Time to Hemostasis Predictive in Traumatic Bleeding

NAPLES, Fla. – New data support the use of time to hemostasis as a surrogate primary end point in traumatic bleeding.

An analysis of 40 consecutive trauma patients admitted from the trauma bay to the operating room with moderate to severe bleeding from at least one primary site found that those who died had a greater than threefold longer time to hemostasis (TTH) than did survivors (P value = .016).

TTH was defined as the time frame between when the attending identified the active primary bleeding site and when hemostasis was achieved.

"To our knowledge, this is the first study to demonstrate that time to hemostasis is highly predictive of blood loss, transfusion requirement, and mortality in trauma patients with active hemorrhage," according to Dr. Grant Bochicchio and his colleagues, who presented their results in a poster at the annual meeting of the Eastern Association for the Surgery of Trauma.

The 40 prospectively followed patients had an average TTH of 12.7 minutes and average estimated blood loss of 1,300 cc (300 cc-5,000 cc). An average of 11 units of packed red blood cells and 10 units of fresh frozen plasma were transfused in the first 24 hours.

Overall mortality was 15%. When evaluated by multiple regression analysis, increasing TTH was associated with a significant increase in the transfusion of packed red blood cells (odds ratio 1.1, P = .02), of fresh frozen plasma (OR 0.5, P = .001), and of platelets (OR .05, P = .006).

In addition, increasing TTH was a significant predictor of greater blood loss (OR 24.7, P = .02).

Most important, for every minute of increase in TTH, mortality increased by 10% (OR 1.1, P = .0001), said Dr. Bochicchio, professor of surgery and director of clinical and outcomes research at the shock trauma center of the University of Maryland, Baltimore.

The Food and Drug Administration, in conjunction with the National Institutes of Health, recently asked the trauma community for surrogate outcome measures to accurately evaluate a growing number of hemostatic products in the pipeline indicated for severe bleeding.

A December 2010 workshop sponsored by the FDA’s Center for Biologics Evaluation and Research on product development for patients with severe bleeding from shock or other causes acknowledged that evaluation of new treatments has been hampered in part by a lack of consistent definitions for trauma-associated pathologic states such as moderate versus severe bleeding. The panel agreed that time to 100% hemostasis was an appropriate clinical end point among trauma patients for trials of local agents, while early mortality and hemostasis were appropriate end points for trials of systemic agents.

The trauma patients in the current trial had a mean age of 32 years. A total of 85% were male, 63% were black, and 63% sustained a penetrating trauma. The most common primary bleeding sites identified were liver, spleen, vascular, heart, and lung. Their mean Injury Severity Score was 22.

Dr. Bochicchio and his coauthors reported no conflicts of interest.