Tranexamic acid corrects fibrinolysis in the presence of acidemia in a swine model of severe ischemic reperfusion.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic with anti-inflammatory properties associated with improved outcomes when administered to trauma patients at risk for bleeding; however, its efficacy is unknown in acidemia. We evaluated the efficacy of TXA on hyperfibrinolysis using an established porcine traumatic hemorrhage ischemic shock model. METHODS: Ten Yorkshire swine underwent a controlled hemorrhage followed by supraceliac aortic cross-clamping. During standard resuscitation, control animals received recombinant tissue plasminogen activator (rtPA) after cross-clamp removal, and experimental animals received rtPA followed by TXA. Rotational thromboelastometry analysis was performed at baseline, 5 minutes and 15 minutes after rtPA dosing, and 4 hours after cross-clamp removal. RESULTS: Control and experimental animals had similar hemodynamics and routine laboratory values at baseline and throughout resuscitation. At the time of TXA administration, average pH was 7.2. Clot formation time was prolonged from baseline and all resuscitation time points in both groups, with no difference at any time point. Maximum clot firmness decreased from baseline at all resuscitation time points in both groups. Maximum lysis increased from baseline (9% control vs. 9% TXA) after tissue plasminogen activator administration in both groups (100% control vs. 99% TXA). In experimental animals, maximum lysis returned to baseline 10 minutes after TXA administration (92% vs. 9%, p < 0.001). CONCLUSION: TXA rapidly and fully reverses hyperfibrinolysis despite severe acidemia in a porcine trauma model. TXA is a promising adjunct to trauma resuscitation that is easily administered in austere or prehospital settings.

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

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.

Initial operative time and metastatic disease recurrence.

Colon cancer metastases are a major source of morbidity and mortality for patients following oncologic resection. The purpose of this study was to identify whether operative time as a surrogate for resident involvement increased the risk of future liver metastases. We performed a retrospective review of patients undergoing curative colon resection from 2001 to 2010 at two military residency training hospitals. Intraoperative time as well as preoperative comorbidities and perioperative factors were gathered from electronic medical records. Liver metastases were identified from the tumor registry and inpatient records. A total of 106 patients underwent resection for colon cancer (Stage I-III) from 2001 to 2005 with 5-year follow-up through 2010. Operative times in patients who had recurrence was 205 +/- 60 minutes and those without recurrence was 187 +/- 73 minutes (p = 0.398). There was no correlation between operative time and time to recurrence (p = 0.452), and Cox regression demonstrated that case duration had no impact on time to metastatic recurrence (p = 0.461). Within our cohort, operative time had no impact on metastatic cancer recurrence. Surgeons should continue to focus on proper oncologic principles and tumor biology rather than the concern that increased operative time or resident training leads to increased metastatic recurrence.