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What Is Sickle Cell Disease?

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What Is Sickle Cell Disease? Blood • Blood has red cells(erythrocyctes) Anemia 101 • White cells (leukocytes) • Platelets (thrombocytes) Allan Platt PA-C, MMSc Emory University PA Program Atlanta GA [email protected] www.EmoryPA.org Blood Components White Blood Cells • Fight infections • Are increased in infections Plasma 54% • Move inside and outside of blood vessels • Are made in the bone marrow White cells and platelets 1% Red Cells 45% White Blood Cells Platelets WBC - White Blood Cells 4.5 - 11.0 K/uL Low = Leukopenia High = Leukocytosis • Plug holes in the body to stop bleeding WBC Differential • Can help cause blood to clot • Neutrophils - Segs 54 -62% Made in the bone marrow Neutrophils - Bands 3 -5 % Lymphocytes - Lymphs 25 - 33% Monocytes - Monos 3 - 7% Eosinophils - Eos 1 - 3% Fibrin Basophils - Basos 0 - 0.75% Atypical Lymphs 0 1 Red Blood Cells Red Blood Cells • Carry oxygen from the lungs • Carry carbon dioxide back to the lungs • Also carry CO and NO • Normally live 120 days • Contains the protein hemoglobin • Made from iron, folic acid, vitamin B12 • Made in the bone marrow Microscope View Red Blood Cells - Shape Red cells travel through very narrow blood vessels Incidence of Sickle Cell Disease and Thalassemia World wide http://www.who.int/genomics/public/geneticdiseases/en/index2.html#SCA Red Blood Cells • Red Cell Flow Blood Vessel 2 Red Blood Cells - Hemoglobin Globin Synthesis in utero Oxygen Normal Hemoglobin A has 2 alpha and 2 beta globin chains with 4 iron binding sites Hemoglobin FA – Biochemistry – Normal Newborn Hemoglobin A – Biochemistry – Normal Adult Chromosome 16 Chromosome 11 Chromosome 16 Chromosome 11 alpha alpha gamma gamma delta beta Mom alpha alpha gamma gamma delta beta Mom alpha alpha gamma gamma delta beta Dad alpha alpha gamma gamma delta beta Dad alpha alpha alpha alpha beta beta 50 – 20 % Hemoglobin A beta beta 95 - 97% Hemoglobin A Hb F (newborn): 50% to 80% alpha alpha alpha alpha 1 – 2 % Hemoglobin F or Fetal gamma gamma (6 months): 8% gamma gamma (over 6 months): 1% to 2% alpha alpha 2% Hemoglobin A2 alpha alpha 2 - 3% Hemoglobin A2 delta delta delta delta Red Blood Cells - Marrow Red Blood Cells - Retics • Reticulocytes, or Retics are young red cells just released from the bone marrow. The Retic count is the best Red cells, white indicator about how the marrow factory is doing. cells and platelets are made in the bone marrow 3 Food with iron Red Blood Cells Red Blood Cells - Recycled Red cells are Red cells are recycled in the and vitamins spleen and liver. The iron made in the is digested and protein are stored and bone marrow bilirubin is released. Liver Red cells live 120 days in the circulation Spleen Hemoglobin Recycled Red Blood Cells - The Kidney Bilirubin must be Directed through the Liver to be Erythropoietin is made by Conjugated the kidney as a signal to Hemoglobin LDH - Lactate the bone marrow to make Indirect Dehydrogenase more red cells Bilirubin Iron – Fe bound to Transferrin Kidney - Liver Hemoglobinuria Direct Bilirubin Increased levels blocks absorption of Hepcidin The History Iron and cell release - inflammation IL6 • Weakness Hormone made in the • Tiredness - Fatigue liver • Dyspnea • Dizzy – non vertigo Decreased levels • Palpitations increase iron • New angina absorption and release from cells – Erythropoetin, low iron 4 The History -2 The History - 3 • - History of melena, abdominal pain, Aspirin or non-steroidal anti- • - History of alcohol abuse - consider folate deficiency or liver disease. If inflammatory agents (NSAIDs) use, past peptic ulcer disease , then moonshine use or lead paint/pipe exposure, consider lead toxicity. consider GI bleeding, platelet dysfunction. • - Family history of blood cell or bleeding disorder: consider Sickle • - In females the menstrual history quantifying the amount of Cell disease, G6PD,Thalassemia, Hemophilia, von Willebrand bloodloss ,or possible pregnancy should be obtained. • - History of jaundice, transfusion, new medication, infection - • - History of pica or abnormal craving for ice, clay, starch...; dysphagia consider hemolytic process then consider iron deficiency. • - History of weight loss, Cancer, HIV, rheumatoid arthritis, thyroid • - Poor diet, then consider iron or folate deficiency, and general disease, renal disease -then consider secondary cause • malnutrition • - History of fever and chills, cough, dyspnea, then consider • - History of gastric surgery, distal paresthesias, gait problems - Infection. consider B12 deficiency • Physical Exam Sclera Spoon Nails – Fe Def. Glossitis and Chelosis – Fe and B12 5 Physical Exam LAB- INITIAL SCREENING TESTS • GENERAL INSPECTION- clubbing in TB or lung cancer • Skin- Hypothyroid, SLE, Bruises, lesions, petechiae or purpura. • Weight - Loss in Cancer, HIV, Chronic disease, gain in hypothyroid • VITAL SIGNS- Pulse: Tachycardia from increased cardiac output • Urinalysis- Hematuria/proteinuria in renal disease • Respirations: Tachypnea from decreased oxygen transport hemoglobinuria in hemolysis. • BP: Orthostatic if volume depleted • CBC, red cell morphology and white blood cell differential, • Temp: Fever in infections and drug or transfusion reactions, Reticulocyte count • HEENT- Eye: Jaundice if hemolysis, pallor in palpebral conjunctiva • Chemistry profile (LDH, Bilirubin- Direct and Indirect, BUN, • Mouth: Glossitis and angular stomatitis in iron or B12 deficiency Creatinine, GPT), • NECK- Thyroid enlargement or nodules, lymph nodes • Hemoglobin Electrophoresis if hereditary hemoglobinopathy is • HEART- Increased output/murmur- consider high output failure suspected • LUNG- consider infection, lesion • ABDOMINAL- Liver/spleen size, masses, tenderness, surgical scars • IF BLEEDING - Platelet Count, PT, aPTT, PFA • RECTAL- Stool guaiac, prostate exam in men • PELVIC/BREAST- Uterine abnormality, Pap smear, Breast nodule • LYMPHNODES- consider lymphoma,leukemia,infection,connective tissue Disease • NEUROLOGIC- Decreased vibratory and position sense in B12 deficiency CBC values by age CBC- Red Cell Measures PARAMETER NORMAL ADULT COMMENTS HB - Hemoglobin Male= 15.5 +/- 2 mg/dl Low = Anemia Female = 13.5 +/- 2 High = polycythemia HCT - Hematocrit Male= 46.0 +/- 6% " Female= 41.0 +/- 6% " RBC - Red Blood Male = 4.3 - 5.9 Million/uL High in Thalassemia Cell Count Female = 4.0 - 5.2 " Red Cell Indices MCH, MCHC Red Cell Indices MCV - RDW MCH - Mean Corpuscular 27 -32 pg Low = Hypochromic MCV - Mean Corpuscular Volume 80 - 94 fl Hemoglobin High = Hyperchromic Low = Microcytosis High = Macrocytosis MCHC - Mean Corpuscular 30 - 36 gm/dl Low = R/O Fe def. RDW - Red Cell Distribution Width 11.5 - 14.5 Variation in RBC size Hemoglobin Concentration High = Spherocytosis 6 RBC Morphology Red Cell Morphology SIGNIFICANCE Platelets Burr Cells Uremia, Low K, artifact, Ca stomach, PUD Spur Cell Post-splenectomy, Alcoholic liver disease Stomatocyte Hereditary, Alcoholic liver disease, • Platelet Count 150 - 400 K cell/uL Spherocyte Hereditary, Immune hemolytic anemia, Low = Thrombocytopenia water dilution, post-transfusion Shistocyte - helmet TTP, DIC, vasculitis, glomerulonephritis, High = Thrombocytosis heart valve, burns Eliptocyte - Ovalocyte Hereditary, Thalassemia, Fe Def., Myelophthistic, megaloblastic anemias Sickle Cells Sickle cell disease Target Cells Thalassemias, hemoglobinopathies Microcytes Thalassemia, Iron Def., Lead Toxic, Macrocytes B12 of Folate Def. Parasites Malaria, Babesiosis, Bartonellosis Retics or Reticulocyte count Correcting the Retic • absolute reticulocyte count (measured) • reticulocyte (%) = absolute number of reticulocytes ÷ number • Retic - Reticulocyte Count 0.5 -1.5 % of RBC × 100 Low in anemia = low marrow output • reticulocyte index = % reticulocytes × actual hematocrit ÷ normal hematocrit High = RBC loss • corrected reticulocyte index (corrects for appropriate bone marrow release of reticulocytes) = reticulocyte index ÷ maturation factor • maturation factor = 3.25 – (actual hematocrit ÷ 20) – if hematocrit 45, maturation factor = 1 – if hematocrit 35, maturation factor = 1.5 – if hematocrit 25, maturation factor = 2 – if hematocrit 15, maturation factor = 2.5 Anemia Diagnosis Diagnostic Pathway • Loosing red cells (high retic count) Reticulocyte Production Index – Bleeding <2 Decreased Production >2 Increased Loss – Hemolysis (High indirect Bili and LDH) Red Cell Indicies MCV Hemolysis Bleeding • Not making enough – (low retic count) >94 80-94 <80 – Low materials – Fe, B12, Folate Macro Normo Micro Extrinsic Intrinsic – Low epo (Kidney disease) Coombs CoombsMembrane Hb Enzyme Positive Negative – Marrow problem (replaced, toxin….) Drug Warm Cold Antibody Antibody 7 Anemia – low Hb/Hct Lab work-up Low Retic count anemias BPH = Bleeding/Production/Hemolysis Anemic- Lab – Next look at the MCV on the CBC CBC, Retic, RBC morphology, Metabolic Profile, • UA MCV < 80 Microcytic Retic Production Retic Production • MCV 80 – 94 Normocytic index < 2 – Marrow Index >2 RBC Loss Production Problem Bleeding or Hemolysis Check MCV • MCV > 94 Macrocytic MCV <80 – Increased Indirect MCV 80 – 100 MCV > 100 Microcytic Bilirubin and LDH = Normocytic Macrocytic Order Iron Order West Sed Hemolysis Order B12, RBC Bleeding studies, HbELP, Rate, TSH, Renal and serum Folate Order Coombs, Hinze Lead Level Hepatic, Preg Test Body stain, HbELP Microcytic Tests Microcytic • MICROCYTIC = "TICS" TESTS TO ORDER: • Serum Iron • T-Thalassemias • TIBC = Transferrin binding sites • I-Iron Deficiency • C-Chronic Inflammation • % Saturation = Transferrin saturation with Iron • S-Sideroblastic - lead, drug,
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