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Overview of Hematology

Overview of Hematology.

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Overview of Hematology

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  1. Overview of Hematology

  2. Hematology includes the study of etiology, diagnosis, treatment, prognosis, and prevention of blood diseases. The laboratory work that goes into the study of blood is frequently performed by a medical technologist. Hematologists physicians also very frequently do further study in oncology - the medical treatment of cancer.

  3. Topics • Hematopoiesis • Complete blood count (CBC) • Anemia • Polycythemia • Leukopenia • Leukemia and lymphoma • Myeloma • Coagulation • Transfusion

  4. Blood • Suspension of cells in a solute of water, proteins, and electrolytes • Average volume is 5 liters • 70mL per kg body weight • Plasma • Blood from which the cellular components (RBCs, WBCs, platelets) have been removed by centrifuge • Color is yellow • Contains coagulation proteins (clotting factors)

  5. Hematopoiesis • Development of blood cells and other formed elements • Sites vary throughout development • Fetal: yolk sac, liver, spleen • Pediatric: axial and appendicular skeleton • Adult: axial skeleton (sternum and pelvis) • Stem cells • Primitive; self-replicate and differentiate to become increasingly specialized progenitor cells which form mature cells • Process regulated by growth factors (interleukins, erythropoietin, thrombopoietin, G-CSF) • Early lineage division between progenitors for lymphoid and myeloid cells

  6. Hematopoiesis

  7. Complete Blood Count • White blood cells (WBC) • Differential • Neutrophils, lymphocytes, monocytes, eosinophils, basophils, bands • Must specify whether to include when ordering study • Red blood cells (RBC, Hgb, Hct) • Platelets (PLT) • Mean corpuscular volume (MCV) • Red cell distribution width (RDW)

  8. Red Blood Cells • Transport oxygen via hemoglobin from lungs to peripheral tissues and organs • Normal lifespan = 120 days • Reticulocytes • Immature red blood cells • Calculating proportion within circulation assists in determining cause of anemia • Normal is 1-2% • Low suggests decreased production (i.e. nutritional or marrow problem) • High suggests bleeding or premature destruction of red blood cells (i.e. hemolysis)

  9. Red Blood Cells • Peripheral blood smear • Normal

  10. Anemia • Defined by measurement of hemoglobin concentration • Normal – 15 in males ; 14 in females • Patients are “anemic” when hgb is > 2 standard deviations below normal • Determining reticulocyte count and MCV are first steps in determining etiology • Almost 1/3 of the world population is anemic!

  11. Anemia • Manifestations related to duration and severity of anemia • May provide important clues as to etiology • Body has physiologic responses to chronic anemia such that many patients are asymptomatic until hgb < 8 g/dL • Fatigue, pallor, dyspnea, dizziness, dyspnea on exertion, ischemic pain, cognitive abnormalities • Symptoms and signs of acute blood loss (hemorrhage) are related to hypovolemia • Hypotension, tachycardia, palpitations, orthostasis, syncope, shock

  12. Anemia • Mechanisms • Blood loss / hemorrhage • Initial focus in ALL anemic patients • Gastrointestinal tract, menstruation • Hemolysis • Shortened RBC survival time not explained by bleeding • Details later • Decreased production (hypoproliferative) • Nutritional deficiency (iron, B12, and folate) • Systemic illness (CKD, cancer, rheumatologic disease, etc.) • Bone marrow disorders

  13. Microcytic Anemia • Microcytosis – small cells (MCV <80) • Most common type of anemia encountered in primary care • Differential diagnosis • Hemoglobinopathy (inherited) • Iron deficiency • Chronic disease (may also be normocytic) • Inflammation • Lead poisoning • Check iron studies for clarification • Be familiar with interpretation (see next slide)

  14. Microcytic Anemia • Peripheral blood smear • Microcytosis, Hypochromic

  15. Microcytic Anemia RDW is often elevated in iron deficiency anemia ; look for this along with low MCV on CBC report

  16. Macrocytic Anemia • Macrocytosis – large cells (MCV >100) • Differential diagnosis • B12 deficiency • Pernicious anemia • Folate deficiency • ETOH • Medication • Check vitamin B12, RBC folate, fasting homocysteine, and methylmalonic acid (MMA) • HC and MMA are elevated in subclinical B12 and folate deficiency

  17. Hemolytic Anemia • History and physical findings • Review of PMH, FH, and medications • Jaundice is common • Occasional LUQ abdominal discomfort (splenomegaly) • Lab findings • Elevated reticulocyte count • Reflects bone marrow compensating for peripheral RBC destruction • Elevated LDH • Elevated total bilirubin (indirect/unconjugated) • Decreased haptoglobin • Abnormal cells on peripheral blood smear examination

  18. Hemolytic Anemia • Congenital • Membrane defects • Hereditary spherocytosis • Hereditary elliptocytosis • Enzyme defects • G6PD deficiency

  19. Hemolytic Anemia • Congenital, continued • Hemoglobin defects – diagnosed by hemoglobin electrophoresis • Thalassemias • Group of diseases characterized by globin chain (alpha and beta) imbalance

  20. Hemolytic Anemia • Congenital, continued • Sickle cell disease • RBCs become sickle-shaped  hemolysis, vascular occlusion • Hgb S gene carried by 8% of African Americans • 1:625 have disease • Genetic counseling available

  21. Hemolytic Anemia • Acquired • Classified according to site of RBC destruction and whether mediated by immune system • Intravascular • Extravascular • Autoimmune • Non-immune • Many causes… be aware of these – • Transfusion of incompatible blood (details later…) • Autoimmune • Warm (IgG-mediated) ; most common • Cold (IgM-mediated) • Prosthetic valves • TTP/HUS • DIC • Cancer • Drugs

  22. Polycythemia / Erythrocytosis • Abnormal elevation of hemoglobin • Rule out “relative” polcythemia caused by contraction of plasma volume, e.g. dehydration • Primary • Polycythemia Vera • RBC production independent of EPO • EPO level is low / positive JAK-2 is diagnostic • Uncommon • May be associated with leukocytosis, thrombocytosis, splenomegaly • Hyperviscosity • Headache, vertigo, visual changes, mental confusion • Risk of transformation into acute leukemia • Refer to hematology • Secondary • RBC production in response to increased EPO production • EPO level is usually high • Very common • Usual etiology is chronic hypoxia (COPD, sleep apnea) • Phlebotomy (250-500 mL) to maintain hct 45-50% ; treat underlying problem!

  23. White Blood Cells • Differential • Neutrophils 45-65% • “Segs” / “Polys” • Lymphocytes 15-40% • Monocytes 2-8% • Eosinophils 0-5% • Basophils 0-3% • Do you remember the physiologic role of each type of WBC?

  24. Benign WBCs Disorders

  25. Leukopenia • Neutropenia is most common cause • Absolute neutrophil count (ANC) < 1.5 x 109 cells/L • Many causes • Benign racial neutropenia common • African Americans and Yemenite Jews may have ANC as low as 1.0 • Viral infections • Epstein-Barr, Hepatitis B, HIV • Drugs * • Careful review of medications ; be suspicious of any medication recently started in patient with acute onset neutropenia • See next slide • Splenomegaly • Autoimmune disorders • SLE (lupus), Rheumatoid Arthritis, etc. • Bone marrow disorders

  26. Neutropenia

  27. Leukocytosis • WBC count > 11,000 • Determine which type of WBC is leading to the leukocytosis • Neutrophilia = most common • Infection • Connective tissue disorders • Medications (especially steroids, growth factors) • Cancer (CML and solid tumors) • Myeloproliferative disorders • Cigarette smoking • Stress (physiologic) • Pain, seizure, trauma • Idiopathic

  28. Leukocytosis • Patients with acute bacterial infection often present with neutrophilia and band formation ; i.e. “left shift” • Bands = young neutrophils • Viral infections are usually associated with low WBCs ; leukocytosis may suggest complications • Ex: bacterial pneumonia with underlying influenza infection

  29. Leukocytosis • Lymphocytosis • Viral infections • HBV, HCV, EBV, CMV • Tuberculosis • Pertussis • Drug Reaction • Stress (physiologic) • Trauma, MI, cardiac arrest, sickle crisis • Malignancy • ALL, CLL, lymphoma

  30. Malignant WBCs Disorders

  31. Myeloid vs. Lymphoid • Myeloid malignancies • • Acute myeloid leukemia • • Chronic myeloproliferative disorders • Lymphoid malignancies • • B-cell malignancies • • Acute lymphoblastic leukemia, B-cell type • • Non-Hodgkin’s lymphoma, B-cell types • • Myeloma • • T-cell malignancies • • Acute lymphoblastic leukemia, T-cell type • • Non-Hodgkin’s lymphoma, T-cell types • • Hodgkin’s disease

  32. Chronic Leukemia • Chronic myelogenous leukemia (CML) • Translocation between long arms of chromosomes 9 and 22 ; “Philadelphia Chromosome” ; bcr/abl protein

  33. Chronic Leukemia • Chronic lymphocytic leukemia (CLL) • Clonal malignancy of B-lymphocytes • Course is usually indolent ; affects older patients, average age at diagnosis is 70 years • Often found incidentally • Fatigue, lymphadenopathy common • Hepatosplenomegaly • Immunodeficiency is major clinical concern • Lymphocytes are defective ; do not make antibodies in response to antigens • Treatment • Observation • Indications for therapy include progressive fatigue, symptomatic lymphadenopathy, anemia, or thrombocytopenia • Rituximab (Rituxan®) and fludarabine +/- cyclophosphamide is initial approach • Gamma globulin (IVIG) used in patients with recurrent or severe bacterial infections • Allogeneic BMT is potentially curative but reserved for select patients • Prognosis improving ; survival is 10-15 years with early disease

  34. Acute Leukemia • Acute Myelogenous Leukemia (AML) • Most common in adults • Usually no apparent cause • Exposure to radiation, benzene, and certain chemotherapy drugs (alkylators) associated with leukemia • Underlying myelodysplastic syndrome (MDS) is risk factor • Symptoms and signs • Related to replacement of marrow space by malignant WBCs • Patients often very ill for period of just days or weeks • Skeletal pain • Bleeding • Gingival hyperplasia • Infection • Pancytopenia with circulating blasts is hallmark ; bone marrow biopsy required • Auer rods on peripheral smear are pathognomonic

  35. Acute Leukemia • AML, continued • Management • Immediate referral to hematologist • Patients often hospitalized for therapy • Anthracycline (daunorubicin or idarubicin) plus cytarabine results in CR in 80% of patients < 60 years • Additional high dose chemotherapy following CR leads to cure rate of 35-40% • Acute Lymphocytic Leukemia (ALL) • More often seen in children

  36. Lymphoma • Hodgkin’s disease • Malignancy of B-lymphocytes • Reed-Sternberg cells • Various subtypes ; “nodular sclerosing” is most common

  37. Lymphoma • Non-Hodgkin’s Lymphoma (NHL) • Heterogeneous group of cancers affecting lymphocytes • Usually classified by histologic grade (low to high) • Follicular lymphoma • Small lymphocytic lymphoma • Diffuse large B-cell lymphoma • Burkitt’s lymphoma • Many others

  38. Myeloma • Malignancy of plasma cells • Abnormal paraproteins are created leading to systemic problems • IgG – 60% • IgM – 20% • Must be able to recognize in primary care setting • “CRAB” – calcium, renal, anemia, bone • Primarily disease of elderly (median age 65 years) • Males > Females • Most common hematologic malignancy among African Americans ; #2 among Caucasians

  39. Myeloma • Osteolytic lesions

  40. Hemostasis

  41. Hemostatic Events Tissue Injury • Vasoconstriction • Neural • Platelet-reinforced • Platelet Activation • Adhesion • Aggregation • Coagulation • Blood Clot • Thrombin generation • Fibrin polymerization • Fibrinolysis • Blood Clot Dissolution • Vascular Patency Restored

  42. Categories of Hemostasis (page 572) Secondary Hemostasis Primary Hemostasis • Primary • Vascular System • Endothelia • Sub endothelia/collagen • Platelets • Secondary • Coagulation System • Plasma Proteins • Cells: Platelets • Fibrinolytic System • Plasma proteins • Cells: Platelets, Endothelia Graphic accessed at URL http://www.kup.at/journals/abbildungen/gross/746.html 9/18/08. Graphic accessed at URL http://www.acta-ortho.gr/v55t4_4/Figure1.jpg 9/18/08.

  43. Bleeding Disorders • Coagulation cascade

  44. Causes of Bleeding(1)Thrombocytopenia: Primary: • ITP • Neonatal Isoimmune • TAR Syndrome • Wiskott-Aldrich Syn. Secondary: *Malignancy *Aplastic Anemia *DIC *Sepsis *HUS *Hypersplenism *Autoimmune(SLE)

  45. Causes of Bleeding(2)Coagulopathy: Primary: • vWF Deficiency • Hemophilia • Platelet dysfunction Secondary: • DIC • Anticoagulants • Vit K deficiency • Hepatic Failure • Renal Failure • Maternal Anticonvulsant

  46. Causes of Bleeding(3)Vascular(Non-Hematologic) • Child Abuse • Vasculitis • Ulcer • Varices • Ehlers-Danlos Syndrome • Telangiectasia • Angiodysplasia

  47. Bleeding Disorders • Patterns of bleeding • Primary hemostasis – platelet and vascular function • Secondary hemostasis – clotting factors

  48. Bleeding Disorders • Petechiae in patient with acute ITP ; platelet count = 10,000

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