1/13/2017. Blood work... when to worry? Part 2. Bryan E. Martin MD Medical Director Benefis Sletten Cancer Institute. Blood work When to worry?

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1 Blood work... when to worry? Part 2 Bryan E. Martin MD Medical Director Benefis Sletten Cancer Institute Blood work When to worry? part 2 Abnormal Iron Studies Abnormal Globulin Tumor markers...next time Normal iron metabolism Iron absorption in duodenum and jejunum Iron loss through GI tract, menses, sweat Enters plasma bound to transferrin receptor and the iron/transferrin complex delivered into cells Storage primarily in RBC s, liver, marrow, REC s Disorders in absorption, storage, iron transfer and iron loss lead to abnormal iron metabolism 1

2 Iron metabolism Iron lab values Serum iron measure the iron bound to transferrin Total Iron Binding Capacity (TIBC) measures the amount of transferrin Percent iron saturatin (% sat) percentage of transferrin bound by iron Ferritin iron storage molecule found in all organs but mostly in the liver. Iron deficiency The primary clinical presentation is iron deficiency anemia 2

3 Iron deficiency Low serum iron Low ferritin Normal TIBC Microcytic RBC s Elevated platelet count Never a normal finding...seek the diagnosis Treatment... Iron... One way or the other Iron overload FERRITIN will fool you Over 300 ng/ml suggests iron overload Over 1000 ng/ml may not be overload Ferritin is easy, but not fool proof, way to assess body iron stores Ferritin elevated by... infection, NASH, inflammation (metabolic syndrome), liver disease, cancer Gold standard for iron overload remains liver biopsy, and maybe MRI Iron Overload Causes Blood transfusions Liberated iron from hemolysis Supplementation Thalassemia (genetically abnormal forms of hemoglobin) Porphyria (dysfunctional synthesis leads to build up of toxic porphyrins) Hepatitis B and C Hemochromatosis 3

4 Iron Overload Elevated ferritin does not mean Hemochromatosis Hemochromatosis Iron overload syndrome resulting from genetic mutation in HFE gene. Leads to increased efficiency in intestinal iron absorption Mutation in the C282Y or H63E gene present. Homozygous state needed for disease Gene mutations present in up to 10% of Celtic, English, Scandinavians There are many individuals with elevated ferritin and abnl HFE genes who do not have hemochromatosis Hemochromatosis Excess iron is stored in various organs and slowly causes organ dysfunction Liver cirrhosis Pancreas diabetes Heart cardiomyopathy Endocrine system Skin bronze Diagnosis requires proof of organ iron overload (biopsy or MRI) and appropriate genetics. Percent Iron saturation over 62% very suggestive 4

5 Hemochromatosis 35 year old female with elevated ferritin on screening labs...no family history. Hemochromatosis Hemochromatosis 5

6 Iron Overload Elevated ferritin does not mean Hemochromatosis Iron overload algorithm 6

7 Serum proteins identified by position on serum protein electrophoresis Primarily represents serum immunoglobulin SIEP allows identification of the immunoglobulin class Gammaglobulin classes IgG, IgA, IgM, IgD, IgE Each class also has kappa and lamda subclasses Causes 7

8 Majority of causes are inflammation, liver diseases, clonal plasma cell disorders Clonal plasma cell disorders MGUS Monoclonal Gammopathy of Uncertain Significance (MGUS) Serum globulin less than 3 g/dl Less than 10% plasma cells in marrow No end organ damage: CRAB Calcium Renal failure Anemia (hg less than 10) Bone Neuropathy? Clonal (malignant) expansion of plasma cells in the marrow or other tissues Diagnosis requires bone marrow bx and CRAB assessment Skeletal survey is convenient, MRI is superior Treatment depends on degree of end organ damage, genetic abnormalities, and is becoming increasingly complicated 8

9 Examples Examples examples 9

10 Example free light chain assay Examples 10

11 Blood work... when to worry? Part 2 Bryan E. Martin MD Medical Director Benefis Sletten Cancer Institute 11

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