Fibrinogen is the Most Common Cause of Elevated ESR
Fibrinogen is MOST often responsible for increasing the erythrocyte sedimentation rate (ESR). 1
Mechanism of ESR Elevation
The erythrocyte sedimentation rate is a physical parameter that measures how quickly red blood cells settle in a tube of blood over a specified time period. Several plasma proteins can affect this rate by influencing red blood cell aggregation:
Fibrinogen: The primary protein responsible for ESR elevation
- Creates a bridging effect between red blood cells, promoting aggregation
- Significantly increases during acute inflammatory responses
- Shows a linear relationship with ESR elevation when exceeding normal thresholds 1
Immunoglobulins: Secondary contributors
- Particularly gamma-globulins (IgG, IgA, IgM)
- Can cause ESR elevation in chronic conditions and monoclonal gammopathies
- Less potent than fibrinogen in causing ESR elevation 1
Alpha-2-globulins and beta-globulins: Tertiary contributors
- Have some association with ESR elevation
- Less significant impact compared to fibrinogen 1
Albumin: Actually decreases ESR
- Higher albumin concentrations slightly decrease the ESR
- Has synergistic effect with gamma-globulins but not with fibrinogen 1
Evidence Supporting Fibrinogen as Primary Cause
Research has consistently demonstrated that fibrinogen is the most significant factor in ESR elevation:
- In acute phase reactions, fibrinogen shows the strongest correlation with ESR elevation 1
- Model studies demonstrate that ESR increases linearly with fibrinogen concentrations above normal thresholds 1
- During inflammation, the increase in fibrinogen leads to formation of larger aggregates of red blood cells, which sediment faster 2
- Fibrinogen is an agent that directly fosters aggregation of red blood cells 2
Clinical Context of ESR Elevation
The most common clinical conditions associated with extremely elevated ESR (≥100 mm/h) include:
- Infectious diseases (36.6%), particularly pulmonary infections
- Hematological diseases (29.6%)
- Autoimmune diseases (17.2%)
- Renal failure 3
In these conditions, the ESR elevation is significantly correlated with:
- Decreased red blood cell count, hemoglobin, and hematocrit
- Increased fibrinogen levels 3
Diagnostic Utility of ESR
While ESR is a non-specific marker, it remains useful in certain clinical scenarios:
- Most valuable in diagnosing temporal arteritis and monitoring treatment response
- Helpful in monitoring disease activity in rheumatoid arthritis when clinical findings are equivocal
- Often elevated in inflammatory conditions where fibrinogen is increased 4
Conclusion
Among the options presented (albumin, gamma-globulins, alpha-2-globulins and beta-globulins, and fibrinogen), fibrinogen is clearly the most common and significant cause of ESR elevation. This is supported by multiple studies showing its direct effect on red blood cell aggregation and sedimentation, particularly during acute inflammatory responses.