1. ANEMIA Pamela L. Charity, MD, FHM Medical University of South Carolina May 23, 2013

2. Objectives Define Anemia Understand variables between certain populations Describe both kinetic and morphologic approach to determining cause of anemia Obtain pertinent history, physical and indicated studies Interpret studies for accurate differential diagnosis

3. Anemia Definition: reduction in one or more of the major RBC measurements ◦ HGB: major oxygen carrying pigment in whole blood ◦ HCT: percent of sample of whole blood occupied by intact RBC ◦ RBC: number of cells contained in volume

4. Normal Range Anemia: Values > 2 standard deviations below the mean Other proposed definitions: ◦ WHO criteria based on international nutrition ◦ WHO/National Cancer Institute’s criteria based on malignancy ◦ NHANES III and Scripps-Kaiser studies based on sex, age, and race

5. Variables Volume status Special populations ◦ High altitude ◦ Carboxyhemoglobin ◦ African-Americans vs Caucasion ◦ Population with high incidence chronic disease ◦ Pregnancy

6. Symptoms Factors: ◦ Decreased oxygen delivery to tissues  Oxyhemoglobin dissociation curve  O2 extraction baseline 25%, up to 60%  SV X HR = CO ◦ Possible hypovolemia with marked acute bleeding

7. Symptoms Occurs generally when: ◦ HGB < 5 at rest, or ◦ higher with exertion or ◦ with cardiac decompensation Primary symptoms: ◦ exertional dyspnea ◦ dyspnea at rest ◦ fatigue ◦ hyperdynamic state ◦ confusion ◦ high output heart failure

8. Causes of Anemia Kinetic ApproachMorphologic Approach Decreased RBC production Increased RBC destruction Blood loss Based on measurement of RBC size ◦ Normocytic ◦ Microcytic ◦ Macrocytic

9. Evaluation of the Patient with Anemia Anemia is never normal and is one of the major signs of disease. ◦ Bleeding? ◦ RBC destruction? ◦ Bone marrow suppression? ◦ Iron deficient? ◦ Deficiency B12 or Folic Acid?

10. Evaluation of the Patient with Anemia History: ◦ Symptoms or medical condition associated with anemia? ◦ Acute or lifelong? ◦ Inherited hemoglobinopathy, hereditary spherocytosis, etc. ◦ Ethnicity and country of origin

11. Physical Exam Assess severity and find signs of organ or multisystem involvement. ◦ Tachycardia ◦ Dyspnea ◦ Fever ◦ Postural hypotension ◦ Jaundice ◦ Pallor ◦ Petechiae, ecchymoses ◦ Stool for occult blood

12. Laboratory Evaluation CBC to include WBC differential, platelet count, and reticulocyte count. Blood smear reviewed

13. Laboratory Evaluation Reticulocyte CountWBC Count and Differential High reflects increased erythropoietic response Low reflects decreased production of RBC, is pancytopenia present? Leukopenia: ◦ bone marrow suppression ◦ Hypersplenism ◦ deficiencies Leukocytosis: ◦ Infection ◦ Inflammation ◦ malignancy

14. Evaluation for Iron Deficiency Anemia (IDA) Iron is necessary for erythrocyte production and maturation:  DNA synthesis, cellular respiration, and oxygen transport History:  blood loss, malabsorption, increased need Microcytosis, anisopoikilocytosis Measure: Iron, IBC (transferrin), Transferrin saturation, and Ferritin (<15)

15. Evaluation for B12 Defeciency Needed for DNA synthesis Transferred from R-binders to intrinsic factor in ileum Stored in reticuloendothelial system with large hepatic reservoir Pernicious anemia involves antibodies directed toward parietal cell membrane, reducing intrinsic factor Glossitis, weight loss, neurologic and psychiatric symptoms Measure cobalamin, folate, homocysteine, methylmalonic acid * May present as hemolysis picture Treatment now with oral B12

16. Evaluation for Folate Deficiency Small stores of folate in body Malnutrition, alcohol dependence, pregnancy Drugs: triamterene, phenytoin Small bowel disease: Celiac, IBD, Amyloidosis Homocysteine levels > 90% sensitivity and specificity when MMA normal Exclude B12 Deficiency before starting treatment as neurologic symptoms will progress

17. Inflammatory Anemia Chronic infections, malignancy, collagen vascular diseases Erythropoetin production inhibited Increased levels of inflammatory cytokines: TNF, IL-6 (hepcidin causes decreased iron absorption), IL-1, interferon Typically, Hbg > 8

18. Inflammatory Anemia vs IDA

19. Anemia of Kidney Disease Decreased renal cortical mass, decreased erythropoetin Normochromic/normocytic Peripheral smear may show Burr cells ESA to achieve target Hbg levels 10 – 12 ESA can lead to HTN, Thrombosis, MI, CVA Iron stores improve efficacy, Ferritin > 100

20. Evaluation for Hemolysis Rapid fall in HGB Reticulocytosis Abnormally shaped RBC Measure: LDH, Indirect bilirubin, Haptoglobin

21. Hemolytic Anemias Diverse group of diseases sharing accelerated erythrocyte destruction Congenital: ◦ Hereditary Spherocytosis ◦ G6PD Deficiency ◦ Thalassemia ◦ Sickle Cell Syndromes Acquired: ◦ Autoimmune ◦ Microangiopathic ◦ Paroxysmal Nocturnal Hemoglobinuria ◦ Infectious, chemical agents

22. Hemolytic Anemias

23. Spherocyte

24. Schistocytes

25. Target Cells

26. Sickle Cells

27. Bone Marrow Examination Indications: ◦ Pancytopenia ◦ Abnormal cells (blasts) Diagnoses: ◦ Aplastic Anemia ◦ Myelodysplasia ◦ Malignancy ◦ Myeloproliferative D

29. Key Messages Apply your understanding of clinical history and physical before ordering extensive laboratory studies Evaluating the blood smear will always provide important information Anemia is never normal

30. References MKSAP 16, Hematology and Oncology, pp 18 – 35. Up to Date; Approach to the adult patient with Anemia; Schrier, Stanley, Jan 2013. Up to Date; Approach to the adult patient with Anemia; Schrier, Stanley, Jan 2013 ESRD Network II, Medical Review Committee 2011 goals.

31. Questions?