ANEMIA - PART IIAnemia of Chronic

Inflammation

BY: Zorawar Noor4/21/2014

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

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)

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.

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

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

Iron Studies in ACI

Finding in Anemia of Chronic Inflammation

Fe Mildly low

TIBC Low

% Sat Mildly low

Ferritin High – very high

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.

…MKSAP Case 2

…MKSAP Case 2

Which of the following is the most likely diagnosis?

(A) inflammatory anemia

(B) iron deficiency

(C) microangiopathic hemolytic anemia

(D) Warm Ab-associated hemolysis

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)

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)

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.

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=9117223. 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.

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