Combined Platelet and Red Blood Cell Recovery during On-pump Cardiac Surgery Using same™ by i-SEP Autotransfusion Device: A First-in-human Noncomparative Study (i-TRANSEP Study).

BACKGROUND: Centrifugation-based autotransfusion devices only salvage red blood cells while platelets are removed. The same™ device (Smart Autotransfusion for ME; i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage both red blood cells and platelets. The authors tested the hypothesis that this new device could allow a red blood cell recovery exceeding 80% with a posttreatment hematocrit exceeding 40%, and would remove more than 90% of heparin and 75% of free hemoglobin. METHODS: Adults undergoing on-pump elective cardiac surgery were included in a noncomparative multicenter trial. The device was used intraoperatively to treat shed and residual cardiopulmonary bypass blood. The primary outcome was a composite of cell recovery performance, assessed in the device by red blood cell recovery and posttreatment hematocrit, and of biologic safety assessed in the device by the washout of heparin and free hemoglobin expressed as removal ratios. Secondary outcomes included platelet recovery and function and adverse events (clinical and device-related adverse events) up to 30 days after surgery. RESULTS: The study included 50 patients, of whom 18 (35%) underwent isolated coronary artery bypass graft, 26 (52%) valve surgery, and 6 (12%) aortic root surgery. The median red blood cell recovery per cycle was 86.1% (25th percentile to 75th percentile interquartile range, 80.8 to 91.6) with posttreatment hematocrit of 41.8% (39.7 to 44.2). Removal ratios for heparin and free hemoglobin were 98.9% (98.2 to 99.7) and 94.6% (92.7 to 96.6), respectively. No adverse device effect was reported. Median platelet recovery was 52.4% (44.2 to 60.1), with a posttreatment concentration of 116 (93 to 146) · 109/l. Platelet activation state and function, evaluated by flow cytometry, were found to be unaltered by the device. CONCLUSIONS: In this first-in-human study, the same™ device was able to simultaneously recover and wash both platelets and red blood cells. Compared with preclinical evaluations, the device achieved a higher platelet recovery of 52% with minimal platelet activation while maintaining platelet ability to be activated in vitro.

Assessment of a Quantra-Guided Hemostatic Algorithm in High-Bleeding-Risk Cardiac Surgery.

OBJECTIVES: To assess whether a Quantra-guided hemostatic algorithm would reduce transfusion requirement and major bleeding compared with laboratory-guided testing in patients facing high-bleeding-risk cardiac surgery. DESIGN: Single-center before-and-after study. SETTING: University hospital. PARTICIPANTS: Patients facing high-bleeding-risk cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Hemostatic algorithm was based on standard laboratory testing during the control period, then on the Quantra during the Quantra period. The primary endpoint was the number of red blood cell (RBC) units transfused on day 1 after surgery. MEASUREMENTS AND MAIN RESULTS: After propensity-score matching, 66 patients were included in the Quantra group and 117 in the control group. The Quantra group received fewer RBC units on day 1 than the control group (2 [0-5] v 4 [2-6], p = 0.016, respectively). Intraoperatively, the Quantra group received fewer RBC (2 [0-3] v 3 [1-5], p = 0.005), less fresh frozen plasma (0 [0-3] v 3[2-5], p < 0.0001), and fewer platelet units (7.5 [0-10] v 8.2 [6.3-11.7], p = 0.014). The intraoperative rates of RBC, plasma, and platelet transfusion were reduced (64% v 78%, p = 0.05; 41% v 85%, p < 0.001; 55% v 82%, p = 0.001, respectively). The RBC and plasma transfusions were reduced on days 1, 2, and 7. The incidence of major bleeding on day 1 also was reduced (36% v 56%, p = 0.014). In multivariate analysis, implementation of the Quantra-guided hemostatic algorithm was associated independently with reductions in major bleeding. CONCLUSION: Implementation of a Quantra-based hemostatic algorithm was associated with a decrease in transfusion requirement and major bleeding after high-bleeding-risk cardiac surgery. Randomized trials are needed to confirm these results.

Prevalence and time-course of diaphragmatic dysfunction following lung resection: A repeated ultrasonic assessment.

PURPOSE: Ultrasound (US) allows non-invasive repeated assessments of diaphragmatic excursion (DE) and thickening fraction (DTF) at the bedside, reflecting diaphragmatic dysfunction (DD). We aimed at determining the prevalence and time-course of DD following elective thoracic surgery and the association with postoperative complications. MATERIAL AND METHODS: Prospective, single-centre, observational study with consecutive patients undergoing thoracic surgery. DE/DTF were measured by two observers blinded to each other at 3 different time-points: prior to surgery, immediately after extubation and on postoperative day 3. The changes in DE/DTF of both hemi-diaphragms over time were compared according to the side (operated/non-operated) using a two-way-ANOVA. The association with postoperative complications was assessed using logistic regression. RESULTS: Fifty patients, 60% males, aged 60 ± 15 years were included. Surgical procedures included lobectomy (n = 30), wedge-resection (n = 17) or pneumonectomy (n = 3). On the operated side, we observed a decrease in DE/DTF at D0 (-0.71 ± 0.12 mm, P < 0.05; -44 ± 30%, P < 0.05) and D3 (-0.82 ± 0.19 mm, P < 0.05; -39 ± 19%, P < 0.05) with respect to preoperative and non-operated side values over the study period. Persistent DD on the operated side was associated with an increased risk of lung infection (OR: 9.0, 95% CI [1.92-65.93], P = 0.001), ICU-admission (OR: 3.9, 95% CI [1.10-15.53], P = 0.04) according to univariate analysis and a prolonged length in hospital (OR: 1.3, 95% CI [1.1-1.7], P = 0.016) according to multivariate analysis. CONCLUSIONS: Thoracic surgery generates DD mainly observed on the operated side, which persists at least up to postoperative D3 and is associated with an increase in hospital stay.

Epinephrine restores platelet functions inhibited by ticagrelor: A mechanistic approach.

Ticagrelor, an antagonist of the platelet adenosine diphosphate (ADP)-P2Y12 receptor is recommended for patients with acute coronary syndromes. However, ticagrelor exposes to a risk of bleeding, the management of which is challenging because platelet transfusion is ineffective, and no antidote is yet available. We hypothesized that the vasopressor drug epinephrine could counter the antiplatelet effects of ticagrelor and restore platelet functions. We assessed in vitro the efficiency of epinephrine in restoring platelet aggregation inhibited by ticagrelor and investigated the underlying mechanisms. Washed platelet aggregation and secretion were measured upon stimulation by epinephrine alone or in combination with ADP, in the presence or absence of ticagrelor. Mechanistic investigations used P2Y1 and phosphoinositide 3-kinase (PI3K) inhibitors and included vasodilator-stimulated phosphoprotein (VASP) and Akt phosphorylation assays as well as measurement of Ca2+ mobilisation. We found that epinephrine restored ADP-induced platelet aggregation, but not dense granule release. Epinephrine alone failed to induce aggregation whereas it fully induced VASP dephosphorylation and Akt phosphorylation regardless of the presence of ticagrelor. In the presence of ticagrelor, blockage of the P2Y1 receptor prevented restoration of platelet aggregation by the combination of epinephrine and ADP, as well as intracellular Ca2+ mobilisation. In combination with ADP, epinephrine induced platelet aggregation of ticagrelor-treated platelets through inhibition of the cAMP pathway and activation of the PI3K pathway, thus enabling the P2Y1 receptor signalling and subsequent Ca2+ mobilisation. This proof-of-concept study needs to be challenged in vivo for the management of bleeding in ticagrelor-treated patients.

Maternal Death Due to Amniotic Fluid Embolism: A National Study in France.

BACKGROUND: A structured definition of amniotic fluid embolism (AFE) based on 4 criteria was recently proposed for use in research by the Society for Maternal-Fetal Medicine (SMFM) and the Amniotic Fluid Embolism Foundation. The main objective of this study was to review all AFE-related maternal deaths in France during 2007-2011 according to the presence or not of all these 4 diagnostic criteria. METHODS: Maternal deaths due to AFE were identified by the national experts committee of the French Confidential Enquiry into Maternal Deaths during 2007-2011 (n = 39). The maternal mortality ratio for AFE was calculated. We applied the structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation to AFE-related maternal deaths identified by the national experts committee. Characteristics of women, pregnancies and deliveries; clinical and biological features of AFE; and specific laboratory tests used were described by the presence or not of all 4 diagnostic criteria. Management of obstetric hemorrhage and quality of care according to the experts were also described. RESULTS: The maternal mortality ratio from AFE was 0.95/100,000 live births (95% confidence interval, 0.67-1.3). Detailed clinical data were collected for 36 women who died from AFE: 21 (58%) had all 4 proposed diagnostic criteria and 15 (42%) had 1 or more missing criterion. Documented early disseminated intravascular coagulopathy was missing for 14 women, and 2 women exhibited more than 1 missing criterion. Ten of the 15 women with missing criteria had clinical coagulopathy, with standard hemostasis tests performed in only 3. Specific diagnostic examinations for AFE were performed in similar proportions by the presence or not of all diagnostic criteria. Opportunities to improve care included timely performance of indicated hysterectomy (n = 13) and improved transfusion practices (n = 9). In the context of maternal cardiac arrest, for 5 of 13 women, fetal extraction was performed within 5 minutes. CONCLUSIONS: The structured definition of AFE for research studies would exclude more than one-third of AFE-related maternal deaths identified by the national experts committee. Inclusion of clinical coagulopathy as a diagnostic criterion for AFE would reduce this proportion to 14%. There is still room for improvement in the management of obstetric hemorrhage and timely fetal extraction in the context of maternal cardiac arrest, frequently observed in AFE-related maternal death.

Ticagrelor reversal: in vitro assessment of four haemostatic agents.

AIM: Management of ticagrelor-induced bleeding is challenging as platelet transfusion is ineffective. An effective strategy is needed. This study aimed to investigate in vitro the efficacy of four haemostatic drugs (HDs), namely recombinant activated factor VII (rFVIIa), fibrinogen concentrate (Fib), tranexamic acid (TXA) and factor XIII concentrate (FXIII) to improve the haemostatic capacity in the presence of ticagrelor. METHODS: Blood was spiked with ticagrelor then supplemented by either HD or control. Several assays were performed: ADP-induced platelet aggregation measured by impedance aggregometry, light transmission and two global assays, thrombolastography with the platelet mapping device (TEG-PM) and a platelet-dependent thrombin generation assay (TGA). RESULTS: Ticagrelor inhibited ADP-induced platelet aggregation and decreased the clot strength maximum amplitude (MA) in TEG-PMADP. None of the HDs corrected these parameters. However, rFVIIa shortened the coagulation time R using TEG-PMthrombin and the time to peak prolonged by ticagrelor in TGA. Fib increased MAthrombin and FXIII decreased LY30. TXA had no effects. CONCLUSIONS: Whereas none of the HDs corrected ticagrelor-induced platelet inhibition, rFVIIa shortened coagulation times, Fib increased clot firmness and FXIII decreased fibrinolysis. Consequently, they may bypass ticagrelor effects by acting on fibrin formation or fibrinolysis. Further studies are needed to confirm these data in vivo.