Causes of Elevated Fibrinogen Levels
Fibrinogen is commonly elevated as part of the acute phase response to inflammation, infection, and tissue damage, but can also be elevated in cardiovascular diseases, malignancy, and certain chronic conditions. 1
Primary Causes of Elevated Fibrinogen
Inflammatory Conditions
- Fibrinogen functions as an acute phase reactant protein that increases during inflammatory processes 1
- Systemic inflammation from any cause can trigger elevated fibrinogen levels 2
- C-reactive protein (CRP) and fibrinogen often rise together during inflammatory responses 1
Cardiovascular Disease
- Elevated fibrinogen is a significant independent risk marker in acute coronary syndromes 1
- Increased fibrinogen levels are associated with both short-term and long-term risk of death and subsequent myocardial infarction 1
- Fibrinogen-mediated erythrocyte aggregation contributes to spontaneous echo contrast in atrial fibrillation, indicating stasis and increased thrombotic risk 1
- Persistent and paroxysmal atrial fibrillation are associated with increased systemic fibrinogen levels, indicating active intravascular thrombogenesis 1
Infectious Diseases
- COVID-19 infection commonly causes elevated fibrinogen levels, especially in severe cases 3
- Fibrinogen levels >528.0 mg/dl in COVID-19 patients predict disease severity with 66.7% sensitivity and 70.3% specificity 3
Coagulation Disorders
- Hyperfibrinogenemia is causally related to atherothrombosis, independent of its role as an acute phase protein 2
- Elevated fibrinogen is associated with reduced fibrinolytic capacity, increasing risk of thrombotic events 1
- High fibrinogen levels (≥5.0 g/l) increase venous thrombosis risk 4-fold 4
Trauma
- Critical fibrinogen levels (<1.5 g/L) are reached in many massively injured trauma patients and predict in-hospital mortality 1
- Fibrinogen levels are monitored as part of goal-directed resuscitation strategies in trauma patients 1
Other Contributing Factors
Genetic Factors
- Genetic polymorphisms of fibrinogen can contribute to elevated levels and increased risk of atherosclerotic cardiovascular disease 5
- Post-translational modifications of fibrinogen may contribute to risk of cardiovascular disease 5
Lifestyle Factors
- Many cardiovascular risk factors are associated with hyperfibrinogenemia 6
- Populations with low cardiovascular risk typically have low fibrinogen levels 6
Clinical Significance
Prognostic Value
- Elevated fibrinogen is associated with excessive inflammation, disease severity, and ICU admission in inflammatory conditions 3
- Fibrinogen levels can predict risk of future cardiovascular events with power equal to or higher than traditional risk factors 6
- In the FRISC trial, elevated fibrinogen was associated with both short and long-term risk of death and subsequent myocardial infarction 1
Important Distinction
- Elevated fibrinogen levels in thrombosis patients are not merely caused by acute phase reactions, supporting a causal relationship between high fibrinogen levels and venous thrombosis 4
- Fibrinogen elevation can be both a cause of atherosclerotic lesions (increasing risk of atherothrombosis) and a biomarker of atherosclerotic cardiovascular disease 5