The appropriate strategy for trauma-induced coagulopathy management is under debate. We report the treatment of major trauma using mainly coagulation factor concentrates. This retrospective analysis included trauma patients who received ≥ 5 units of red blood cell concentrate within 24 hours. Coagulation management was guided by thromboelastometry (ROTEM®). Fibrinogen concentrate was given as first-line haemostatic therapy when maximum clot firmness (MCF) measured by FibTEM (fibrin-based test) was 1.5 times normal. Lack of improvement in EXTEM MCF after fibrinogen concentrate administration was an indication for platelet concentrate. The observed mortality was compared with the mortality predicted by the trauma injury severity score (TRISS) and by the revised injury severity classification (RISC) score. Of 131 patients included, 128 received fibrinogen concentrate as first-line therapy, 98 additionally received PCC, while 3 patients with recent coumarin intake received only PCC. Twelve patients received FFP and 29 received platelet concentrate. The observed mortality was 24.4%, lower than the TRISS mortality of 33.7% (P = 0.032) and the RISC mortality of 28.7% (P > 0.05). After excluding 17 patients with traumatic brain injury, the difference in mortality was 14% observed versus 27.8% predicted by TRISS (P = 0.0018) and 24.3% predicted by RISC (P = 0.014). ROTEM®-guided haemostatic therapy, with fibrinogen concentrate as first-line haemostatic therapy and additional PCC, was goal-directed and fast. A favourable survival rate was observed. Prospective, randomized trials to investigate this therapeutic alternative further appear warranted.

https://epub.ub.uni-muenchen.de/23300/1/cc8948.pdf

Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate

Introduction
Thromboelastometry (TEM)-guided haemostatic therapy with fibrinogen concentrate and prothrombin complex concentrate (PCC) in trauma patients may reduce the need for transfusion of red blood cells (RBC) or platelet concentrate, compared with fresh frozen plasma (FFP)-based haemostatic therapy.

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Transfusion in trauma: thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy

Principles and practice of thromboelastography in clinical coagulation management and transfusion practice

Glycosylation is the most abundant and complex protein modification, and can have a profound structural and functional effect on the conjugate. The oligosaccharide fraction is recognized to be involved in multiple biological processes, and to affect proteins physical properties, and has consequentially been labeled a critical quality attribute of biopharmaceuticals. Additionally, due to recent advances in analytical methods and analysis software, glycosylation is targeted in the search for disease biomarkers for early diagnosis and patient stratification. Biofluids such as saliva, serum or plasma are of great use in this regard, as they are easily accessible and can provide relevant glycosylation information. Thus, as the assessment of protein glycosylation is becoming a major element in clinical and biopharmaceutical research, this review aims to convey the current state of knowledge on the N-glycosylation of the major plasma glycoproteins alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein, alpha-2-macroglobulin, antithrombin-III, apolipoprotein B-100, apolipoprotein D, apolipoprotein F, beta-2-glycoprotein 1, ceruloplasmin, fibrinogen, immunoglobulin (Ig) A, IgG, IgM, haptoglobin, hemopexin, histidine-rich glycoprotein, kininogen-1, serotransferrin, vitronectin, and zinc-alpha-2-glycoprotein. In addition, the less abundant immunoglobulins D and E are included because of their major relevance in immunology and biopharmaceutical research. Where available, the glycosylation is described in a site-specific manner. In the discussion, we put the glycosylation of individual proteins into perspective and speculate how the individual proteins may contribute to a total plasma N-glycosylation profile determined at the released glycan level.

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Human plasma protein N-glycosylation

Blood platelets aggregate to form clots that prevent haemorrhage. Knowledge of single-platelet mechanics is scarce, however. Atomic force microscopy experiments now show that platelets contract rapidly on contact with fibrinogen, and adhere strongly to multiple fibrin polymers, enhancing the elasticity of clots. These findings are relevant to disorders of platelet function, such as thrombosis.

/pdf/mechanics-and-contraction-dynamics-of-single-platelets-and-53y83lk844.pdf

Mechanics and contraction dynamics of single platelets and implications for clot stiffening

BACKGROUND:The binding of fibrinogen and fibrin to platelets is important in normal hemostasis. The extent of platelet-fibrin interaction can be measured as the viscoelastic strength of clot by rotational thromboelastometry (ROTEM®). In this study, we investigated the effect of fibrinogen concentrat

The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia.

Thromboelastometry ROTEM (Pentapharm, Munich, Germany) is a viscoelastic method of whole blood clotting assessment with applications in perioperative hemostasis and hematology. The different tests available for the investigation of distinct coagulation aspects are performed with combinations of liquid reagents. The use of liquid reagents for the ROTEM measurement requires several pipetting steps, which complicates their application in clinical routine even though pipetting is performed semiautomatically. New single portion reagents (SPR) containing in one vial all lyophilized reagents necessary for each test have been recently developed. SPR require only addition of blood into the single-use reagent vial in a unique pipetting step in order to mix reagents with the blood sample. Our study compared SPR and standard liquid reagents (Pentapharm) in 21 blood samples from normal subjects and 46 samples from patients in three study centers. Following ROTEM tests were performed: EXTEM (extrinsically activated TEM), INTEM (intrinsically activated TEM), FIBTEM (fibrin-based TEM), APTEM (aprotinin-controlled TEM) and HEPTEM (heparin-insensitive TEM). In the second part of the study, the stability of SPR at 37 degrees C was also assessed on 23 blood samples in one center. Very good correlation was found between SPR and liquid reagents for all clotting parameters (correlation coefficient between 0.85-0.99). The SPR reagents showed excellent stability against thermic stress and the measurements were easier to perform than with the conventional liquid reagents system.

Thomas Lang

Papers

The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia.

Multicentric comparison of single portion reagents and liquid reagents for thromboelastometry.