partial thromboplastin time. Premixtures of procaine with acetaldehyde produce an additive anticoagulant effect on activated partial thromboplastin time, suggesting independent action of these compounds upon clotting factors. Premixtures of amphetamine with acetaldehyde, as well as atenolol with acetaldehyde, generate a detoxication of the anticoagulant effect of acetaldehyde upon activated partial thromboplastin time. A similar statistically significant decrease in activated partial thromboplastin time is seen when procainamide is premixed with acetaldehyde for 20 minutes at room temperature. Premixtures of DOPA and isoproterenol with acetaldehyde do not affect an alteration in activated partial thromboplastin time relative to acetaldehyde alone. Hence, a selective interaction of atenolol, procaine, and amphetamine with acetaldehyde to produce detoxication of the acetaldehyde is suggested, undoubtedly due to the presence of amino, hydroxyl, or amide groups in these drugs. La'Teese Hall, Sarah J. Murrey, and Arthur S. Brecher Copyright © 2014 La'Teese Hall et al. All rights reserved. Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update Thu, 27 Nov 2014 07:32:43 +0000 Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis. Paola Villafuerte-Gutierrez, Lucia Villalon, Juan E. Losa, and Cesar Henriquez-Camacho Copyright © 2014 Paola Villafuerte-Gutierrez et al. All rights reserved. Post-Autologous (ASCT) Stem Cell Transplant Therapy in Multiple Myeloma Mon, 24 Nov 2014 07:27:51 +0000 Autologous stem cell transplant (ASCT) is the standard of care in transplant-eligible multiple myeloma patients and is associated with significant improvement in progression-free survival (PFS), complete remission rates (CR), and overall survival (OS). However, majority of patients eventually relapse, with a median PFS of around 36 months. Relapses are harder to treat and prognosis declines with each relapse. Achieving and maintaining “best response” to initial therapy is the ultimate goal of first-line treatment and sustained CR is a powerful surrogate for extended survival especially in high-risk multiple myeloma. ASCT is often followed by consolidation/maintenance phase to deepen and/or maintain the response achieved by induction and ASCT. Novel agents like thalidomide, lenalidomide, and bortezomib have been used as single agents or in combination. Thalidomide use has been associated with a meaningful improvement in PFS and EFS, however, with substantial side effects. Data with lenalidomide maintenance after-ASCT is favorable, but the optimal duration of lenalidomide maintenance is still unclear. Bortezomib use has been associated with superior outcomes, predominantly in high-risk myeloma patients. Combination regimens utilizing a proteasome inhibitor (i.e., bortezomib) with an immunomodulatory drug (thalidomide or lenalidomide) have provided the best outcomes. This review article serves as a review of the best available evidence in post-ASCT approaches in multiple myeloma. Zeina Al-Mansour and Muthalagu Ramanathan Copyright © 2014 Zeina Al-Mansour and Muthalagu Ramanathan. All rights reserved. Outcome of Adolescents with Acute Lymphoblastic Leukemia Treated by Pediatrics versus Adults Protocols Mon, 17 Nov 2014 12:01:16 +0000 Objective. Several studies showed better outcome in adolescents and young adults with acute lymphoblastic leukemia (ALL) treated with pediatrics protocols than similarly aged patients treated with adults protocols, while other studies showed similar outcome of both protocols. We conducted this study to compare the outcome of our pediatrics and adults therapeutic protocols in treatment of adolescents ALL. Patients and Methods. We retrospectively reviewed files of 86 consecutive adolescent ALL patients aged 15–18 years who attended to outpatients clinic from January 2003 to January 2010. 32 out of 86 were treated with pediatrics adopted BFM 90 high risk protocol while 54 were treated with adults adopted BFM protocol. We analyzed the effect of different treatment protocols on achieving complete remission (CR), disease-free survival (DFS), and overall survival (OS). Results. The 2 patients groups have almost similar characteristics. The CR was significantly higher in pediatrics protocol 96% versus 89% . Despite the fact that the toxicity profiles were higher in pediatrics protocol, they were tolerable. Moreover, the pediatrics protocol resulted in superior outcome in EFS 67% versus 39% (), DFS 65% versus 41% , and OS 67% versus 45% . Conclusion. Our study’s findings recommend using intensified pediatrics inspired protocol to treat adolescents with acute lymphoblastic leukemia. Abeer Ibrahim, Amany Ali, and Mahmoud M. Mohammed Copyright © 2014 Abeer Ibrahim et al. All rights reserved. Evaluation of Prothrombin Time and Activated Partial Thromboplastin Time in Hypertensive Patients Attending a Tertiary Hospital in Calabar, Nigeria Sun, 16 Nov 2014 06:20:03 +0000 Introduction. Several biomedical findings have established the effects of hypertension on haemostasis and roles of blood coagulation products in the clinical course of hypertension. Methods. This cross-sectional study aimed at determining effects of hypertension on prothrombin time (PT) and activated partial thromboplastin time (APTT) in hypertensive patients in comparison with normotensive subjects attending a tertiary hospital in Calabar. Forty-two (42) hypertensive patients and thirty-nine (39) normotensive control subjects were investigated for PT and APTT using Quick one-stage methods. Results. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) correlated positively with APTT (, ; ) in hypertensive patients. DBP, SBP, PT, and APTT were significantly higher in hypertensive patients when compared to normotensive subjects (). DBP correlated negatively with duration of illness (; ) in hypertensive patients and positively with age of normotensive subjects (; ). Conclusion. The results obtained indicated that measurements of PT and APTT may serve as indices for evaluating hemostatic abnormalities in hypertensive patients and guide for antihypertensive therapy. However, to have better understanding of hemostatic activities in hypertension, it is recommended to conduct D-dimer, platelet factors, and protein assays. Nnamani Nnenna Adaeze, Anthony Uchenna Emeribe, Idris Abdullahi Nasiru, Adamu Babayo, and Emmanuel K. Uko Copyright © 2014 Nnamani Nnenna Adaeze et al. All rights reserved. Determining Risk Factors of Bleeding in Patients on Warfarin Treatment Sun, 09 Nov 2014 06:50:05 +0000 Background. Warfarin is a commonly used oral anticoagulant agent. The most common adverse effects of warfarin are bleeding complications. Methods. We performed a 1-year retrospective chart review of emergency department patients using warfarin. A total of 65 patients with bleeding disorder (study group) and 63 patients without bleeding (control group) were included, making up a total of 128 subjects. Demographic data, frequency of international normalized ratio (INR) checks, and routine blood results were extracted. Logistic regression analysis was used to determine which factors were most closely associated with bleeding complications. Results. Median age was and for study group and control group, respectively. Educational status and frequency of INR checks were similar in both groups ( and , resp.). INR levels were higher in the study group ( versus , ). Creatinine levels were also higher in the study group ( mg/dL versus  mg/dL, ). Acetylsalicylic acid use was more frequent in the study group and was associated with a 9-fold increase in bleeding complications . Conclusions. High INR levels, high creatinine levels, and acetylsalicylic acid use were associated with bleeding complications in ED patients using warfarin. Evren Uygungül, Cuneyt Ayrik, Huseyin Narci, Semra Erdoğan, İbrahim Toker, Filiz Demir, and Ulas Karaaslan Copyright © 2014 Evren Uygungül et al. All rights reserved. Eculizumab Therapy Leads to Rapid Resolution of Thrombocytopenia in Atypical Hemolytic Uremic Syndrome Wed, 22 Oct 2014 00:00:00 +0000 Eculizumab is highly effective in controlling complement activation in patients with the atypical hemolytic uremic syndrome (aHUS). However, the course of responses to the treatment is not well understood. We reviewed the responses to eculizumab therapy for aHUS. The results show that, in patients with aHUS, eculizumab therapy, when not accompanied with concurrent plasma exchange therapy, led to steady increase in the platelet count and improvement in extra-renal complications within 3 days. By day 7, the platelet count was normal in 15 of 17 cases. The resolution of hemolytic anemia and improvement in renal function were less predictable and were not apparent for weeks to months in two patients. The swift response in the platelet counts was only observed in one of five cases who received concurrent plasma exchange therapy and was not observed in a case of TMA due to gemcitabine/carboplatin. In summary, eculizumab leads to rapid increase in the platelet counts and resolution of extrarenal symptoms in patients with aHUS. Concurrent plasma exchange greatly impedes the response of aHUS to eculizumab therapy. Eculizumab is ineffective for gemcitabine/carboplatin associated TMA. Han-Mou Tsai and Elizabeth Kuo Copyright © 2014 Han-Mou Tsai and Elizabeth Kuo. All rights reserved. Prevalence and Specificity of RBC Alloantibodies in Indian Patients Attending a Tertiary Care Hospital Thu, 16 Oct 2014 08:06:46 +0000 Background. Red blood cell (RBC) alloimmunization results from genetic disparity of RBC antigens between donor and recipients. Data about alloimmunization rate in general patient population is scarce especially from resource limited countries. We undertook this study to determine prevalence and specificity of RBC alloantibodies in patients admitted in various clinical specialties at a tertiary care hospital in North India. Methods. Antibody screening was carried out in 11,235 patients on automated QWALYS 3 platform (Diagast, Loos, France). Antibody identification was carried out with an 11-cell identification panel (ID-Diapanel, Diamed GmbH, Switzerland). Results. The overall incidence of RBC alloimmunization in transfused patients was 1.4% (157/11235), with anti-E being the most common specificity (36.3%), followed by anti-D (16%), anti-c (6.4%), anti-c + E (6.4%), anti-C + D (5.1%), and anti-K (4.5%). The highest incidence of alloimmunization was observed in hematology/oncology patients (1.9%), whereas in other specialties the range was 0.7–1%. Conclusion. As alloimmunization complicates the transfusion outcomes, authors recommend pretransfusion antibody screening and issue of Rh and Kell matched blood to patients who warrant high transfusion requirements in future. Shamsuz Zaman, Rahul Chaurasia, Kabita Chatterjee, and Rakesh Mohan Thapliyal Copyright © 2014 Shamsuz Zaman et al. All rights reserved. Ethical and Clinical Aspects of Intensive Care Unit Admission in Patients with Hematological Malignancies: Guidelines of the Ethics Commission of the French Society of Hematology Wed, 01 Oct 2014 08:56:04 +0000 Admission of patients with hematological malignancies to intensive care unit (ICU) raises recurrent ethical issues for both hematological and intensivist teams. The decision of transfer to ICU has major consequences for end of life care for patients and their relatives. It also impacts organizational human and economic aspects for the ICU and global health policy. In light of the recent advances in hematology and critical care medicine, a wide multidisciplinary debate has been conducted resulting in guidelines approved by consensus by both disciplines. The main aspects developed were (i) clarification of the clinical situations that could lead to a transfer to ICU taking into account the severity criteria of both hematological malignancy and clinical distress, (ii) understanding the process of decision-making in a context of regular interdisciplinary concertation involving the patient and his relatives, (iii) organization of a collegial concertation at the time of the initial decision of transfer to ICU and throughout and beyond the stay in ICU. The aim of this work is to propose suggestions to strengthen the collaboration between the different teams involved, to facilitate the daily decision-making process, and to allow improvement of clinical practice. Sandra Malak, Jean-Jacques Sotto, Joël Ceccaldi, Philippe Colombat, Philippe Casassus, Dominique Jaulmes, Henri Rochant, Morgane Cheminant, Yvan Beaussant, Robert Zittoun, and Dominique Bordessoule Copyright © 2014 Sandra Malak et al. 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.