Program: Oral and Poster Abstracts
Session: 321. Blood Coagulation and Fibrinolytic Factors: Poster I (61 abstracts)
Methods. Eighty trauma patients presenting to a major urban level 1 trauma center (47 with blunt trauma and 33 with penetrating trauma) were enrolled. 62 patients were male and 18 female. The age of patients varied between 18 and 90 years (average 42.6±19.2 years) and the Injury Severity Score (ISS) varied between 1 and 75 (average 19.3±17.2). Blood was collected immediately upon emergency department arrival prior to any resuscitation or blood product transfusion. For analysis our cohort was divided into 4 groups (20 patients/group) based on their ISS and presence of shock (base deficit BD):
Group 1: Non-severe injury, no shock (ISS≤15; BD>-6)
Group 2: Non-severe injury, with shock (ISS≤15; BD≤-6)
Group 3: Severe injury, no shock (ISS>15; BD>-6)
Group 4: Severe injury, with shock (ISS>15; BD≤-6)
Citrate plasma was prepared, frozen and stored at -80°C. No additional freeze/thaw cycles were involved prior to FXIa, FIXa and TF activity assays. The assays were based on a response of thrombin generation to corresponding monoclonal inhibitory antibodies (αFXIa-2, αFIXa-91 and αTF-5, respectively; all at 0.1 mg/mL).
Results. The frequency of TF in less injured patients was relatively low (table) and increased by at least 3-fold in patients with severe injury (groups 3 and 4). The concentration of TF varied in a wide range in all 4 groups, but was the lowest in group 1 patient samples and the highest in groups 3 and 4. FXIa was observed in 91% of plasma samples and was high in all 4 groups of patients. Similar to TF, the concentration of FXIa varied in a wide range in the entire study population. Unlike TF however, FXIa was present in patients with shock at a higher concentration and did not correlate with the severity of injury. Only 9 of 20 group 1 plasma samples had detectable FIXa, whereas in groups 2-4 only 1 or 2 plasma samples had no FIXa activity. The median concentration of this protein varied in a relatively narrow range between all 4 groups, although the lowest was observed in group 1. For the entire cohort, there was a good correlation between FIXa and FXIa concentrations (R2=0.33), but no correlation between TF and FIXa or FIXa. These data suggest that FXIa in trauma patient blood is generated primarily through the contact pathway, although the input of the TF pathway to FXI activation cannot be excluded.
Patient Group |
TF |
FXIa |
FIXa |
||||||
Frequency |
Concentration (pM) |
Frequency |
Concentration (pM) |
Frequency |
Concentration (pM) |
||||
Range |
Median |
Range |
Median |
Range |
Median |
||||
1 |
4/20 (20%) |
0.1 - >6.4 |
0.28 |
18/20 (90%) |
0.9 - >64 |
7.3 |
9/20 (45%) |
73 - >1000 |
175 |
2 |
3/20 (15%) |
0.5 - >6.4 |
1.00 |
19/20 (95%) |
3.2- >64 |
23.4 |
18/20 (90%) |
38 - >1000 |
270 |
3 |
12/20 (60%) |
0.3 - >6.4 |
3.50 |
17/20 (85%) |
0.7 - >64 |
11.1 |
18/20 (90%) |
75 - >1000 |
252 |
4 |
14/20 (70%) |
0.2 - >6.4 |
2.48 |
19/20 (95%) |
1.8 - >64 |
26.5 |
19/20 (95%) |
26 - >1000 |
205 |
Overall |
33/80 (41%) |
0.1 - >6.4 |
1.01 |
73/80 (91%) |
0.7 - >100 |
17.0 |
64/80 (80%) |
26 - >1000 |
250 |
Conclusions. 1) Frequency and concentration of TF is higher in patients with a higher trauma severity, but it is independent of shock; 2) The vast majority of plasma samples from trauma patients contain active FIXa and FXIa; 3) Concentration of FXIa is higher in patients with shock and does not appear to be affected by the trauma severity. Taken together, these data suggest separate mechanisms for contact pathway activation after injury driven by shock and TF pathway activation driven by tissue injury.
Disclosures: No relevant conflicts of interest to declare.
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