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Published on: September 9, 2012
D-dimer corrected for thrombin and plasmin generation is a strong predictor of mortality in patients with sepsis
Fabrizio Semeraro1, Concetta T Ammollo1, Pietro Caironi2
1Department of Biomedical Sciences and Human Oncology, "Aldo Moro" University, Bari, Italy.
Insights
A new corrected D-dimer (DDcorr) marker improves sepsis prognosis by reflecting the coagulation-fibrinolysis balance, outperforming standard DD measurements for predicting patient mortality.
Area of Science:
- Biochemistry
- Medical Diagnostics
- Critical Care Medicine
Background:
- D-dimer (DD) is a common marker for fibrin-related products and sepsis prognosis.
- DD levels can be falsely negative in sepsis due to inhibited fibrinolysis.
- A need exists for improved prognostic markers in sepsis.
Purpose of the Study:
- To evaluate if correcting D-dimer (DD) for thrombin and plasmin generation improves its prognostic significance in sepsis patients.
- To assess the relationship between a corrected DD (DDcorr) and 90-day mortality in sepsis.
Main Methods:
- A nested study of 269 septic patients from the ALBIOS trial was conducted.
- D-dimer (DD), prothrombin fragment 1+2 (F1+2), and plasmin-antiplasmin complex (PAP) were measured.
- Corrected DD (DDcorr) was calculated as DD×PAP/F1+2 to assess coagulation-fibrinolysis balance.
Main Results:
- DDcorr demonstrated a J-shaped relationship with mortality, with highest risk in the lowest and highest tertiles (imbalanced fibrinolysis).
- DDcorr was an independent prognostic factor and significantly improved risk stratification compared to DD, PAP, or F1+2 alone.
- A combined score using DDcorr and SOFA tertiles showed high discriminatory power for mortality.
Conclusions:
- Corrected D-dimer (DDcorr) effectively indicates the in vivo coagulation-fibrinolysis balance in sepsis.
- DDcorr offers significantly higher prognostic value for sepsis mortality than standard DD measurements.
Background:
D-dimer (DD) is the most used fibrin-related marker and has been proposed, either alone or in combination with other variables, as prognostic factor in patients with sepsis. However, DD generation depends on both coagulation and fibrinolysis, meaning that it may give false negative results in conditions associated with marked fibrinolytic inhibition such as sepsis. In this study, we tested whether correction of DD for thrombin and plasmin generation could improve its prognostic significance in septic patients.
Material And Methods:
We performed a nested study in 269 septic patients from the ALBIOS trial. DD, prothrombin fragment 1+2 (F1+2) and plasmin-antiplasmin complex (PAP) were assayed at day 1. Corrected DD (DDcorr) was calculated by the formula DD×PAP/F1+2, such that the lower the DDcorr the greater the imbalance in favour of fibrin formation over fibrin lysis, and vice-versa. Primary outcome was 90-day mortality.
Results:
DDcorr showed a J-shaped relationship with mortality, which was highest in the first DDcorr tertile (low fibrinolysis), intermediate in the 3rd (high fibrinolysis), and lowest in the 2nd (balanced fibrinolysis), suggesting an increased risk whenever the coagulation-fibrinolysis balance is tilted (p<0.0001). Neither DD, nor PAP or F1+2 showed a comparable association with mortality. DDcorr was an independent prognostic factor in multivariable Cox models and significantly improved risk stratification (cNRI≥0.28). Finally, by combining DDcorr and SOFA tertiles, we developed a score with high discriminatory power.
Discussion:
DDcorr is a good marker of the in vivo coagulation-fibrinolysis balance and displays a prognostic value in sepsis much higher than DD.
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