Hematology Lecture Notes

HEMATOPATHOLOGY:Dr. RAWAND P. SHAMOONHawlerMedical UniversityCollege of DentistryDepartment: Pathology NORMALBLOODFILMThe red blood cells are normal. They have a zone of central pallor about 1/3 the size of the RBC. The RBC's demonstrate minimal variation in size (anisocytosis) and shape (poikilocy...

HEMATOPATHOLOGY:Dr. RAWAND P. SHAMOONHawlerMedical UniversityCollege of DentistryDepartment: Pathology NORMALBLOODFILMThe red blood cells are normal. They have a zone of central pallor about 1/3 the size of the RBC. The RBC's demonstrate minimal variation in size (anisocytosis) and shape (poikilocytosis). A few small fuzzy blue platelets are seen. In the center of the field are a band neutrophilon the left and a segmented neutrophilon the right. MaleFemaleUniteRBCs:4-5.53.6-5.0x10^6/ulHb: 13.5-17.411 . 5-15.5g/dlPCV:40-5035-45%MCV:75-10075-100flMCH:25-3425-34pgMCHC:32-3632-36g/dlPlatelets150-450150-450x10^3/ulWBCs total4-11 . 54-11 . 5x10^3/ul REDCELLINDICES REDCELLINDICES NORMALBLOODFILMA normal mature lymphocyte is seen on the left compared to a segmented PMN on the right. An RBC is seen to be about 2/3 the size of a normal lymphocyte. NORMALBLOODFILMHere is a monocyte. It is slightly larger than a lymphocyte and has a folded nucleus. Monocytescan migrate out of the bloodstream and become tissue macrophages under the influence of cytokines. Note the many small smudgy blue platelets between the RBC's. In the center of the field is an eosinophilwith a bilobednucleus and numerous reddish granules in the cytoplasm. Just underneath it is a small lymphocyte. Eosinophilscan increase with allergic reactions and with parasitic infestations. NORMALBLOODFILM There is a basophilin the center of the field which has a lobed nucleus (like PMN's) and numerous coarse, dark blue granules in the cytoplasm. They are infrequent in a normal peripheral blood smear, and their significance is uncertain. A band neutrophilis seen on the left, and a large, activated lymphocyte on the right. NORMALBLOODFILM NORMALBLOODFILM WHITEBLOODCELLS ANEMIAReduction in red blood cell mass, or reduce Hb, usually accompanied by decrease red blood cell count and PCVCLASSIFICATIONSAccording to mechanism-Reduce production of red blood cell.-Reduce life span of the red blood cell.-Blood loss.-Splenic pooling. ACCORDINGTOSIZEOFREDBLOODCELL¢-Microcytic hypochromic:IDA, Thalassemia, Anemia of chronic disease, Congenital Sideroblasticanemia, Lead poisoning.¢-Normocytic: Early IDA, anemia of chronic disease, hemolytic anemia.¢-Macrocytic:Megaloblasticanemia (B12 deficiency, Folic acid deficiency), Liver disease, Alcoholic, Hypothyroidism, Aplasticanemia. Blood loss. IDA -HYPOCHROMICMICROCYTICRBCSThe RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic(less hemoglobin in each RBC) microcytic(smaller size of each RBC) anemia. There is also increased anisocytosis(variation in size) and poikilocytosis(variation in shape). SEVEREIRONDEFICIENCYANEMIA MEGALOBLASTICANAEMIAHypersegmentedneutrophilthat is present with megaloblasticanemias. There are 8 lobes instead of the usual 3 or 4. Such anemiascan be due to folateor to B12 deficiency. The size of the RBC's is also increased (macrocytosis, which is hard to appreciate in a blood smear). MEGALOBLASTICANEMIAHYPERSEGMENTEDNEUTROPHIL HEMOLYTICANEMIAS LAB. FINDINGS1-Raised serum bilirubin (unconjugated); increased urine urinobilinogen, increased faecalstercobilinogenas features of increased red cell breakdown. 2-Reticulcytosis and bone marrow erythroid hyperplasia as features of increased red cell production.3-Features of RBC destruction, eg. fragmented forms; or microspherocytes.3-Particular features of intravascular haemolysissuch as hemoglobinaemia, hemoglobinuria. HEMOLYTICBLOODPICTURE Hemolytic anemia or Bleeding CAUSESOFHEMOLYTICANEMIASA-Hereditary 1-Membranedefect: e.g. hereditary spherocytosis, hereditary elliptocytosis.2-Defect in metabolism (enzymes): e.g. G6PD deficiency, pyruvatekinasedeficiency.3-Genetic defect of hemoglobin: e.g. Thalassemias and sickle cell anemia. MembraneHbEnzymesHSHEHemoglobinopathiesThalassemiaSickleG6PD ↓PK ↓ALL CONGENITAL B-Acquired:1-Immune AutoimmuneAlloimmune•Haemolytictransfusion reactions•Haemolyticdisease of the newbornIdiopathicLymphoma, S.L.E 2-DRUGASSOCIATED3-REDCELLFRAGMENTATIONSYNDROMESE.G. ARTERIALGRAFTS, CARDIACVA LV E SANDMAHA.4-INFECTIONS: E.G. MALARIA5-CHEMICAL(E.G. INDUSTRIALAGENTS) ANDPHYSICALAGENTS(BURNS).6-SECONDARYASINLIVERANDRENALDISEASE. HEREDITARYSPHEROCYTOSIS(HS):¢Inheritance: AutosomalDominant¢Pathogenesis:HS is due to a defect in the main structural protein (spectrin) of the red cell membrane. LABORATORYFINDING: ¢The blood filmshows Microspherocytes(densely stained cells, smaller than normal RC, no central pallor)Reticulocytosis.¢Increased osmotic fragility. AnemiaJaundiceSplenomegaly.CLINICALFEATURES: DEFINITIONOFTHALASSEMIA¢A group of inherited disorders of Hemoglobin synthesis, characterized by reduced or absent synthesis of one or more of the globinchains of Hemoglobin. ¢They are called aor bthalassemiasaccording to the affected globinchain. TYPESOFNORMALHEMOGLOBINSAll Normal Hemoglobins consists of two pairs of globin chains, at the centre of each is one heme group.¢HbA ( A d u l t Hb) :a2 b2 (~96%).¢HbF (Fetal Hb) :a2 g2 (<1.0%).¢HbA2 (minor Adult Hb) :a2 d2 (1.8-3.5%).These percentages are for those from age of 6 months through adult life.At birth the major Hb is Hb F, and it decreases to adult level of <1% by 6 months of age. TYPESOFNORMALHEMOGLOBINSNormal Hb(HbA) : a2b2aabbggg2Fddd2A2 Clinically β thalassemia could be classified into:βThalassemia Major βThalassemia minorβThalassemia Intermediaβ thalassemia bbbbbbDefective bgeneNormal bgeneNormal beta genesHeterozygous to beta thalassaemia genetic defectHomozygous to beta thalassaemia genetic defectThalassamiaMinorThalassamiaMajorChr 11Chr 11Chr 11Chr 11Chr 11Chr 11 CLINICALFEATURES–THALASSAEMIAMAJOR BLOODPICTUREHemoglobin is usually 3-7 g/dl.MCV and MCH are both reduced (HypochromicMicrocytic).Reticulocytes: usually range 2-8%.Hb-Electrophorsis: shows increase of HbF fraction; HbF will range between 20 –98% (normal is <1%). BLOODFILMINbTHALASSAEMIAMAJORNucleated red cellHypochromic, anisocytosis, poikilocytosis, target cells BLOODFILMINbTHALASSAEMIAMAJOR BLOODFILMINbTHALASSAEMIAMAJOR BLOODFILMINbTHALASSAEMIAMAJOR b-THALASSAEMIAMINOR¢Due to heterozygosityto a b+or bodefect.bHeterozygous to beta thalassaemia genetic defectbMildly reduced overall Beta Chain production LAB. FINDINGSOFTHAL. MINORHb is usually reduced 1-2 g/dl less than normal for age and sex.MCH and MCV are reduced RBC count is usually elevated >5 x 1012/L.Reticulocytecount is slightly increased or normal.Hb-electrophorsis: shows elevated HbA2 level; from 3.6-7.5% (normal is 2.5-3.5%). BLOODFILMINTHALMINORThalassemia minorNormal blood film BLOODFILMINTHALASSAEMIAMINOR ¢ThalassaemiaMajor¢ThalassemiaMinor aaaNormal achain productionreduced achain productiona+aoNormalagenomeNo Alpha chain productionAn over-Simplified diagramaticrepresentation of the a+and aothalassaemiagenetic defectsNormal ageneDeleted ageneTwo agenesOne ageneNo agenesChromosome 16ALPHATHALASSAEMIA aoaoNo alpha genesNo alpha chains1. Hb Barts Hydropes Fetalisa+aoOne Alpha geneMarkedly reduced alpha chain production2. Hb H diseaseIncompatible with lifeClinical Phenotypes of Alpha thalassaemia(relevant to number of alpha genes remaining):Thalassaemiaintermediaphenotype Two alpha genes Three Alpha genesModerately reduced Alpha chainsMinimally reduced Alpha chains3. aThalassemia minor4. Silentathal. carrier statea+a+a+Normalagenes HbBart’s HydropsFetalis Blood picture in Hydropsfetalis Blood film in Hb-H disease