Presentation on theme: "Overview of Hematology"— Presentation transcript:
1Overview of Hematology Dr. Gamal BadrPhD in Immunology (Paris Sud University, France)Associate Professor of ImmunologyAssiut University, EgyptTel:Fax:s: orWebsites: https://www.researchgate.net/profil/Gamal_Badr/ orcid.org/
2HematologyHematology, also spelled haematology, is the branch of internal medicine, physiology, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases. Hematology includes the study of etiology, diagnosis, treatment, and prevention of blood diseases.
4BLOOD IS A TYPE OF CONNECTIVE TISSUE WHAT DOES BLOOD DO? TransportationOxygenNutrientsHormonesWaste ProductsRegulationFluid, electrolyteAcid-Base balanceBody temperatureProtectionCoagulationFight Infections
5Components of Blood Blood components are: Suspension of cells in a solute of water, proteins, and electrolytesAverage volume is 5 liters70mL per kg body weightBlood components are:A. Liquid component -Plasma (55%)Plasma is a yellow colored solution containing a mixture of water, amino acids, proteins, clotting factors, carbohydrates, lipids, vitamins, hormones, electrolytes, and cellular wastes.
6B. Cellular component (45%) Thrombocytes/PlateletsLeukocytes/ white blood cells (WBCs)Erythrocytes/ red blood cells (RBCs)
7Complete Blood Count (CBC) White blood cells (WBCs) Normal 4, ,000 /µℓDifferential cells: Neutrophils, lymphocytes, monocytes, eosinophils, basophils, Dendritic cells.Red blood cells (RBCs) ♂ 4.5 – 5.5 x 106/µℓ ♀ 4.0 – 5.0 x 106/µℓHemoglobin (Hgb), Hematocrit (Hct)The hematocrit is the percent of whole blood that is composed of red blood cells. The hematocrit is a measure of both the number of RBCs and the size of red blood cells.Mean corpuscular volume (MCV)is a measure of the average volume of a red blood corpusclePlatelets (PLT) Normal 15, ,000 /µℓ
8Hematopoiesis Development of all blood cells and other formed elements Sites vary throughout developmentBefore birth: liver, spleenAdult: bone marrow (BM) of axial skeleton.Stem cellsPrimitive; self-replicate and differentiate to become increasingly specialized progenitor cells which form mature cellsProcess regulated by growth factors (interleukins, erythropoietin, thrombopoietin, G-CSF)Early lineage division between progenitors for lymphoid and myeloid cells
10Thrombocytes/Platelets Must be present for clotting to occurInvolved in hemostasis
11Leukocytes/White Blood Cells (WBCs) GranulocytesContain granules in their cytoplasmBasophilsEosinophilsNeutrophilsAgranulocytesContain no granules in their cytoplasmMonocytesLymphocytes
12Types and Functions of Leukocytes CELL FUNCTIONGranulocytesNeutrophilEosinophilBasophilPhagocytosis: early phase of inflammationPhagocytosis: parasitic infectionsInflammatory response, allergic responseAgranulocytesLymphocyteMonocyteCellular and humoral immune responsePhagocytosis: cellular immune response
13Erythrocytes/Red Blood Cells (RBCs) Immature RBC (circle and nucleated), while mature RBC is circle and non nucleatedComposed of hemoglobin (Hb or Hgb)Erythropoiesis is the production of RBCsStimulated by hypoxia (decrease of O2 in the blood)Controlled by erythropoietin (hormone synthesized in kidney)Hemolysis is the destruction of RBCsReleases bilirubin into blood streamNormal lifespan of RBC = 120 days
14Structures of the Hematologic System Bone Marrow a primary lymphoid organ (Hematopoiesis)Soft connective tissue in core of bonesThe production of all types of blood cells (Hematopoiesis) generated by a remarkable self-regulated system that is responsive to the demands put upon it.LiverReceives 24% of the cardiac output (1500 ml of blood each minute)Liver has many functions. The hematologic functions:Liver synthesis plasma proteins including clotting factors and albuminLiver clears damaged and non-functioning RBCs/erythrocytes from circulationSpleen a secondary lymphoid organ exerts many functions:Hematopoietic function: Produces fetal RBCsFilter function: Filter and reuse certain cellsImmune function: Lymphocytes, monocytesStorage function: 30% platelets stored in spleen
15RBCs (erythrocytes)Mature RBCs are biconcave disks that contain oxygen-carrying hemoglobin, discard their nuclei during development and so cannot reproduce or produce proteins.In the embryo and fetus, RBCs production occurs in the liver and spleen; but after birth, it occurs in the bone marrow. Normal lifespan = 120 daysReticulocytes (Immature red blood cells)Calculating proportion within circulation assistsin determining cause of anemiaNormal % is 1-2%Low % (< 0.4%) suggests decreased production (i.e. nutritional or marrow problem)High % (< 3%) suggests bleeding or premature destruction of red blood cells (i.e. hemolysis)
17RBC Production and Its Control The total number of red blood cells remains relatively constant due to a negative feedback mechanism utilizing he hormone erythropoietin, which is released from the kidneys and liver in response to the detection of low oxygen levels.
18Factors Affecting RBCs Production Dietary Vitamins B12 and folic acid are needed for DNA synthesis, so they are necessary for the reproduction of all body cells, especially in hematopoietic tissue.Dietary Iron is needed for hemoglobin synthesis.Destruction of RBCs with age, RBCs become increasingly fragile and are damaged by passing through narrow capillaries.Macrophages in the liver and spleen phagocytize damaged red blood cells.Hemoglobin from the decomposed RBC is converted into heme and globin.Heme is decomposed into iron which is stored or recycled and biliverdin and bilirubin which are excreted in bile.
21RBCs Disorders Anemia Almost 1/3 of the world population is anemic! Anemia is defined as a reduction in one or more of the major RBC measurements: Hgb, Hct, or RBC countNormal Hgb concentration– 15 in males ; 14 in femalesPatients are “anemic” when Hgb is < 12 g/dLDetermining reticulocyte count and MCV are first steps in determining etiologyMCV = 10 x HCT(percent) ÷ RBC numbers (millions/µL)Almost 1/3 of the world population is anemic!Increase in hgb that occurs in men is mostly related to effect of androgens on release of erythropoietin ; gender disparity becomes less significant in advanced age
22RBCs Disorders - Anemia Manifestations related to duration and severity of anemia:May provide important clues as to etiologyBody has physiologic responses to chronic anemia such that many patients are asymptomatic until Hgb < 8 g/dLFatigue, pallor, dyspnea, dizziness, ischemic pain, cognitive abnormalitiesTwo main approaches that are not mutually exclusive:Morphological approach.Biologic or kinetic approach.
23Anemia - (Morphological approach) By calculation from an independently-measured RBCs count and hematocrit:MCV (femtoliters) = 10 x HCT(percent) ÷ RBC (millions/µL)The normal MCV ( fL)Microcytosis – small cells (MCV <80) – microcytic anemiaMacrocytosis – large cells (MCV >100) – macrocytic anemiaNormocytic anemiais defined as an anemia with a MCV of which is the normal range, but the HCT and Hbg is decreased
24Microcytic Anemia (MCV <76 fL) The normal MCV ( fL)Microcytosis – small cells (MCV <80)Most common type of anemia encountered in primary careDifferential diagnosisHemoglobinopathy (inherited)Iron deficiencyChronic disease (may also be normocytic)InflammationLead poisoning
26Macrocytic Anemia Macrocytosis – large cells (MCV >100) Differential diagnosisB12 deficiencyPernicious anemia: (Biermer's anemia, Addison's anemia) is caused by loss of gastric parietal cells, which are responsible for the secretion of factors that are responsible for absorption of vitamin B12 in the ileum.Folate deficiencyCheck vitamin B12, RBC folate, fasting homocysteine (HC), and methylmalonic acid (MMA)HC and MMA are elevated in subclinical B12 and folate deficiencyMedications associated with elevated MCV include…
27Anemia - (kinetic approach) Abnormality?Production of RBCs(hypoproliferation)Survival/Destruction of RBCsThe key test is the reticulocyte countMechanisms of AnemiaDecreased erythrocyte production Erythrocyte lossDecreased erythropoietin production HemorrhageInadequate marrow response to erythropoietin Hemolysis
28Anemia - (kinetic approach) MechanismsShort survival/Destruction of RBCs/ loss of RBCsBlood loss / hemorrhageAccidentsUlcer or surgery in Gastrointestinal tract (GI), menstruationHemolysisShortened RBC survival time.Decreased production (hypoproliferative)Nutritional deficiency (iron, B12, and folate)Systemic illness (chronic kidney disease (CKD), cancer, rheumatologic disease, etc.)Bone marrow disorders
30RBCs Disorders - Red cell destruction Causes:Elevated reticulocyte countMechanicalAutoimmuneDrugCongenital
31Red cell destruction -Hemolytic Anemia History and physical findingsHemolytic anemias are either acquired or congenital. The laboratory signs of hemolytic anemias include:Increased LDH (Lactate dehydrogenase).Increased bilirubin.Increased reticulocyte count.Decreased haptoglobin.Urine hemosiderinJaundice is commonOccasional pain in the left upper abdominal region. (splenomegaly)
32Red cell destruction -Hemolytic Anemia CongenitalMembrane defectsHereditary spherocytosis : auto-hemolytic anemia characterized by the production (RBCs) that are sphere-shaped, rather than bi-concave disk shapedHereditary elliptocytosis: also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the patient's RBCs are elliptical rather than the typical biconcave disc shape.Enzyme defectsGlucose-6-phosphate dehydrogenase (G6PD) deficiency: X-linked recessive hereditary disease.Pyruvate kinase deficiency: is an inherited metabolic disorder of the enzyme Pyruvate kinase which affects the survival of RBCs and causes them to deform into echinocytes on peripheral blood smears.
33Red cell destruction -Hemolytic Anemia CongenitalHemoglobin defects: diagnosed by hemoglobin electrophoresis.Thalassemias: Genetic defect in hemoglobin synthesisdecreased synthesis of one of the 2 globin chains ( or )Imbalance of globin chain synthesis leads to depression of hemoglobin production and precipitation of excess globin (toxic)“Ineffective erythropoiesis”Found in people of African, Asian, and Mediterranean heritageFe stores are usually elevatedThe only treatments are stem cell transplant and simple transfusion.Chelation therapy (administration of chelating agents to remove heavy metals from the body) to avoid iron overload has to be started early.
34Red cell destruction -Hemolytic Anemia CongenitalHemoglobin defects:Sickle cell diseaseSingle base pair mutation results in a single amino acid change.Under low oxygen, Hgb becomes insoluble forming long polymersThis leads to membrane changes (“sickling”) and vasoocclusionOXY-STATEDEOXY-STATE
35Red cell destruction -Hemolytic Anemia AquiredClassified according to site of RBC destruction and whether mediated by immune systemIntravascularExtravascularAutoimmuneNon-immuneMany causes… be aware of these –Transfusion of incompatible bloodProsthetic valvesCancerDrugs
37Marrow Production - Aplastic Anemia Aplastic anemia is a disease in which the bone marrow, and the blood stem cells that reside there, are damaged. This causes a deficiency of all three blood cell types: red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia).AcquiredImmunologicalToxins – BenzeneDrugs – methotrexate, chloramphenicolViruses – EBV, hepatitisHereditaryFanconi anemia (FA) is the result of a genetic defect in a cluster of proteins responsible for DNA repair
38Marrow Production - Aplastic Anemia All lineages affected.Most patients require red cell transfusions.Transplant when possible.Transfusions should be used selectively to avoid sensitization (no family donors!).
39Polycythemia / Erythrocytosis Polycythemia is increased total RBC mass - Hct > 65%Above 65% blood viscosity rises exponentiallyComplications: Polycythemic hyperviscosity is increased viscosity of the blood resulting from increased numbers of RBCsPolycythemia occurs in 2-4% of newborns, half of them are symptomaticClinical signs result from regional effects of hyperviscosity and from the formation of microthrombiTissue hypoxia, Acidosis, HypoglycemiaOrgans affected: CNS, kidneys, adrenals, cardiopulmonary system, GI tractTreatmentPhlebotomy (to cut a vein) is the process of making an incision in a vein.Myelosupressive agents: new therapeutic agents such as: interferon alfa-2b (Intron A) therapy, agents that target platelet number (e.g., anagrelide [Agrylin]), and platelet function (e.g., aspirin).
41Leukopenia (Leukocytopenia) - Leukopenia: is a decrease in the number of WBCsNeutropenia is most common causeAbsolute neutrophil count (ANC) < 1.5 x 109 cells/LMany causesBenign racial neutropenia commonAfrican Americans and Yemenite Jews may have ANC as low as 1.0Viral infectionsEpstein-Barr, Hepatitis B, HIVDrugsCareful review of medications ; be suspicious of any medication recently started in patient with acute onset neutropeniaSplenomegalyAutoimmune disordersSLE (lupus), Rheumatoid Arthritis, etc.Bone marrow disorders
42Leukocytosis Leukocytosis: is an increase in the number of WBCs WBC count > 11,000Determine which type of WBC is leading to the leukocytosisNeutrophilia = most commonCauses:InfectionConnective tissue disordersMedications (especially steroids, growth factors)Cancer Myeloproliferative disordersCigarette smokingStress (physiologic)Pain, traumaIdiopathic (unknown cause)
43LeukocytosisPatients with acute bacterial infection often present with neutrophilia and band formationBands = young neutrophilsViral infections are usually associated with low WBCs ; leukocytosis may suggest complicationsEx: bacterial pneumonia with underlying influenza infection
44LeukocytosisLymphocytosis: is an increase in the number or proportion of lymphocytes in the bloodCauses:Viral infections: HBV, HCV, EBV, CMVTuberculosisPertussisDrug ReactionStress (physiologic): Trauma, cardiac arrest, etcMalignancy: ALL, CLL, lymphoma
47LeukemiaLeukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature WBCs called “blasts".Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader group of diseases affecting the blood, bone marrow, and lymphoid system.
48Chronic Leukemia Chronic myelogenous leukemia (CML) Translocation between long arms of chromosomes 9 and 22 ; “Philadelphia Chromosome” ; bcr/abl protein
49Chronic Leukemia Chronic lymphocytic leukemia (CLL) Clonal malignancy of B-lymphocytesCourse is usually indolent ; affects older patients, average age at diagnosis is 70 yearsOften found incidentallyFatigue, lymphadenopathy commonHepatosplenomegalyImmunodeficiency is major clinical concernLymphocytes are defective ; do not make antibodies in response to antigensTreatmentObservationIndications for therapy include progressive fatigue, symptomatic lymphadenopathy, anemia, or thrombocytopeniaGamma globulin (IVIG) used in patients with recurrent or severe bacterial infectionsAllogeneic BMT is potentially curative but reserved for select patientsPrognosis improving ; survival is years with early disease
50Acute Leukemia Acute Myelogenous Leukemia (AML) Most common in adults Usually no apparent causeExposure to radiation, benzene, and certain chemotherapy drugs (alkylators) associated with leukemiaUnderlying myelodysplastic syndrome (MDS) is risk factorSymptoms and signsRelated to replacement of marrow space by malignant WBCsPatients often very ill for period of just days or weeksSkeletal painBleedingGingival hyperplasiaInfectionPancytopenia with circulating blasts is hallmark ; bone marrow biopsy requiredAuer rods on peripheral smear are pathognomonic
51Acute Leukemia AML Acute Lymphocytic Leukemia (ALL) Management Immediate referral to hematologistPatients often hospitalized for therapyAnthracycline (daunorubicin or idarubicin) plus cytarabine results in CR in 80% of patients < 60 yearsAdditional high dose chemotherapy following CR leads to cure rate of 35-40%Acute Lymphocytic Leukemia (ALL)More often seen in children
52Lymphoma Hodgkin’s disease Malignancy of B-lymphocytes Reed-Sternberg cellsVarious subtypes ; “nodular sclerosing” is most commonNon-Hodgkin’s Lymphoma (NHL)Heterogeneous group of cancers affecting lymphocytesUsually classified by histologic grade (low to high)Follicular lymphomaSmall lymphocytic lymphomaDiffuse large B-cell lymphomaBurkitt’s lymphomaMany others
53Myeloma Malignancy of plasma cells Abnormal paraproteins are created leading to systemic problemsIgG – 60%IgM – 20%Primarily disease of elderly (median age 65 years)Most common hematologic malignancy among African Americans ; #2 among Caucasians