Acute myocardial infarction in a patient with hemophilia A and factor V Leiden mutation

Factor VIII:C, epsilon amino-caproic acid or tranexamic acid are prophylactic agents used in preventing hemorrhage pre-operatively in patients with hemophilia A. Although hemophilia A seems to be a factor that avoids the development of acute myocardial infarction (AMI) as it tends to be associated with increased bleeding, it should be kept in mind that prothrombotic agents used pre-operatively for prophylaxis may increase the risk for AMI in the presence of the factor V Leiden mutation. In this report, we discuss the development of AMI following the use of recombinant factor VIII and tranexamic acid for prophylaxis in a patient with known hemophilia before a tooth extraction in conjunction with the relevant literature

Acquired disorders of platelet function

Acquired disorders of platelet function are among the most common hematologic abnormalities, a reflection of the sensitivities of platelets to external and internal perturbations. The clinical challenge in evaluating acquired disorders of platelet function is to determine whether observed derangements in platelet function pose a threat to the patient.CONTENTS PART I MOLECULAR AND CELLULAR BASIS OF HEMATOLOGY 1 Chapter 1 Anatomy and Physiology of the Gene 2 Andrew J. Wagner, Nancy Berliner, and Edward J. Benz, Jr. Chapter 2 Genomic Approaches to Hematology 16 Todd R. Golub Chapter 3 Regulation of Gene Expression, Transcription, Splicing, and RNA Metabolism 27 Christopher R. Cagle, Amy Meacham, and Robert A. Hromas Chapter 4 Protein Synthesis, Processing, and Trafficking 35 Randal J. Kaufman and Laura Popolo Chapter 5 Protein Architecture: Relationship of Form and Function 48 Jia-huai Wang, Angela Toms, Ming-Ming Zhou, and Michael J. Eck Chapter 6 Signaling Transduction and Regulation of Cell Metabolism 55 Pere Puigserver Chapter 7 Pharmacogenomics and Hematologic Diseases 65 Leo Kager and William E. Evans PART II CELLULAR BASIS OF HEMATOLOGY 77 Chapter 8 Hematopoietic Stem Cell Biology 78 John P. Chute Chapter 9 Hematopoietic Microenvironment 88 Lev Silberstein and David Scadden Chapter 10 Cell Adhesion 97 Rodger P. McEver and Francis W. Luscinskas Chapter 11 Hematopoietic Cell Trafficking and Chemokines 105 Steffen Massberg, Alexander G. Khandoga, and Ulrich H. van Andrian Chapter 12 Dynamic Interactions Between Hematopoietic Stem and Progenitor Cells and the Bone Marrow: Current Biology of Stem Cell Homing and Mobilization 117 Shiri Gur-Cohen, Karin Golan, Kfir Lapid, Jonathan Canaani, Orit Kollet, and Tsvee Lapidot Chapter 13 Vascular Growth in Health and Disease 126 Janusz Rak Chapter 14 Principles of Cytokine Signaling 136 Montaser Shaheen and Hal E. Broxmeyer Chapter 15 Control of Cell Division 147 William MI. Lee and Chi V. Dang Chapter 16 Cell Death 158 Nika N. Danial and David M. Hockenbery PART III IMMUNOLOGIC BASIS OF HEMATOLOGY 171 Chapter 17 Overview and Compartmentalization of the Immune System 172 Leland D. Powell, Peter Chung, and Linda G. Baum Chapter 18 B-Cell Development 182 Kenneth Dorshkind and David J. Rawlings Chapter 19 T-Cell Immunity 193 Shannon A. Carty, Matthew J. Riese, and Gary A. Koretzky Chapter 20 Natural Killer Cell Immunity 210 Don M. Benson, Jr., and Michael A. Caligiuri Chapter 21 Dendritic Cell Biology 217 Olivier Manches, Viswanathan Lakshmanan, Zbigniew M. Szczepiorkowski, and Nina Bhardwaj Chapter 22 Complement and Immunoglobulin Biology 228 David E. Isenman, Robert Mandie, and Michael C. Carroll Chapter 23 Tolerance and Autoimmunity 247 Mark J. Shlomchik PART V DISORDERS OF HEMATOPOIETIC CELL DEVELOPMENT 257 Chapter 24 Biology of Erythropoiesis, Erythroid Differentiation, and Maturation 258 Thalia Papayannopoulou and Anna Rita Migliaccio Chapter 25 Granulocytopoiesis and Monocytopoiesis 280 Arati Khanna-Gupta and Nancy Berliner Chapter 26 Thrombocytopoiesis 292 Alan B. Cantor Chapter 27 Inherited Forms of Bone Marrow Failure 307 Yİgal Dror and Melvin H. Freedman Chapter 28 Aplastic Anemia 350 Neal S. Young and Jaroslaw P. Maciejewski Chapter 29 Paroxysmal Nocturnal Hemoglobinuria 373 Robert A. Brodsky Chapter 30 Acquired Disorders of Red Cell, White Cell, and Platelet Production 383 Jaroslaw P. Maciejewski and Ramon V. Tiu PART V RED BLOOD CELLS 405 Chapter 31 Pathobiology of the Human Erythrocyte and Its Hemoglobins 406 Martin H. Steinberg, Edward J. Benz, Jr., Adeboye H. Adewoye, and Benjamin L. Ebert Chapter 32 Approach to Anemia in the Adult and Child 418 Peter W. Marks Chapter 33 Pathophysiology of Iron Homeostasis 427 Gary M. Brittenham Chapter 34 Disorders of Iron Homeostasis: Iron Deficiency and Overload 437 Gary M. Brittenham Chapter 35 Anemia of Chronic Diseases 450 Jane A. Little, Edward J. Benz, Jr., and Lawrence B. Gardner Chapter 36 Heme Biosynthesis and Its Disorders: Porphyrias and Sideroblastic Anemias 457 Stephen J. Fuller and James S. Wiley Chapter 37 Megaloblastic Anemias 473 Asok C. Antony Chapter 38 Thalassemia Syndromes 505 Patricia J. Giardina and Stefano Rivella Chapter 39 Pathobiology of Sickle Cell Disease 536 Robert P. Hebbel Chapter 40 Sickle Cell Disease: Clinical Features and Management 548 Yogen Saunthararajah and Elliott P. Vichinsky Chapter 41 Hemoglobin Variants Associated With Hemolytic Anemia, Altered Oxygen Affinity, and Methemoglobinemias 573 Edward J. Benz, Jr., and Benjamin L. Ebert Chapter 42 Red Blood Cell Enzymopathies 581 Elizabeth A. Price, Stavroula Otis, and Stanley L. Schrier Chapter 43 Red Blood Cell Membrane Disorders 592 Patrick G. Gallagher Chapter 44 Autoimmune Hemolytic Anemia 614 Ulrich Jager and Klaus Lechner Chapter 45 Extrinsic Nonimmune Hemolytic Anemias 628 Elizabeth A. Price and Stanley L. Schrier PART VI NON-MALIGNANT LEUKOCYTES 639 Chapter 46 Neutrophilic Leukocytosis, Neutropenia, Monocytosis, and Monocytopenia 640 Lawrence Rice and Moonjung Jung Chapter 47 Lymphocytosis, Lymphocytopenia, Hypergammaglobulinemia, And Hypogammaglobulinemia 647 Martha P. Mims Chapter 48 Disorders of Phagocyte Function 655 Mary C. Dinauer and Thomas D. Coates Chapter 49 Congenital Disorders of Lymphocyte Function 674 Sung- Yun Pai and Luigi D. Notarangelo Chapter 50 Histiocytic Disorders 686 Michael B. Jordan and Alexandra Hult Filipovich Chapter 51 Lysosomal Storage Diseases: Perspectives and Principles 701 Edward H. Schuchman and Melissa P. Wasserstein Chapter 52 Infectious Mononucleosis and Other Epstein-Barr Virus-Associated Diseases 708 Carl Allen, Cliona M. Rooney, and Stephen Gottschalk PART VI HEMATOLOGIC MALIGNANCIES 721 Chapter 53 Progress in the Classification of Myeloid Neoplasms: Clinical Implications 722 John Anastasi and Ronald Hoffman Chapter 54 Conventional and Molecular Cytogenetic Basis of Hematologic Malignancies 728 Vesna Najfeld Chapter 55 Pharmacology and Molecular Mechanisms of Antineoplastic Agents for Hematologic Malignancies 781 Stanton L. Gerson, Paolo F. Caimi, Erica Campagnaro, Kapil N. Bhalla, Steven Grant, and Richard J. Creger Chapter 56 Radiation Therapy in the Treatment of Hematologic Malignancies 844 Andrea K. Ng and Peter M. Mauch Chapter 57 Pathobiology of Acute Myeloid Leukemia 853 Michael Andreeff and Alfonso Quintas-Cardama Chapter 58 Clinical Manifestations and Treatment of Acute Myeloid leukemia 863 Stefan Faderl and Hagop M. Kantarjian Chapter 59 Myelodysplastic Syndromes: Biology and Treatment 882 Daniel J. DeAngelo and Richard M. Stone Chapter 60 Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome in Adults 904 John Koreth, Joseph H. Antin, and Corey Cutler Chapter 61 Acute Myeloid leukemia in Children 913 Michael C. Wei, Gary V. Dahl, and Howard J. Weinstein Chapter 62 Myelodysplastic and Myeloproliferative Neoplasms in Children 926 Franklin O. Smith and Mignon L. Loh Chapter 63 Pathobiology of Acute lymphoblastic Leukemia 935 Alejandro Gutierrez, Scott A. Armstrong, and A. Thomas Look Chapter 64 Clinical Manifestations and Treatment of Acute lymphoblastic Leukemia in Children 951 Sima Jeha and Ching-Hon Pui Chapter 65 Acute lymphoblastic leukemia in Adults 960 Nitin Jain, Sandeep Gurbuxani, Charles Rhee, and Wendy Stock Chapter 66 Chronic Myeloid Leukemia 981 Ravi Bhatia Chapter 67 The Polycythemias 998 Marina Kremyanskaya, Vesna Najfeld, John Mascarenhas, and Ronald Hoffman Chapter 68 Essential Thrombocythemia 1034 Ronald Hoffman, Marina Kremyanskaya, Vesna Najfeld, and John Mascarenhas Chapter 69 Primary Myelofibrosis 1053 John Mascarenhas, Vesna Najfeld, Marina Kremyanskaya, and Ronald Hoffman Chapter 70 Eosinophilia, Eosinophil-Associated Diseases, Chronic Eosinophil leukemia, and the Hypereosinophilic Syndromes 1077 Marina Kremyanskaya, Steven J. Ackerman, Joseph H. Butterfield, John Mascarenhas, and Ronald Hoffman Chapter 71 Mast Cells and Systemic Mastocytosis 1095 John Mascarenhas, Animesh Pardanani, Marina Kremyanskaya, and Ronald Hoffman Chapter 72 Pathologic Basis for the Classification of Non-Hodgkin and Hodgkin Lymphomas 1112 Elaine S. Jaffe, Stefania Pittaluga, and John Anastasi Chapter 73 Origin of Hodgkin Lymphoma 1130 Ralf Küppers Chapter 74 Hodgkin lymphoma: Clinical Manifestations, Staging, and Therapy 1138 Dennis A. Eichenauer, Andreas Engert, and Volker Diehl Chapter 75 Origin of Non-Hodgkin Lymphoma 1157 Matthew S. McKinney and Sandeep S. Dave Chapter 76 Chronic lymphocytic leukemia 1170 Thomas S. Un, Farrukh T. Awan, and John C. Byrd Chapter 77 Hairy Cell Leukemia 1192 Farhad Ravandi Chapter 78 Clinical Manifestations and Treatment of Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal) 1204 Carlos A. Ramos Chapter 79 Clinical Manifestations, Staging, and Treatment of Follicular Lymphoma 1215 John G .Gribben Chapter 80 Mantle Cell Lymphoma 1226 Michael Wang, Liang Zhang, Zhishuo Ou, Madhav V. Desai, Ken H. Young, Richard E. Champlin, Larry W. Kwak, and Jorge E. Romaguera Chapter 81 Diagnosis and Treatment of Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma 1236 Kieran Dunleavy and Wyndham H. Wilson Chapter 82 Virus-Associated Lymphoma 1245 Jennifer A. Kanakry and Richard F. Ambinder Chapter 83 Malignant Lymphomas in Childhood 1255 Kala Y. Kamdar, John T. Sandlund, Jr., and Catherine M. Bollard Chapter 84 T-Cell Lymphomas 1267 Owen A. O'Connor, Enrica Marchi, Govind Bhagat, Paolo Corradini, Joan Guitart, Steven T. Rosen, and Timothy M. Kuzel Chapter 85 Plasma Cell Neoplasms 1303 Nikhil C. Munshi and Sundar Jagannath Chapter 86 Waldenstrom Macroglobulinemia and Lymphoplasmacytic Lymphoma 1338 Steven P. Treon and Giampaolo Merlini Chapter 87 Immunoglobulin Light-Chain Amyloidosis (Primary Amyloidosis) 1350 Morie A. Gertz, Francis K. Buadi, Steven R. Zeldenrust, and Suzanne R. Hayman PART VIII COMPREHENSIVE CARE OF PATIENTS WITH HEMATOLOGIC MALIGNANCIES 1375 Chapter 88 Clinical Approach to Infections in the Compromised Host 1376 Samuel A. Shelburne, Russell E. Lewis, and Dimitrios P. Kontoyiannis Chapter 89 Indwelling Access Devices 1391 Franklin W. Huang and Janet L. Abrahm Chapter 90 Nutritional Issues in Patients With Hematologic Malignancies 1405 Regina S. Cunningham Chapter 91 Psychosocial Aspects of Hematologic Disorders 1418 Ruth McCorkle and Elizabeth Cooke Chapter 92 Pain Management and Antiemetic Therapy in Hematologic Disorders 1429 Kathy J. Selvaggi, Bridget Fowler Scullion, Craig D. Blinderman, and Janet L. Abrahm Chapter 93 Palliative Care 1444 Kristen G. Schaefer, Janet L. Abrahm, and Joanne Wolfe Chapter 94 Late Complications of Hematologic Diseases and Their Therapies 1452 Wendy Landier and Smita Bhatia PART IX CELL-BASED THERAPIES 1469 Chapter 95 Overview and Historical Perspective of Current Cell-Based Therapies 1470 Leslie E. Silberstein and Helen E. Heslop Chapter 96 Practical Aspects of Hematologic Stem Cell Harvesting and Mobilization 1472 Scoff D. Rowley and Michele L. Donato Chapter 97 Preclinical Process of Cell-Based Therapies 1486 Robert Lindblad, Deborah Wood, Traci Heath Mondora, and Leslie E. Silberstein Chapter 98 Graft Engineering and Cell Processing 1492 Adrian P. Gee Chapter 99 Principles of Cell-Based Genetic Therapies 1503 David A. Williams Chapter 100 Mesenchymal Stromal Cells 1513 Edwin M. Horwitz Chapter 101 T-Cell Therapy of Hematologic Diseases 1521 Gianpietra Doffi and Malcolm K. Brenner Chapter 102 Natural Killer Cell-Based Therapies 1527 Sarah Cooley, Michael R. Verneris, and Jeffrey S. Miller Chapter 103 Dendritic Cell Therapies 1534 Karolina Palucka and Jacques Banchereau PART X TRANSPLANTATION 1541 Chapter 104 Overview of Hematopoietic Stem Cell Transplantation 1542 Helen E. Heslop Chapter 105 Indications and Outcome of Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies in Adults 1546 Parameswaran Hari and Mary Horowitz Chapter 106 Unrelated Donor Hematopoietic Cell Transplantation 1557 Effie W. Petersdorf and Claudio Anasetti Chapter 107 Haploidentical Hematopoietic Cell Transplantation 1569 Bimalangshu R. Deyand Thomas R. Spitzer Chapter 108 Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies 1580 Doris M. Ponce and Juliet N. Barker Chapter 109 Graft-Versus-Host Disease and Graft-Versus-Leukemia Responses 1592 Pavan Reddy and James L.M. Ferrara Chapter 110 Complications After Hematopoietic Stem Cell Transplantation 1612 Navneet S. Majhail and Daniel J. Weisdorf PART XI TRANSFUSION MEDICINE 1627 Chapter 111 Human Blood Group Antigens and Antibodies 1628 Connie M. Westhoff, Jill R. Storry, and Beth H. Shaz Chapter 112 Principles of Red Blood Cell Transfusion 1642 Melissa M. Cushing and Paul M. Ness Chapter 113 Principles of Platelet Transfusion Therapy 1653 Richard M. Kaufman Chapter 114 Human Leukocyte Antigen and Human Neutrophil Antigen Systems 1659 Ena Wang, Sharon Adams, David F. Stroncek, and Francesco M. Marincola Chapter 115 Principles of Neutrophil (Granulocyte) Transfusions 1676 Ronald G. Strauss Chapter 116 Principles of Plasma Transfusion: Plasma, Cryoprecipitate, Albumin, and Immunoglobulins 1683 Matthew S. Karafin, Christopher D. Hillyer, and Beth H. Shaz Chapter 117 Preparation of Plasma-Derived and Recombinant Human Plasma Proteins 1695 David B. Clark Chapter 118 Transfusion Therapy for Coagulation Factor Deficiencies 1705 Elizabeth Roman, Peter J. Larson, and Catherine S. Manno Chapter 119 Hemapheresis 1716 Diarmaid Q Donghaile and Harvey G. Klein Chapter 120 Transfusion Reactions to Blood and Cell Therapy Products 1727 Jacquelyn D. Choate, Robert W. Maitta, Christopher A. Tormey, YanYun Wu, and Edward L. Snyder Chapter 121 Transfusion-Transmitted Diseases 1738 Louis M. Katz and Jay E. Menitove Chapter 122 Transfusion Medicine in Hematopoietic Stem Cell and Solid Organ Transplantation 1755 Richard M. Kaufman Chapter 123 Pediatric Transfusion Medicine 1765 Cassandra Josephson and Steven R. Sloan PART XII HEMOSTASIS AND THROMBOSIS 1773 Chapter 124 Overview of Hemostasis and Thrombosis 1774 Jeffrey I. Weitz Chapter 125 The Blood Vessel Wall 1784 Aly Karsan and John M. Harlan Chapter 126 Megakaryocyte and Platelet Structure 1797 Joseph E. Italiano, Jr., and John H. Hartwig Chapter 127 Molecular Basis for Platelet Function 1809 Charles S. Abrams and Edward F. Plow Chapter 128 Molecular Basis of Blood Coagulation 1821 Kathleen Brummel-Ziedins and Kenneth G. Mann Chapter 129 Regulatory Mechanisms in Hemostasis 1842 Charles T. Esmon and Naomi L. Esmon Chapter 130 Clinical Approach to the Patient With Bleeding or Bruising 1847 Catherine P.M. Hayward Chapter 131 Laboratory Evaluation of Hemostatic and Thrombotic Disorders 1857 Alvin H. Schmaier Chapter 132 Acquired Disorders of Platelet Function 1867 Reyhan Diz-Küçükkaya and Jose A. Lopez Chapter 133 Diseases of Platelet Number: Immune Thrombocytopenia, Neonatal Alloimmune Thrombocytopenia, and Posttransfusion Purpura 1883 Donald M. Arnold, Christopher Patriquin, Lisa J. Toltl Ishac Nazi, James Smith, and John Kelton Chapter 134 Thrombocytopenia Caused by Platelet Destruction, Hypersplenism, or Hemodilution 1895 Theodore E. Warkentin Chapter 135 Heparin-Induced Thrombocytopenia 1913 Theodore E. Warkentin Chapter 136 Thrombotic Thrombocytopenic Purpura and the Hemolytic Uremic Syndrome 1925 Keith R. McCrae, J. Evan Sadler, and Douglas B. Cines Chapter 137 Hemophilia A and B 1940 Manuel Carcao, Paul Moorehead, and David Lillicrap Chapter 138 Inhibitors in Hemophilia A and B 1961 Guglielmo Mariani, Barbara A. Konkle, and Craig M. Kessler Chapter 139 Rare Coagulation Factor Deficiencies 1971 David Gailani and Anne T. Neff Chapter 140 Structure, Biology, and Genetics of von Willebrand Factor 1987 Paula James and Natalia Rydz Chapter 141 Disseminated Intravascular Coagulation 2001 Marcel Levi Chapter 142 Hypercoagulable States 2013 Julia A. Anderson and Jeffrey I. Weitz Chapter 143 Antiphospholipid Syndrome 2025 Jacob H. Rand and Lucia R. Wolgast Chapter 144 Venous Thromboembolism 2039 Wendy Lim Chapter 145 Mechanical Interventions in Arterial and Venous Thrombosis 2048 Steven Sauk and Suresh Vedantham Chapter 146 Atherothrombosis 2057 Roy L. Silverstein Chapter 147 Stroke 2067 Michelle Canavan, Emer McGrath, and Martin O'Donnell Chapter 148 Acute Coronary Syndromes 2076 John W. Eikelboom and Jeffrey I. Weitz Chapter 149 Atrial Fibrillation 2086 Stavros Apostolakis and Gregory Y.H Lip Chapter 150 Peripheral Artery Disease 2094 Reena L. Pande and Mark A. Creager Chapter 151 Antithrombotic Drugs 2102 Jeffrey I. Weitz Chapter 152 Disorders of Coagulation in the Neonate 2120 Christine A. Macartney, Nethnapha Paredes, and Anthony K. C. Chan PART XIII CONSULTATIVE HEMATOLOGY 2131 Chapter 153 Hematologic Changes in Pregnancy 2132 Caroline Cromwell Chapter 154 Hematologic Manifestations of Childhood Illness 2144 Arthur Kim Ritchey, Frank G. Keller, and Sarah H. O'Brien Chapter 155 Hematologic Manifestations of Liver Disease 2167 Andrea Lee and Wendy Lim Chapter 156 Hematologic Manifestations of Systemic Disease: Renal Disease 2173 Peter W. Marks, Rachel Rosovsky, and Edward J. Benz, Jr. Chapter 157 Hematologic Manifestations of Cancer 2176 Gerald A. Soft, David L. Green, and Lawrence B. Gardner Chapter 158 Integrative Therapies in Patients With Hematologic Diseases 2183 David S. Rosenthal, Kara M. Kelly, and Donald I. Abrams Chapter 159 Hematologic Manifestations of HIV/AIDS 2191 Howard A. Liebman and Anil Tulpule Chapter 160 Hematologic Aspects of Parasitic Diseases 2208 David J. Roberts Chapter 161 Hematologic Problems in the Surgical Patient: Bleeding and Thrombosis 2234 Mark T. Reding and Nigel S. Key Chapter 162 The Spleen and Its Disorders 2252 Nathan T. Connell, Susan B. Shurin, and Fred J. Schiffman Chapter 163 Hematology in Aging 2266 Andrew S. Artz and William B. Ershler Chapter 164 (online only) Resources for the Hematologist: Interpretive Comments and Selected Reference Values for Neonatal, Pediatric, and Adult Populations Andrea M. Sheehan and Donald L. Ye

Inherited disorders of platelets membrane glycoprotein disorders

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Platelet membrane glycoproteins play a key role in hemostasis and thrombosis. Although disorders of platelet membrane glycoproteins are rare, their effects on the lives of those affected are very important. Severe deficiencies manifest themselves early during childhood with mucocutaneous bleeding. Mild deficiencies may not be diagnosed until adulthood or until the hemostatic system is stressed by surgery or trauma. The diagnosis of these disorders requires detailed laboratory investigation. Management of bleeding in patients with inherited platelet disorders requires both preventive measures and the treatment of individual bleeding episodes according to severity. The study of platelet membrane disorders also has yielded important insights into the functions of affected proteins, information that has produced some of the most successful antithrombotic drugs currently in use

Correction: Inhibition of IGF-1R Prevents Ionizing Radiation-Induced Primary Endothelial Cell Senescence

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent thrombosis and fetal mortality. Thrombotic microangiopathy (TMA) is an important histological finding in catastrophicAPS (CAPS) and in APS patients with nephropathy. Analysis of familial thrombotic thrombocytopenic purpura patients showed that there are mutations in the ADAMTS-13 gene that lead to functional defects in the ADAMTS-13 enzyme. The aim of this study was to investigate the prevalence of the aforementioned mutations in APS, as well as to evaluate the level and activity of the ADAMTS-13 enzyme in patients with APS. C365del, Q449stop codon, P475S, and C508Y mutations were analyzed in APS patients. Transcriptions were analyzed using real-time PCR, and the level and activity of ADAMTS-13 were analyzed via fluorogenic assay. None of the mutations tested were present in the patient or control groups. The level of ADAMTS-13 mRNA in the patient group was 50% lower than that in the control group. Although a significant difference in ADAMTS-13 activity was not observed between the patient and control groups, a significant association was observed with the level of ADAMTS-13 (p<0.0001). The level and activity of ADAMTS-13 were not associated with thrombotic complications, thrombocytopenia, or pregnancy complications in the patients with APS.Antifosfolipid sendrom (AFS), tekrarlayan tromboz ve fetal kayıplar ile karakterize olan otoimmün bir hastalıktır. Trombotik mikroanjiyopati (TMA), katastrofik AFS ve nefropatinin eşlik ettiği AFS olgularında önemli bir histolojik bulgudur. Ailesel trombotik trombositopenik purpura olgularının incelenmesi sonucu, ADAMTS-13 enziminin işlev bozukluğuna yol açan mutasyonların varlığını göstermiştir. Bu çalışmada ADAMTS-13 mutasyonları ile, enzimin aktivite ve miktarının AFS’ye katkısının olup olmadığının araştırılması amaçlanmıştır. Bu kapsamda C365del, Q449stop kodonu, P475S ve C508Y mutasyonları analiz edildi. Transkripsiyon aşaması gerçek zamanlı polimeraz zincir reaksiyonu, enzimin aktivite ve miktarı ise florojenik bir yöntem ile incelendi. Varlığı araştırılan mutasyonlar kontrol ve hasta gruplarında tespit edilmedi. ADAMTS-13 mRNA ve protein miktarının hasta grubunda kontrol grubundaki düzeyin yarısı kadar olduğu saptandı. (p<0.0001). Enzim aktivitesi açısından ise iki grup arasında istatistik olarak anlamlı bir fark gözlenmedi. Sonuç olarak, ADAMTS-13 enzim aktivitesi ve miktarının AFS hastalarında trombotik komplikasyonlar, trombositopeni ve gebelik komplikasyonları ile ilişkili olmadığı saptandı

MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms

Objective: The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K) were described in patients with essential thrombocythemia (ET) and primary (idiopathic) myelofibrosis (PMF). The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. Materials and Methods: A total of 77 patients (66 were diagnosed with ET and 11 with PMF) and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. Results: In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66) and 6 had PMF (54.5%, 6/11). In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively), had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies. Conclusion: MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation. Conflict of interest:None declared

Kronik miyeloproliferatif neoplazmlarda MPL W515l/K mutasyonları

İstanbul Bilim Üniversitesi, Tıp Fakültesi.The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K) were described in patients with essential thrombocythemia (ET) and primary (idiopathic) myelofibrosis (PMF). The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. MATERIALS AND METHODS: A total of 77 patients (66 were diagnosed with ET and 11 with PMF) and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. RESULTS: In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66) and 6 had PMF (54.5%, 6/11). In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPLW515L/K mutations had long follow-up times (124 months and 71 months, respectively), had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies.Amaç: MPL geni trombopoietin reseptörünü kodlamaktadır. Son yıllarda ET ve PMF hastalarında MPL mutasyonları tanımlanmıştır (W515L veya W515K). Bu mutasyonların sıklığı ve klinik önemi henüz net şekilde anlaşılmış değildir. Çalışmamızda, ET ve PMF hastalarında bu mutasyonların sıklığını ve klinik önemini araştırmayı amaçladık. YÖNTEMLER: Çalışmaya toplam 77 hasta (66 ET ve 11 PMF) ve 42 sağlıklı kontrol bireyi dahil edildi. MPL W515L/K ve JAK-2 V617F mutasyon varlığı periferik kan örnekleri kullanılarak gerçek zamanlı polimeraz zincir reaksiyonu yöntemi ile analiz edildi. Bulgular: Sağlıklı kontrol bireylerinde W515L/K veya JAK-2 V617F mutasyonu saptanmadı. 29’u ET (%43,9, 29/66) ve 6’sı PMF (%54,5, 6/11) olan 35 hastada JAK-2 V617F pozitif saptandı. MPL W515L/K mutasyonları JAK-2 V617F negatif olan yalnızca 2 PMF olgusunda pozitif saptandı. MPL W515L/K sıklığı toplam hasta grubunda %2,6, JAK-2 V617F negatif hastalarda ise %4,8 olarak hesaplandı. MPL W515L/K pozitif olan bu 2 hastada herhangi bir trombotik veya kanama komplikasyonu gelişmemiş, sitogenetik anomali saptanmamış, 124 ve 71 ay olan uzun sağkalımları hesaplanmıştır