Endogenous thrombin potential following hemostatic therapy with 4-factor prothrombin complex concentrate: a 7-day observational study of trauma patients

Abstract

Introduction: Purified prothrombin complex concentrate (PCC) is increasingly used as hemostatic therapy for trauma-induced coagulopathy (TIC). However, the impact of PCC administration on coagulation status among patients with TIC has not been adequately investigated.

Methods: In this observational, descriptive study, data relating to thrombin generation were obtained from plasma samples gathered prospectively from trauma patients upon emergency room (ER) admission and over the following 7 days. Standard coagulation tests, including measurement of antithrombin (AT) and fibrinogen, were performed. Three groups were investigated: patients receiving no coagulation therapy (NCT group), patients receiving fibrinogen concentrate only (FC group), and patients treated with PCC and fibrinogen concentrate (FC-PCC group).

Results: The study population (77 patients) was predominantly male (84.4%); mean age was 40 ± 15 years and mean injury severity score was 25.6 ± 12.7. There were no significant differences between the three study groups in thrombin-related parameters upon ER admission. Endogenous thrombin potential (ETP) was significantly higher in the FC-PCC group compared with the NCT group on days 1 to 4 and the FC group on days 1 to 3. AT levels were significantly lower in the FC-PCC group from admission until day 3 (versus FC group) or day 4 (versus NCT group). Fibrinogen increased over time, with no significant between-group differences after ER admission. Despite ETP being higher, prothrombin time and activated partial thromboplastin time were significantly prolonged in the FC-PCC group from admission until day 3 to 4.

Conclusions: Treatment with PCC increased ETP for several days, and patients receiving PCC therapy had low AT concentrations. These findings imply a potential pro-thrombotic state not reflected by standard coagulation tests. This is probably important given the postoperative acute phase increase in fibrinogen levels, although studies with clinical endpoints are needed to ascertain the implications for patient outcomes. We recommend careful use of PCC among trauma patients, with monitoring and potentially supplementation of AT.

Figure 1

Parameters relating to thrombin generation, from emergency room (ER) admission until day 7. Endogenous thrombin potential was significantly higher over the first 3 to 4 days in the prothrombin complex concentrate-fibrinogen concentrate group (FC-PCC group) (dark gray) compared to the fibrinogen concentrate group (FC group) (light gray) and patients receiving no coagulation therapy (NCT group) (white). AUC, area under curve. *P <0.05; **P <0.01; ***P <0.001; ****P <0.0001; no indication = not significant. Data are presented as box and whisker plots (Tukey). Student t-test or Mann-Whitney rank sum test was used as appropriate for between-group comparisons.

Figure 2

Prothrombin time, activated partial thromboplastin time, fibrinogen concentration and antithrombin activity from emergency room (ER) admission until day 7. The prothrombin complex concentrate-fibrinogen concentrate group (FC-PCC group) (dark gray) was compared with the fibrinogen concentrate group (FC group) (light gray) and patients receiving no coagulation therapy (NCT group) (white). *P <0.05; **P <0.01; ***P <0.001; ****P <0.0001; no indication = not significant. Data are presented as box and whisker plots (Tukey). Student t-test or Mann-Whitney rank sum test was used as appropriate for between-group comparisons.

Figure 3

Hemoglobin and platelet count from emergency room (ER) admission until day 7. The prothrombin complex concentrate-fibrinogen concentrate group (FC-PCC group) (dark gray) was compared with the fibrinogen concentrate group (FC group) (light gray) and patients receiving no coagulation therapy (NCT group) (white). *P <0.05; **P <0.01; ****P <0.0001; no indication = not significant. Data are presented as box and whisker plots (Tukey). Student t-test or Mann-Whitney rank sum test was used as appropriate for between-group comparisons.

Figure 4

Relationship between change in endogenous thrombin potential and change in antithrombin, from emergency room (ER) admission until day 7 following trauma. In the FC-PCC group, a pronounced gap between endogenous thrombin potential and antithrombin was observed. ETP, endogenous thrombin potential (solid symbols); AT, antithrombin (open symbols); NCT group (triangles), patients who received no coagulation therapy; FC group (squares), patients who received fibrinogen concentrate only; FC-PCC group (circles), patients who were treated with prothrombin complex concentrate and human fibrinogen concentrate. *P <0.05; ***P <0.001; not indicated = not significant (within-group comparison versus ER admission). Data are presented as median (interquartile range).