Ann Lab Med.  2014 Mar;34(2):85-91. 10.3343/alm.2014.34.2.85.

Changes in Plasma Levels of Natural Anticoagulants in Disseminated Intravascular Coagulation: High Prognostic Value of Antithrombin and Protein C in Patients with Underlying Sepsis or Severe Infection

Affiliations
  • 1Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. lukekhk@snu.ac.kr
  • 2Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 3Department of Laboratory Medicine, Seoul Medical Center, Seoul, Korea.

Abstract

BACKGROUND
Dysfunctional natural anticoagulant systems enhance intravascular fibrin for mation in disseminated intravascular coagulation (DIC), and plasma levels of natural anti coagulants can be used in the diagnosis and prognosis of DIC. Herein, the diagnostic value of 4 natural anticoagulants was assessed, and the prognostic value of antithrombin and protein C were validated in a large population.
METHODS
Part 1 study included 126 patients with clinically suspected DIC and estimated plasma levels of 4 candidate anticoagulant proteins: antithrombin, protein C, protein S, and protein Z. Part 2 comprised 1,846 patients, in whom plasma antithrombin and protein C levels were compared with other well-known DIC markers according to the underlying dis eases. The 28-day mortality rate was used to assess prognostic outcome.
RESULTS
Antithrombin and protein C showed higher areas under the ROC curve than pro tein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan-Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hemato logic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high.
CONCLUSIONS
Decreased plasma anticoagulant levels reflect florid consumption of the phys iologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/severe infection.

Keyword

Disseminated intravascular coagulation; Natural anticoagulant; Antithrombin; Protein C; Protein S; Protein Z

MeSH Terms

Adult
Aged
Anticoagulants/*blood
Antithrombins/*blood
Blood Platelets/cytology
Blood Proteins/analysis
Disseminated Intravascular Coagulation/complications/*diagnosis/mortality
Female
Fibrin Fibrinogen Degradation Products/analysis
Humans
Male
Middle Aged
Platelet Count
Prognosis
Protein C/*analysis
Protein S/analysis
Prothrombin Time
Regression Analysis
Sepsis/complications/*diagnosis
Severity of Illness Index
Anticoagulants
Antithrombins
Blood Proteins
Fibrin Fibrinogen Degradation Products
Protein C
Protein S

Figure

  • Fig. 1 Receiver operating characteristic curve analyses and calculated values of area under the curves (AUC) for antithrombin, protein C, protein S, and protein Z for prediction of overt-disseminated intravascular coagulation. The AUCs between protein C and protein Z showed significant difference (P<0.05).

  • Fig. 2 Relation of plasma antithrombin (black bars) and protein C (gray bars) levels with disseminated intravascular coagulation (DIC) scores. Error bars indicate 95% confidence intervals. As the DIC score increases, both antithrombin and protein levels correspondingly decrease (P<0.001).

  • Fig. 3 Changes in plasma levels of (A) antithrombin and (B) protein C according to the underlying diseases of 28-day mortality. The central middle lines and boxes represent medians and interquartile ranges, respectively. The error bars indicate 95% confidence ranges.

  • Fig. 4 Kaplan-Meier survival analysis stratified for (A) antithrombin and (B) protein C in all patients. The cutoff values were set as the values at which the prognostic power to predict 28-day mortality was highest.


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