Effects of whole blood leukoreduction on platelet function and hemostatic parameters.

AIMS/OBJECTIVES: The aim of this study was to evaluate the hemostatic consequences of whole blood leukoreduction (LR). BACKGROUND: Whole blood is being used for trauma resuscitation in the military, and an increasing number of civilian trauma centres across the nation. The benefits of LR, such as decreased infectious and transfusion-related complications, are well established, but the effects on hemostatic parameters remain a concern. METHODS: Twenty-four units of whole blood were assigned to one of the four groups: non-leukoreduced (NLR), leukoreduced at 1 h and a height of 33 in. (LR-1), leukoreduced at 4 h and a height of 33 in. (LR-4(33)), or leukoreduced at 4 h and a height of 28 in. (LR-4(28)). Viscoelastic parameters, platelet aggregation, cell counts, physiological parameters and thrombin potential were evaluated immediately before and after LR, and on days 1, 7, 14 and 21 following LR. RESULTS: The viscoelastic parameters and thrombin generation potential were unchanged between the groups. Platelet aggregation was reduced in the LR-1 group compared with NLR after 7 days. The LR-4(28) group also showed a trend of reduced platelet aggregation compared with NLR. Aggregation in LR-4(33) was similar to NLR throughout the storage time. Physiological and electrolyte changes over the whole blood storage period were not affected by LR. CONCLUSION: Our study shows that whole blood can be LR at 4 h after collection and a height of 33 in. while maintaining platelet count and without altering platelet function and hemostatic performance.

The Dead Sea needs salt water massively bleeding patients need whole blood: The evolution of blood product resuscitation.

Whole blood, that is blood that is not manufactured into its component red blood cells (RBC) plasma, and platelets (PLT) units, was the mainstay of transfusion for many years until it was discovered that the component parts of a blood donation could be stored under different conditions thereby optimizing the storage length of each product. The use of low anti-A and -B titer group O whole blood (LTOWB) has recently been rediscovered for use in massively bleeding trauma patients. Whole blood has several advantages over conventional component therapy for these patients, including simplifying the logistics of the resuscitation, being more concentrated than whole blood that is reconstituted from conventional components, and providing cold-stored PLTs, amongst other benefits. While randomized controlled trials to determine the efficacy of using LTOWB in the resuscitation of massively bleeding trauma patients are currently underway, retrospective data has shown that massively bleeding recipients of LTOWB with traumatic injury do not have worse outcomes compared to patients who received conventional components and, in some cases, recipients of LTOWB have more favourable outcomes. This paper will describe some of the advantages of using LTOWB and will discuss the emerging evidence for its use in massively bleeding patients.

Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

Factors influencing plasma transfusion practices in paediatric intensive care units around the world.

BACKGROUND AND OBJECTIVES: Plasma transfusions are a frequent treatment worldwide, but many studies have reported a wide variation in the indications to transfuse. Recently, an international paediatric study also showed wide variation in frequency in the use of plasma transfusions: 25% of the centres transfused plasma to >5% of their patients, whereas another 25% transfused plasma to <1% of their patients. The objective of this study was to explore the factors associated with different plasma transfusion practices in these centres. MATERIALS AND METHODS: Online survey sent to the local investigators of the 101 participating centres, in February 2016. Four areas were explored: beliefs regarding plasma transfusion, patients' case-mix in each unit, unit's characteristics, and local blood product transfusion policies and processes. RESULTS: The response rate was 82% (83/101). 43% of the respondents believed that plasma transfusions can arrest bleeding, whereas 27% believe that plasma transfusion can prevent bleeding. Centres with the highest plasma transfusion rate were more likely to think that hypovolaemia and mildly abnormal coagulation tests are appropriate indications for plasma transfusions (P = 0·02 and P = 0·04, respectively). Case-mix, centre characteristics or local transfusion services were not identified as significant relevant factors. CONCLUSION: Factors influencing plasma transfusion practices reflect beliefs about indications and the efficacy of transfusion in the prevention and management of bleeding as well as effects on coagulation tests. Educational and other initiatives to target these beliefs should be the focus of research.

A survey of US and Canadian hospitals' paediatric massive transfusion protocol policies.

BACKGROUND: Trauma is the leading cause of death in children >1 year of age, with haemorrhage as the most common cause of medically preventable deaths. While massive transfusion protocols (MTPs) have been investigated and used in adults to reduce death from haemorrhage, there are a paucity of published data on MTP practices and outcomes in children. This study aimed to survey current MTP policies and the frequency of activation at paediatric care centres. STUDY DESIGN AND METHODS: We conducted a survey of MTPs at hospitals in the United States and Canada, including children's general hospitals, children's specialty hospitals and children's units in general hospitals. We collected information on how the MTP is activated, what therapeutics are given, frequency of its use, and how it is audited for compliance. RESULTS: Forty-six survey responses were analysed. Physician discretion was the most common activation criteria (89%). A majority of sites (78%) targeted a 'high' (≥1 : 2) ratio of plasma to red blood cells (RBC). Fifteen percent of sites use antifibrinolytics in their MTPs. Eighty nine percent of sites have type-O RBC units and 48% of sites had thawed plasma units stored in an immediately available location. CONCLUSION: There is a wide variation in MTPs among paediatric hospitals with regard to both activation criteria and products administered. This underscores the need for future prospective studies to determine the most effective resuscitation methods for paediatric populations to improve outcomes and therapeutic safety for massive bleeding.

Spray-dried plasma and fresh frozen plasma modulate permeability and inflammation in vitro in vascular endothelial cells.

BACKGROUND: After major traumatic injury, patients often require multiple transfusions of fresh frozen plasma (FFP) to correct coagulopathy and to reduce bleeding. A spray-dried plasma (SDP) product has several logistical benefits over FFP use in trauma patients with coagulopathy. These benefits include ease of transport, stability at room temperature, and rapid reconstitution for infusion. Our past work suggests that FFP promotes endothelial stability by inhibiting endothelial permeability. STUDY DESIGN AND METHODS: The main goal of this project is to determine if solvent-detergent-treated SDP is equivalent to FFP in inhibiting vascular endothelial cell (EC) permeability and inflammation in vitro. Furthermore, this study aimed to determine if solvent-detergent treatment and spray drying of plasma alters the protective effects of FFP on EC function. The five groups tested in our studies are the following: 1) fresh frozen-thawed plasma (FFP); 2) solvent-detergent-treated FFP; 3) solvent-detergent-treated SDP; 4) lactated Ringer's solution; and 5) Hextend. RESULTS: This study demonstrates that in vitro SDP and FFP equivalently inhibit vascular EC permeability, EC adherens junction breakdown, and endothelial white blood cell binding, an effect that is independent of changes in Vascular Cell Adhesion Molecule 1, Intracellular Adhesion Molecule 1, or E-selectin expression on ECs. Solvent-detergent treatment of FFP does not alter the protective effects of FFP on endothelial cell function in vitro. CONCLUSION: These data suggest the equivalence of FFP and SDP on modulation of endothelial function and inflammation in vitro.

[Epidemiology, risk stratification and outcome of severe pediatric trauma]. / Epidemiologie, Risikostratifizierung und Behandlungsergebnisse nach schwerem kindlichen Trauma.

Accidents and trauma are the leading cause of hospital admissions and major contributors to mortality in children and adolescents. There are age-specific injury patterns and differences in the clinical presentation of pediatric trauma and treatment both at the scene and in the emergency department can be observed. In general, pediatric trauma-scores to appreciate injury severity are adapted from the adult population.The most important factor to increase mortality in the severely injured pediatric population is the extent of a concomitant traumatic brain injury (TBI). In addition, the acute trauma-associated coagulopathy, which is triggered multifactorial, is an independent prognostic marker for mortality in severe trauma. The complexity of all currently available trauma-scores for the pediatric population is one reason why these scores are not unequivocal recommended for the early use in pediatric trauma care. The pediatric BIG-Score was developed to allow an early prognostic stratification for pediatric trauma patients and includes with base excess (BE), INR (International Normalized Ratio) and GCS (Glasgow Coma Scale) relevant prognostic factors for poor outcome. Early risk stratification is crucial in pediatric trauma due to mortality rates ranging between 9% and 15% and with 50% of all fatalities to occur within the first 24 h of hospital admission.

IGF-I/IGFBP system: metabolism outline and physical exercise.

The GH/IGF-I system plays a well-known hormonal role and its effects, mainly anabolic and insulin-sensitizing, are mediated through endocrine as well as paracrine/ autocrine mechanisms. This system includes the binding proteins, namely GH binding proteins and IGF-I binding proteins (IGFBP). As expected, this axis plays a key role in organism modification in consequence of a physical exercise. Physical activity, training, and exercise capacity chiefly involve anabolism process modifications of various tissues, in particular muscular adjustments. Numerous investigators found a correlation among the level of exercise tolerance, muscle strength or walking speed and IGF-I/IGFBP-3 concentrations. However, also inverse and absent correlations between circulating IGF-I concentrations and acute or chronic exercise responses have been reported. IGF-I is generally accepted as an important GH mediator with metabolic effects, through both endocrine and paracrine or autocrine mechanisms. GH is the main regulator of the hepatic synthesis of IGF-I and IGFBP-3, which is the most abundant IGF carrier in human plasma. Recently, it has been shown that the physical exercise stimulatory impact on skeletal muscles is mediated through an increased local IGF-I synthesis with an IGFPB involvement. An absent association of exercise performance and circulating IGF-I may indicate that exercise will exert muscle strength by predominately locally derived paracrine or autocrine mediators rather than endocrine circulating IGF-I. The present review considers the general aspects of the IGF/IGFPB system and the role of the IGF/IGFPB system in relation to physical exercise (type, duration, etc.) taking into account the training aspects.

The effect of FFP:RBC ratio on morbidity and mortality in trauma patients based on transfusion prediction score.

BACKGROUND AND OBJECTIVES: The empiric use of a high plasma to packed red-blood-cell [fresh frozen plasma:red-blood-cells (FFP:RBC)] ratio in trauma resuscitation for patients with massive bleeding has become well accepted without clear or objective indications. Increased plasma transfusion is associated with worse outcome in some patient populations. While previous studies analyse only patients who received a massive transfusion, this study analyses those that are at risk to receive a massive transfusion, based on the trauma-associated severe haemorrhage (TASH) score, to objectively determine which patients after severe trauma would benefit or have increased complications by the use of a high FFP:RBC ratio. METHODS: Multicentre retrospective study from the Trauma Registry of the German Trauma Society. Multivariate logistic regression and statistical risk adjustments utilized in analyses. RESULTS: A high ratio of FFP:RBC in the ≥15 TASH group was independently associated with survival, with an odds ratio of 2·5 (1·6-4·0), while the <15 TASH group was associated with increased multi-organ failure, 47% vs. 38%, (P<0·005). CONCLUSIONS: A predictive model of massive transfusion upon admission might be able to rapidly identify which severe trauma patients would benefit or have increased complications from the immediate application of a high ratio of FFP:RBCs. This study helps to identify the appropriate population for a prospective, interventional trial.

Glycaemic fall after a glucose load. A population-based study.

BACKGROUND AND AIMS: A blood glucose (BG) fall after an oral glucose load has never been described previously at a population level. This study was aimed at looking for a plasma glucose trend after an oral glucose load for possible blood glucose fall if any, and for its impact on coronary mortality at a population level. METHODS AND RESULTS: In subjects from an unselected general population, BG and insulin were detected before and 1 and 2h after a 75-g oral glucose load for insulin sensitivity and ß-cell function determination. Blood pressure, blood examinations and left ventricular mass were measured, and mortality was monitored for 18.8±7.7 years. According to discriminant analysis, the population was stratified into cluster 0 (1-h BG < fasting BG; n=497) and cluster 1 (1-h BG ≥ fasting BG; n=1733). To avoid any interference of age and sex, statistical analysis was limited to two age-gender-matched cohorts of 490 subjects from each cluster (n=940). Subjects in cluster 0 showed significantly higher insulin sensitivity and ß-cell function, lower visceral adiposity and lower blood pressure values. Adjusted coronary mortality was 8 times lower in cluster 0 than 1 (p<0.001). The relative risk of belonging to cluster 1 was 5.40 (95% CI 2.22-13.1). CONCLUSION: It seems that two clusters exist in the general population with respect to their response to an oral glucose load, independent of age and gender. Subjects who respond with a BG decrease could represent a privileged sub-population, where insulin sensitivity and ß-cell function are better, some risk factors are less prevalent, and coronary mortality is lower.

[The mediterranean diet model in inflammatory rheumatic diseases]. / Il modello nutrizionale mediterraneo nelle malattie reumatiche infiammatorie.

The Mediterranean diet is based on a pattern of eating closely tied to the Mediterranean region, which includes Greece and southern Italy. Essentially, the traditional diet emphasizes foods from plant sources, limited meat consumption, small amounts of wine and olive oil as the main fat source. The beneficial effects of the Mediterranean diet has been proven not only to cardiovascular diseases but also for diabetes, obesity, arthritis and cancer. Its anti-inflammatory and protective properties are linked to the large presence of omega-3 polyunsaturated fatty acids, vitamins, but especially to the constituents of extra virgin olive oil: oleic acid, phenolic compounds olecanthal, a new recently discovered molecule, with natural anti-inflammatory properties. It has been shown that the Mediterranean diet can reduce disease activity, pain and stiffness in patients with inflammatory arthritis and may thus constitute a valuable support for patients suffering from these diseases.

Urine cortisol and cortisone and water intake in athletes.

AIM: The aim of this study was to investigate the urine cortisol (F) and cortisone (E) relation, having a well-defined water intake. METHODS: Urine specimens were collected from 10 male trained cyclists (19+/-1 year, 70+/-4 kg, 179+/-4 cm), at rest just before the test (pre-exe) and until 45 min after the cycle ergometer exercise test (45 min at 50-60% VO2max) (post-exe) in the morning. This investigation measured the diuresis in the pre-exe and post-exe after each athlete had drunk 1 L of water from waking-up, after bladder emptying, to the start of the test (pre-exe) and 1 L during the 45 min after the exercise (post-exe). RESULTS: Urinary F and E concentrations demonstrated a significant decrease comparing pre-exe with post-exe (177+/-134 vs 64+/-21 and 706+/-475 vs 372+/-178 nmol.L(-1) respectively, p < 0.05). This significant decrease was verified when diuresis and urinary creatinine were taken into account and the ratio measured. CONCLUSION: One litre of water intake after exercise seemed to have no effect on urine F and E excretion. Moreover the urine F/E ratio was not statistically different comparing pre-exe with post-exe.

[Fish oil supplementation in rheumatoid arthritis]. / La supplementazione dietetica con olio di pesce nell'artrite reumatoide.

The beneficial properties of fish oil are well known and are related to its fatty acid composition rich in omega-3 polyunsaturated fatty acids. In the last years a variety of epidemiological and clinical studies have demonstrated the efficacy of fish oil supplementation in the rheumatic diseases, in particular in rheumatoid arthritis. The anti-inflammatory effects of fish oil are linked to the production of alternative eicosanoids, to the reduction of proinflammatory cytokines, to the inhibition of the activation of T lymphocytes and of catabolic enzymes. Fish oil supplementation could represent a valuable support to the traditional pharmacological treatment of rheumatoid arthritis.

[Role of omega-3 polyunsaturated fatty acids in diet of patients with rheumatic diseases]. / Ruolo degli acidi grassi omega-3 nella dieta dei pazienti affetti da patologie reumatiche infiammatorie.

The beneficial effects of omega-3 polyunsaturated fatty acids have been widely described in the literature in particular those on cardiovascular system. In the last decade there has been an increased interest in the role of these nutrients in the reduction of articular inflammation as well as in the improvement of clinical symptoms in subjects affected by rheumatic diseases, in particular rheumatoid arthritis (RA). Nutritional supplementation with omega-3 may represent an additional therapy to the traditional pharmacological treatment due to the anti-inflammatory properties which characterize this class of lipids: production of alternative eicosanoids, reduction of inflammatory cytokines, reduction of T-lymphocytes activation, reduction of catabolic enzymes activity. The encouraging results of dietetic therapy based on omega-3 in RA are leading researchers to test their effectiveness on patients with other rheumatic conditions such as systemic lupus erythematosus and ankylosing spondylitis. Nutritional therapy based on food rich in omega-3 or on supplementation with fish oil capsules, proved to be a valid support to he treatment of chronic inflammatory rheumatic diseases.

Measurement of free IGF-I saliva levels: perspectives in the detection of GH/IGF axis in athletes.

OBJECTIVES: To examine an immunoassay for measuring free IGF-I in a saliva specimen (free sIGF-I) and to study the levels in relation to the training conditions comparing young athletes and sedentary females. DESIGN AND METHODS: The analysis was carried out by modifying a commercial kit for plasma matrix to measure the free sIGF-I. The plasma free and total IGF-I fractions, hGH and salivary total proteins were also measured. Saliva and blood specimens were collected from 15 well-trained young female volleyball athletes and from a control group of 14 young sedentary females. RESULTS: The calibration curve to assay free sIGF-I covered the range 0.05-5.00 microg/L. The detection limit was 0.07 microg/L. The within-run and between-run imprecision CVs were 10% and 13% respectively. The average recovery was 88%. Free sIGF-I, measured in 15 athletes and in 14 young sedentary females, was 0.10+/-0.03 and 0.20+/-0.05 micarog/L respectively (p<0.001). CONCLUSIONS: There were decreased levels of free sIGF-I in well-trained athletes, compared with sedentary females. This decrease could be related to a greater tissue requirement by the active muscle subjected to intense exercise for several days.

Effect of licorice on the reduction of body fat mass in healthy subjects.

The history of licorice, as a medicinal plant, is very old and has been used in many societies throughout the millennia. The active principle, glycyrrhetinic acid, is responsible for sodium retention and hypertension, which is the most common side-effect. We show an effect of licorice in reducing body fat mass. We studied 15 normal-weight subjects (7 males, age 22-26 yr, and 8 females, age 21-26 yr), who consumed for 2 months 3.5 g a day of a commercial preparation of licorice. Body fat mass (BFM, expressed as percentage of total body weight, by skinfold thickness and by bioelectrical impedance analysis, BIA) and extracellular water (ECW, percentage of total body water, by BIA) were measured. Body mass index (BMI) did not change. ECW increased (males: 41.8+/-2.0 before vs 47.0+/-2.3 after, p<0.001; females: 48.2+/-1.4 before vs 49.4+/-2.1 after, p<0.05). BFM was reduced by licorice: (male: before 12.0+/-2.1 vs after 10.8+/-2.9%, p<0.02; female: before 24.9+/-5.1 vs after 22.1+/-5.4, p<0.02); plasma renin activity (PRA) and aldosterone were suppressed. Licorice was able to reduce body fat mass and to suppress aldosterone, without any change in BMI. Since the subjects were consuming the same amount of calories during the study, we suggest that licorice can reduce fat by inhibiting 11beta-hydroxysteroid dehydrogenase Type 1 at the level of fat cells.

GH/IGF system, cirrhosis and liver transplantation.

The GH-related effects are primarily mediated by insulin-like growth factor I (IGF-I), a peptide hormone almost completely produced by the liver. Liver cirrhosis is usually accompanied by a fall in protein turnover. Furthermore, an important consequence of chronic liver disease (CLD) is growth hormone/insulin-like growth factor (GH/IGF) axis modification and growth failure. Nutritional status also suffers in this condition, and IGF-I has been proposed as a marker of hepatocellular dysfunction, malnutrition and survival. CLD is characterised by alterations of various clinical biochemistry laboratory parameters. Aminotransferases, bilirubin, plasma proteins, together with prothrombin time and gamma globulins, are usually examined for laboratory diagnostic and/or monitoring purposes. These traditional parameters are also used in the perioperative liver transplantation, but an early signal of graft functioning has still not been established. The aim of the present work is a review of the possibility offered by the clinical biochemistry laboratory GH/IGF investigation in the outcome of liver transplantation.

Plasma atrial natriuretic peptide (ANP) fragments proANP (1-30) and proANP (31-67) measurements in chronic heart failure: a useful index for heart transplantation?

The family of the atrial natriuretic peptides, proANP fragments and the active alphaANP, is strongly related to heart disease. The aim was to study in CHF subjects the relation of mdANP and NtANP with brain natriuretic peptide (BNP) and with other traditional medical parameters. Sixteen CHF patients (aged 51.9+/-13.7 years) and 16 healthy subjects age matched (50.8+/-5.9 years) were selected. Both NtANP and mdANP were higher in CHF patients than in healthy subjects (1436+/-288 vs. 288+/-22 pmol/l p<0.001 and 2305+/-383 vs. 423+/-65 pmol/l p<0.0001, respectively). BNP in CHF patients was 28.0+/-9 pmol/l (reference values 1.7+/-1.8 pmol/l). Both NtANP and mdANP demonstrated positive correlation with BNP, p<0.0001 and with left atrial end-systolic volume, p<0.05. BNP correlated with left ventricular mass, p<0.03. In conclusion, plasma NtANP and mdANP analyses are useful laboratory markers in CHF patient investigation and follow up. In particular, they could be employed as non-invasive parameters to follow up worsening of systolic dysfunction until heart transplantation is required.