Elevated ESR in Anemia
Yes, elevated erythrocyte sedimentation rate (ESR) is characteristically seen in anemia, particularly anemia of chronic disease (also called anemia of inflammation), where both the anemia itself and the underlying inflammatory process contribute to ESR elevation.
Mechanism of ESR Elevation in Anemia
The relationship between anemia and ESR is bidirectional and mechanistically distinct:
Anemia directly accelerates ESR through altered blood rheology—lower hematocrit reduces the resistance to red blood cell aggregation and rouleaux formation, artificially elevating the sedimentation rate independent of inflammation 1, 2, 3.
Hemoglobin concentration inversely correlates with ESR throughout the entire range of measured values, not just in anemic patients. Even within the non-anemic range, patients in the lowest hemoglobin quartile have significantly higher median ESR compared to those in the highest quartile (P < 0.001) 3.
In hemodialysis patients with chronic renal failure, the mean Westergren ESR was 49 ± 26 mm/h in non-dialysis patients and 60 ± 33 mm/h in hemodialysis patients—both significantly elevated—with low hematocrit being an independent predictor of ESR elevation (p < 0.0001) 2, 4.
Anemia of Chronic Disease: The Prototypical Example
Anemia of chronic disease represents the specific anemia type where ESR elevation has the greatest clinical significance, as both the inflammatory process and the resultant anemia contribute to marked ESR elevation:
This occurs in conditions with chronic inflammation including rheumatoid arthritis, inflammatory bowel disease, chronic infections, and malignancies 1, 5.
In failed kidney allografts with graft intolerance syndrome, ESA-resistant anemia (erythropoietin-stimulating agent resistant anemia) occurs alongside elevated ESR as part of the chronic inflammatory state 6.
The American Heart Association notes that in Kawasaki disease, anemia may develop with normal red blood cell indices, particularly with prolonged duration of active inflammation, and ESR elevation is nearly universal 6.
Clinical Interpretation Challenges
A critical pitfall is that anemia artificially elevates ESR regardless of whether inflammation is present, making interpretation difficult:
In chronic renal failure patients free of complicating illnesses, ESR remains significantly elevated due to both anemia and plasma factors (primarily fibrinogen), rendering an elevated ESR diagnostically useless in this population 4.
The National Kidney Foundation reports that both anemia and azotemia can artificially elevate ESR values 1.
To correct for this confounding effect, use the hematocrit-corrected ESR formula: ESR × (Hct/45). In hemodialysis patients, this correction improved diagnostic accuracy for inflammation to 100% sensitivity and specificity when using appropriate cut-off values 2.
Practical Algorithm for ESR Interpretation in Anemic Patients
When encountering elevated ESR in an anemic patient:
Calculate hematocrit-corrected ESR [ESR × (Hct/45)] to determine if elevation is solely due to anemia or reflects true inflammation 2.
Measure CRP concurrently—CRP is unaffected by anemia and provides complementary information. If CRP is normal but ESR is elevated, suspect the elevation is primarily due to anemia rather than active inflammation 1, 2.
In hemodialysis patients, a hematocrit-corrected ESR <23 mm/h with normal CRP and albumin indicates absence of significant inflammation, while values >59 mm/h with elevated CRP and hypoalbuminemia indicate severe inflammation 2.
Consider plasma viscosity measurement as an alternative to ESR in anemic patients, as it is not affected by hemoglobin concentration and resolves interpretative difficulties 3.
Disease-Specific Contexts
Beyond anemia of chronic disease, ESR elevation occurs in specific anemia-associated conditions:
Hemolytic anemia can rarely occur in Kawasaki disease, sometimes related to IVIG infusion, and is accompanied by markedly elevated ESR (often >100 mm/h) 6, 1.
Macrocytic anemia leads to increased ESR due to altered red cell size affecting aggregation 7.
In contrast, abnormal red cell shapes and decreased deformability (as in sickle cell disease or spherocytosis) actually decrease ESR despite anemia being present 7.