Red Blood Cell Disorders

1. Red Blood Cell Disorders Stephen Medlin D.O. FACP

2. High Yield Board Topics • Anemia and Presentations for Multiple Myeloma • Types of Anemia • B12 deficiency • Anemia of Inflammation • IV iron

3. Myeloma-Properties of Plasma Cells • Proliferate • Secrete Immunoglobulins • “Make space” • Influence bone turnover • Secrete Inflammatory mediators

5. SPEP polyclonal monoclonal

6. Myeloma Presentations • 65 year old patient with normocytic anemia (hgb 10.7, MCV 85), may or may not have symptoms • What is the next laboratory test most likely to obtain a diagnosis • Low Albumin and Normal Total Protein • Creatinine of 1.35 • albumin 2.2 • total protein 7.2 • calcium level of 10.7 (12.4) • Answer is Serum Protein Electrophoresis or Bone Marrow Biopsy

7. Myeloma Presentations-variations • 65 year old patient with normocytic anemia (hgb 10.7, MCV 85), may or may not have symptoms • Slightly Low Albumin and elevated Total Protein • Creatinine of 1.35 • albumin 3.2 • total protein 9.2 • calcium level of 11.0 • Easy if there is an imaging study with a lytic lesion • What is the next laboratory test most likely to obtain a diagnosis • Answer is Serum Protein Electrophoresis or Bone Marrow Biopsy

8. Same Stem as Prior Slide but with Acute Pain Requiring Imaging Ten Causes for Renal Failure in Myeloma Related to Monoclonal protein (only one per patient) • Amyloid formation • “Myeloma Kidney”-Intratubular cast formation of immunoglobulin leading to cast nephropathy (40-60% of MM cases) • Nephrotic syndrome due to amyloid / glomerular damage • Cryoprecipitates / vasculitis Other causes for Renal Failure • Hypercalcemia with nephrocalcinosis • ATN secondary to dehydration with or without hypercalcemia • iv ct contrast (predisposes to light chain precipitation/cast nephropathy or can cause renal tubular precipitation of light chains) 1.5% of the pt with myeloma develop this • uric acid nephropathy • plasma cell infiltration • NSAIDs

9. Anemia-Background • Normal Erythropoiesis • Erythropoietin regulates rbc production • Immature rbc= reticulocytes • RBC’s pass through spleen and old or damaged cells are ingested by macrophages, iron transported to liver • Iron absorption is through the gut by the protein ferroportin which releases to transferrin • Hepcidindecreases absorption by binding ferroportin and increases with inflammation (IL-6 especially)

10. Red Blood Cell Disorders • Workup of Iron Deficiency • IDA • Thalassemia • Anemia of Inflammation • Diagnosing B12 deficiency • Unsteady gait/neurologic deficient • Macrocytic anemia/pancytopenia

11. Workup of Anemia • MCV is the 1st step in anemia workup • Categorize into microcytic, normocytic, macrocytic group • Microcytic has a narrow differential • Macrocytic has a narrow differential • Hyperprolilferative (>2%) versus Hypo-proliferative is also a helpful distinction • IDA is HYPO-proliferative • Retic count more than 5% should trigger consideration of hemolysis

12. Approach to Microcytosis • Check Iron Studies • Serum Fe, TIBC, %sat • Ferritin (gold standard) • Watch for ESR elevation • (Anemia of inflammation) • Hemoglobin electrophoresis may be the answer if ferritin is normal and esr normal

13. Evaluation of Anemia • Frequently Fe Studies are not clear (% sat is low is NOT SPECIFIC) • Ferritin is KEY-NO FALSE LOW FERRITIN • 65 year old female with fatigue, 85 kg • WBC 9.0 Hemoglobin 9.0 L • MCV 74.8 L Hematocrit 27.7 L • Platelets 319 Creatinine 1.0 • Ferritin 160, iron % sat low (14) and TIBC normal or low (250), ESR 80 • Normal Transaminases (elevated transaminases cause falsely elevated ferritin) • Anemia of Inflammation/Chronic Disease

14. Evaluation of Anemia • 65 year old female with • WBC 9.0 Hemoglobin 9.0 L • MCV 74.8 L Hematocrit 27.7 L • Platelets 319 • Ferritin 15, iron % sat low (14) and TIBC high (450) • ESR 20 • Answer: Iron Deficiency • A simplistic stem may ask diagnosis but more likely is a management question “The patient has already been on oral iron and anemia has not improved, what is the next best step?” • Bone marrow • B12 administration • pursue workup-colonoscopy

15. Gestational Anemia • Typically results in Hgb more than 11 in the first and third trimesters and greater than 10.5 in the second trimester • In pregnant women without obvious blood loss, and iron deficiency, no further workup is warranted • Oral iron supplementation • Make sure the patient is on folic acid supplementation

16. Evaluation of Anemia • 45 year old male with chronic anemia • WBC: 5.1, Hemoglobin: 13.7, Hematocrit: 40.7, MCV: 73.5 (L), Platelets: 197 • Iron: 54, Ferritin: 285.8, % Iron Saturation: 17.3, TIBC: 312 • ESR 13, normal transaminases • Question would be “what is the best test to obtain the most likely diagnosis” • Hemoglobin Electrophoresis • Sickle Thal Trait

17. Sickle Cell Questions on Key Points • IV fluids and adequate pain management are key points • Preoperative transfusion is recommended for major surgery with patients with Hb SS (GOAL is 10) • Low risk procedures such as skin biopsies, anesthesia with imaging not included • Pregnancy • SS anemia have increased complications but routine transfusions not helpful • Severely anemic and signs of heart failure are indications • Opiates are appropriate in pregnancy (except meperidine) but no hydroxyurea

18. Macrocytic Anemia • Evaluate Macrocytic anemia • B12/folate • Hemolytic workup-could be Retic’s • Ldh,haptoglobin, periph.smear, retic count, coombs test • Review drug list-Hydroxyurea classic • Mcv often over 110 • Liver disease • Etoh hx • Splenomegaly ? • Myelodysplasia • Need BM biopsy to confirm

19. B12 Pearls • Elevated serum methylmalonic acid is more sensitive and specific than B12 levels • Oral B12 is an option • Folate can correct anemia in B12 deficiency but not neurologic symptoms