Markus Mittermayr

Prevalence and impact of abnormal ROTEM® assays in severe blunt trauma: results of the ‘Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIA-TRE-TIC) study’

BACKGROUND ROTEM(®)/TEG(®) (rotational thromboelastometry) assays appear to be useful for the treatment of bleeding trauma patients. However, data on the prevalence and impact of abnormal ROTEM(®) assays are scarce. METHODS This is a prospective cohort study of blunt trauma patients (Injury Severity Score ≥15 or Glasgow Coma Score ≤14) admitted to Innsbruck Medical University Hospital between July 2005 and July 2008. Standard coagulation tests, antithrombin (AT), prothrombin fragments (F1+2), thrombin-antithrombin complex (TAT), and ROTEM(®) assays were measured after admission. Data on 334 patients remained for final analysis. RESULTS ROTEM(®) parameters correlated with standard coagulation tests (all Spearman r>0.5), and significant differences in mortality were detected for defined ROTEM(®) thresholds [FIBTEM 7 mm (21% vs 9%, P=0.006), EXTEM MCF (maximum clot firmness) 45 mm (25.4% vs 9.4%, P=0.001)]. EXTEM MCF was independently associated with early mortality [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.9-0.99] and MCF FIBTEM with need for red blood cell transfusion (OR 0.92, 95% CI 0.87-0.98). In polytrauma patients with or without head injury (n=274), the prevalence of low fibrinogen concentrations, impaired fibrin polymerization, and reduced clot firmness was 26%, 30%, and 22%, respectively, and thus higher than the prolonged international normalized ratio (14%). Hyperfibrinolysis increased fatality rates and occurred as frequently in isolated brain injury (n=60) as in polytrauma (n=274) (5%, 95% CI 1.04-13.92 vs 7.3%, 95% CI 4.52-11.05). All patients showed elevated F1+2 and TAT and low AT levels, indicating increased thrombin formation. CONCLUSIONS Our data enlarge the body of evidence showing that ROTEM(®) assays are useful in trauma patients. Treatment concepts should focus on maintaining fibrin polymerization and treating hyperfibrinolysis.

The exclusive use of coagulation factor concentrates enables reversal of coagulopathy and decreases transfusion rates in patients with major blunt trauma

BACKGROUND FFP and coagulation factor concentrates are used to correct trauma-induced coagulopathy (TIC). However, data on coagulation profiles investigating effects of therapy are scarce. METHODS This is an analysis of 144 patients with major blunt trauma ((ISS)≥15), who were enrolled in a prospective cohort study investigating characteristics and treatment of TIC. Patients who received fibrinogen concentrate and/or prothrombin complex concentrate alone (CF Group) were compared with those additionally receiving FFP transfusions (FFP Group). RESULTS Sixty-six patients exclusively received CF, while 78 patients additionally received FFP. Overall, patients were comparable regarding age, gender and ISS (CF Group, ISS 37 (29, 50); FFP Group ISS 38 (33, 55), p=0.28). Patients treated with CF alone showed sufficient haemostasis and received significantly fewer units of red blood cells (RBC) and platelets than did those also receiving FFP [(RBC 2(0, 4) U vs. 9 (5, 12) U; platelets 0 (0, 0) U vs. 1 (0, 2) U, p<0.001)]. In addition, fewer patients in the CF Group developed multiorgan failure (MOF) (18.2% vs. 37.2%, p=0.01) or sepsis (16.9% vs. 35.9%, p=0.014) than in the FFP Group. Propensity score-matching (n=28 pairs) used to reduce the impact of treatment selection confirmed that additional FFP administration showed no benefit in restoring haemostasis, but was associated with significantly higher transfusion rates for RBC and platelets. CONCLUSION The use of CF alone effectively corrected coagulopathy in patients with severe blunt trauma and concomitantly decreased exposure to allogeneic transfusion, which may translate into improved outcome.

Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial

BACKGROUND Effective treatment of trauma-induced coagulopathy is important; however, the optimal therapy is still not known. We aimed to compare the efficacy of first-line therapy using fresh frozen plasma (FFP) or coagulation factor concentrates (CFC) for the reversal of trauma-induced coagulopathy, the arising transfusion requirements, and consequently the development of multiple organ failure. METHODS This single-centre, parallel-group, open-label, randomised trial was done at the Level 1 Trauma Center in Innsbruck Medical University Hospital (Innsbruck, Austria). Patients with trauma aged 18-80 years, with an Injury Severity Score (ISS) greater than 15, bleeding signs, and plasmatic coagulopathy identified by abnormal fibrin polymerisation or prolonged coagulation time using rotational thromboelastometry (ROTEM) were eligible. Patients with injuries that were judged incompatible with survival, cardiopulmonary resuscitation on the scene, isolated brain injury, burn injury, avalanche injury, or prehospital coagulation therapy other than tranexamic acid were excluded. We used a computer-generated randomisation list, stratification for brain injury and ISS, and closed opaque envelopes to randomly allocate patients to treatment with FFP (15 mL/kg of bodyweight) or CFC (primarily fibrinogen concentrate [50 mg/kg of bodyweight]). Bleeding management began immediately after randomisation and continued until 24 h after admission to the intensive care unit. The primary clinical endpoint was multiple organ failure in the modified intention-to-treat population (excluding patients who discontinued treatment). Reversal of coagulopathy and need for massive transfusions were important secondary efficacy endpoints that were the reason for deciding the continuation or termination of the trial. This trial is registered with ClinicalTrials.gov, number NCT01545635. FINDINGS Between March 3, 2012, and Feb 20, 2016, 100 out of 292 screened patients were included and randomly allocated to FFP (n=48) and CFC (n=52). Six patients (four in the FFP group and two in the CFC group) discontinued treatment because of overlooked exclusion criteria or a major protocol deviation with loss of follow-up. 44 patients in the FFP group and 50 patients in the CFC group were included in the final interim analysis. The study was terminated early for futility and safety reasons because of the high proportion of patients in the FFP group who required rescue therapy compared with those in the CFC group (23 [52%] in the FFP group vs two [4%] in the CFC group; odds ratio [OR] 25·34 [95% CI 5·47-240·03], p<0·0001) and increased needed for massive transfusion (13 [30%] in the FFP group vs six [12%] in the CFC group; OR 3·04 [0·95-10·87], p=0·042) in the FFP group. Multiple organ failure occurred in 29 (66%) patients in the FFP group and in 25 (50%) patients in the CFC group (OR 1·92 [95% CI 0·78-4·86], p=0·15). INTERPRETATION Our results underline the importance of early and effective fibrinogen supplementation for severe clotting failure in multiple trauma. The available sample size in our study appears sufficient to make some conclusions that first-line CFC is superior to FFP. FUNDING None.

Intraoperatively salvaged red blood cells contain nearly no functionally active platelets, but exhibit formation of microparticles: results of a pilot study in orthopedic patients

BACKGROUND: Previous data show improved clot formation after retransfusion of salvaged red blood cells (RBCs). This study was conducted to explore whether such RBCs contain clinically relevant numbers of active residual platelets (PLTs) or exhibit formation of microparticles (MPs).