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.

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.