Hematology Course:an overview of Clinical

Hematology

Dr. Ahmed Elshebiny , MDDr. Ahmed Elshebiny , MDLecturer of Internal MedicineLecturer of Internal Medicine

Faculty of Medicine, Menoufyia UniversityFaculty of Medicine, Menoufyia University

Former Clinical Research FellowFormer Clinical Research Fellow,,Joslin Diabetes Center, Harvard UniversityJoslin Diabetes Center, Harvard University

Course includes1. Hematology an Overview : The blood and bone marrow2. Clinical Hematology : The full blood count3. Anemia : a Clinical approach4. Deficiency anemias5. Hemolytic anemia : Acquired6. Hemolytic anemia : inherited7. Bone marrow failure syndromes ( aplastic, myeloysplastic, PNH)8. Hypoproliferative anemias (of chronic disease)9. Myeloproliferative disorders10. Leukemias11. Lymphomas & Myelomas 12. Porphyria & Hemochromatosis13. Leukocyte disorders14. Interpretation of standard hematologic tests

Structure and Function

Blood as a circulatory fluid A protein rich fluid called plasma in which

cellular elements are suspended Carrier of O2 and CO2

Carries nutrients Carries waste Hormones Immunity Hemostasis

Blood is continuously renewed

The Bone Marrow is the blood Factory

May be exposed to damage or failure

Spleen? Blood filter Immunity

Red blood cells A nucleated Diameter and thickness Membrane Metabolism

Red cell membrane Phospholipid bilayer Intracellular protein network 50% cholestrol Membrane proteins

( glycophorin c and band 3) Reticuloproteins

( spectrin , actin, ankyrin)

Hemoglobin Tetramer of 4 globin chains (proteins) Each with a heme group containing iron Can be distinguished by electrophoresis Chain types

Alpha Beta Gamma Delta Zeta and epsilon are embryonic

Fetal and neonatal hemoglobins

HB and MCV values with age & sex

Haemopooiesis Yolk sac ( 3 rd week) Liver and spleen ( 6 wk to 7 months) Bone marrow Red marrow & yellow marrow Extramedullary ---- When?

Aplastic Anemia

Bone marrow aspiration and biopsy

Bone marrow aspiration

P.N.H

Hematology Course (2):Clinical Hematology

Manifestations of blood diseases Anemia High hemoglobin Bleeding Thrombosis Infections Lymphadenopathy Splenomegaly

Full blood count Common investigation Can point to hematological disorders Cornerstone of hematological diagnosis Manual or automated Automated counting and sizing by different methods

e.g. ( Aperture impedance) They also measure the hemoglobin by

spectrophotometry Some other parameters are calculated ( MCH,

MCHC) The automated analyzers can diffrentiate leukocyte

N.B. 5% of the normal population lie outside the

normal range Race may affect the CBC Be careful of artifacts

Anemia Definition Morphological approach Etiological( kinetic ) approach RBCs in the blood film

Polycythemia True Polycythemia( Primary and secondary) Relative ( decreased plasma volume)

Leucocytosis Examine the differential count Examine a blood film Commonest is neutrophilia

WBCs 5 WBCs line ( diffrential)

Neutrophils Lymphocytes Monocytes Eosinophils Basophils

Neutropenia Clinically evident when ANC < 500 Congenital and acquired

Congenital ( e.g Kostman;s syndrome and cyclic neutropenias)

Most cause of acquired neutropenia is drugs

Drugs associated with neutropenia Anticonvulsants ---- phenytoin Antithyropid ------- carbimazole Phenothiazines ------ carbamazepine Antibacterial -------- phenylbutazone Anti-inflammatory ------ co trimoxazole Cytotoxic Others ----- gold, penicillamine, imipramine

Neutrophil disorders

NetrophiliaNeutroppenia

Infections ( bact, fungal)Surgery, BurnsInfarctions Inflammation ( gout, RA, IBD)Malignancy (CML)Physiological

Infections( viral, salmonella, protozoal, malaria) DrugsAutoimmuneAlcoholCongenital

Lymphocytic count disorders

LymphocytosisLymphopenia

Infections ( viral, pertussis, glandular fever) Lymphoproliferative ( CLL, lymphoma )Post splenectomy

Infections( recent viral) (immunosuppressive, cortisone)Autoimmune & CT diseasesSarcoidosisChronic renal failureCongenital : severe combined immunodifficiency

Eosinophils

EosinophiliaEosinopenia

Allergy ( asthma, eczema)Infections ( Helminths, viral)Skin disease C.T disease e.g PAN Malignancy ( solid tumors and lymphomas)Gold therapy

Acute inflammation SteroidsCatecholamines

Basophils

Basophilia ( rare)basopenia

Inflammation ( Acute hypersensitivity, IBD) Iron difficiencyMyeloproliferative disorders ( Polythycemia, CML)

Hyperthyroidism

Monocytosis Viral and fungal infections T.B infection C.T diseases Inflammatory bowl disease Myeloproliferative Chronic Myelomonocytic leukemia ( one of

MDS) Malignancy e.g solid tumors

Platelets (thrombocytopenia) Spurious Increased consumption Decreased production

Platelets (thrombocytosis) Reactive Primary

Blood film Abnormal shape ( poikilocytosis) Spherocytes Target cells Polychromasia Dimorphic film Lobulation and toxic granulation A typical cells Blast cells Malaria others

Hematology Course (3):Clinical Hematology

Anemia is operationally defined as a reduction in one or more of the major RBC measurements:

hemoglobin concentration, hematocrit, or RBC count

Keep in mind these are all concentration measures

…most accurately measured by obtaining a RBC mass via isotopic dilution methods.

Definition:

Kinetic approach to anemias Decreased erythrocyte production

Decreased erythropoietin production Inadequate marrow response to erythropoietin

Erythrocyte loss Hemorrhage Hemolysis

Normal blood film

Morphological approach

Reticulocytes Increased reticulocytes

(greater than 2-3% or 100,000/mm3 total) are seen in blood loss and hemolytic processes, although up to 25% of hemolytic anemias will present with a normal reticulocyte count due to immune destruction of red cell precursors.

Retic counts are most helpful if extremely low (<0.1%) or greater than 3% (100,000/mm3 total).

Reticulocytes

Low MCV Iron Deficiency Thalassemia Lead poisoning Sideroblastic Anemia Anemia of chronic disease

Iron difficiency anemia Thalassemia

Thalassemia

Sickle cell anemia

Spherocytosis

Hemolytic anemia

Normocytic anemia Causes Approach Reticulocytic count Coomb’s test

Macrocytic anemia

B 12 and folate deficiency

References Merck manual : online textbook

E-medicine , online textbook , specialties,. Bethesda Handbook of Clinical Hematology Problem solving in Hematology Essential Revisoin notes for MRCP 2009 Kumar & Klark : Clinical Medicine 2009 Davidson’s : Clinical and practice of Medicine 1999 Ganong’s physiology 2010 Other Web Resources & books