DOCSLIB.ORG

Bleeding Fevers! Thrombocytopenia and Neutropenia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Bleeding fevers! Thrombocytopenia and neutropenia Faculty of Physician Associates 4th National CPD Conference Monday 21st October 2019, Royal College of Physicians, London @jasaunders90 | #FPAConf19 Jamie Saunders MSc PA-R Physician Associate in Haematology, Guy’s and St Thomas’ NHS Foundation Trust Board Member, Faculty of Physician Associates Bleeding fevers; Thrombocytopenia and neutropenia Disclosures / Conflicts of interest Nothing to declare Professional Affiliations Board Member, Faculty of Physician Associates Communication Committee, British Society for Haematology Education Committee, British Society for Haematology Bleeding fevers; Thrombocytopenia and neutropenia What’s going to be covered? - Thrombocytopenia (low platelets) - Neutropenia (low neutrophils) Bleeding fevers; Thrombocytopenia and neutropenia Thrombocytopenia Bleeding fevers; Thrombocytopenia (low platelets) Pluripotent Haematopoietic Stem Cell Myeloid Stem Cell Lymphoid Stem Cell A load of random cells Lymphoblast B-Cell Progenitor Natural Killer (NK) Precursor Megakaryoblast Proerythroblast Myeloblast T-Cell Progenitor Reticulocyte Megakaryocyte Promyelocyte Mature B-Cell Myelocyte NK-Cell Platelets Red blood cells T-Cell Metamyelocyte IgM Antibody Plasma Cell Secreting B-Cell Basophil Neutrophil Eosinophil IgE, IgG, IgA IgM antibodies antibodies Bleeding fevers; Thrombocytopenia (low platelets) Platelet physiology Mega Liver TPO (Thrombopoietin) TPO-receptor No negative feedback to liver Plt Bleeding fevers; Thrombocytopenia (low platelets) Platelet physiology Mega Liver TPO (Thrombopoietin) TPO-receptor Plt Plt Plt Plt Plt Plt Bleeding fevers; Thrombocytopenia (low platelets) Platelet physiology Mega Liver TPO (Thrombopoietin) TPO-receptor Plt Plt Plt Plt Plt Plt Bleeding fevers; Thrombocytopenia (low platelets) How bad is the thrombocytopenia? 150 – 400 x109 Severe Mild Moderate <50 149 - 100 99 - 50 ITP <30 There is little variation in platelet count for a single person A change by 98 x109 in the platelet count should prompt investigation Bleeding fevers; Thrombocytopenia (low platelets) Causes Chronic liver disease Medications Alcohol Bone Marrow Disorders - Isolated thrombocytopenia - Antibiotics - Nutritional deficiencies - Would typically cause other - Liver produces TPO - Piperacillin - Folate deficiency cytopenias - Usually mild to moderate (>50) - Vancomycin - Direct bone marrow - Leukaemia (acute) - NAFLD - Rifampicin suppression - Lymphoma - Antiepileptics - Alcoholic liver disease - Myeloma - Quinine - Myelodysplastic syndrome Infection - Metformin Nutritional Deficiencies - Viral - VitB12 deficiency - Usually associated with Autoimmune - HIV - Proton pump inhibitors (PPI) anaemia - SLE - Hepatitis B and C - Reduced nutrient - Vitamin B12 - APS - CMV and EBV absorption, incl. iron - Folate - Rheumatoid arthritis - MMR - Heparin induced (HIT) - Parvovirus - Cytotoxics - Bacterial - Chemotherapy - Direct bone marrow suppression in severe sepsis Idiopathic thrombocytopenic purpura (ITP) Thrombotic thrombocytopenic purpura (TTP) Bleeding fevers; Thrombocytopenia (low platelets) Causes Chronic Liver Disease - Liver produces TPO (hormone), which stimulates the bone marrow to produce megakaryocytes - May be the presenting feature in portal hypertension with splenomegaly - (Spleen sequestrates platelets) Chronic Alcohol Abuse - Leads to alcoholic liver disease, same as above - Direct bone marrow suppression - Should usually lead to a degree of pancytopenia - Reduced folate absorption Nutritional Deficiencies - Iron, Vitamin B12 and folate are vital for the formation of red cells in the bone marrow - Particularly Hb, but platelets also - Usually leads to a pancytopenia Bleeding fevers; Thrombocytopenia (low platelets) Causes Viral Infections Directly infect megakaryocytes, leading to apoptosis Platelet interaction with virus, causing platelet activation and consumption Direct TPO reduction from liver injury / interaction with TPO receptors - Acute - Rubella, mumps, varicella, parvovirus, Epstein-Barr virus (EBV) - Hepatitis C - Thrombocytopenia can resolve spontaneously after virus has cleared - Chronic - Human immunodeficiency virus (HIV) - direct toxicity to megakaryocytes - secondary ITP - primary HIV associated thrombocytopenia (or PHAT) - Cytomegalovirus (CMV) - Hepatitis B - Same mechanism as liver disease Bleeding fevers; Thrombocytopenia (low platelets) Causes Bacterial Infections - Overwhelming infections (proper sepsis), usually requiring ICU admission - Pancytopenia due to bone marrow suppression - Antimicrobials or direct marrow suppression - Mycoplasma infection - Helicobacter pylori infection - Tick-borne infections - Eptospirosis, brucellosis, anaplasmosis Bleeding fevers; Thrombocytopenia (low platelets) Causes Antibiotics Neurologics OTC Beta-lactam Abx Quinine Carbamazepine Vancomycin Ranitidine Phenytoin The ‘Pip’ in Pip/Taz Simvastatin Haloperidol Rifampicin Metformin Trimethoprim Proton pump inhibitors (PPIs) Aspirin/Clopidogrel/Warfarin/DOACs do not inherently reduce the platelet count Bleeding fevers; Thrombocytopenia (low platelets) Causes Heparin-induced Thrombocytopenia (HIT) - Thrombocytopenia following exposure of heparin - Rapid production of IgG antibodies, with absence of IgM antibodies - Suggesting secondary immune response - Hypothesis of sensation of antiheparin/platelet factor 4 (PF4) antibody occurs in presence of other factors (e.g. bacterial infection) UH > LMWH > Fondaparinux Bleeding fevers; Thrombocytopenia (low platelets) Causes Heparin-induced Thrombocytopenia (HIT) Diagnostic Features + Thrombocytopenia Received heparin within last 100 days 50% drop in platelet count - Typically 5-10 days - Does not need to fall below 150 x 109 - UH > LMWH > Fondaparinux Nadir ≥20 × 10⁹ Recent venous or arterial thrombosis - MI, PE, DVT, CVA, Injection site necrosis Recent orthopaedic or cardiovascular surgery Risk Assessment Absence of other causes of thrombocytopenia 4Ts score for HIT Jo et al. J Thromb Haemost. 2006 - Sepsis - Degree of thrombocytopenia - Medications (e.g. Vancomycin) - Timing of platelet count fall - Thrombosis or other sequelae Absence of bleeding - Other causes for thrombocytopenia - No or minimal petechiae/ecchymosis Bleeding fevers; Thrombocytopenia (low platelets) Causes Haematological - Myelodysplastic syndrome (MDS) - A group of malignant hematopoietic stem cell disorders, characterized by dysplastic and ineffective blood cell production - Can be cytopenia, bicytopenia or pancytopenia - Typically presents with a macrocytic anaemia and mild thrombocytopenia, that progresses - Lymphoproliferative disorders - CLL - Lymphoma Bleeding fevers; Thrombocytopenia (low platelets) Causes Haematological Thrombotic Thrombocytopenic Purpura Medical emergency New onset neurological symptoms Continuous cardiac monitoring (immediately) - Often vague - Don’t follow logical clinical pattern Immediate admission to Critical Care / Intensive Care Unit . New onset thrombocytopenia (20-30) at TTP centre . - Profound avoid delaying transfer for further investigations, unless life threatening Mild normocytic anaemia (90-100 g/L) - Intravascular haemolytic anaemia . DO NOT GIVE PLATELETS (unless discussed with haematology) Red cell fragments (schistocytes) on blood film Bleeding fevers; Thrombocytopenia (low platelets) An approach to the adult patient with unexplained thrombocytopenia Bleeding fevers; Thrombocytopenia (low platelets) Is the patient bleeding? Bleeding fevers; Thrombocytopenia (low platelets) What kind of bleeding? Mucocutaneous Bleeding Haematomas = Platelet = Coagulation System CNS Gum bleeding Skin New headache? Seizure Active Stopped Petechiae Bruising GI Spontaneous Traumatic Anaemia Epistaxis Upper GI? Lower GI? Bilateral Unilateral Normal creat / Raised urea? Acute? Chronic? Bleeding fevers; Thrombocytopenia (low platelets) Coagulation Status Mild Moderate Severe 149 - 100 99 - 50 <50 “Unlikely” to be the cause of their bleeding “Potentially” the cause of their bleeding Check coagulation status Platelet transfusion may be indicated (INR, aPTTr, Fibrinogen) (Platelets don’t solve everything) Bleeding fevers; Thrombocytopenia (low platelets) How bad is the thrombocytopenia? Mild Moderate Severe 149 - 100 99 - 50 <50 Investigate in Prim Care Not Bleeding – Same day referral to / review by Refer to haematology haematology (Send first line bloods) Bleeding – Same day discussion with haematology Bleeding fevers; Thrombocytopenia (low platelets) FBC – Plt <150 x10^9 Haematinics Virology Iron studies HIV Blood film Iron level, TIBC, TSat, Ferritin Hepatitis B surg Ag, surf Ab, core Ab Hepatitis C IgG Vitamin B12 Confirm true thrombocytopenia Serum +/- MMA Anisocytosis / Clumping EBV IgG, IgM CMV IgG, IgM Myelodysplastic Syndrome (MDS) Serum folate Hypogranular platelets Dysplastic neutrophils Liver/Bone Profiles Specialist Tests Macrocytosis Acute Leukaemia (AML/ALL) Raised LFTs Myeloma Screen Circulating peripheral blasts ALT, ALP, GGT Serum protein electrophoresis (myeloblasts, lymphoblasts) Serum free light chains Auer rods / Promyelocytes Raised calcium MAHA / TTP ?Malignancy Hep2ANA (autoimmune screen) Red cell fragments Bleeding fevers; Thrombocytopenia (low platelets) Immune thrombocytopenic purpura (ITP) Bleeding fevers; Thrombocytopenia (low platelets) Idiopathic Thrombocytopenic Purpura (ITP) - Acquired immune disorder - Isolated thrombocytopenia (<100 x109) - Primary ITP; Autoimmune in nature - Acquired anti-platelet autoantibodies (IgG) - Bind to GPIIb/IIIA receptors 30-40% patients
Recommended publications
  • Mass Cytometric Functional Profiling of Acute Myeloid Leukemia Defines Cell-Cycle and Immunophenotypic Properties That Correlate with Known Responses to Therapy

    Mass Cytometric Functional Profiling of Acute Myeloid Leukemia Defines Cell-Cycle and Immunophenotypic Properties That Correlate with Known Responses to Therapy

    Published OnlineFirst June 19, 2015; DOI: 10.1158/2159-8290.CD-15-0298 ReseaRch aRticle Mass Cytometric Functional Profiling of Acute Myeloid Leukemia Defines Cell-Cycle and Immunophenotypic Properties That Correlate with Known Responses to Therapy Gregory K. Behbehani1,2,3, Nikolay Samusik1, Zach B. Bjornson1, Wendy J. Fantl1,4, Bruno C. Medeiros2,3, and Garry P. Nolan1 Downloaded from cancerdiscovery.aacrjournals.org on September 25, 2021. © 2015 American Association for Cancer Research. Published OnlineFirst June 19, 2015; DOI: 10.1158/2159-8290.CD-15-0298 abstRact Acute myeloid leukemia (AML) is characterized by a high relapse rate that has been attributed to the quiescence of leukemia stem cells (LSC), which renders them resistant to chemotherapy. However, this hypothesis is largely supported by indirect evidence and fails to explain the large differences in relapse rates across AML subtypes. To address this, bone mar- row aspirates from 41 AML patients and five healthy donors were analyzed by high-dimensional mass cytometry. All patients displayed immunophenotypic and intracellular signaling abnormalities within CD34+CD38lo populations, and several karyotype- and genotype-specific surface marker patterns were identified. The immunophenotypic stem and early progenitor cell populations from patients with clinically favorable core-binding factor AML demonstrated a 5-fold higher fraction of cells in S-phase compared with other AML samples. Conversely, LSCs in less clinically favorable FLT3-ITD AML exhib- ited dramatic reductions in S-phase fraction. Mass cytometry also allowed direct observation of the in vivo effects of cytotoxic chemotherapy. SIGNIFICANCE: The mechanisms underlying differences in relapse rates across AML subtypes are poorly understood.
  • A Comparative Study of Murine Mast Cell Progenitors

    A Comparative Study of Murine Mast Cell Progenitors

    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2001 A Comparative Study of Murine Mast Cell Progenitors Shirley K. DeSimone Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Other Medicine and Health Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/4529 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Virginia Commonwealth University School of Medicine This is to certifythat the dissertation prepared by Shirley K. DeSimone entitled "A Comparative Study of Murine Mast Cell Progenitors" has been approved by her committee as satisfactory completion of the disse1tation requirement for the degree of Doctor of Philosophy. Francine M. Marciano-Cabral, Ph.D., School of Medicine Jack L. Haar, Ph.D., Dean, School of Graduate Studies A Comparative Study of Murine Mast Cell Progenitors A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University By Shirley K. DeSimone Director: Thomas F. Huff, Ph.D. Professor, Microbiology and Immunology Virginia Commonwealth University Richmond, Virginia May, 2001 11 Acknowledgments I wish to thank my advisor, Dr. Thomas F. Hufffor his insight, guidance, and patience. also which to acknowledge the invaluable, unwavering, and loving support of my husband, friend and companion, Dr. John A. DeSimone. Thanks are also due to the consistently helpful graduate students of Dr.
  • Effects of Heterologous Antineutrophil Serum in Guinea Pigs Hematologic and Ultrastructural Observations

    Effects of Heterologous Antineutrophil Serum in Guinea Pigs Hematologic and Ultrastructural Observations

    Effects of Heterologous Antineutrophil Serum in Guinea Pigs Hematologic and Ultrastructural Observations David M. Simpson and Russell Ross Two pools of rabbit anti-guinea pig neutrophil serum (ANS) were prepared using an intravenous (ANS I) or subcutaneous (ANS II) route of immunization with proteose peptone-stimulated peritoneal exudate neutrophils (PMNs) from albino guinea pigs. In vitro, both pools of ANS contained high titers of agglutinating antibodies to neutrophils and lower titers against lymphocytes and red cells. Ag- glutinins against all three cell types could be selectively removed by absorption. The in vivo hematologic effects of both the absorbed and unabsorbed antisera were examined after intraperitoneal administration, and the effects of ANS on neu- trophils in blood, bone marrow, and peritoneal cavity were examined by light and electr microscopy of spleen, liver, lung, lymph node, buffy coat, bone mar- row and pellets of peritoneal cells removed at various time intervals within 24 hours. Injection of either antisera caused a rapid decrase in circulating neu- trophils and lymphocytes, whi reached thefr lowest levels within 12 hours. Neutrophils that disappeared from the circulation were sequestered primarily in liver and spleen where they were phagocytized, as morphologically intact cells, by macrophages and then rapidly digested. Immature bone marow neutrophils as young as early myelocytes were ingested by macrophages in the marrow at 6 hours or later after ANS. Neutrophils that were phagocytized were apparently opsonized by ANS since there was no ultrastructurl evidence of neutrophil lysis in blood or bone manrow after ANS treatment. However, both lysed and ingested neubrophils were observed in the peritoneal cavity.
  • The Term Meaning White Blood Cells Is

    The Term Meaning White Blood Cells Is

    The Term Meaning White Blood Cells Is Micro Angelico still desalinate: venatic and unclimbed Elliot originate quite significatively but globes her proximocracoviennes and admeasuring catechetically. politely. Welsh Hazardableis attritional orand pollened, endows Sherwood voicelessly never as statant comb-outs Ira interpenetrates any output! Trophoblast cells are destined to give rise to many of the extraembryonic tissues. Genetic disorders and blood the cells is a permanent hair shaft, great care provider first line reported by lab technician may be included in circulation, the superficial veins. The part of the brain that controls coordinated movement. What Is A Medical Technologist? Inflammation of the liver. MPV is used along with platelet count to diagnose some diseases. After circulating in the bloodstream for about a day, monocytes enter body tissues to become macrophages, which can destroy some germs by surrounding and digesting them. The legacy of this great resource continues as the Merck Veterinary Manual in the US and Canada and the MSD Manual outside of North America. An abnormal increase in the volume of circulating blood. These small cells seem to sound an alarm when infectious agents invade your blood. Comparisons may be useful for a differential diagnosis. Finally, emotional or physical stress can also cause elevated white blood cell counts. The ability of the body to learn to fight specific infections after being exposed to the germs that cause them. However, you may also visit the Cookie Settings at any time to provide controlled consent, and you can withdraw your consent there. Severe pain that occurs suddenly and usually lasts a short while.
  • Erythroid Lineage Cells in the Liver: Novel Immune Regulators and Beyond

    Erythroid Lineage Cells in the Liver: Novel Immune Regulators and Beyond

    Review Article Erythroid Lineage Cells in the Liver: Novel Immune Regulators and Beyond Li Yang*1 and Kyle Lewis2 1Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 2Division of Gastroenterology, Hepatology & Nutrition Developmental Biology Center for Stem Cell and Organoid Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Abstract evidenced by both in vivo and in vitro studies in mouse and human. In addition, we also shed some light on the emerging The lineage of the erythroid cell has been revisited in recent trends of erythroid cells in the fields of microbiome study and years. Instead of being classified as simply inert oxygen regenerative medicine. carriers, emerging evidence has shown that they are a tightly regulated in immune potent population with potential devel- Erythroid lineage cells: Natural history in the liver opmental plasticity for lineage crossing. Erythroid cells have been reported to exert immune regulatory function through Cellular markers for staging of erythroid cells secreted cytokines, or cell-cell contact, depending on the conditions of the microenvironment and disease models. In There are different stages during erythropoiesis. The cells of this review, we explain the natural history of erythroid cells in interest for this review, referred as “erythroid lineage cells” the liver through a developmental lens, as it offers perspec- or “CD71+ erythroid cells”, represent a mix of erythroblasts, tives into newly recognized roles of this lineage in liver including basophilic, polychromatic, and orthochromatic biology. Here, we review the known immune roles of erythroid erythroblasts. A widely used assay relies on the cell- cells and discuss the mechanisms in the context of disease surface markers CD71 and Ter119, and on the flow-cyto- models and stages.
  • Development of Megakaryoblastic Leukaemia in Runx1-Evi1 Knock-In Chimaeric Mouse

    Development of Megakaryoblastic Leukaemia in Runx1-Evi1 Knock-In Chimaeric Mouse

    Letter to the Editor 1458 control. The Mcl-1-specific T-cell clone did not kill this cell line Ms. Bodil K. Jakobsen, Department of Clinical Immunology, (Figure 1c). University Hospital, Copenhagen, for HLA-typing of patient blood The lower rates of relapse in allogeneic transplantation samples. This study was supported by grants from the Danish compared with autologous bone marrow transplantation, the Medical Research Council, The Novo Nordisk Foundation, The striking clinical benefit of donor-lymphocyte infusions as well as Danish Cancer Society, The John and Birthe Meyer Foundation, the finding that human T cells can destroy chemotherapy- and Danish Cancer Research Foundation. resistant cell lines from chronic myeloid leukemia and multiple RB Sørensen1, OJ Nielsen2, P thor Straten1 and MH Andersen1 myeloma, have prompted development of immunotherapeutic 1 strategies against hematological cancers.3 Among these ap- Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark and proaches, active specific immunization or vaccination is 2Department of Hematology, State University Hospital, emerging as a valuable tool to boost the adaptive immune Copenhagen, Denmark. system against malignant cells. In this regard, the identification E-mail: [email protected] of leukemia-associated antigens is crucial. However, very few antigens are characterized in a conceptual framework in which the biology, microenvironment, and conventional disease management have been taken into consideration. Myeloid cell References factor-1 (Mcl-1) is a death-inhibiting member of the Bcl-2 family that is expressed in early monocyte differentiation. Elevated 1 Andersen MH, Becker JC, thor Straten P. The anti-apoptotic member levels of Mcl-1 have been reported for a number of solid and of the Bcl-2 family Mcl-1 is a CTL target in cancer patients.
  • Erythroid and Megakaryocytic Transformation

    Erythroid and Megakaryocytic Transformation

    Oncogene (2007) 26, 6803–6815 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc REVIEW Erythroid and megakaryocytic transformation A Wickrema1 and JD Crispino2 1Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA and 2Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA Red blood cells and megakaryocytes arise from a common Accumulated evidence mostly from studies with precursor, the megakaryocyte-erythroid progenitor and mouse models and human primary cells suggests that share many regulators including the transcription factors cellular expansion and differentiation occur concur- GATA-1 and GFI-1B and signaling molecules such as JAK2 rently until the late stages of erythroid differentiation and STAT5. These lineages also share the distinction (polychromatic/orthochromatic) at which point the cells of being associated with rare, but aggressive malignancies exit the cell cycle and undergo terminal maturation that have very poor prognoses. In this review, we (Wickrema et al., 1992; Ney and D’Andrea, 2000; will briefly summarize features of normal development of Koury et al., 2002). A disruption of the balance between red blood cells and megakaryocytes and also highlight erythroid cell expansion and differentiation results in events that lead to their leukemic transformation. It is either myeloproliferative disorders (MPDs) such as clear that much more work needs to be done to improve our polycythemia vera, myelodysplastic syndrome, or rarely understanding of the unique biology of these leukemias in erythroleukemia. Furthermore, some patients initially and to pave the way for novel targeted therapeutics. diagnosed with MPDs ultimately progress to erythro- Oncogene (2007) 26, 6803–6815; doi:10.1038/sj.onc.1210763 leukemia.
  • CDG and Immune Response: from Bedside to Bench and Back Authors

    CDG and Immune Response: from Bedside to Bench and Back Authors

    CDG and immune response: From bedside to bench and back 1,2,3 1,2,3,* 2,3 1,2 Authors: Carlota Pascoal , Rita Francisco , Tiago Ferro , Vanessa dos Reis Ferreira , Jaak Jaeken2,4, Paula A. Videira1,2,3 *The authors equally contributed to this work. 1 Portuguese Association for CDG, Lisboa, Portugal 2 CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies – PPAIN), Caparica, Portugal 3 UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal 4 Center for Metabolic Diseases, UZ and KU Leuven, Leuven, Belgium Word count: 7478 Number of figures: 2 Number of tables: 3 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jimd.12126 This article is protected by copyright. All rights reserved. Abstract Glycosylation is an essential biological process that adds structural and functional diversity to cells and molecules, participating in physiological processes such as immunity. The immune response is driven and modulated by protein-attached glycans that mediate cell-cell interactions, pathogen recognition and cell activation. Therefore, abnormal glycosylation can be associated with deranged immune responses. Within human diseases presenting immunological defects are Congenital Disorders of Glycosylation (CDG), a family of around 130 rare and complex genetic diseases. In this review, we have identified 23 CDG with immunological involvement, characterised by an increased propensity to – often life-threatening – infection.
  • Lesson-1 Composition of Blood and Normal Erythropoiesis

    Lesson-1 Composition of Blood and Normal Erythropoiesis

    Composition of Blood and Normal Erythropoiesis MODULE Hematology and Blood Bank Technique 1 COMPOSITION OF BLOOD AND Notes NORMAL ERYTHROPOIESIS 1.1 INTRODUCTION Blood consists of a fluid component- plasma, and a cellular component comprising of red cells, leucocytes and platelets, each of them with distinct morphology and a specific function. Erythrocytes or red cells are biconcave discs. They do not have a nucleus and are filled with hemoglobin which carries oxygen to tissues and carbon dioxide from the tissues to the lungs. Platelets are small cells. They also do not have a nucleus and are essential for clotting of blood. Leucocytes play an important role in fighting against infection. All these cells arise from a single cell called as the Hematopoietic stem cell. The process of formation of these cells is called Hematopoiesis. In this lesson we will learn the different stages in the development of red cells. The process of formation of red cells is called erythropoiesis. OBJECTIVES After reading this lesson, you will be able to: z explain the composition of blood z describe various stages in the formation of red cells z explain the precautions in handling blood and blood products z explain steps for preventing injury from sharp items. 1.2 SITES OF HEMATOPOIESIS It begins in the early prenatal period, within the first two weeks, in the yolk sac in the form of blood islands and is known as primitive hematopoiesis. The red cells formed at this time are nucleated and contain embryonic type of hemoglobin which differs in the type of globin chains from the adult hemoglobin.
  • Haematopoiesis to Describe the Components of Normal Blood, Their Relative Proportions and Their Functions

    Haematopoiesis to Describe the Components of Normal Blood, Their Relative Proportions and Their Functions

    Haematopoiesis To describe the components of normal blood, their relative proportions and their functions Blood 8% of body weight Plasma (55%) clear, 90% water, contains salts, enzymes, proteins WBCs and platelet (1%) RBCs (45%) bioconcave– disc, no nucleus = anuclear- 120days lifespan Immature = blasts– Mature= cytes In white blood cells myeloblast goes to neutrophils, basophils, eosinophils Monoblast= monocyte can also become dendritic cells and macrophages – White blood cells (leukocytes)– Polymorphonuclear= neutrophils, eosinophil s, basophils Mononuclear= lymphocytes= T cells, B cells and’ monocytes Lymphoid= NK cells, T-Lymphocyte, B-lymphocyte Myeloid= Monocyte, erythrocyte, neutrophils, basophils, eosinophils, mast cells, megakaryocyte, mast cells BOTH Dendritic cells (from monocyte in myeloid) (lymphoid precursor) Neutrophil – protection from bacteria and fungi Eosinophil- protection against parasites Basophil – increase during allergic reactions Lymphocytes – T cells- protection against viruses, B cells immunoglobulin synthesis Monocyte- protection from back bacteria and fungi phagocytosis – How do blood go from bone to blood vessels? – The bones are perfused with blood vessels- How do we investigate blood? In venepuncture, the superficial veins of the upper limbs are selected and hollow needle is inserted through the skin into the veins. Blood is then collected into evacuated tubes. These veins are present in numbers and are easily accessible. Anticoagulant, EDTA is used to stop blood clotting 1.Using Automated the sample full collected…. blood count Whole blood for a FBC is usually taken into an EDTA tube to stop it from clotting. The blood is well mixed and put through a machine called an automated analyser, counts the numbers and size of RBC and platelets within the blood using sensors Reticulocyte Assessing the young RBCs numbers performed by automated cell counters give indication of output of young RBC by bone marrow – 2.
  • 1 the Potential Role of Cytokines and Growth Factors in the Pathogenesis

    1 the Potential Role of Cytokines and Growth Factors in the Pathogenesis

    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 10 August 2021 doi:10.20944/preprints202108.0237.v1 The Potential Role of Cytokines and growth factors in the pathogenesis of Alzheimer's Disease Gilbert Ogunmokun1, Saikat Dewanjee2, Pratik Chakraborty2, Chandrasekhar Valupadas3,4 Anupama Chaudhary5, Viswakalyan Kolli6, Uttpal Anand7, Jayalakshmi Vallamkondu8, Parul Goel9, Hari Prasad Reddy Paluru10, Kiran Dip Gill11, P. Hemachandra Reddy12-16 , Vincenzo De Feo17*, ,Ramesh Kandimalla18,19*, 1The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, Texas, USA 2Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India 3Professor, Internal Medicine & Medical Superintendent, MGM Hospital, Warangal, India 4In charge Medical Superintendent, KMC Superspeciality Hospital, Warangal, India 5Orinin-BioSystems, LE-52, Lotus Road 4, CHD City, Karnal, Karnal, Haryana -132001, India 6Professor, Department of Biochemistry, GITAM Institute of Medical Sciences and Research, Visakhapatnam, India 7Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel 8National Institute of Technology, Warangal 506004, Telangana, India 9Department of Biochemistry, Maharishi Markandeshwar Institute of Medical Sciences & Research, Mullana, Ambala, India 10Sri Krsihnadevaraya University, Anantapur, Andhra Pradesh, India 11Department of Biochemistry, Posgraduate Institute
  • Neutrophil-Mediated Treatment of Neurodegenerative and Other Inflammatory Disorders Alain L

    Neutrophil-Mediated Treatment of Neurodegenerative and Other Inflammatory Disorders Alain L

    RESEARCH ARTICLE Neutrophil-mediated Treatment of Neurodegenerative and Other Inflammatory Disorders Alain L. Fymat Professor, International Institute of Medicine and Science, California, USA ABSTRACT Conventionally, neuroinflammation has been seen as a branch of immunology linked to neurodegenerative and other inflammatory disorders. The diagnosis and treatment of these disorders are dependent on the ability of delivering diagnostic and therapeutic pharmaceuticals through the blood–brain barrier. While itself contributing to the inflammatory process, the barrier largely hinders or even forbids this delivery but allows neutrophils to pass freely through it. This article discusses the use of a nanobiotechnology-based, neutrophil-mediated treatment of neurodegenerative and other inflammatory disorders. Key words: Dopamine, levodopa, paclitaxel INTRODUCTION A schematic representation of the cells and molecules involved in cerebral inflammation is shown in Figure 1. onventionally, neuroinflammation has been seen as The schema summarizes the pathogenic paths that may a central nervous system (CNS) -centric and specific link intravascular inflammatory events to proepileptogenic branch of immunology. Thus, a great deal of effort events in the brain parenchyma. The BBB and its component C cells forming tight junctions are diagrammed by the oblique has been made to find immunocompetent or inflammatory cells in the brain (or spinal cord) parenchyma. The purpose descending gray lines. External activated microglia and of this article is to query whether neutrophils, which pass gliotic astrocytes interact with the BBB being mediated by freely through the blood–brain barrier (BBB), can mediate the interleukin (IL-1β, IL-6, and IL-12) and tumor necrosis factor delivery of diagnostic and therapeutic drugs to the brain to alpha (TNF-α).