Rheumatoid arthritis and Anaemia 

The causes of anemia in RA :

1. Iron utilization is impaired, with decreased serum iron and transferrin concentrations. and an increased synthesis of ferritin. There is increased lactoferrin which binds and lowers serum iron.
2. Reduced erythropoietin levels
3. Decreased bone marrow response to erythropoietin.
4. Premature destruction of red blood cells. Red blood cell life span may be reduced
5. Drug associated anemia :

Especially :
NSAID induced bleeding and secondary iron deficiency.
Bone marrow suppression from drug therapy i.e.
gold / penicillamine / Methotrexate.

6. Intercurrent infection

The degree of anemia in RA is related to the activity of the underlying disease and inflammation. Treatment of the underlying activity will usually improve the anaemia- as will erythropoietin therapy. The anemia of chronic disorder will not respond to iron. It is usually normochromic and normocytic. Iron deficiency may cause microcytic anemia.

When to Investigate the Anaemia ?

It depends on the individual patient as to when you consider the anemia from Chronic deficiency of RA versus Iron or other vit deficiency. Certainly - it is helpful knowing the baseline level of the patient. Then any change can be seen in the clinical context and the cause determined. i.e. Any change then becomes more significant.

I would do iron studies B12 and folate.
A bone marrow can be done if there is uncertainty of iron deficiency.
A bowel workup may be required if the patient has iron deficiency.
I get more likely to investigate if the anemia is under 9-10 g/dl , but will investigate earlier if there has been a change compared to a previously known baseline level.

Journal articles of interest 


The use of serum ferritin estimation in the investigation of anemia in patients with rheumatoid arthritis.

Author Porter DR; Sturrock RD; Capell HA Address Centre for Rheumatic Diseases, Glasgow Royal Infirmary, U.K. Source Clin Exp Rheumatol, 12: 2, 1994 Mar-Apr, 179-82

Abstract We report a retrospective study of 101 patients with rheumatoid arthritis and anemia undergoing investigation in a teaching hospital rheumatology unit. Patients with anemia of chronic disorder had significantly higher serum ferritin (p < 0.0001), mean corpuscular volume (p < 0.05), and acute phase reactants (p < 0.001). The sensitivity, predictive value and validity of measuring serum ferritin to predict the absence of bone marrow iron stores was studied. Maximum validity (89%) was achieved by defining iron deficiency as occurring when serum ferritin was < 75 ng/ml. 93% of patients with ferritin < 50 ng/ml were iron deficient on bone marrow examination. 91% of patients with ferritin > 100 ng/ml were iron replete on bone marrow examination. 86% of patients had ferritin < 50 or > 100 ng/ml. Age was not a significant confounding factor. Serum ferritin concentration is an informative investigation in rheumatoid patients with anemia. Correct interpretation of the results eliminates the need for bone marrow aspiration in the majority of cases. 


Anaemia in rheumatoid arthritis: pathogenesis, diagnosis and treatment.
Author Vreugdenhil G; Swaak AJ Address Zuiderziekenhuis, Department of Internal Medicine, Rotterdam, The Netherlands. Source Rheumatol Int, 9: 6, 1990, 243-57

Abstract The pathogenesis, diagnosis and treatment of the anemia of chronic disorders (ACD) in rheumatoid arthritis (RA) were reviewed. Causes of anemia other than ACD frequently present in RA. Decreased iron absorption was shown to be the result of active RA rather than a cause of ACD or iron deficiency. It has been hypothesized that bone marrow iron availability decreases due to decreased iron release by the mononuclear phagocyte system or that the anemia in ACD is due to ineffective erythropoiesis; these remain controversial theories. Studies considering a decreased erythropoietin responsiveness have not produced consistent results. Erythroid colony growth is suppressed in vitro by interleukins and tumour necrosis factor but their role in vivo in ACD is unknown. The diagnosis of ACD is made by exclusion. Iron deficiency is detected by transferrin, ferritin, and cellular indices after adaptation of their normal values. Treatment of the anemia consists merely of antirheumatic treatment. Iron administration is counterproductive since iron chelators or exogenous erythropoietin administration might increase erythropoiesis.


Anaemia of chronic disease: diagnostic significance of erythrocyte and serological parameters in iron deficient rheumatoid arthritis patients.

Author Vreugdenhil G; Baltus CA; van Eijk HG; Swaak AJ Address Zuiderziekenhuis, Department of Internal Medicine, Rotterdam, The Netherlands. Source Br J Rheumatol, 29: 2, 1990 Apr, 105-10 Abstract Erythrocyte and serological parameters were assessed in 44 anaemic rheumatoid arthritis (RA) patients to detect iron deficiency as assessed by stainable bone marrow iron. The anemia was normochromic normocytic in 60% and hypochromic normocytic in 30% of those with anemia of chronic disease (ACD). Iron deficiency was present in 55% and the anemia was hypochromic microcytic in 54% and hypochromic normocytic or normochromic normocytic in 21%. Iron absorption was found to be higher in iron deficient patients. In ACD patients, iron absorption correlated inversely with ESR and CRP. For the detection of iron deficiency among RA patients with ACD, the MCV showed the highest specificity (90%) and predictive value (87%). Serum ferritin was the most sensitive (82%) and valid (86%) test. Combination of MCV, ferritin and transferrin resulted in 100% validity. It was concluded that iron deficiency can be detected accurately without bone marrow aspiration using combinations of blood parameters.


Structured approach to the investigation of anemia in patients with rheumatoid arthritis.

Author Doube A; Davis M; Smith JG; Maddison PJ; Collins AJ Address Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom. Source Ann Rheum Dis, 51: 4, 1992 Apr, 469-72

Abstract A group of 28 patients with rheumatoid arthritis who were severely anaemic were investigated for iron deficiency. On the basis of bone marrow studies, the patients were divided into two groups, those with and those without signs of stainable iron in the marrow. This grouping did not distinguish between the severity of their rheumatoid arthritis measured by clinical parameters. Measurement of the red cell count and biochemical parameters in the peripheral blood showed a statistical difference in red cell size, hemoglobin content, and iron binding capacity between the two groups. The statistical variation of these parameters, however, did not allow these measurements to predict bone marrow iron deficiency in any subject. Investigation of the upper gastrointestinal tract by endoscopy showed that acute macroscopic lesions were infrequently associated with anemia. It was concluded that anemia in association with rheumatoid arthritis may mimic iron deficiency anemia, and that simple investigations of the peripheral blood do not accurately show the iron status of the reticuloendothelial system in the presence of a chronic inflammatory disease. For the investigation of severe anemia in rheumatoid arthritis, bone marrow assessment of iron status should be performed as the initial investigation. In addition, iron deficient patients require investigation of the lower and the upper gastrointestinal tract.

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