Martin Ponschab

Trauma patients admitted to an intensive care unit (ICU) may potentially experience a deficiency of coagulation factor thirteen (FXIII). In this retrospective cohort study conducted at a specialized trauma center, ICU patients were studied to determine the dependency of FXIII activity levels on clinical course and substitution with blood and coagulation products. A total of 189 patients with a median injury severity score (ISS) of 25 (16–36, IQR) were included. Abbreviated injury scores for extremities (r = −0.38, p < 0.0001) but not ISS (r = −0.03, p = 0.45) showed a negative correlation with initial FXIII levels. Patients receiving FXIII concentrate presented with a median initial FXIII level of 54 (48–59)% vs. 88 (74–108)%, p < 0.0001 versus controls; they had fewer ICU-free days: 17 (0–22) vs. 22 (16–24), p = 0.0001; and received higher amounts of red blood cell units: 5 (2–9) vs. 4 (1–7), p < 0.03 before, and 4 (2–7) vs. 1 (0–2), p < 0.0001 after FXIII substitution. Matched-pair analyses based on similar initial FXIII levels did not reveal better outcome endpoints in the FXIII-substituted group. The study showed that a low initial FXIII level correlated with the clinical course in this trauma cohort, but a substitution of FXIII did not improve endpoints within the range of the studied FXIII levels. Future prospective studies should investigate the utility of FXIII measurement and lower threshold values of FXIII, which trigger substitution in trauma patients.

Traumatic brain injury (TBI) is the leading cause of death among trauma patients. Patients under antithrombotic therapy (ATT) carry an increased risk for intracranial haematoma (ICH) formation. There is a paucity of data about the role of direct oral anticoagulants (DOACs) among TBI patients. In this retrospective study, we investigated all TBI patients ≥60-years-old who were admitted to the intensive care unit (ICU) from January 2014 until May 2017. Patients were grouped into those receiving vitamin K antagonists (VKA), platelet inhibitors (PI), DOACs and no antithrombotic therapy (no-ATT). One-hundred-eighty-six, predominantly male (52.7%) TBI patients with a median age of 79 years (range: 70–85 years) were enrolled in the study. Glasgow Coma Scale and S-100β were not different among the groups. Patients on VKA and DOACs had a higher Charlson Comorbidity Index compared to the PI group and no-ATT group (p = 0.0021). The VKA group received reversal agents significantly more often than the other groups (p < 0.0001). Haematoma progression in the follow-up cranial computed tomography (CCT) was lowest in the DOAC group. The number of CCT and surgical interventions were low with no differences between the groups. No relevant differences in ICU and hospital length of stay were observed. Mortality in the VKA group was significantly higher compared to DOAC, PI and no-ATT group (p = 0.047). Data from huge registry studies displayed higher efficacy and lower fatal bleeding rates for DOACs compared to VKAs. The current study revealed comparable results. Despite the fact that TBI patients on VKAs received reversal agents more often than patients on DOACs (84.4% vs. 24.2%, p < 0.001), mortality rate was significantly higher in the VKA group (p = 0.047). In patients ≥60 years suffering from TBI, anticoagulation with DOACs appears to be safer than with VKA. Anti-thrombotic therapy with VKA resulted in a worse outcome compared to DOACs and PI. Further studies are warranted to confirm this finding.

Amputations in general and amputations of upper extremities, in particular, have a major impact on patients’ lives. There are only a few long-term follow-up reports of patients after macro-replantation. We present our findings in contrast with the existing literature. Sixteen patients with traumatic macro-amputation of an upper extremity were eligible for inclusion in this study. Altogether, the patients underwent replantation in 3 institutions between 1983 and 2011. Twelve male and four female patients with an average age at injury of 40.6 years (range, 14–61 years) were included in this study. The mean follow-up period was 13.5 years (range, 4.4–32.6 years; SD, 5.7 years). The mean disabilities of the arm, shoulder and hand (DASH) outcome measure was 41 (range, 5.2–94.8; SD, 18.2), functional independence measurement (FIM) was 125 (range, 120–126; SD, 1.8). Chen I representing very good function was accounted in six, Chen II representing good function in eight, Chen III (fair) in one and Chen IV (bad function) in one patient. We found that while the majority of the included patients exhibited good or very good function of the extremity, none of the replanted appendages regained normal levels of functionality. In addition, all participants were very satisfied with their outcomes. Positive long-term results with high rates of subjective satisfaction are possible after replantation of upper extremities.

Fibrinogen concentrate (FC) is increasingly used as first line therapy in bleeding trauma patients. It remains unproven whether FC application increases post-traumatic plasma fibrinogen concentration (FIB) in injured patients, possibly constituting a prothrombotic risk. Thus, we investigated the evolution of FIB following trauma in patients with or without FC therapy. At the AUVA Trauma Centre, Salzburg, we performed a retrospective study of patients admitted to the emergency room and whose FIB levels were documented thereafter up to day 7 post-trauma. Patients were categorized into those with (treatment group) or without (control group) FC therapy during the first 24 h after hospital admission. A subgroup analysis was carried out to investigate the influence of the amount of FC given. The study enrolled 435 patients: treatment group, n = 242 (56 %); control group, n = 193 (44 %), with median Injury Severity Score of 34 vs. 22 (P < 0.001) and massive transfusion rate of 18.4 % vs. 0.2 % (P < 0.001). In the treatment group (median FC dose 6 g), FIB was lower on admission and up to day 2 compared with the control group. In patients receiving high (≥10 g) doses of FC, FIB was lower up to day 5 as compared to controls. At other timepoints, FIB did not differ significantly between the groups. In the treatment vs. the control group, other coagulation parameters such as prothrombin time index and platelet count were consistently lower, while activated partial thromboplastin time was consistently prolonged at most timepoints. Inflammatory parameters such as C-reactive protein, interleukin-6 and procalcitonin were generally lower in controls. The rise of FIB levels from day 2 onwards in our study can be attributed to an upregulated fibrinogen synthesis in the liver, occurring in both study groups as part of the acute phase response after tissue injury. The treatment of severe trauma patients with FC during bleeding management in the first 24 h after hospital admission does not lead to higher FIB levels post-trauma beyond that occurring naturally due to the acute phase response.

Purified coagulation factor concentrates, such as fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are increasingly used as haemostatic therapy for trauma-induced coagulopathy (TIC). The impact of FC and PCC administration on ROTEM parameters among patients with TIC has not been adequately investigated. In this retrospective observational study, changes to ROTEM parameters, induced by three different therapeutic interventions, were investigated: patients receiving FC only (FC-group); patients treated with FC and PCC (FC + PCC-group) and patients treated with PCC only (PCC-group). The study population comprised 96 patients who were predominately male (69 [71.9 %]), median age was 45.0 (26.3–60.0) years, and the median injury severity score was 34.0 (25.0–44.5). Administration of FC resulted in a significant reduction of the clotting time (CT) in both the EXTEM and FIBTEM assays but had no effect on INTEM CT. Clot amplitude (CA) increased significantly in the FIBTEM assay but remained unchanged in the EXTEM and INTEM assays. The combined administration of FC and PCC increased FIBTEM maximum clot firmness (MCF) and normalized EXTEM CT but did not change either INTEM or FIBTEM CT. Following PCC therapy, EXTEM and FIBTEM CT normalized; CA at 10 min after CT measurements decreased significantly in EXTEM, INTEM and FIBTEM. Administration of FC alone or in combination with PCC resulted in a significant improvement of fibrin polymerisation as measured by an increase in FIBTEM MCF. CT is dependent not only on thrombin generation but also on the availability of substrate (fibrinogen). Accelerated fibrin polymerisation rate results in earlier clot formation and consequently shorter CT. PCC administration normalised EXTEM CT below the upper threshold of 80 s. This study was performed at the AUVA Trauma Centre Salzburg, Salzburg, Austria.

Fluid resuscitation is a core stone of hemorrhagic shock therapy, and crystalloid fluids seem to be associated with lower mortality compared to colloids. However, as redistribution starts within minutes, it has been suggested to replace blood loss with a minimum of a three-fold amount of crystalloids. The hypothesis was that in comparison to high volume (HV), a lower crystalloid volume (LV) achieves a favorable coagulation profile and exerts sufficient haemodynamics in the acute phase of resuscitation. In 24 anaesthetized pigs, controlled arterial blood loss of 50 % of the estimated blood volume was either (n = 12) replaced with a LV (one-fold) or a HV (three-fold) volume of a balanced, acetated crystalloid solution at room temperature. Hemodynamic parameters, dilution effects and coagulation profile by standard coagulation tests and thromboelastometry at baseline and after resuscitation were determined in both groups. LV resuscitation increased MAP significantly less compared to the HV, 61 ± 7 vs. 82 ± 14 mmHg (p < 0.001) respectively, with no difference between lactate and base excess between groups. Haematocrit after fluid replacement was 0.20 vs. 0.16 (LV vs. HV, p < 0.001), suggesting a grade of blood dilution of 32 vs. 42 % (p < 0.001) compared to baseline values. Compared to LV, HV resulted in decreased core temperature (37.5 ± 0.2 vs. 36.0 ± 0.6 °C, p < 0.001), lower platelet count (318 ± 77 vs. 231 ± 53 K/μL, p < 0.01) and lower plasma fibrinogen levels (205 ± 19 vs. 168 ± 24 mg/dL, p < 0.001). Thromboelastometric measurements showed a significant impairment on viscoelastic clot properties following HV group. While prothrombin time index decreased significantly more in the HV group, activated partial thromboplastin time did not differ between both groups. HV did not result in hyperchloraemic acidosis. Coagulation parameters represented by plasma fibrinogen and ROTEM parameters were also less impaired with LV. With regrad to hematocrit, 60 % of LV remained intracascular , while in HV only 30 % remained in circulation within the first hour of administration. In the acute setting of 50 % controlled blood loss, a one fold LV crystalloid replacement strategy is sufficient to adequately raise blood pressure up to a mean arterial pressure >50 mm Hg. The concept of damage control resuscitation (DCR) with permissive hypotension may be better met by using LV as compared to a three fold HV resuscitation strategy. High volume administration of an acetated balanced crystalloid does not lead to hyperchloraemic acidosis, but may negatively influence clinical parameters, such as higher blood pressure, lower body temperature and impaired coagulation parameters, which could potentially increase bleeding after trauma. Replacement of acute blood loss with just an equal amount of an acetated balanced crystalloid appears to be the preferential treatment strategy in the acute phase after controlled bleeding.

Introduction: Fibrinogen plays a key role in hemostasis and is the first coagulation factor to reach critical levels in massively bleeding trauma patients. Consequently, rapid estimation of plasma fibrinogen (FIB) is essential upon emergency room (ER) admission, but is not part of routine coagulation monitoring in many centers. We investigated the predictive ability of the laboratory parameters hemoglobin (Hb) and base excess (BE) upon admission, as well as the Injury Severity Score (ISS), to estimate FIB in major trauma patients. Methods: In this retrospective study, major trauma patients (ISS ≥16) with documented FIB analysis upon ER admission were eligible for inclusion. FIB was correlated with Hb, BE and ISS, alone and in combination, using regression analysis. Results: A total of 675 patients were enrolled (median ISS 27). FIB upon admission correlated strongly with Hb, BE and ISS. Multiple regression analysis showed that Hb and BE together predicted FIB (adjusted R² = 0.46; log_e(FIB) = 3.567 + 0.223.Hb - 0.007.Hb² + 0.044.BE), and predictive strength increased when ISS was included (adjusted R² = 0.51; log_e(FIB) = 4.188 + 0.243.Hb - 0.008.Hb² + 0.036.BE - 0.031.ISS + 0.0003.ISS²). Of all major trauma patients admitted with Hb <12 g/dL, 74% had low (<200 mg/dL) FIB and 54% had critical (<150 mg/dL) FIB. Of patients admitted with Hb <10 g/dL, 89% had low FIB and 73% had critical FIB. These values increased to 93% and 89%, respectively, among patients with an admission Hb <8 g/dL. Sixty-six percent of patients with only a weakly negative BE (<−2 mmol/L) showed low FIB. Of patients with BE <−6 mmol/L upon admission, 81% had low FIB and 63% had critical FIB. The corresponding values for BE <−10 mmol/L were 89% and 78%, respectively. Conclusions: Upon ER admission, FIB of major trauma patients shows strong correlation with rapidly obtainable, routine laboratory parameters such as Hb and BE. These two parameters might provide an insightful and rapid tool to identify major trauma patients at risk of acquired hypofibrinogenemia. Early calculation of ISS could further increase the ability to predict FIB in these patients. We propose that FIB can be estimated during the initial phase of trauma care based on bedside tests.