7^th World Hematologists Congress May 08-09, 2017 Barcelona, Spain

Biography:

Igor Križaj completed his Doctoral studies at Jožef Stefan Institute in Ljubljana (JSIL) and at Imperial College in London. He completed his Post-doctorate studies at Institute Pasteur in Paris. He is Head of Department of Molecular and Biomedical Sciences at JSIL and full Professor of Biochemistry at University of Ljubljana. He has published more than 130 research papers in the SCI-journals. He has been serving as an Editorial Board Member at several scientific journals and as Secretary of the European Section of the International Society on Toxinology.

Abstract:

Most frequently used anticoagulant therapies may induce severe complications. To overcome these limitations, new anticoagulants have been intensively searched for. We report here the purification and characterization of a glycoprotein from the venom of the nose-horned viper (Vipera ammodytes), which significantly prolonged activated partial thromboplastin time in human plasma. Amino acid sequence of this protein (VaaSPH) revealed it as a serine protease possessing two mutations in its catalytic triad that renders it enzymatically inactive. Detailed analysis of the mechanism of blood coagulation inhibition by VaaSPH unveiled that the molecule inhibits the activity of tenase and prothrombinase complexes, with IC₅₀ values of 142 nM and 134 nM, respectively. It was demonstrated that inhibition of the complexes formation was due to the binding of VaaSPH to blood coagulation factors VII, IX and X, to their activated forms and to FVa and FII. In addition, VaaSPH was also found to bind specifically to phosphatidylserine, a negatively charged phospholipid, which directed the assembly of the enzyme–cofactor complexes on membrane surface of platelets. Three-dimensional structure comparison of FVII, FIX, FX, FII and their respective activated forms suggested two areas on their surfaces, in proximity of their active sites, where VaaSPH binds. Such a proposal was also experimentally supported. As a potent non-enzymatic and coagulation factor active-site independent inhibitor of blood coagulation process, VaaSPH is unique and therefore, very interesting for a further characterization to design, based on its structure, a novel family of selective coagulation factor inhibitors of therapeutic relevance for anticoagulant therapy. 

Biography:

Natalia Neparidze completed her Medical Degree at Aieti Medical School in Tbilisi, Georgia in 2000. She completed her Post-doctoral Research Fellowship at Emory University, Northwestern University and at Yale University, followed by Internal Medicine Residency and Hematology/Medical Oncology Fellowship at Yale University. She is an Assistant Professor at Yale University, with the research focus on Multiple Myeloma, with specific interests in “Advanced imaging and tumor heterogeneity, as well as strategies for intensification of maintenance therapy in multiple myeloma”.

Abstract:

Advanced imaging modalities are being increasingly utilized for initial evaluation in patients with multiple myeloma. Whole body magnetic resonance imaging (WB-MRI) is far superior to standard metastatic bone survey (MBS), and may even outperform positron-emission tomography (PET). We performed both baseline MBS and WB-MRI on 15 myeloma patients prior to initiation of therapy. Multi-planar, multi-sequence MRI of the whole body was acquired without intravenous contrast. The imaging studies were evaluated to determine their respective merits for disease staging and their impact on treatment decisions. WB-MRI detected myeloma lesions in 33% of patients (5/15), whereas MBS identified lesions in only 6% (1/15). Overall, information obtained from WB-MRI significantly influenced the patient’s staging in 73% of patients (11/15), and directly impacted treatment decisions whether or not to begin induction therapy in 46% of patients (7/15). WB-MRI identified myeloma bone lesions, which otherwise would have been missed by standard bone survey in 27% of patients (4/15). Myeloma related bone lesions occurred predominantly in the axial skeleton, most commonly seen in cervical, thoracic, lumbar spine and pelvis. We conclude that WB-MRI at diagnosis provides valuable information on the extent and the stage of the disease, significantly influences treatment decisions and is worth to be incorporated in initial diagnostic evaluation of patients with multiple myeloma.

Biography:

Rouslan Kotchetkov has completed his MD in 1994 at Minsk University, Belarus and PhD in 1998 at Frankfurt University, Germany. After re-training at Queens University, he acknowledged his MD degree in Ontario in 2007, followed by Post-gradual training in Internal Medicine at McMaster University, Adult Hematology at University of Toronto, and fellowship in Mature Lymphoproliferative Disorders and Lymphoma at Princess Margaret Cancer Center. Since July 2013, he is a staff Hematologist-Oncologist at Simcoe Muskoka Regional Cancer Program. He is an Assistant Professor of Medicine at University of Toronto. He has published over 50 papers and has 40 oral and 12 poster presentations at scientific conferences.

Abstract:

Characterization and management of patients with a synchronous dual hematological malignancy (SDHM) is not well described. In our database, we identified 41 patients with clonally unrelated SDHM, a prevalence of 1.35%, median age 75 years (23-90) and male predominance. 31.7% had concomitant solid cancers, suggesting increased susceptibility to SDHM or impaired immunity. Referrals from general practitioners were for a general diagnosis (65%) or for a non-specific symptom (35%). With referrals from specialists only asymptomatic secondary diagnoses were missed. SDHMs were diagnosed incidentally or because of discordance in clinical/laboratory findings. Three combinations of SDHMs were identified. In the myeloid+lymphoid group, concomitant MGUS was most frequent. Within the lymphoid+lymphoid group, SDHM combinations were random. There were only three myeloid+myeloid SDHMs. 70.7% required therapy for primary malignancy, 29.3% needed active surveillance. For a secondary diagnosis, 70.7% patients were actively monitored, and 29.3% needed treatment. At the completion of treatment for primary malignancy, 90% were either in remission/non-progressing disease or 10% progressed. Overall SDHM survival was 82.9% vs. 87.2% of control. Our management experience of SDHM is following: Have low threshold for intensive investigations if there are discordant data; patients with low-grade/low-acuity SDHM can be on active surveillance with early re-evaluation of both diseases if conditions change; if two malignancies require treatment, aim therapy at the more aggressive one; ABVD chemotherapy completely resolves cutaneous T-cell lymphoma lesions; cladribine has no effect on concomitant chronic myelomonocytic leukemia; ruxolitinib precipitates chronic lymphocytic leukemia; hydroxyurea decreases M-spikes in MGUS, regardless of type; azacitidine improves mast cell leukemia, bone marrow fibrosis, but has no effect on follicular lymphoma and; phlebotomized patients with polycythemia vera may develop profound anemia on chemotherapy, requiring holding phlebotomies, IV iron, erythropoietin-stimulating agents/red cell transfusions. Further studies of SDHM, exploring different cohorts and ethnicities, are needed.

Biography:

Soad K Al Jaouni is a Professor and Consultant of Hematology; Professor/Consultant of Pediatric Hematology/Oncology and Senior Researcher in Hematology department, Faculty of Medicine, King Abdulaziz University Hospital- a tertiary care medical center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. She received her certificate of Royal College of Physician and Surgeon in Medicine in 1989. She yearly participates in international and local conferences with more than 260 research and 74 publications. She is well known for her dedication, active role in research on Hereditary Blood Disease, Cancer Research. She has an active role in Public Education to minimize and control inherited blood diseases, environmental pollution and cancer prevention.

Abstract:

Background & Aim: Spleen plays an important part in the immune system which helps the body to fight against infection and has a major role in children. Splenectomy has been decline in hemoglobin disorders in recent years. Aim of this study is to assess the role of hydroxyurea and to eliminate the risk of splenectomy in sickle cell disease (SCD) and thalassemia at our medical center.

Methods: Total of 54 patients enrolled in the study from 2004 to 2016 at King Abdulaziz University Hospital, Faculty of Medicine and King Abdulaziz University, Saudi Arabia. 25 sickle cell disease (SCD), 17 thalassemia major (TM) were suboptimal transfusion dependents and hypersplenism, 12 thalassemia inter media (TI).

Results: Risk of splenectomy has been avoided in 24/25 SCD, 15/17 in TM and 12/12 in TI.

Conclusion: Hydroxyurea is an effective and safe therapy can eliminate risk of splenectomy in SCD and thalassemia. Recent studies and meta-analysis showed that hydroxyurea is safe and non-carcinogenic.

Biography:

Antonella Bianchi completed her Graduation in Medicine and Surgery in 1991 and Post-graduate Diploma in Pathology at Catholic University of Rome in 1996. She is an Assistant at Pathology Unit of University Hospital Campus Bio Medico of Rome (Italy) and she is the referent for hematological pathology with numerous published papers in reputed journals. She attends national and international conferences and she is a member of two scientific societies (SIAPEC and FIL). She performs teaching and tutorial activity for the School of Medicine.

Abstract:

The PD1-PDL1 axis is one of the major mechanisms of immune escaping exerted by several cancer types in which up-regulation of PDL1 is observed. The success of checkpoint blockade therapy in the treatment of different solid tumor encouraged the research for similar results in the spectrum of lymphoproliferative diseases. Several clinical trials of PD1-PDL1 blockade have been conducted in hematologic malignancies, in particular, in Hodgkin lymphoma. In order to improve the therapeutic usefulness of this approach, several studies were performed to investigate and quantify the PD1-PDL1 expression levels by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tissue sections, in different B-cell and T-cell lymphoma entities and in classical Hodgkin lymphoma. As for other predictive biomarkers, reliable results are achieved by performing the staining in a standardized setting of pathology laboratory practice. Numerous critical issues are under evaluation to determine the reproducibility of PD1-PDL1 immunohistochemistry. The IHC labeling is sensitive to pre-analytical parameters (e.g. cold ischemia, the type and duration of fixation). Negative and positive control slides should be included in each staining run. An expert pathologist using a light microscope should assess the staining pattern, both in morphologically unequivocal tumor cells and in ineffective inflammatory infiltrating cells. The scoring may be achieved using 10-20x objectives and confirmed at 40x if needed. PDL1 expression should be semi-quantitatively evaluated in representative areas with the higher percentage of neoplastic cells while tumor areas with necrosis should be excluded. Cytological material usually does not allow correct evaluation of the cell stained with anti-PDL1 antibodies.

Biography:

Osaro Erhabor is a Professor of Hematology, Transfusion Medicine and Laboratory of Total Quality Management. He is an Alumni of Rivers State University of Science and Technology, Nigeria, University of Greenwich in the United Kingdom and Francis Tuttle College of Technology in Oklahoma, USA. He is the Author of five scientific books. He has published more than 190 scientific papers in the field of Infectious Diseases, Hematology, Blood Transfusion Science and Total Quality Management. He is a member of the editorial board as well as an article Reviewer of several international scientific journals.

Abstract:

The spectrum of haemolytic disease of the new-born has changed over the last decade. With the implementation of rhesus D immunoprophylaxis, haemolytic disease due to ABO incompatibility and other alloantibodies has now emerged as major causes of this condition. In this present study, we investigated ABO and rhesus D blood group distribution and haemolytic disease among the new-born in Sokoto Specialist Hospital Nigeria. The study included a total of 79 samples each collected from mothers and neonates delivered in Sokoto Specialist Hospital. ABO and rhesus D blood group was determined on samples from the mothers and the neonates. Direct anti-globulin test (IgG and complements) was carried out on the samples from the neonates. ABO, rhesus D and direct anti-globulin (IgG and complements C3b and C3d) was carried out using the column agglutination technique (Ortho Diagnostics, USA). ABO blood group distribution indicated that a total of 44 mothers were of blood group O (55.7%), 22 were of blood group A (27.8%), 12 were of blood group B (15.2%) and one was AB (1.3%). Among the neonates, rhesus D positive has the highest frequency of 57 (72.2%) and rhesus D negative with a frequency of 22 (27.8%). Rhesus D group distribution among the mothers indicated that 74 mothers were rhesus D positive (93.7%) and only 5 were grouped as rhesus D negative (6.3%). Of the 79 neonates tested, 36 were of blood group O (45.6%), 21 were of blood group A (26.6%), 20 were of blood group B (25.3%), 2 were of blood group AB (2.5%). Haemolytic disease of the fetus and new-born (HDFN) status of the neonates indicated that four neonates were positive (5.1%). Two (2.5%) cases were ABO incompatibility-related while rhesus D related incompatibility accounted for two (2.5%). Among the four cases of HDFN, two cases (2.5%) of due to the effects of complements while two (2.5%) were due to IgG antibodies. Findings from this study indicates that haemolytic disease of the fetus and newborn due to ABO and rhesus D incompatibility between mothers and their babies is prevalent in Sokoto, North Western Nigeria. We recommend that universal antenatal screening in all pregnant women can be initiated. A close follow up throughout pregnancy is required to detect the presence of irregular antibodies. There is need to consider universal antenatal screening and provision of prophylactic anti-D prophylaxis to prevent rhesus D negative pregnant women from producing immune anti-D following potentially sensitizing events and HDFN in subsequent pregnancies.

Biography:

Aisha Patel has completed her BSc (Honours) in Life Sciences and Psychology at Queen’s University of Canada and MBBS at Imperial College, London. She is currently a Doctor in Emergency department at Gloucester Royal Hospital, UK. She has keen interest in Oncology.

Abstract:

This study presents a case report of a 54 year old female recently diagnosed with pancreatic cancer. Sudden onset of right leg pain with subsequent diagnosis of acute limb ischaemia and death two days later from septicaemia was observed. Venous thrombosis is a common complication of cancer, especally pancreatic cancer. However, the research available on arterial thrombosis as a complication of pancreatic cancer is sparse and it is hoped that there will be a greater vigilance for both venous and arterial thrombus as this is a very serious complication and can be difficult to manage. This case report includes in depth look at the research available on arterial thrombosis in pancreatic cancer.

Biography:

Elvira Maličev is an Assistant Professor at University of Ljubljana and Head of Laboratory for flow cytometry at Blood Transfusion Centre of Slovenia, where she works on Platelets, Erythrocytes and Stem cells. Her main research interests include Mesenchymal and Hematopoietic Stem Cell Biology.

Abstract:

Heparin-induced thrombocytopenia (HIT) is induced by the antibodies against neoepitopes in complexes of heparin with a platelet factor 4 (PF4). Anti-heparin/PF4 antibodies are capable of platelet activation by cross-linking to platelet Fcγ receptor IIa. Patients with HIT usually have thrombocytopenia between 5-10 days after heparin therapy has started and are at an increased risk of developing venous or/and arterial thromboses. However, not all patients with detected anti-heparin/PF4 antibodies go on to develop HIT. The diagnosis is a challenge and requires an exact analysis of the clinical and laboratory parameters. Laboratory testing includes both serological and functional assays. Enzyme immunoassays (ELISA) are most often used for detecting the presence or absence of anti-heparin/PF4 antibodies in a patient`s serum. ELISA is highly sensitive but has a low specificity because it detects both platelet activating and platelet non-activating anti-heparin/PF4 antibodies. To confirm the presence of pathogenic platelet activating antibodies, one of the functional assays has to be done. Functional assays generally require technical expertise, special equipment and the use of fresh donor platelets; therefore, laboratories rarely perform them. The serotonin release assay (SRA) and the heparin-induced platelet activation assay (HIPA) are the most well-known functional assays. Another possibility to confirm HIT could be the use of flow cytometry. We have introduced the functional flow cytometric assay for routine testing of suspect HIT patients. The assay is based on detection of CD61 antigens, and CD62P molecules (P-selectins), expressed on platelet surface after α-granule exocytosis. Each sample (patient’s serum, positive and negative control) is tested against fresh platelets obtained from four healthy donors. The assay is positive when at least two of four donor platelets are activated at a low concentration of heparin, and at the same time the parallel reaction is inhibited in the presence of excess heparin.

Biography:

Salem Khalil completed his MBBS at King Saud University Riyadh in 1984; fellowship of the Royal College of Pathologists of Australasia, Australia in 1992 and; fellowship in Molecular Hematopathology at MD Anderson Cancer Center, Huston, Texas, USA.

Abstract:

Background & Aim: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematopoietic stem cell disorder, characterized by the deficiency of glycophosphatidylinositol (GPI) that anchors proteins in cell membranes. PNH is manifested variously with hemoglobinuria, thrombosis, or bone marrow failure. This multi-central retrospective study was aimed at assessing the incidence and characteristics of patients diagnosed with PNH in Saudi Arabia.

Methods: Patients referred for PNH diagnosis at King Faisal Specialist Hospital and Research Centre, Riyadh during the 3-year period (2007-2009) and the 2-year period (2012-2013), also at King Faisal Specialist Hospital and Research Centre, Jeddah, King Abdulaziz Medical City (NG), Riyadh, King Abdulaziz Medical City (NG), Jeddah data during the last year 2014, were included in the analysis. Peripheral blood samples were used for multi-parametric flow cytometry analysis based on fluorescent inactive aerolysin (FLAER), and the markers, CD235a and CD59 on red blood cells (RBCs), and CD14, CD45, CD64, CD24, and CD15 on white blood cells (WBCs) exclusively monocytes and granulocytes. Univariate analysis of the disease characteristics was performed.

Results: Of the 843 samples submitted for PNH screening, 40 were positive (4.7%). Of the 40 patients analyzed, 22 patients (55%) presented with aplastic anemia, 4 patients (10%) with pancytopenia, and 3 patients with thrombosis (7.5%) one with Budd-Chiari syndrome and 2 with portal vein thrombosis. Hemolytic anemia represented 5% (2 patients) of all cases. Other positive cases were presented with unrelated diseases such as immune thrombocytopenic purpura (ITP) in 2 cases (5%) and non-specific diagnosis in the rest. All samples showed type II and III GPI-deficient clones with a median clone size of 12 (range, 0.04%-85%) in the RBCs, and 56 (range, 1%-100%) in WBCs (monocytes and granulocytes).

Conclusions: This study confirms the rarity of PNH and its predominant presentation as aplastic anemia or thrombosis in a Saudi Arabian population, similar to the worldwide incidence.

Biography:

Yulia Einav completed her PhD at Tel Aviv University. She works at Holon Institute of Technology (Israel). Currently, she has published 20 papers and book chapters in reputed journals and textbooks. In addition, she serves as Dean of Students of Holon Institute.

Abstract:

Thalassemia minor (TM) condition is often unrecognized and undiagnosed due to technical or cost issues. The benefit of early diagnosis of TM patients is a prevention of unnecessary treatments and costly tests and a referral to a genetic counseling. The use of complete blood count (CBC) parameters to screen for TM condition has been proposed in the past decade and performed with variable success. Here, we propose to use artificial neural networks (ANNs), which are successfully applied to various fields of medicine and beyond to find patterns in ambiguous data. ANN model comprises of an interconnected group of artificial neurons that learn through experience. Like a biological neuron network, the ANN is designed to obtain an input, analyze the data and supply the output, which in most cases would be some prediction about the patterns and behavior of the studied system. In this study, we created more than 1,500 ANNs and selected the networks that gave highest accuracy results. Input consisted of six CBC parameters: MCV, RBC, RDW, HB, MCH, and platelet count. This broad approach allowed us to provide a differential diagnosis for TM patients with specificity above 0.96 and sensitivity of 1. In addition, we show that in our method MCV, RBC, and RDW counts are of greater importance than the other three parameters. The low cost of our model makes it important worldwide and especially in the developing countries. Moreover, similar ANN-based method can be applied for the screening of other diseases that change CBC parameters.

Biography:

Chintan Shah, is working as a Clinical Assistant Professor at the University of Florida, Florida, USA. After being born and raised in India, he moved to the United States in 2011. He completed his graduate training in the field of internal medicine from the Western Michigan University School of Medicine and is currently working as an internist. He has done quite a few presentations at the national and international conferences and has published in peer-reviewed journals. His goal is to achieve clinical excellence, provide compassionate care to patients and pursue a carrier in the field of Hematology and Oncology.

Abstract:

Introduction & Aim: Unanticipated cardiotoxicity is now identified as a significant clinical problem associated with new anti-cancer targeted agents. Risk factors and natural history are still poorly understood and are the main aim of this study.

Methods: We used 114 diagnosis codes for HM and 17 for cardiac diseases in order to identify patients in our electronic medical records (EPIC) over 10-year period. Cardiotoxicity was defined by left ventricular ejection fraction (LVEF) of <50%, arrhythmias, or ischemic cardiovascular event that occurred after initiation of the drug of interest. The targeted agents of interest include tyrosine kinase inhibitors (TKIs), proteasome inhibitors, monoclonal antibodies, hypomethylating agents, and immunomodulatory agents. Multivariable logistic regression, Kaplan-Meier analysis and log-rank test were used for statistical calculations.

Results: Of 820 patients with both HM and cardiac diagnosis, 29 patients (3.5%) developed cardiotoxicity after initiation of targeted therapies. We selected 70 matched controls based on type of targeted therapy. In the study group, the median time from exposure to cardiac event was 120 days (interquartile range, 30-180). Multiple variables, including conventional risk factors for heart disease, were not different between the two groups except prior history of DVT/PE (P=0.011), and Karnofsky score of ≥80% (P=0.005). With median follow-up of 27 months, two patients in the study group died of cardiac causes. Repeat echocardiograms showed stable/improved LVEF in 23 patients. There was a trend towards worse OS in the study group (P=0.071).

Conclusions: About 3.5% of patients with HM experienced unanticipated cardiotoxicity due to targeted anti-cancer agents with related mortality of 6.8%. Most patients do well with stable compensated cardiac function. Risk of cardiotoxicity was significantly higher in patients with known history of DVT/PE. Future studies of possible underlying genetic predisposition will be of great importance.