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Hematology Data. Anemia. Understanding anemia Disease - to be treated on its own merits Condition - a secondary manifestation of another disease Causes Decreased production Blood loss Hemolysis. Classification of Anemia. Acute vs. chronic Signs and symptoms Red cell kinetics
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Anemia • Understanding anemia • Disease - to be treated on its own merits • Condition - a secondary manifestation of another disease • Causes • Decreased production • Blood loss • Hemolysis
Classification of Anemia • Acute vs. chronic • Signs and symptoms • Red cell kinetics • Determined by reticulocyte count • Red cell size • Determined by MCV
Laboratory Evaluation of Anemia • Complete blood count • Reticulocyte count • Peripheral smear
Mild (MCV > 70 fl) Iron deficiency Thalassemia Lead toxicity Sideroblastic anemia Anemia of chronic disease Microcytic Hypochromic Anemia: Diagnosis
Iron Deficiency Anemia • A world-wide problem • 3% of toddlers age 1-2 years • 2-5% of women of child bearing age • Iron metabolism • Iron stores • Laboratory findings of iron deficiency • Causes of iron deficiency • Treatment
Body Iron Distribution and Storage Duodenum • Storage • Iron storage 0-1000 mg • Transit Serum iron 3 mg • Total 3000-4000 mg Dietary iron (average, 1 - 2 mg Utilization Utilization per day) • Metabolic • Hemoglobin 1800-2500 mg • Myoglobin 300-500 mg Plasma transferrin (3 mg) Bone Muscle marrow (myoglobin) (300 mg) Circulating (300 mg) erythrocytes Storage (hemoglobin) iron (1,800 mg) Sloughed mucosal cells Desquamation/Menstruation Other blood loss (average, 1 - 2 mg per day) Reticuloendothelial Liver macrophages (1,000 mg) Iron loss (600 mg)
Increased Utilization iron requirements Blood loss Gastrointestinal tract Genitourinary tract Blood donation Pregnancy and lactation Inadequate availability iron supply Insufficient dietary iron Impaired iron absorption Gastric surgery Intestinal malabsorption Celiac disease Causes of Iron Deficiency
Systemic Manifestations of Iron Deficiency • Behavioral and neuropsychiatric manifestations • Pica (pagophagia) • Angular stomatitis • Glossitis • Esophageal webs and strictures • Koilonychia (spooning)
Treatment with Oral Iron: General Principles • Ferrous salts are absorbed better than ferric • All ferrous salts are absorbed to the same extent • Ascorbic acid increases absorption and toxicity • Iron is absorbed best on an empty stomach • Iron should not be given with antacids • Iron polysaccharide complex (Niferex) seems to be better tolerated than other iron salts
Anemia of Chronic Disease • Associated conditions • Chronic infection (TB, HIV, osteomyelitis) • Chronic inflammatory disorder (rheumatoid arthritis) • Neoplasm • Etiology • Impaired erythropoietin production • Impaired iron utilization from RE system • Direct inhibition of erythropoiesis • Consequence of inflammatory cytokines
Anemia of Chronic Disease • Characteristics • Anemia of variable severity (mild-severe) • Low erythropoietin level • Low reticulocyte count • WBC and platelet counts are normal • Treatment • Underlying condition • Erythropoietin
Anemia of Chronic Renal Disease • Characteristics • Widespread - 8% of US population has increased creatinine • 23% of patients with chronic renal disease have HCT ≤ 30% • Long-term anemia is a risk for LVH • Risk factor for mortality • Etiology • Insufficient production of erythropoietin
Anemia in Other Clinical Conditions Condition treated with RBC or Erythropoietin Outcome measured Critical care patients Trend to improved survival Elderly patients with Improved 30 day survival myocardial infarction Congestive heart failure Decreased hospital days Cancer and cancer therapy Improved quality of life Improved local control with radiation
Macrocytic Anemia with Low Reticulocyte Count • Megaloblastic anemia • Vitamin B12 deficiency • Folate deficiency • Non-megaloblastic macrocytic anemia • Liver disease • Hypothyroidism • Drug-induced (DNA synthesis block) • Myelodysplastic syndrome
Folate and Cobalamin Daily Requirements Diet Vitamin B12 (Cobalamin) Folate Source Animal products Widespread Body stores 5 mg 5 mg Daily requirement 2-5 µg 50-200 µg Daily intake 10-20 µg 400-800 µg Dietary deficiency Rare Common
Vitamin B12 Deficiency: Common Mechanisms • Intragastric events • Total or partial gastrectomy • Absent intrinsic factor secretion • Bacterial overgrowth • Diphylobothrium latum (fish tapeworm) • Disease of the terminal ileum
Pernicious Anemia • Most common cause of vitamin B12 deficiency • Associated with-autoimmune diseases • Screen for thyroid disease every 1-2 years • Pernicious anemia is a systemic disease • Gastrointestinal tract involvement • Neurologic involvement
Pernicious Anemia: Laboratory Diagnosis • Anti-intrinsic factor antibodies • Anti-parietal cell antibodies • Schilling test • Procedure • Absorption of radiolabeled cobalamin ± Intrinsic factor • Measure urinary excretion of radioactivity
Treatment of Vitamin B12 Deficiency • Parenteral cobalamin • 1 mg/day x 7 days • 1 mg/week x 4 weeks • 1 mg/month for life • Oral cobalamin • 1 mg/day for life
Folate (Vitamin B9) Deficiency • Minimum daily folate requirement is 50 µg • Usual dietary folate 50-500 µg • Absorption in upper small intestine • Causes of folate deficiency- • Dietary (90%) • Alcohol abuse • Pregnancy • Malabsorption • Drug-induced • Treatment - oral folic acid supplementation
Glucose-6-Phosphate Dehydrogenase Deficiency • G-6-PD: reduces NADP/oxidizes glucose-6-phosphate • Detoxifies free radicals and peroxides • Sex-linked disorder • Effects > 200 million people • Hemolytic anemia occurs in the presence of stress (infection or drugs) • African form - mild hemolysis • Mediterranean form - more severe • Unique sensitivity to fava beans
Overview • Concepts, biology • Epidemiology • Clinical and laboratory manifestations • Diagnosis • Management and prognosis
Classification of leukemias Acute Chronic Myeloid origin Acute Myeloid Leukemia (AML) Chronic Myeloid Leukemia (CML) Lymphoid origin Acute Lymphoblastic Leukemia (ALL) Chronic Lymphocytic Leukemia (CLL)
ALL naïve germinal center B-lymphocytes Plasma cells Lymphoid progenitor T-lymphocytes Neutrophils AML Myeloid progenitor Eosinophils Hematopoietic stem cell Basophils Monocytes Platelets Red cells
Acute Leukemia • accumulation of blasts in the marrow
Significance of adult acute leukemia • a hematologic urgency • usually fatal within weeks to months without chemotherapy • with treatment, high mortality due to disease or treatment-related complications (unlike childhood acute leukemia) • notify Hematologist promptly if acute leukemia is suspected
ALL mainly children M > F curable in 70% of children curable in minority of adults AML mainly adults M > F curable in minority of adults Classification of acute leukemias
Causes of acute leukemias • idiopathic (most) • underlying hematologic disorders • chemicals, drugs • ionizing radiation • viruses (HTLV I) • hereditary/genetic conditions
Clincal manifestations • symptoms due to: • marrow failure • tissue infiltration • leukostasis • constitutional symptoms • other (DIC) • usually short duration of symptoms
Marrow failure • neutropenia: infections, sepsis • anemia: fatigue, pallor • thrombocytopenia: bleeding
Infiltration of tissues/organs • enlargement of liver, spleen, lymph nodes • gum hypertrophy • bone pain • other organs: CNS, skin, testis, any organ
Leukostasis • accumulation of blasts in microcirculation with impaired perfusion • lungs: hypoxemia, pulmonary infiltrates • CNS: stroke • only seen with WBC >> 50 x 109/L
Constitutional symptoms • fever and sweats common • weight loss less common
Laboratory features • WBC usually elevated, but can be normal or low • blasts in peripheral blood • normocytic anemia • thrombocytopenia • neutropenia • DIC
Bone marrow in acute leukemia • necessary for diagnosis • useful for determining type • useful for prognosis • Acute leukemias are defined by the presence of > 20% blasts in bone marrow (% of nucleated marrow cells)
Treatment of acute leukemias Choice of Rx is influenced by: • type (AML vs ALL) • age • curative vs palliative intent
Principles of treatment • combination chemotherapy • first goal is complete remission • further Rx to prevent relapse • supportive medical care • transfusions, antibiotics, nutrition • psychosocial support • patient and family
Hematopoietic stem cell transplantation • permits “rescue” from otherwise excessively toxic treatment • additional advantage of graft-vs-leukemia effect in allogeneic transplants • trade-off for allogeneic transplantation: greater anti-leukemic effect but more toxic
Topics to be Covered • Non-Hodgkin’s Lymphoma • Hodgkin’s Disease • Multiple Myeloma
Lymphoma and Multiple Myeloma2004 U.S. Predicted Values Malignancy New Cases Deaths All Cancer s 1,368,030 563,700 Non-Hodgkin’s Lymphoma 54,370 19,410 Hodgkin’s Disease 7,880 1,320 Multiple Myeloma 15,270 11,070 CA Cancer J Clin 2004; 54:8-29
Non-Hodgkin’s Lymphoma (NHL) • 6th most common cause of cancer death in United States. • Increasing in incidence and mortality. • Since 1970, the incidence of lymphoma has almost doubled.
Types of Lymphoma • Indolent (low grade) • Life expectancy in years, untreated • 85-90% present in Stage III or IV • Incurable • Intermediate • Aggressive (high grade) • Life expectancy in weeks, untreated • Potentially curable
Etiology of NHL • Immune suppression • congenital (Wiskott-Aldrich) • organ transplant(cyclosporine) • AIDS • increasing age • DNA repair defects • ataxia telangiectasia • xeroderma pigmentosum
Etiology of NHL • Chronic inflammation and antigenic stimulation • Helicobacter pylori inflammation, stomach • Chlamydia psittaci inflammation, ocular tissues • Sjögren’s syndrome • Viral causes- EBV and Burkitt’s lymphoma HTLV-I and T cell leukemia-lymphoma HTLV-V and cutaneous T cell lymphoma Hepatitis C