Advances in Hematology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Sucrose-Formulated Recombinant Factor VIII Dosing Flexibility in Prophylaxis Regimens: Experience from Postmarketing Surveillance Studies Wed, 19 Aug 2015 11:12:50 +0000 http://www.hindawi.com/journals/ah/2015/431268/ Objectives. Prophylaxis regimens for severe hemophilia A allowing more flexible dosing while maintaining efficacy may improve adherence and decrease the cost of prophylaxis. Here, we compared the clinical effectiveness of once- or twice-weekly versus ≥3-times-weekly prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS) in a “real-world” practice setting. Methods. Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A receiving ≥1 prophylaxis infusion/wk of rFVIII-FS for ≥80% of a prophylaxis observation period (≥5 months) were included. Patients were categorized based on physician-assigned treatment regimens of 1-2 prophylaxis injections/wk () or ≥3 prophylaxis injections/wk (). Descriptive statistics were determined for annualized bleeding rates (ABRs). Results. Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the 1-2 prophylaxis injections/wk group and 3.9 (1.5; 9.3) in the ≥3 prophylaxis injections/wk group. Median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower with 1-2 prophylaxis injections/wk. As an estimate of prophylaxis success, 63% (≥3 prophylaxis injections/wk) to 84% of patients (1-2 prophylaxis injections/wk) had ≤4 annualized joint bleeds. Conclusions. Dosing flexibility and successful prophylaxis with rFVIII-FS were demonstrated. Very good bleeding control was achieved with both once-twice-weekly and ≥3-times-weekly prophylaxis dosing regimens. Thomas J. Humphries, Stephan Rauchensteiner, Claudia Tückmantel, Alexander Pieper, Monika Maas Enriquez, and Prasad Mathew Copyright © 2015 Thomas J. Humphries et al. All rights reserved. Corrigendum to “Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage” Wed, 19 Aug 2015 09:55:32 +0000 http://www.hindawi.com/journals/ah/2015/526854/ Arunima Ghosh, Andy Vo, Beverly K. Twiss, Colin A. Kretz, Mary A. Jozwiak, Robert R. Montgomery, and Jordan A. Shavit Copyright © 2015 Arunima Ghosh et al. All rights reserved. Plasmablastic Lymphoma: A Review of Current Knowledge and Future Directions Tue, 18 Aug 2015 11:20:56 +0000 http://www.hindawi.com/journals/ah/2015/315289/ Plasmablastic lymphoma (PBL) is an aggressive subtype of non-Hodgkin’s lymphoma (NHL), which frequently arises in the oral cavity of human immunodeficiency virus (HIV) infected patients. PBL shows diffuse proliferation of large neoplastic cells resembling B-immunoblasts/plasmablasts, or with plasmacytic features and an immunophenotype of plasma cells. PBL remains a diagnostic challenge due to its peculiar morphology and an immunohistochemical profile similar to plasma cell myeloma (PCM). PBL is also a therapeutic challenge with a clinical course characterized by a high rate of relapse and death. There is no standard chemotherapy protocol for treatment of PBL. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens have been the backbone while more intensive regimens such as cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, high-dose cytarabine (CODOX-M/IVAC), or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) are possible options. Recently, a few studies have reported the potential value of the proteasome inhibitor bortezomib and thalidomide in PBL patients. The introduction of genes encoding artificial receptors called chimeric antigen receptors (CARs) and CAR-modified T cells targeted to the B cell-specific CD19 antigen have demonstrated promising results in multiple early clinical trials. The aim of this paper is to review the recent advances in epidemiology; pathophysiology; clinical, pathologic, and molecular characteristics; therapy; and outcome in patients with PBL. Ghaleb Elyamany, Eman Al Mussaed, and Ali Matar Alzahrani Copyright © 2015 Ghaleb Elyamany et al. All rights reserved. Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence Sun, 16 Aug 2015 08:17:17 +0000 http://www.hindawi.com/journals/ah/2015/920361/ Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed. Ali Zalpour and Thein Hlaing Oo Copyright © 2015 Ali Zalpour and Thein Hlaing Oo. All rights reserved. Prospects of Vitamin C as an Additive in Plasma of Stored Blood Sun, 09 Aug 2015 06:43:33 +0000 http://www.hindawi.com/journals/ah/2015/961049/ There is a dire necessity to improve blood storage and prolong shelf-life of blood. Very few studies have focused on oxidative stress (OS) in blood and its influence on plasma with storage. This study attempts to (i) elucidate the continuous changes occurring in plasma during storage through oxidant levels and antioxidant status and (ii) evaluate the influence of vitamin C (VC) as an additive during blood storage. Blood was drawn from male Wistar rats and stored for 25 days at 4°C. Blood samples were divided into control and experimental groups. Plasma was isolated every 5 days and the OS markers, antioxidant enzymes, lipid peroxidation, and protein oxidation products, were studied. Catalase activity increased in all groups with storage. Lipid peroxidation decreased in VC (10) but was maintained in VC (30) and VC (60). Although there were variations in all groups, carbonyls were maintained towards the end of storage. Advanced oxidation protein products (AOPP) increased in VC (30) and were maintained in VC (10) and VC (60). Sulfhydryls were maintained in all groups. Vitamin C could not sufficiently attenuate OS and hence, this opens the possibilities for further studies on vitamin C in combination with other antioxidants, in storage solutions. R. Vani, R. Soumya, H. Carl, V. A. Chandni, K. Neha, B. Pankhuri, S. Trishna, and D. P. Vatsal Copyright © 2015 R. Vani et al. All rights reserved. Association of ABO Blood Group Phenotype and Allele Frequency with Chikungunya Fever Tue, 21 Apr 2015 14:30:13 +0000 http://www.hindawi.com/journals/ah/2015/543027/ Background. The objective of this study was to investigate the association of the ABO blood group phenotype and allele frequency with CHIK fever. Methods. A rural community survey in Southern Thailand was conducted in August and September 2010. A total of 506 villagers were enrolled. Cases were defined as individuals having anti-CHIK IgG by hemagglutination ≥1 : 10. Results. There were 314 cases (62.1%) with CHIK seropositivity. Females were less likely to have positive anti-CHIK IgG with odds ratio (OR) (95% CI) of 0.63 (0.43, 0.93). All samples tested were Rh positive. Distribution of CHIK seropositivity versus seronegativity (P value) in A, B, AB, and O blood groups was 80 versus 46 (0.003), 80 versus 48 (0.005), 24 versus 20 (0.55), and 130 versus 78 (<0.001), respectively. However, chi-square test between ABO and CHIK infection showed no statistical significance . Comparison of the ABO blood group allele frequency between CHIK seropositivity and seronegativity was not statistically significant. Conclusion. This finding demonstrated no association of the ABO blood group phenotypes and allele frequencies with CHIK infection. Pairaya Rujirojindakul, Virasakdi Chongsuvivatwong, and Pornprot Limprasert Copyright © 2015 Pairaya Rujirojindakul et al. All rights reserved. Impaired Fibrinolysis in Angiographically Documented Coronary Artery Disease Mon, 23 Feb 2015 12:03:43 +0000 http://www.hindawi.com/journals/ah/2015/214680/ 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 http://www.hindawi.com/journals/ah/2014/470242/ 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 http://www.hindawi.com/journals/ah/2014/375915/ 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 http://www.hindawi.com/journals/ah/2014/854124/ 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 http://www.hindawi.com/journals/ah/2014/735751/ 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 http://www.hindawi.com/journals/ah/2014/986938/ 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 http://www.hindawi.com/journals/ah/2014/652395/ 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 http://www.hindawi.com/journals/ah/2014/697675/ 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 http://www.hindawi.com/journals/ah/2014/932039/ 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 http://www.hindawi.com/journals/ah/2014/369084/ 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 http://www.hindawi.com/journals/ah/2014/295323/ 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 http://www.hindawi.com/journals/ah/2014/749218/ 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 http://www.hindawi.com/journals/ah/2014/704318/ 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 http://www.hindawi.com/journals/ah/2014/604165/ 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 http://www.hindawi.com/journals/ah/2014/473482/ 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 http://www.hindawi.com/journals/ah/2014/192173/ 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 http://www.hindawi.com/journals/ah/2014/923593/ 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 http://www.hindawi.com/journals/ah/2014/932306/ 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 http://www.hindawi.com/journals/ah/2014/297057/ 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 http://www.hindawi.com/journals/ah/2014/924030/ 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 http://www.hindawi.com/journals/ah/2014/864058/ 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 http://www.hindawi.com/journals/ah/2014/705290/ 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 http://www.hindawi.com/journals/ah/2014/103175/ 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 http://www.hindawi.com/journals/ah/2014/512508/ 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.