Markers of coagulation, fibrinolysis and inflammation in relation to post-thrombotic syndrome

J Thromb Haemost. 2012 Aug;10(8):1532-8. doi: 10.1111/j.1538-7836.2012.04798.x.

Abstract

Background: Post-thrombotic syndrome (PTS) occurs in 20-50% of patients after a deep venous thrombosis (DVT). It is difficult to accurately predict which patients will develop PTS. Biomarkers could be a valuable tool for PTS risk assessment.

Objectives: To investigate whether increased levels of factor (F)VIII, C-reactive protein (CRP) or D-dimer, over time, are associated with the development of PTS in patients after an acute DVT.

Methods: PTS status was assessed using the Villalta scale. Blood sampling was performed at three points during follow-up.

Results: A cohort of 228 consecutive patients was included after an acute DVT. At T1 (12 months after index DVT), both levels of D-dimer (median 725 ng mL(-1) [interquartile range, IQR 400-1400[ vs. 378 ng mL(-1) [251-652] P=0.004) and CRP (median 3.9 mg L(-1) [IQR 1.6-8.5] vs. 2.4 mg L(-1) [1.0-4.3] P=0.018) were increased in patients with PTS, compared with patients without PTS. Factor (F)VIII was not associated with PTS. In the multivariate logistic regression analysis, varicosities (odds ratio [OR] 13.4 95% confidence interval [CI] 3.0-59.1 P=0.001), a previous ipsilateral DVT (OR 6.3 95% CI 1.5-26.9 P=0.012) and CRP>5 mg L(-1) on T1 (OR 8.0 95% CI 2.4-26.4 P=0.001) were significantly associated with PTS.

Conclusions: Besides previous ipsilateral DVT and varicosities, CRP>5 mg L(-1) at T1 was strongly and independently associated with PTS. Persistent inflammation rather than hypercoagulability might be the most important etiological factor in PTS, and may be a target for future therapy. The development of a risk score for PTS, including both clinical risk factors and biomarker levels, such as CRP, might be desirable.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Coagulation*
  • C-Reactive Protein / metabolism
  • Factor VIII / metabolism
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinolysis*
  • Humans
  • Inflammation / blood*
  • Inflammation / immunology
  • Inflammation Mediators / blood*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Netherlands
  • Odds Ratio
  • Postthrombotic Syndrome / blood
  • Postthrombotic Syndrome / diagnosis
  • Postthrombotic Syndrome / etiology*
  • Postthrombotic Syndrome / immunology
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Venous Thrombosis / blood
  • Venous Thrombosis / complications*
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / immunology
  • Young Adult

Substances

  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Inflammation Mediators
  • fibrin fragment D
  • Factor VIII
  • C-Reactive Protein