ANEMIA

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 vsCaucasion • 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: • exertionaldyspnea • dyspnea at rest • fatigue • hyperdynamic state • confusion • high output heart failure

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

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. Reticulocyte Count WBC 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 Laboratory Evaluation

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. • ESRD Network II, Medical Review Committee 2011 goals.

31. Questions?