Diagnosis of Anemia of Chronic Diseases

The diagnosis of ACD is primarily one of exclusion and often is difficult. Various laboratory tests have been suggested, but few have proven value in the general population because ACD occurs in too large a variety of acute and chronic illnesses. The best way to diagnose ACD, at least provisionally, is to document an anemia of underproduction (i.e., low reticulocyte index) with low serum iron and low transferrin levels and an elevated serum ferritin level in the setting of a systemic, usually inflammatory, illness. A thorough search may be necessary to document the precise underlying illness.

Other causes of anemia, such as hemolysis, nutritional deficiency, or sequestration, should be ruled out, and a component of iron deficiency should be strongly considered in a patient with systemic inflammation and a low or “normal” serum ferritin concentration. These other causes of anemia often accompany ACD. Bone marrow examination usually is not essential for the diagnosis but may be necessary to rule out other diagnoses, including malignancy (including MDS), infection, or iron deficiency.

Figure 9-1 ANEMIA OF CHRONIC DISEASE.

A, Peripheral blood typically exhibits a normochromic, normocytic anemia. B and C, Bone marrow examination is sometimes performed to rule out other causes of anemia. Typically, the bone marrow is morphologically normal. D and E, Prussian blue iron stain shows increased iron stores with increased histiocytic iron but decreased sideroblastic iron.

Treatment of Anemia of Chronic Diseases

Treating ACD often is unnecessary if the patient is asymptomatic. However, if the anemia is symptomatic or severe, treatment of the anemia itself may be indicated. Epidemiologic studies, such as those in patients with heart failure, HIV, cancer, or kidney disease, suggest physiologic and subjective improvement in signs and symptoms after treatment for anemia.^1,2 However, treatments need to be individualized because the risks of erythropoiesis-stimulating agents or iron therapy in non–iron deficient subjects are theoretically real and practically unknowable given the variety of underlying conditions that are incorporated under the rubric of chronic disease. A trial of ACD-directed therapy may be indicated in symptomatic patients.

The first priority in ACD should be to correct any reversible contributors to the anemia. Because the extent of ACD mirrors the activity of the underlying disease, all efforts should be made to treat the underlying disease. Furthermore, efforts to correct anemia should be modulated by the recognition that the “optimal” target hemoglobin for subjects with ACD is not known. Reports of anemia in subjects without inflammation but religiously opposed to transfusions have suggested a physiologic cutoff for anemia of 5 g/dL, below which increased mortality is seen.^3,4 In addition, acutely ill patients have not been shown to benefit, in randomized, controlled studies, from transfusion “triggers” above 7 g/dL.⁴ Nonetheless, symptomatic improvement is seen in subjects with a range of chronic diseases who were treated for anemia of a more modest degree.¹

Transfusion therapy may be the most common form of treatment of symptomatic ACD, albeit with the potential for transmitting infection; inducing alloimmunization; or, rarely, leading to graft-versus-host disease.