1. ANEMIA - PART II Anemia of Chronic Inflammation BY: Zorawar Noor 4/21/2014

2. Objectives  Understand the pathogenesis of anemia of chronic inflammation (ACI)  Review 4 Simple Laboratory Steps to diagnose anemia (from Part I)  Learn the characteristics lab findings of ACI  Learn how to find coexisting iron deficiency

3. When to Suspect Anemia of Chronic Inflammation?  In inflammatory, infectious, and malignant conditions (RA, SLE, osteomyelitis…)  In cases with normocytic and normochromic anemia (usually mild and asymptomatic)

5. Pathogenesis  Inflammatory cytokine release (IL-6) triggers:  Hepcidin  Hepcidin decreases iron absorption in GI tract, and makes macrophages hold onto iron  Bone marrow is hypoproliferative despite having slightly increased EPO levels  EPO levels are not as high as they should be  Unlike in iron deficiency anemia, where peripheral RBCs gain a longer circulating half-life, there is shorter RBC life span.

6.  Step 1 – Characterize by MCV  Microcytic, normocytic, macrocytic  Step 2 - Identify Morphologies on Peripheral Smear  E.g. hypochromia, bite cells, etc.  Step 3 – Calculate Reticulocyte Index  Reticulocyte Index (RI) = ReticCount * 0.5(Hct/45)  Step 4 – Use iron studies, bone marrow biopsy, etc. 4 Steps to Classify Anemia (Review from Part I) See presentation “Anemia, Part I” for more explanation of each step

7. Diagnosis  History: collagen vascular diseases, malignancies, osteomyelitis, etc.  Step 1) MCV initially normal  Step 2) if chronic, can see mirocytosis and hypochromia  Step 3) Low Retic Count  Step 4) normal or low iron, low TIBC, high ferritin

8. Iron Studies in ACI Finding in Anemia of Chronic Inflammation FeMildly low TIBCLow % SatMildly low FerritinHigh – very high

9. MKSAP Case 2  A 22-year old woman undergoes a new patient evaluation. She was recently diagnosed with SLE. Her menstrual pattern is normal, and her medical history is otherwise noncontributory, her only medications are hydroxychloroquine and a multivitamin.  On Physical exam: T37.2C, BP 126/78, P88, RR17, and the patient has a malar rash, thinning hair, but no joint abnormalities, oral lesions, pericardial or pleural rubs, or heart murmurs.  Laboratory studies: Hgb 8.2, WBC 3900, Ferritin 556, Iron 18, Retic Count 2%, TIBC 180, Transferrin sat 10%, and creatinine 1.0.

10. …MKSAP Case 2

11.  Which of the following is the most likely diagnosis?  (A) inflammatory anemia  (B) iron deficiency  (C) microangiopathic hemolytic anemia  (D) Warm Ab-associated hemolysis

12. Answer Explanation  History of SLE  Step 1) MCV is low late in inflammatory anemia  Step 2) Hypochromia is noticeable, also late finding  Step 3) low RI is consistent with Inflammatory Anemia  Step 4) Ferritin is high from inflammation, TIBC is low ( think of iron being stored away from pathogens needing it for their own use through hepcidin)

13. Finding Coexisting Iron Deficiency  Transferrin will often be reduced, not increased like it is in iron deficiency anemia (IDA)  Unlike usual Inflammatory anemia,  Soluble transferrin receptor (sTfR)-ferritin index  Ration of the sTfR to logarithm of ferritin  If index <1.0 suggests pure inflammatory anemia  If index >2.0, could be IDA or combination  Bone Marrow biopsy (macrophages with iron in ACD)

14. Summary  Just approach it one step at a time!  Remember the pathogenesis of ACI, cytokines cause hypo-proliferation and low-iron because it stays in macrophages  Always watch out for coexisting iron deficiency  Treat the underlying cause.

15. References  Harrison’s Principles of Internal Medicine  Adamson JW. Chapter 103. Iron Deficiency and Other Hypoproliferative Anemias. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw- Hill; 2012. http://www.accessmedicine.com/content.aspx?aID=91172 23. Accessed December 7, 2011  Wians, F.H. and Urban JE. “Discriminating between Anemia of Chronic disease Using Traditional Indices of Iron Status v. Transferring Receptor Concentration”. 2001. American Journal of Clinical Pathology. Volume 115.  UptoDate