Thrombin generation and procoagulant microparticle profiles after acute trauma

Abstract

Objective The two sides of Trauma Induced Coagulopathy (TIC), the hypo- and the hyper- coagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant MPs and thrombin activity during hospitalization for trauma. Methods Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24 and 72 hours after injury, and discharge. Platelet poor plasma was harvested and stored at −80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lagtime (minutes), peak height (nM thrombin) and time to reach peak height (ttPeak - minutes). The concentration of total procoagulant MPs (number/uL]) was measured by flow cytometry. Data are presented as median [interquartile range]. Results Among 443 trauma patients (1734 samples; ISS=13.0 [6.0, 22.0], hospital LOS=4.0 [2.0, 10.0] days, age=48 [28, 65] years, 70.7% male, 95% with blunt mechanism, mortality 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 [285, 395] nM and 400 [211, 772] per uL plasma, respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible “hypercoagulable state” (lagtime ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2278) were reached within 12 hours after acute trauma, while extreme values representing a possible “hypocoagulable state” (lagtime ≥ 18.6, peak height ≤ 17.8 and ttPeak ≥ 29.45) were not reached until 1-3 days. Conclusion Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters.

Dynamics of fibrinogen in acute phases of trauma

“…Various cell-derived microparticles have been detected during the acute phase of severe trauma [27][28][29][30][31][32]. Plateletderived microparticles are well-known pro-coagulants in the acute phase of trauma [27][28][29].…”

“…Plateletderived microparticles are well-known pro-coagulants in the acute phase of trauma [27][28][29]. Furthermore, leukocyte-, erythrocyte-, and endothelial cell-derived microparticles are also released into the systemic circulation in the acute phase of trauma (29,30).…”

“…2) [14][15][16][17]. These circulating pro-coagulants are known as damage-associated molecular patterns (DAMPs) [18][19][20][21][22][23][24][25][26] and microparticles [27][28][29][30][31][32] released from injured organs/tissues. Extracellular DNA and DNA-binding proteins are the principal DAMPs that comprise the pro-coagulants detected in severe trauma patients.…”

Cryoprecipitate transfusion: current perspectives

“…66 However, a recent prospective study in acute trauma did not show any changes in microparticle levels over time. 67 There is uncertainty regarding their role in trauma and hemostasis and the robustness of quantitative and qualitative assays may need addressing before their role in trauma coagulopathy can be elucidated.…”

Validation of acute traumatic coagulopathy in an ovine model of trauma and haemorrhage

“…The PROMMT study demonstrated an association between decreased levels of PMPs and poor clot strength, increased blood product requirements and mortality in coagulopathic trauma patients (149). An alternate study demonstrated no significant difference in microparticle concentration with time in trauma patients (150), while a third study reported elevated PMPs in trauma patients at hospital admission that were implicated in the development of post injury multi-organ failure (151). Alterations in PMP levels may be a separate component of platelet dysfunction developing independently to impaired aggregation capacity, and may play an important part in the haemostatic and inflammatory responses to trauma.…”