Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis.

INTRODUCTION: Female sex may provide a survival benefit after trauma, possibly attributable to protective effects of estrogen. This study aims to compare markers of coagulation between male and female trauma patients across different ages. METHODS: Secondary analysis of a prospective cohort study at six trauma centers. Trauma patients presenting with full trauma team activation were eligible for inclusion. Patients with a penetrating trauma or traumatic brain injury were excluded. Upon hospital arrival, blood was drawn for measurement of endothelial and coagulation markers and for rotational thromboelastometry (ROTEM) measurement.Trauma patients were divided into four categories: males <45 years, males ≥45 years, females <45 years and females ≥45 years. In a sensitivity analysis, patients between 45 - 55 years were excluded to control for menopausal transitioning. Groups were compared with a Kruskall-Wallis test with Bonferroni correction. A logistic regression was performed to assess whether the independent effect of sex and age on mortality. RESULTS: 1345 patients were available for analysis. Compared to the other groups, mortality was highest in females ≥45, albeit not independent from injury severity and shock. In the group of females ≥45 there was increased fibrinolysis, demonstrated by increased levels of plasmin-antiplasmin complexes with a concomitant decrease in α2-antiplasmin. Also, a modest decrease in coagulation factors II and X was observed. Fibrinogen levels were comparable between groups. The sensitivity analysis in 1104 patients demonstrated an independent relationship between female sex and age ≥ 55 years and mortality. ROTEM profiles did not reflect the changes in coagulation tests. CONCLUSION: Female trauma patients past their reproductive age have an increased risk of mortality compared to younger females and males, associated with augmented fibrinolysis and clotting factor consumption. ROTEM parameters did not reflect coagulation differences between groups. LEVEL OF EVIDENCE: Level III prognostic and epidemiological data.

An explorative metabolomic analysis of the endothelium in pulmonary hypertension.

Pulmonary hypertension (PH) is classified into five clinical diagnostic groups, including group 1 [idiopathic pulmonary arterial hypertension (IPAH) and connective tissue disease-associated PAH (CTD-aPAH)] and group 4 (chronic thromboembolic pulmonary hypertension (CTEPH)). PH is a progressive, life-threatening, incurable disease. The pathological mechanisms underlying PH remain elusive; recent evidence has revealed that abnormal metabolic activities in the endothelium may play a crucial role. This research introduces a novel approach for studying PH endothelial function, building on the genome-scale metabolic reconstruction of the endothelial cell (EC) to investigate intracellular metabolism. We demonstrate that the intracellular metabolic activities of ECs in PH patients cluster into four phenotypes independent of the PH diagnosis. Notably, the disease severity differs significantly between the metabolic phenotypes, suggesting their clinical relevance. The significant metabolic differences between the PH phenotypes indicate that they may require different therapeutic interventions. In addition, diagnostic capabilities enabling their identification is warranted to investigate whether this opens a novel avenue of precision medicine.

Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial.

PURPOSE: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34). CONCLUSION: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

Low dose Iloprost effect on platelet aggregation in comatose out-of-hospital cardiac arrest patients: A predefined sub-study of the ENDO-RCA randomized -phase 2- trial.

PURPOSE: This is a predefined sub-study of the Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA) trial. We aim to investigate Iloprost, a prostacyclin analogue, safety by evaluating change in whole blood platelet aggregometry (Multiplate) in out of hospital cardiac arrest (OHCA) patients from baseline to 96-h post randomization. METHODS: A randomized, placebo controlled double-blinded trial in 46 OHCA patients. Patients were allocated 1:2 to 48 h Iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Platelet aggregation was determined by platelet aggregation tests ASPI-test (arachidonic acid); TRAP-test (thrombin-receptor activating peptide (TRAP)-6; RISTO test (Ristocetin); ADP test (adenosin diphosphat). RESULTS: There was no significant difference between the iloprost and placebo groups according to ASPI, TRAP, RISTO and ADP platelet aggregation assays. Further, no significant differences regarding risk of bleeding were found between groups (Risk of bleeding: ASPI <40 U; TRAP <92 U; RISTO <35 U; ADP <50 U). CONCLUSIONS: In conclusion, the iloprost infusion did not influence platelet aggregation as evaluated by the ASPI, TRAP, RISTO and ADP assays. There was no increased risk of bleeding or transfusion therapy. A decline in platelet aggregation was observed for the ASPI and ADP assays during the initial 96 h after OHCA. TRIAL REGISTRATION: Trial registration at clinicaltrials.gov (identifier NCT02685618) on 18-02-2016.

Platelet increment is not associated with endothelial damage in haematological patients: a prospective observational study.

The aim of this study was to investigate if thrombocytopenic haematology patients show signs of endothelial damage when transfused with platelets and if that damage correlates with platelet increment measured with corrected count increment (CCI). Endothelial damage secondary to radiation or chemotherapy may lead to consumption of transfused platelets but research in this field is scarce. Patients were divided into four groups: Group 1: Acute leukaemia; Group 2: Autologous stem cell transplantation (SCT); Group 3: Allogenic SCT; and Group 4: patients receiving platelets prior to interventions. Blood was sampled before (baseline) and immediately after (0 h) transfusion and then at 1, 4, 8, 16 and 24 h after transfusion. The biomarkers syndecan-1, soluble thrombomodulin (sTM) and vascular endothelial growth factor (VEGF) were analysed. The plasma concentration differences between baseline and later sampling times were referred to as delta (Δ). Fifty-four platelet transfusion events were studied. All biomarkers were within the normal ranges both before and after the transfusions. The Δsyndecan-1 increased at 0 h (p = .02), but there was no significant correlation between Δsyndecan-1 and CCI. There was no change in any of the other biomarkers after transfusion compared to before. There were no differences between the groups and no correlations were found between CCI and C-reactive protein, Δsyndecan-1, ΔsTM or ΔVEGF. There were no signs of endothelial damage before or after platelet transfusions. A transient significant change in syndecan-1 immediately after platelet transfusion did not influence platelet count or platelet CCI.

Hyaluronic Acid Is a Biomarker for Allograft Dysfunction and Predicts 1-Year Graft Loss After Liver Transplantation.

BACKGROUND: Allograft dysfunction after liver transplantation has a profound impact on the risks of death and retransplantation within the first year. We tested whether elevated hyaluronic acid (HA; a glycosaminoglycan cleared by hepatic sinusoidal endothelium) levels may predict excess risk of graft loss. METHODS: This was a retrospective single-center prognostic cohort study. Patients with either a plasma sample before transplantation, an early post-transplantation sample nearest day 30 (range 10-89 d, 80% within days 15-60), or both were included. Plasma HA was measured with the use of enzyme-linked immunosorbent assays. The primary end point was 1-year graft loss (all-cause mortality and retransplantation). A secondary end point was biliary stricture. RESULTS: In this study, 169 of 196 patients who received a liver transplant in the study period were included. Pre-transplantation HA (n = 152) did not predict graft loss. Post-transplantation HA (n = 124) was higher among patients with graft loss (median, 177 µg/L [interquartile range (IQR), 89-465] vs 54 µg/L [IQR 37-93]) and was a strong predictor of this outcome (hazard ratio per 50 µg/L, 1.24 [95% confidence interval [CI], 1.14-1.34]). The discriminatory ability of HA was high (area under the receiver operating characteristic curve, 0.86 [95% CI, 0.77-0.94]) and noninferior to other liver function tests. When adjusted for known risk factors of graft loss, HA remained an independent predictor of graft loss. CONCLUSIONS: High post-transplantation plasma HA level was a strong predictor of 1-year all-cause mortality and retransplantation, whereas pre-transplantation levels were not, despite variety in the time span of blood sampling. Prospective studies are warranted to assess the utility of HA in liver transplantation.

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.

Administration of platelets to ruptured abdominal aortic aneurysm patients before open surgery: a prospective, single-blinded, randomised study.

BACKGROUND: In patients undergoing open surgery for a ruptured abdominal aortic aneurysm (rAAA), survivors demonstrate a high platelet count, and proactive administration of platelets (and fresh frozen plasma) appears to influence mortality. OBJECTIVES: This trial investigated the effect of platelets administered before transport to surgery. METHODS: In a prospective study design, patients were randomised to receive platelets (intervention; n = 61) or no platelets (control; n = 61) before transport to vascular surgery from 11 local hospitals. The study was terminated when one of the vascular surgical centres implemented endovascular repair for rAAA patients. RESULTS: Thirty days after surgery, mortality was 36% for patients with intervention vs 31% for controls (P = 0·32). Post-operative thrombotic events (14 vs 15; P = 0·69), renal failure (11 vs 10; P = 0·15) and pulmonary insufficiency (34 vs 39; P = 0·15) were similar in the two groups of patients. No adverse reactions to platelet administration were observed. In addition, length of stay in the intensive care unit was unaffected by intervention. CONCLUSIONS: For patients planned for open repair of a rAAA, we observed no significant effect of early administration of platelets with regard to post-operative complications and stay in the ICU or in hospital and also no significant effect on mortality.

Randomised feasibility study of a more liberal haemoglobin trigger for red blood cell transfusion compared to standard practice in anaemic cancer patients treated with chemotherapy.

OBJECTIVES: The primary objective of this feasibility study was to identify quality of life (QoL) scores and symptom scales as tools for measuring patient-reported outcomes (PRO) associated with haemoglobin level in chemotherapy-treated cancer patients. Secondary objectives included comparing QoL and symptoms between randomisation arms. BACKGROUND: Anaemia in cancer patients undergoing chemotherapy is associated with decreased QoL. One treatment option is red blood cell transfusion (RBCT). However, the optimal haemoglobin trigger for transfusion is unknown. METHODS: Patients were randomised to a haemoglobin trigger for RBCT of either < 9·7 g dL-1 (arm A) or < lower normal level, female: 11·5 g dL-1 , male: 13·1 g dL-1 (arm B). Four PROs were used: Functional Assessment of Cancer Therapy-General (FACT-G) and the FACT-Anaemia (FACT-An), a Numeric Rating Scale on symptoms of anaemia and self-reported Performance Status (PS). The association between haemoglobin and PRO variables was assessed using a linear mixed model with random effects. RESULTS: A total of 133 patients were enrolled, of which 86 patients received RBCT (28 in arm A, 58 in arm B). Baseline questionnaires were filled out in 79·7% of cases. Haemoglobin levels were significantly correlated with FACT-An, FACT-An Total Outcome Index (TOI), Functional Well-Being, fatigue and PS. Improvement on several PRO variables was observed in both arms after RBCT, with clinically minimal important differences observed in FACT-G, Physical Well-Being, FACT-An, FACT-An TOI, fatigue and dyspnoea. CONCLUSIONS: QoL scores of physical and functional domains as well as self-reported anaemia-related symptoms correlated well with haemoglobin level in chemotherapy-treated cancer patients.

Effects of red blood cell storage time on transfused patients in the ICU-protocol for a systematic review.

BACKGROUND: Patients in the intensive care unit (ICU) are often anaemic due to blood loss, impaired red blood cell (RBC) production and increased RBC destruction. In some studies, more than half of the patients were treated with RBC transfusion. During storage, the RBC and the storage medium undergo changes, which lead to impaired transportation and delivery of oxygen and may also promote an inflammatory response. Divergent results on the clinical consequences of storage have been reported in both observational studies and randomised trials. Therefore, we aim to gather and review the present evidence to assess the effects of shorter vs. longer storage time of transfused RBCs for ICU patients. METHODS: We will conduct a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials, and also include results of severe adverse events from large observational studies. Participants will be adult patients admitted to an ICU and treated with shorter vs. longer stored RBC units. We will systematically search the Cochrane Library, MEDLINE, Embase, BIOSIS, CINAHL and Science Citation Index for relevant literature, and we will follow the recommendation by the Cochrane Collaboration and the Preferred Reporting Items for Systemtic Review and Meta-Analysis (PRISMA)-statement. We will assess the risk of bias and random errors, and we will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the overall quality of evidence. CONCLUSION: We need a high-quality systematic review to summarise the clinical consequences of RBC storage time among ICU patients.

The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised, double-blind, placebo-controlled trial.

We wished to evaluate whether inhibition of the systemic inflammatory response by a single pre-operative dose of methylprednisolone reduced markers of early endothelial damage after fast-track total knee arthroplasty. We randomly allocated 70 patients undergoing elective unilateral total knee arthroplasty (1:1) to receive either pre-operative intravenous methylprednisolone 125 mg (methylprednisolone group) or isotonic saline (control group). All procedures were performed under spinal anaesthesia without a tourniquet, using a standardised multimodal analgesic regime. The outcomes included changes in Syndecan-1 concentrations, a marker of glycocalyx degradation, markers of endothelial cell damage and activation (plasma soluble thrombomodulin and sE-Selectin), and permeability by vascular endothelial growth factor, as well as C-reactive protein concentrations. Blood samples were collected at baseline and 2 h, 6 h and 24 h after surgery, with complete sampling from 63 patients for analyses. Methylprednisolone significantly reduced markers of endothelial damage at 24 h following surgery compared with saline (methylprednisolone group vs. control group, adjusted means (SEM)) expressed by circulating Syndecan-1: 11.6 (1.0) ng.ml-1 vs. 13.4 (1.1) ng.ml-1 p = 0.046; soluble thrombomodulin: 5.1 (0.1) ng.ml-1 vs. 5.7 (0.2) ng.ml-1 , p = 0.009; sE-Selectin: 64.8 (1.8) ng.ml-1 vs. 75.7 (1.9) ng.ml-1 , p = 0.001, and vascular endothelial growth factor: 35.3 (2.7) ng.ml-1 vs. 58.5 (2.8) ng.ml-1 , p < 0.001. The effect of the intervention increased with time for soluble thrombomodulin, sE-Selectin and vascular endothelial growth factor, and was more pronounced in patients with high baseline values. Finally, methylprednisolone reduced the C-reactive protein response 24 h postoperatively; 31.1 (1.1) mg.l-1 vs. 68.4 (1.1) mg.l-1 , p < 0.001. Pre-operative administration of methylprednisolone 125 mg reduced circulating markers of endothelial activation and damage, as well as the systemic inflammatory response (C-reactive protein) early after fast-track total knee arthroplasty. These findings may have a positive effect on surgical outcome, but require studies in major surgery.

Red blood cell storage duration and long-term mortality in patients undergoing cardiac intervention: a Danish register study.

OBJECTIVES: To study the effect of red blood cell (RBC) storage duration on long-term mortality in patients undergoing cardiac intervention. BACKGROUND: RBCs undergo numerous structural and functional changes during storage. Observational studies have assessed the association between RBC storage duration and patient outcomes with conflicting results. METHODS: Between January 2006 and December 2014, 82 408 patients underwent coronary angiography. Of these, 1856 patients received one to four RBC units within 30 days after this procedure. Patients were allocated according to length of RBC storage duration: short-term (≤11 days), intermediate (IM)-term (12-23 days) and long-term (≥24 days). The study endpoints were 30-day and long-term all-cause mortality. RESULTS: A total of 4168 RBC units were given to 1856 patients. The mean RBC storage duration was 8.5 ± 2.1, 17.7 ± 3.4 and 29.9 ± 3.4 days in the short-term, IM-term and long-term storage groups, respectively. There was no difference in baseline characteristics between the groups. The long-term storage group received significantly more units (2.4 ± 1.0 units) as compared to the short-term (2.0 ± 1.0 units; P < 0.001) and IM-term storage group (2.2 ± 1.0 units; P < 0.01). In the survival analysis, there was no significant difference in all-cause mortality between the groups (log-rank: 0.509 for 30-days mortality; 0.493 for 5-year mortality). Additional stratified analysis demonstrated no association between RBC storage duration and long-term mortality. CONCLUSION: This study did not find an association between RBC storage duration and 30-days or long-term mortality in patients undergoing cardiac intervention.

Three-year follow-up of implementation of evidence-based transfusion practice in a tertiary hospital.

BACKGROUND AND OBJECTIVES: Traditionally, Denmark has had a high rate of allogeneic red blood cell transfusion caused by a liberal transfusion practice despite the existence of restrictive guidelines. We established a Patient Blood Management programme in a tertiary hospital and report the results of the implementation of evidence-based transfusion practice. MATERIALS AND METHODS: Red blood cell transfusion quality indicators were compared with the evidence-based guideline at hospital and department level. Based on this evaluation, wards were selected for interventions targeting doctors and nurses. The implementation process was monitored by transfusion quality and utilization data over a 3-year period with totally 166 341 admissions in 98 960 mixed, adult medical and surgical patients. RESULTS: At the hospital level, transfusion above the upper guideline limit decreased from 23 to 10% (P < 0·001), and transfusion at or below the restrictive haemoglobin trigger of 7·3 g/dl increased from 7 to 19% (P < 0·001). The percentage of single-unit transfusions increased from 72 to 78% (P < 0·001), and the majority of transfusion rates and volumes decreased significantly. Red cell use decreased with 41% in surgical procedures and 28% in admissions (P < 0·001). CONCLUSION: The intervention was associated with a significant and sustained overall increase in compliance with national guidelines for red blood cell transfusion for non-bleeding patients, and led to significantly fewer patients being exposed to transfusion.

Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy.

BACKGROUND: The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing fibrinogen on the outcome of injured patients with bleeding. METHODS: A prospective multicentre observational study was performed in six level 1 trauma centres. Injured patients who received at least 4 units of red blood cells (RBCs) were analysed and divided into groups receiving a low (less than 1 : 1) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes 'alive and free from massive transfusion' (at least 10 units of RBCs in 24 h) and early 'normalization of coagulopathy' (defined as an international normalized ratio of 1·2 or less). RESULTS: A total of 385 injured patients with ongoing bleeding were included in the study. Strategies that were independently associated with an increased number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies were associated with correction of coagulopathy. CONCLUSION: A high platelet or plasma to RBC ratio, and use of tranexamic acid were associated with a decreased need for massive transfusion and increased survival in injured patients with bleeding. Early normalization of coagulopathy was not seen for any transfusion ratio, or for use of tranexamic acid or fibrinogen products.

Higher vs. lower haemoglobin threshold for transfusion in septic shock: subgroup analyses of the TRISS trial.

BACKGROUND: Using a restrictive transfusion strategy appears to be safe in sepsis, but there may be subgroups of patients who benefit from transfusion at a higher haemoglobin level. We explored if subgroups of patients with septic shock and anaemia had better outcome when transfused at a higher vs. a lower haemoglobin threshold. METHODS: In post-hoc analyses of the full trial population of 998 patients from the Transfusion Requirements in Septic Shock (TRISS) trial, we investigated the intervention effect on 90-day mortality in patients with severe comorbidity (chronic lung disease, haematological malignancy or metastatic cancer), in patients who had undergone surgery (elective or acute) and in patients with septic shock as defined by the new consensus definition: lactate above 2 mmol/l and the need for vasopressors to maintain a mean arterial pressure above 65 mmHg. RESULTS: The baseline characteristics were mostly similar between the two intervention groups in the different subgroups. There were no differences in the intervention effect on 90-day mortality in patients with chronic lung disease (test of interaction P = 0.31), haematological malignancy (P = 0.47), metastatic cancer (P = 0.51), in those who had undergone surgery (P = 0.99) or in patients with septic shock by the new definition (P = 0.20). CONCLUSION: In exploratory analyses of a randomized trial in patients with septic shock and anaemia, we observed no survival benefit in any subgroups of transfusion at a haemoglobin threshold of 90 g/l vs. 70 g/l.

A randomized trial of the effect of low dose epinephrine infusion in addition to tranexamic acid on blood loss during total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is associated with both intraoperative and postoperative blood loss resulting in anaemia and, in some patients, transfusion of red blood cells. Epinephrine enhances coagulation by several mechanisms. We evaluated the effect of intraoperative low dose infusion of epinephrine on intraoperative and early postoperative blood loss. METHODS: After consent, 106 subjects undergoing THA under spinal anaesthesia were randomly assigned to receive an i.v. infusion of either epinephrine 0.05 µg kg(-1) min(-1) or placebo (saline 0.9%) during the entire surgical procedure. Intraoperative tranexamic acid (TXA) was administered to all subjects. The primary outcome was intraoperative blood loss directly measured by drains and weighing swabs. Secondary outcome was total blood loss at 24 h postoperatively calculated using the Gross formula. RESULTS: Of 106 subjects randomized, 6 were excluded, leaving 100 subjects for analyses. Mean duration of surgery was 58 (21) min. Intraoperative blood loss was 343 (95% CI 300-386) ml in the epinephrine group compared with 385 (353-434) ml in the placebo group, P = 0.228. 24 h blood loss was 902 (800-1004) ml in the epinephrine group compared with 1080 (946-1220) ml in the placebo group, P = 0.038. CONCLUSION: In subjects also receiving TXA, intraoperative low dose epinephrine infusion did not reduce intraoperative blood loss in THA but calculated 24 h blood loss was reduced by 180 ml compared with placebo. Further studies on low dose epinephrine in patients at high risk of significant bleeding are warranted. CLINICAL TRIAL REGISTRATION: NCT 01708642.

Haemostatic function and biomarkers of endothelial damage before and after platelet transfusion in patients with acute myeloid leukaemia.

OBJECTIVES: The beneficial effect of platelet transfusion on haemostasis is well established, but there is emerging evidence that platelet transfusion induces an inflammatory response in vascular endothelial cells. BACKGROUND: We investigated haemostatic function and endothelial biomarkers before and after platelet transfusion in patients with acute myeloid leukaemia. MATERIALS AND METHODS: Blood was sampled before, 1 and 24 h after platelet transfusion. Primary and secondary haemostasis was evaluated by whole blood aggregometry (Multiplate) and thromboelastography (TEG). Endothelial biomarkers (sICAM-1, syndecan-1, sThrombomodulin, sVE-Cadherin) and platelet activation biomarkers (sCD40L, TGF-beta) were investigated along with haematology/biochemistry analyses. RESULTS: Twenty-two patients were included. Despite continued low platelet counts, platelet transfusion normalised the median values of most TEG parameters and slightly increased platelet aggregation (all P < 0·05). Endothelial biomarkers were not significantly affected by transfusion. The 1 h sCD40L level correlated positively with Syndecan-1 and soluble thrombomodulin delta values, biomarkers of endothelial damage (both P = 0·005). CONCLUSION: Platelet transfusion improved haemostasis, whereas post-transfusion increases in sCD40L were associated with endothelial damage, indicating that transfused platelets and platelet-derived pro-inflammatory mediators may have opposite effects on the endothelium.

Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non-anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double-blind placebo-controlled clinical trial (the PROTECT trial).

BACKGROUND AND OBJECTIVES: This trial explores whether intravenous iron isomaltoside 1000 (Monofer®) results in a better regeneration of haemoglobin levels and prevents anaemia compared to placebo in preoperative non-anaemic patients undergoing cardiac surgery. STUDY DESIGN AND METHODS: The trial is a prospective, double-blind, comparative, placebo-controlled trial of 60 non-anaemic patients undergoing cardiac surgery. The patients were randomized 1:1 to either 1000 mg intravenous iron isomaltoside 1000 administered perioperatively by infusion or placebo. RESULTS: Mean preoperative haemoglobin in the active treatment group was 14·3 g/dl vs. 14·0 g/dl in the placebo group. At discharge 5 days after surgery, haemoglobin levels were reduced to 10·7 and 10·5 g/dl, respectively. One month after surgery, haemoglobin concentration had increased to an average of 12·6 g/dl vs. 11·8 g/dl (p = 0·012) and significantly more patients were non-anaemic in the intravenous iron isomaltoside 1000-treated group compared to the placebo group (38·5% vs. 8·0%; p = 0·019). There were no differences in side-effects between the groups. CONCLUSION: A single perioperative 1000 mg dose of intravenous iron isomaltoside 1000 significantly increased the haemoglobin level and prevented anaemia 4 weeks after surgery, with a short-term safety profile similar to placebo. Future trials on potential clinical benefits of preoperative treatment with intravenous iron in non-anaemic patients are needed.

Haemostatic function and biomarkers of endothelial damage before and after RBC transfusion in patients with haematologic disease.

BACKGROUND AND OBJECTIVES: Transfusion of red blood cells (RBC) is beneficial for the patient but can also be harmful, as randomized trials have demonstrated increased infection rates, bleeding and mortality. The study aim was to investigate the response of the vascular system (the haemostatic function and the endothelium) to RBC transfusion. MATERIALS AND METHODS: Blood was sampled from patients with various transfusion-dependent haematologic diseases before 1 and 24 h after RBC transfusion. Primary and secondary haemostasis was evaluated by whole-blood impedance aggregometry (Multiplate) and by thromboelastography (TEG). Samples were analysed by ELISA for biomarkers reflecting endothelial activation and damage (sICAM-1, syndecan-1, sThrombomodulin (sTM), sVE-Cadherin), platelet activation (sCD40L) and inflammation (hsCRP). RESULTS: A total of 58 patients were enrolled in the study. Median age was 71 years. Compared to before transfusion, patients had slightly reduced coagulability 1 h after RBC transfusion, assessed by TEG. However, transfusion of older RBC products (>14 days) was associated with increased coagulability (all P < 0·05). The level of syndecan-1 increased slightly 24 h after transfusion (median 12·4 (IQR 9-23) vs. 13·2 (9-25) ng/ml, P < 0·01), indicating increased glycocalyx degradation. CONCLUSION: Overall, RBC transfusion was associated with reduced coagulability and endothelial glycocalyx degradation. Transfusion of older RBCs was however associated with increased coagulability. The changes observed were small to moderate and the clinical relevance of these findings should be investigated in larger studies.