A simple laboratory test to measure protein C—a natural anti-blood-clotting substance that also reflects the level of inflammation in the body—may offer a useful new indicator of the severity of illness and risk of death among critically ill patients.
The July issue of the journal Anesthesiology features the new study by Dr. Frank Brunkhorst and colleagues of Friedrich Schiller University in Jena, Germany. "Protein C may be a new target for therapy for patients with non-infectious-induced organ failure/dysfunction in the intensive care unit," said Dr. Brunkhorst. "The possibility to measure protein C levels at the bedside in critically ill patients—without time-delay by the central lab—would be a great step forward in assessing prognosis, and may influence clinical decision making at an early stage of the evolution of organ dysfunction."
The researchers analyzed the relationship between protein C and indicators of organ failure in 312 patients admitted to the ICU after major surgery. Changes in protein C levels over time were analyzed, along with their ability to predict the patients' risk of death.
About half of the patients had lower-than-normal protein C levels—reflecting an increased risk of abnormal blood clotting—when they first arrived at the ICU. Protein C decreased further over the next three to four days before returning to normal by about two weeks.
Lower protein C concentrations were correlated with increased severity of sepsis and with greater organ dysfunction. In contrast, patients with less-severe illness—based on standard severity scores—had higher protein C levels.
Overall, 15 percent of patients died. Particularly during their first four days in the ICU, this group had lower protein C levels than patients who survived.
With adjustment for other factors, the risk of death was four times higher for patients whose minimum protein C level was below a certain cutoff point. Protein C was the strongest predictor of risk of death—even stronger than the standard severity scores.
Previous studies have noted low protein C levels in critically ill patients, but most have focused on patients with sepsis. Gaining a better understanding of the factors associated with protein C might help ICU specialists to identify patients at high risk of severe illness and death—and possibly provide an opportunity for treatments to lower those risks.
The new study—the largest so far to look at protein C levels in critically ill patients—suggests that protein C may be a valuable indicator of severity of illness and risk of death in the ICU. "Severe sepsis is responsible for 750,000 deaths a year in the U.S.," commented Dr. Michael A. Gropper of University of California, San Francisco, author of an editorial accompanying the new study. "The ability to identify these patients and treat them early will significantly improve their chance of survival. This study is important because it identifies a strategy to easily identify patients with severe sepsis and multisystem organ failure."
The results add to previous studies suggesting that treatments targeting the protein C pathway might benefit critically ill patients. Although much more research will be needed, treatment with recombinant protein C could offer a new way of interrupting the progression to sepsis and organ failure in high-risk patients. In his editorial, Dr. Gropper concludes, "We await further studies of the coagulation pathway in the hopes of new therapies for this devastating syndrome."
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