Jakob Stensballe

A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients.

Objective: To investigate the association between markers of acute endothelial glycocalyx degradation, inflammation, coagulopathy, and mortality after trauma. Background: Hyperinflammation and acute coagulopathy of trauma predict increased mortality. High catecholamine levels can directly damage the endothelium and may be associated with enhanced endothelial glycocalyx degradation, evidenced by high circulating syndecan-1. Methods: Prospective cohort study of trauma patients admitted to a Level 1 Trauma Centre in 2003 to 2005. Seventy-five patients were selected blindly post hoc from 3 predefined injury severity score (ISS) groups (<16, 16–27, >27). In all patients, we measured 17 markers of glycocalyx degradation, inflammation, tissue and endothelial damage, natural anticoagulation, and fibrinolysis (syndecan-1, IL-6, IL-10, histone-complexed DNA fragments, high-mobility group box 1 (HMGB1), thrombomodulin, von Willebrand factor, intercellular adhesion molecule-1, E-selectin, protein C, tissue factor pathway inhibitor (TFPI), antithrombin, D-dimer, tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), soluble uPA receptor, and plasminogen activator inhibitor-1), hematology, coagulation, catecholamines, and assessed 30-day mortality. Variables were compared in patients stratified according to syndecan-1 median. Results: Patients with high circulating syndecan-1 had higher catecholamines, IL-6, IL-10, histone-complexed DNA fragments, HMGB1, thrombomodulin, D-dimer, tPA, uPA (all P < 0.05), and 3-fold increased mortality (42% vs. 14%, P = 0.006) despite comparable ISS (P = 0.351). Only in patients with high glycocalyx degradation was higher ISS correlated with higher adrenaline, IL-6, histone-complexed DNA fragments, HMGB1, thrombomodulin, and APTT, lower protein C (all P < 0.05), unchanged TFPI and blunted D-dimer response (P < 0.001) because D-dimer was profoundly increased even at low ISS. After adjusting for age and ISS, syndecan-1 was an independent predictor of mortality (OR: 1.01 [95%CI, 1.00–1.02]; P = 0.043). Conclusions: In trauma patients, high circulating syndecan-1, a marker of endothelial glycocalyx degradation, is associated with inflammation, coagulopathy and increased mortality.

Effect of Haemostatic Control Resuscitation on mortality in massively bleeding patients: a before and after study

Background and Objectives  Evidence supporting the use of platelets and plasma in resuscitation of massive bleedings is questionable. Current consensus guidelines recommend restrictive use. Our aim was to determine the effect of changing the transfusion practice on 30‐day survival in massively bleeding patients.

Proactive administration of platelets and plasma for patients with a ruptured abdominal aortic aneurysm: evaluating a change in transfusion practice

BACKGROUND: Continued hemorrhage remains a major contributor of mortality in massively transfused patients and those who survive have a higher platelet (PLT) count and a shorter prothrombin time and activated partial thromboplastin time (APTT) than nonsurvivors. It was considered that early substitution with PLTs and fresh‐frozen plasma (FFP) would prevent development of coagulopathy and thus improve survival.

Hemostatic resuscitation for massive bleeding: the paradigm of plasma and platelets—a review of the current literature

BACKGROUND: Continued hemorrhage remains a major contributor of mortality in massively transfused patients and controversy regarding the optimal management exists. Recent studies indicate a possible survival benefit in patients receiving a higher ratio of plasma and platelets (PLTs) to red blood cells (RBCs) than what is recommended in current transfusion guidelines.

How I treat patients with massive hemorrhage.

Massive hemorrhage is associated with coagulopathy and high mortality. The transfusion guidelines up to 2006 recommended that resuscitation of massive hemorrhage should occur in successive steps using crystalloids, colloids, and red blood cells (RBCs) in the early phase and plasma and platelets in the late phase. With the introduction of the cell-based model of hemostasis in the mid-1990s, our understanding of the hemostatic process and of coagulopathy has improved. This has contributed to a change in resuscitation strategy and transfusion therapy of massive hemorrhage along with an acceptance of the adequacy of whole blood hemostatic tests to monitor these patients. Thus, in 2005, a strategy aiming at avoiding coagulopathy by proactive resuscitation with blood products in a balanced ratio of RBC:plasma:platelets was introduced, and this has been reported to be associated with reduced mortality in observational studies. Concurrently, whole blood viscoelastic hemostatic assays have gained acceptance by allowing a rapid and timely identification of coagulopathy along with enabling an individualized, goal-directed transfusion therapy. These strategies joined together seem beneficial for patient outcome, although final evidence on outcome from randomized controlled trials are lacking. We present how we in Copenhagen and Houston, today, manage patients with massive hemorrhage.

High circulating adrenaline levels at admission predict increased mortality after trauma

Background: Trauma-induced acute coagulopathy predicts a poor outcome. Although its pathophysiology is unclear, severe injury and shock (hypoperfusion) are proposed drivers. This study investigated the association between sympathoadrenal activation (circulating catecholamines) and biomarkers of coagulopathy. Methods: Prospective study of 75 adult trauma patients admitted to a Level I trauma center directly from the scene of accident. Patients were selected blinded post hoc from three predefined Injury Severity Score groups (<16, 16–27, and >27) and had available blood samples on arrival. We measured activated partial thromboplastin time, international normalized ratio, hematology, biochemistry, circulating adrenaline and noradrenaline, 11 biomarkers of tissue and endothelial damage, glycocalyx degradation, natural anticoagulation and fibrinolysis (histone-complexed DNA fragments, high-mobility group box 1, syndecan-1, von Willebrand factor, soluble thrombomodulin, protein C, tissue factor pathway inhibitor, antithrombin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer) and registered 30-day mortality. Biomarkers were compared between survivors and nonsurvivors. Results: The adrenaline level was increased in nonsurvivors (p = 0.026), it was independently associated with increased activated partial thromboplastin time (p = 0.034) and syndecan-1 (p = 0.007), a marker of glycocalyx degradation, and it correlated with biomarkers of tissue and endothelial damage (histone-complexed DNA, high-mobility group box 1, soluble thrombomodulin) and hyperfibrinolysis (tissue-type plasminogen activator, D-dimer). Furthermore, nonsurvivors had higher syndecan-1, tissue factor pathway inhibitor, and D-dimer levels (all p < 0.05). Circulating adrenaline was independently associated with 30-day mortality (OR, 5.92 [95% CI, 1.48–23.73]; p = 0.012) together with age (p = 0.001) and severe head injury (Abbreviated Injury Scale head >3; p = 0.011). Conclusions: The trauma-induced catecholamine surge is closely associated with biomarkers of tissue and endothelial damage, glycocalyx degradation, coagulopathy including hyperfibrinolysis and independently predicts mortality.

Low hemorrhage‐related mortality in trauma patients in a Level I trauma center employing transfusion packages and early thromboelastography‐directed hemostatic resuscitation with plasma and platelets

Hemorrhage accounts for most preventable trauma deaths, but still the optimal strategy for hemostatic resuscitation remains debated.

The early IL-6 and IL-10 response in trauma is correlated with injury severity and mortality

Background: Trauma has previously been shown to influence interleukin (IL)‐6 and IL‐10 levels, but the association of injury severity and mortality with IL‐6 and IL‐10 responses in the early phase of accidental trauma remains to be investigated. We wished to describe serum levels of IL‐6 and IL‐10 in the first 24 h after trauma and to assess the relationship with severity of injury and mortality.

Current management of massive hemorrhage in trauma.

Hemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution, and consumption of clotting factors and platelets. Concepts of damage control surgery have evolved prioritizing early control of the cause of bleeding by non-definitive means, while hemostatic control resuscitation seeks early control of coagulopathy.Hemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients. Although early and effective reversal of coagulopathy is documented, the most effective means of preventing coagulopathy of massive transfusion remains debated and randomized controlled studies are lacking.Viscoelastical whole blood assays, like TEG and ROTEM however appear advantageous for identifying coagulopathy in patients with severe hemorrhage as opposed the conventional coagulation assays.In our view, patients with uncontrolled bleeding, regardless of it´s cause, should be treated with hemostatic control resuscitation involving early administration of plasma and platelets and earliest possible goal-directed, based on the results of TEG/ROTEM analysis. The aim of the goal-directed therapy should be to maintain a normal hemostatic competence until surgical hemostasis is achieved, as this appears to be associated with reduced mortality.

Hypocoagulability, as evaluated by thrombelastography, at admission to the ICU is associated with increased 30-day mortality.

Thrombelastography (TEG), a cell-based whole blood assay, may better reflect haemostatic competence than conventional coagulation assays and this was therefore evaluated including the clot forming parameters: R, angle and maximal amplitude in patients at ICU admission. This was a prospective, observational study of patients admitted to a general ICU at a tertiary care university hospital with an expected stay of more than 24 h. Blood samples for TEG and standard coagulation analysis were obtained at admission. The APACHE II and sequential organ failure assessment (SOFA) scores and 30-day mortality were recorded. At ICU admission, 106 patients (42%) showed hypocoagulability as evaluated by TEG and these patients had higher first day SOFA score (P < 0.0001) and higher 30-days (42 vs. 13%, P < 0.0001) mortality than patients presenting with a normal TEG. In 30-day survivors, admission platelet count (P = 0.05), angle (P < 0.001) and maximal amplitude (P = 0.001) were higher and R decreased (P = 0.0013) compared with nonsurvivors. Hypocoagulability at admission as evaluated by TEG was an independent risk factor for 30-day mortality [adjusted odds ratio (OR) 3.5; 95% confidence interval (CI) 1.7–7.1]. Hypocoagulability as evaluated by TEG was frequent at admission in general ICU patients and associated with a higher rate of ventilator treatment, higher rate of renal replacement therapy and a higher use of blood products. Hypocoagulability is an independent risk factor for 30-day mortality.