The effects of tranexamic acid and prothrombin complex concentrate on the coagulopathy of trauma: an in vitro analysis of the impact of severe acidosis.

Abstract

BACKGROUND:

Bleeding is the most frequent cause of preventable death after severe injury. Our purposes were to study the efficacy of tranexamic acid (TXA) and prothrombin complex concentrate (PCC) on a traumatic coagulopathy with a severe native metabolic acidosis and compare the efficacy of PCC versus fresh frozen plasma (FFP) to reverse a dilutional coagulopathy.

METHODS:

In vitro effects of TXA and PCC were assessed with standard laboratory analysis (prothrombin time [PT]/international normalized ratio [INR]) and rotational thromboelastometry in a porcine hemorrhage with ischemia-reperfusion (H/I) model. FFP was used in comparison with PCC. In vitro doses were calculated to be the equivalent of 1-g TXA, 100-mg tissue plasminogen activator, 45-IU/kg PCC, and 4-U FFP. Agents were tested at baseline and then with severe metabolic acidosis after 6 hours of resuscitation.

RESULTS:

Thirty-one swine were studied. Baseline hematocrit was 24%, pH was 7.56, INR was 1.0, and lactate level was 1.47. Six hours after H/I, the hematocrit was 15.9%, pH was 7.1, INR was 1.7, and lactate level was 10.26. Rotational thromboelastometry revealed that maximum clot firmness at baseline was 71.71 mm and decreased to 0.29 mm with tissue plasminogen activator, representing severe fibrinolysis. Following TXA dosing, the maximum clot firmness was immediately corrected to 69.06 mm. There was no difference (p = 0.48) between TXA function at baseline pH (mean, 7.56) or acidotic pH (mean, 7.11). The mean baseline PT was 13 ± 0.49 seconds (INR, 1). After H/I and resuscitation, the mean PT was 23.03 seconds (INR, 2.1). PCC reduced the PT to 20 (INR, 1.75; p = 0.001) and FFP to 17.44 (INR, 1.47; p = 0.001).

CONCLUSION:

Both TXA and PCC seem to function well in reversing a traumatic coagulopathy in vitro, and TXA seems to have no loss of function in a severe metabolic acidosis. Further investigations are warranted.

• Authors: Christopher Rees Porta, Daniel Nelson, Derek McVay, Shashikumar Salgar, Matthew Eckert, Seth Izenberg, Matthew J Martin
• Journal: The journal of trauma and acute care surgery (J Trauma Acute Care Surg) Vol. 75 Issue 6 Pg. 954-60 (Dec 2013) ISSN: 2163-0763 [Electronic] United States
• PMID: 24256666 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antifibrinolytic Agents
• Blood Coagulation Factors
• Lactic Acid
• prothrombin complex concentrates
• Tranexamic Acid
• Prothrombin

Topics

• Acidosis (blood, complications, therapy)
• Animals
• Antifibrinolytic Agents (administration & dosage)
• Blood Coagulation Disorders (blood, complications, therapy)
• Blood Coagulation Factors (administration & dosage)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Hemorrhage (blood, etiology, therapy)
• Lactic Acid (blood)
• Plasma
• Prothrombin (metabolism)
• Prothrombin Time
• Resuscitation (methods)
• Swine
• Tranexamic Acid (administration & dosage)
• Wounds and Injuries (blood, complications)