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

Ann Lab Med. 2014 Mar;34(2):85-91. doi: 10.3343/alm.2014.34.2.85. Epub 2014 Feb 13.


Background: Dysfunctional natural anticoagulant systems enhance intravascular fibrin formation 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 protein 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 physiologic 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.

Keywords: Antithrombin; Disseminated intravascular coagulation; Natural anticoagulant; Protein C; Protein S; Protein Z.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / blood*
  • Antithrombins / blood*
  • Blood Platelets / cytology
  • Blood Proteins / analysis
  • Disseminated Intravascular Coagulation / complications
  • Disseminated Intravascular Coagulation / diagnosis*
  • Disseminated Intravascular Coagulation / 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
  • Sepsis / diagnosis*
  • Severity of Illness Index


  • Anticoagulants
  • Antithrombins
  • Blood Proteins
  • Fibrin Fibrinogen Degradation Products
  • Protein C
  • Protein S
  • fibrin fragment D
  • plasma protein Z