Prospective assessment of platelet function in patients undergoing elective resection of glioblastoma multiforme.

This prospective study was aimed to test changes in hemostasis in patients with GBM, occurring at baseline (before surgery, time 0, T0) and 2 (T2), 24 (T24), and 48-hour (T48) after surgery. We enrolled consecutive patients subjected to GBM resection (GBR group; N = 60), laparoscopic colon cancer resection (comparative CCR group; N = 40), and healthy blood donors (HBD group; N = 40). We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01-1.06)). This study suggests that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.

What is the context? Glioblastoma has an impact on the platelet number and the functional state of platelets. Platelets can be activated by tumor cells, and platelets count and function may impact patient survival. It has been showed an association between thrombocytosis and a decreased overall survival, with a small reduction in glioma risk associated with the long-term use of low-dose aspirin.Platelet function before and during the perioperative period in patients with glioblastoma has not been systematically investigated. Limited data suggest that platelet function may be impaired before and throughout the perioperative period, and that impaired platelet function affects clinical outcome.What is new? In this prospective study, we systematically investigated how glioblastoma provokes systemic alterations of hemostasis. We enrolled 60 consecutive patients (sample size calculated) subjected to resection of glioblastoma multiforme, and other 40 consecutive patients undergoing laparoscopic resection of colon cancer, as a comparative group, in order to differentiate hemostasis and coagulation profiles of two tumors (glioblastoma and colon adenocarcinoma) with high prothrombotic power. Forty healthy volunteers were also included to establish local reference values.We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. All these analyses were carried out at baseline (T0, time 0, before surgery) and 2 (T2), 24(T24) and 48-hour (T48) after surgery.We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01­1.06)).What is the impact? This study provides further evidence that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.The cut-offs obtained can potentially to provide risk stratification for clinical outcome and to be hypothesis generating research to be confirmed by RCTs.

Whole Blood Platelet Aggregation Assessed by ROTEM Platelet Equipment in Healthy Volunteers from Southern Europe: A Verification Study.

BACKGROUND: This study aimed to verify the reference intervals (RIs) recently established in the Danish population for platelet aggregation induced by a specific agonist of the rotational thromboelastometry (ROTEM) platelet impedance aggregometer. Our local results were also compared with those published by the manufacturer. METHODS: This prospective study included healthy blood donors. Subjects with a history of coagulopathy, those on antiplatelet/anticoagulant therapy, or those taking nonsteroidal anti-inflammatory drugs were excluded. Blood samples were collected for ROTEM® platelet arachidonic acid thromboelastometry (ARATEM), adenosine-di-phosphate thromboelastometry (ADPTEM), and thrombin receptor-activating peptide-6 thromboelastometry (TRAPTEM). The parameters determined were the area under the curve (AUC, ohm·min), maximum amplitude at 6 min (A6, ohm), and maximum slope (MS, ohm/min). Values are expressed as 2.5th-97.5th percentiles. Comparisons are expressed as local vs Danish and manufacturer population RIs. Number (n) and percentage (%) of local tests below (<2.5th percentile) of the Danish and manufacturer population are shown. RESULTS: Forty donors (19 male; mean, 58 [range: 56 to 60] years) were included. There were no differences between our results and those published for the Danish population. In contrast, all ARATEM and ADPTEM values were lower in the local vs manufacturer group. CONCLUSIONS: Our results confirm those published for the Danish population, with respect to the ROTEM platelet aggregometer. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT02652897.

Variations and obstacles in the use of coagulation factor concentrates for major trauma bleeding across Europe: outcomes from a European expert meeting.

PURPOSE: Trauma is a leading cause of mortality, with major bleeding and trauma-induced coagulopathy (TIC) contributing to negative patient outcomes. Treatments for TIC include tranexamic acid (TXA), fresh frozen plasma (FFP), and coagulation factor concentrates (CFCs, e.g. prothrombin complex concentrates [PCCs] and fibrinogen concentrate [FCH]). Guidelines for TIC management vary across Europe and a clear definition of TIC is still lacking. METHODS: An advisory board involving European trauma experts was held on 02 February 2019, to discuss clinical experience in the management of trauma-related bleeding and recommendations from European guidelines, focusing on CFC use (mainly FCH). This review summarises the discussions, including TIC definitions, gaps in the guidelines that affect their implementation, and barriers to use of CFCs, with suggested solutions. RESULTS: A definition of TIC, which incorporates clinical (e.g. severe bleeding) and laboratory parameters (e.g. low fibrinogen) is suggested. TIC should be treated immediately with TXA and FCH/red blood cells; subsequently, if fibrinogen ≤ 1.5 g/L (or equivalent by viscoelastic testing), treatment with FCH, then PCC (if bleeding continues) is suggested. Fibrinogen concentrate, and not FFP, should be administered as first-line therapy for TIC. Several initiatives may improve TIC management, with improved medical education of major importance; generation of new and stronger data, simplified clinical practice guidance, and improved access to viscoelastic testing are also critical factors. CONCLUSIONS: Management of TIC is challenging. A standard definition of TIC, together with initiatives to facilitate effective CFC administration, may contribute to improved patient care and outcomes.

Current perspective on fibrinogen concentrate in critical bleeding.

INTRODUCTION: . Massive hemorrhage continues to be a treatable cause of death. Its management varies from prefixed ratio-driven administration of blood components to goal-directed therapy based on point-of-care testing and administration of coagulation factor concentrates. AREAS COVERED: . We review the current role of fibrinogen concentrate (FC) for the management of massive hemorrhage, either administered without coagulation testing in life-threatening hemorrhage, or within an algorithm based on viscoelastic hemostatic assays and plasma fibrinogen level. We identified relevant guidelines, meta-analyzes, randomized controlled trials, and observational studies that included indications, dosage, and adverse effects of FC, especially thromboembolic events. EXPERT OPINION: . Moderate- to high-grade evidence supports the use of FC for the treatment of severe hemorrhage in trauma and cardiac surgery; a lower grade of evidence is available for its use in postpartum hemorrhage and end-stage liver disease. Pre-emptive FC administration in non-bleeding patients is not recommended. FC should be administered early, in a goal-directed manner, guided by early amplitude of clot firmness parameters (A5- or A10-FIBTEM) or hypofibrinogenemia. Further investigation is required into the early use of FC, as well as its potential advantages over cryoprecipitate, and whether or not its administration at high doses leads to a greater risk of adverse events.

A prospective study on the correlation between thromboelastometry and standard laboratory tests - influence of type of surgery and perioperative sampling times.

This prospective study aimed at investigating the influence of surgery type and perioperative sampling times on the correlations between rotational thromboelastometry (ROTEM) parameters and standard laboratory coagulation tests assessing comparable coagulation phases. Patients undergoing glioblastoma multiforme resection (GBR group, n = 60) or laparoscopic colon cancer resection (CCR group, n = 40) were prospectively included. Blood samples for ROTEM and laboratory assessments were consecutively drawn within 24-hours prior to surgery (baseline), and at 2, 24 and 48-hours after surgery. Correlations between perioperative ExTEM clotting-time (CT-exTEM) and prothrombin time (PT), and between FibTEM maximum clot firmness (MCF-fibTEM) with and plasma fibrinogen (pFB) concentration (Clauss method), were evaluated using the Spearman's rho test. The efficiency of recommended cut-offs of CT-exTEM (>75 s) and MCF-fibTEM (<10 mm) for predicting a prolonged PT (>15 s) or a low pFB (<2 g/L), respectively, was assessed using Receiver-Operator Characteristic curves. Correlations between CT-exTEM and PT were weak in GBR (rho = 0.25 [0.12-0.38], p < .01), and very weak in CCR (rho = 0.06 [-0.12-0.27]). Those between MCF-fibTEM and pFB, were strong in both GBR (rho = 0.69 [0.61-0.76], p < .01) and CCR (rho = 0.70 [0.60-0.78], p < .01). These correlations remained largely unchanged over the studied perioperative period in both groups. Recommended CT-exTEM and MCF-fibTEM cut-offs had poor sensitivity for predicting a prolonged PT (17% [8-31]) or a low pFB (46% [32-62]), without group-related differences. Neither the type of surgery nor the perioperative sampling times had a significant influence on the correlations between ROTEM parameters and standard laboratory tests. ClinicalTrials.gov ID: NCT02652897.

Relationship of thromboelastography and conventional clotting test values with severe bleeding in critically ill patients with coagulopathy: A prospective study.

INTRODUCTION: This study aimed to ascertain the associations of thromboelastography (TEG® ) and standard laboratory test (SLTs) values with the presence of bleeding in critically ill patients with known coagulopathy. METHODS: Three groups of coagulopathic patients with (a) hepatic failure, (b) postoperative period after prolonged cardiac surgery, and (c) complex abdominal surgery with sepsis were prospectively included in this study. On intensive care unit (ICU) admission, patients were stratified into two groups according to whether they had major bleeding (MB) (evident overt bleeding, important bleeding apparent on imaging studies, and/or need for moderate-massive blood transfusion and hemodynamic instability). Blood samples were drawn for the SLTs (international normalized ratio [INR], activated partial thromboplastin time [aPTT], platelet count, and fibrinogen level [Clauss]) and TEG whole blood coagulation assays. Receiver operating characteristic (ROC) curves were generated to determine the efficiency of TEG and SLTs for detecting bleeding. The correlations between SLTs and TEG parameters with similar coagulation profiles were evaluated by Spearman rank-order analysis. RESULTS: Eighty-three patients were included, and bleeding was confirmed in 45 (54%). The fibrinogen level demonstrated the best accuracy for detecting bleeding with an area under the curve and 95% confidence intervals [AUC (95% CI)] of 0.74 (0.63-0.85) with the best cutoff value of ≤ 2 g/L. Regarding TEG-MA, the AUC (CI) obtained with the optimal cutoff value of ≤ 51 mm was 0.68 (0.56-0.80). CONCLUSIONS: Both conventional clotting tests and TEG values were poorly associated with bleeding in this critically ill cohort of patients with coagulopathy.

Reliability of the portable coagulometer qLabs to accurately measure the activated thromboplastin time and international normalized ratio: a prospective study in critically ill patients.

: The current prospective study was aimed at investigating whether a portable coagulometer (qLabs) can be used to reliably monitor activated thromboplastin time (aPTT) and international normalized ratio (INR) in critically ill patients, as compared with standard central laboratory measurement. Both precision and accuracy of INR and aPTT measured by qLabs were assessed in this observational study by finger prick group (N = 30 patients) and blood droplet group from central venous catheter drawn (N = 60). For accuracy, clinical agreement percentage was ±0.3 for INR and ±10 s for aPTT. Precision of INR measurement in qLabs showed excellent intraclass correlation coefficient (ICC > 90%). Precision of aPTT measurement in qLabs was less acceptable for both finger prick [ICC: 0.70; Bland-Altman plot: 2.2 s (-19.8, 24.2)] and blood droplet [ICC: 0.50; Bland-Altman plot: 0.4 s (-70.9, 71.8)] groups. Accuracy of qLabs was acceptable for INR assessment (clinical agreement 90 and 81%, for finger prick and blood droplet groups, respectively), but not for aPTT (clinical agreement 55 and 68%, respectively). Accuracy of finger prick and blood droplet measurements in qLabs was better for INR and aPTT values near-to-normal (1.2 and 37 s, respectively). INR values from qLabs were consistent with the 'gold standard'. qLabs measurement is only reliable for aPTT values near-to-normal.

Uso de hierro intravenoso en pacientes anémicos ingresados en cuidados intensivos / Use of intravenous iron in critically ill patients with anemia

No disponible

Red Blood Cell Transfusion Guided by Near Infrared Spectroscopy in Neurocritically Ill Patients with Moderate or Severe Anemia: A Randomized, Controlled Trial.

In neurocritically ill patients (NCPs), the use of hemoglobin level as the sole indicator for red blood cell transfusion (RBCT) can result in under- or over-transfusion. This randomized controlled trial was conducted to ascertain whether a transcranial oxygen saturation (rSO2) threshold, as measured by near-infrared spectroscopy, reduces RBCT requirements in anemic NCPs (closed traumatic brain injury, subarachnoid, or intracerebral hemorrhage), compared with a hemoglobin threshold alone. Patients with hemoglobin 70-100 g/L received RBCTs to attain an rSO2 > 60% (rSO2 arm) or to maintain hemoglobin between 85 and 100 g/L (hemoglobin arm). A total of 102 NCPs (51 in each group) were included in the intention-to-treat analysis, and 97 were included in the per-protocol analysis (51 and 46, respectively). Compared with those from the hemoglobin arm, patients in rSO2 arm received fewer RBC units (1.0 ± 0.1 vs. 1.5 ± 1.4 units/patient; p < 0.05) and showed lower hemoglobin levels while in protocol. There were no differences between the study arms regarding the percentage of transfused patents (59% vs. 71%; relative risk 0.83 [95% CI 0.62-1.11]), stay on neurocritical care unit (21 vs. 20 days), unfavorable Glasgow Outcome Scale scores on hospital discharge (57% vs. 71%), in-hospital mortality (6% vs. 10%), or 1 year mortality (24% vs. 24%). Among NCPs with hemoglobin concentrations of 70-85 g/L, withholding transfusion until rSO2 is <60% may result in reduced RBCs requirements compared with routinely transfusing to attain a hemoglobin level >85 g/L. Further studies are required to confirm this finding and its possible impact on clinically significant outcomes.

Effects of Red Blood Cell Transfusion on Long-Term Disability of Patients with Traumatic Brain Injury.

BACKGROUND: This 3-year prospective study examined the association between red blood cell transfusion (RBCT) and 1-year neurocognitive and disability levels in 309 patients with traumatic brain injury (TBI) admitted to the neurological intensive care unit (NICU). METHODS: Using a telephone interview-based survey, functional outcomes were assessed by the Glasgow Outcome Scale (GOS), Rancho Los Amigos Levels of Cognitive Functioning Scale (RLCFS), and Disability Rating Scale (DRS) and dichotomized as favorable and unfavorable (dependent variable). The adjusted influence of RBCT on unfavorable results was assessed by conventional logistic regression, controlling for illness severity and propensity score (introduced as a continuous variable and by propensity score-matched patients). RESULTS: Overall, 164 (53 %) patients received ≥1 unit of RBCT during their NICU stay. One year postinjury, transfused patients exhibited significantly higher unfavorable GOS (46.0 vs. 22.0 %), RLCFS (37.4 vs. 15.4 %), and DRS (39.6 vs. 18.7 %) scores than nontransfused patients. Although transfused patients were more severely ill upon admission, their adjusted odds ratios (95 % confidence intervals) for unfavorable GOS, RLCFS, and DRS scores were 2.5 (1.2-5.1), 3.0 (1.4-6.3), and 2.3 (1.1-4.8), respectively. These odds ratios remained largely unmodified when the calculated propensity score was incorporated as an independent continuous variable into the multivariate analysis. Furthermore, in 76 pairs of propensity score-matched patients, the rate of an unfavorable RLCFS score at the 1-year (but not 6-month) follow-up was significantly higher in transfused than nontransfused patients [3.0 (1.1-8.2)]. CONCLUSION: Our results strongly suggest an independent association between RBCT and unfavorable long-term functional outcomes of patients with TBI.

Administration of fibrinogen concentrate for refractory bleeding in massively transfused, non-trauma patients with coagulopathy: a retrospective study with comparator group.

BACKGROUND: This retrospective, single centre study was conducted to investigate the efficacy of fibrinogen concentrate (FBNc) in decreasing blood requirements and reaching optimal fibrinogen level, in non-trauma, massively transfused, bleeding patients with coagulopathy. METHODS: Over a 3-years period, all patients for whom a massive transfusion protocol was activated and had received ≥ 4 units of allogeneic blood components within a ≤ 4 h period, were included. Patients were classified according to whether they received FBNc or achieved an optimal fibrinogen level of ≥ 2 g/L within 24 h after FBNc administration. RESULTS: Seventy-one patients received 2 [2,4] g of FBNc (FBNc group) and 72 did not (comparator group). FBNc was administered after transfusing 5 [5,9] blood component units, 3 [2,6] hours after massive transfusion protocol activation. Linear regression analysis showed that SOFA (AOR 0.75 [95% CI:0.08-1.43]) and admission fibrinogen level (AOR -2.7 [95% CI:-4.68 - -0.78]), but not FBNc administration, were independently associated with total transfused units. There was a significant inverse relation between both admission and target fibrinogen levels, and total transfused components. Logistic regression showed a direct relationship between admission fibrinogen level and achieving a target level ≥ 2 g/L (AOR 3.29 [95% CI;1.95-5.56]). No thromboembolic events associated with FBNc were observed. CONCLUSIONS: In massively transfused, non-trauma patients with coagulopathy and refractory bleeding, late administration of low FBNc dosage was not associated with decreased blood transfusion or increased post-infusion fibrinogen level. Given that both fibrinogen upon admission and target fibrinogen levels were associated with decreased blood transfusion, earlier administration and higher doses of FBNc could be needed.

Efficacy of the prothrombin complex concentrate prothromplex in patients requiring urgent reversal of vitamin K antagonists or presenting with uncontrolled bleeding: a retrospective, single center study.

The objective of the present study was to investigate the efficacy of a four-factor prothrombin complex concentrate (Prothromplex, PTX) in shortening prolonged international normalized ratio or controlling life-threatening bleeding. The study was a retrospective single-centre study that included 142 patients treated with PTX and allocated in three groups: patients on vitamin K antagonists (VKA) (acenocumarol) and undergoing invasive procedure or presenting with severe bleeding (n = 76), patients treated with VKA presenting with intracranial haemorrhage (n = 22), and patients not on VKA and presenting with uncontrolled bleeding (n = 44). The primary outcome variable was international normalized ratio (INR) return to the norm after PTX infusion. Secondary outcome variables included bleeding control and reduction of transfusion rate. Overall, patients received a median of 1200 IU (≈15 IU/kg) of PTX, and INR decreased from 4 ±â€Š3 to 1.7 ±â€Š1.2 (P < 0.01) in all groups, although it remained at least 1.4 in 38% of patients (29.3% among patients receiving 25 IU/kg vs. 42.6% among those receiving 15 IU/kg; P < 0.05). Patients with initial INR at least 4 benefited the most from treatment. After PTX administration, there was a significant reduction in both transfused blood components units (P < 0.01) and estimated blood loss volume (from 1500 ±â€Š1500 to 200 ±â€Š100 ml; P < 0.01), and only one episode of deep venous thrombosis was observed. Administration of fixed doses of PTX shortened prolonged international normalized ratio and improved life-threatening bleeding in patients with or without VKA therapy. Higher dose attained a more adequate post-infusion INR.