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.

Impact of peri-procedural management of direct oral anticoagulants on pocket haematoma after cardiac electronic device implantation: the StimAOD multicentre prospective study.

AIMS: The study aims to investigate the impact of direct oral anticoagulant (DOAC) management on the incidence of pocket haematoma in patients undergoing pacemaker or implantable cardioverter-defibrillator implantation. METHODS AND RESULTS: All consecutive patients receiving DOAC and undergoing cardiac electronic device implantation were included in a large multicentre prospective observational study (NCT03879473). The primary endpoint was clinically relevant haematoma within 30 days after implantation. Overall, 789 patients were enrolled [median age 80 (IQR 72-85) years old, 36.4% women, median CHA2DS2-VASc score 4 (IQR 0-8)], of which 632 (80.1%) received a pacemaker implantation. Antiplatelet therapy was combined with DOAC in 146 patients (18.5%). Direct oral anticoagulants (DOACs) were interrupted 52 (IQR 37-62) h before the procedure and resumed 31 (IQR 21-47) h later. Ninety-six percent of the patients had at least 12 h DOAC interruption before the procedure, and 78% had at least 12 h DOAC interruption after the procedure. Overall, anticoagulation was interrupted for 72 (IQR 48-96) h. Pre- or post-procedural heparin bridging was used in 8.2% and 3.9%, respectively. Timing of DOAC interruption of resumption was not associated with clinically relevant haematoma. Clinically relevant haematoma occurred in 26 patients (3.3%), and thromboembolic events occurred in 5 patients (0.6%). CONCLUSION: In this large real-life registry where most patients had DOAC interruption, clinically relevant haematoma was rare. Despite DOAC interruption and high CHA2DS2-VASc score, thromboembolic events occurred seldomly, highlighting that bleeding exceeds thromboembolic risk in this peri-procedural period. Future research is needed to identify risk factors for clinically relevant haematoma and meaningfully guide clinicians in optimizing DOAC management.

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.

Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022.

BACKGROUND: Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN: A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS: These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION: Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION: All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.

Regional anaesthesia in patients on antithrombotic drugs: Joint ESAIC/ESRA guidelines.

BACKGROUND: Bleeding is a potential complication after neuraxial and peripheral nerve blocks. The risk is increased in patients on antiplatelet and anticoagulant drugs. This joint guideline from the European Society of Anaesthesiology and Intensive Care and the European Society of Regional Anaesthesia aims to provide an evidence-based set of recommendations and suggestions on how to reduce the risk of antithrombotic drug-induced haematoma formation related to the practice of regional anaesthesia and analgesia. DESIGN: A systematic literature search was performed, examining seven drug comparators and 10 types of clinical intervention with the outcome being peripheral and neuraxial haematoma. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the methodological quality of the included studies and for formulating recommendations. A Delphi process was used to prepare a clinical practice guideline. RESULTS: Clinical studies were limited in number and quality and the certainty of evidence was assessed to be GRADE C throughout. Forty clinical practice statements were formulated. Using the Delphi-process, strong consensus (>90% agreement) was achieved in 57.5% of recommendations and consensus (75 to 90% agreement) in 42.5%. DISCUSSION: Specific time intervals should be observed concerning the adminstration of antithrombotic drugs both prior to, and after, neuraxial procedures or those peripheral nerve blocks with higher bleeding risk (deep, noncompressible). These time intervals vary according to the type and dose of anticoagulant drugs, renal function and whether a traumatic puncture has occured. Drug measurements may be used to guide certain time intervals, whilst specific reversal for vitamin K antagonists and dabigatran may also influence these. Ultrasound guidance, drug combinations and bleeding risk scores do not modify the time intervals. In peripheral nerve blocks with low bleeding risk (superficial, compressible), these time intervals do not apply. CONCLUSION: In patients taking antiplatelet or anticoagulant medications, practitioners must consider the bleeding risk both before and after nerve blockade and during insertion or removal of a catheter. Healthcare teams managing such patients must be aware of the risk and be competent in detecting and managing any possible haematomas.

Major bleeding complications in critically ill patients with COVID-19 pneumonia.

As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14-23) days versus 9(3-11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3-5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and D-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.

Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring.

COVID-19 is an infection induced by the SARS-CoV-2 coronavirus, and severe forms can lead to acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) management. Severe forms are associated with coagulation changes, mainly characterized by an increase in D-dimer and fibrinogen levels, with a higher risk of thrombosis, particularly pulmonary embolism. The impact of obesity in severe COVID-19 has also been highlighted.In this context, standard doses of low molecular weight heparin (LMWH) may be inadequate in ICU patients, with obesity, major inflammation, and hypercoagulability. We therefore urgently developed proposals on the prevention of thromboembolism and monitoring of hemostasis in hospitalized patients with COVID-19.Four levels of thromboembolic risk were defined according to the severity of COVID-19 reflected by oxygen requirement and treatment, the body mass index, and other risk factors. Monitoring of hemostasis (including fibrinogen and D-dimer levels) every 48 h is proposed. Standard doses of LMWH (e.g., enoxaparin 4000 IU/24 h SC) are proposed in case of intermediate thrombotic risk (BMI < 30 kg/m2, no other risk factors and no ARDS). In all obese patients (high thrombotic risk), adjusted prophylaxis with intermediate doses of LMWH (e.g., enoxaparin 4000 IU/12 h SC or 6000 IU/12 h SC if weight > 120 kg), or unfractionated heparin (UFH) if renal insufficiency (200 IU/kg/24 h, IV), is proposed. The thrombotic risk was defined as very high in obese patients with ARDS and added risk factors for thromboembolism, and also in case of extracorporeal membrane oxygenation (ECMO), unexplained catheter thrombosis, dialysis filter thrombosis, or marked inflammatory syndrome and/or hypercoagulability (e.g., fibrinogen > 8 g/l and/or D-dimers > 3 µg/ml). In ICU patients, it is sometimes difficult to confirm a diagnosis of thrombosis, and curative anticoagulant treatment may also be discussed on a probabilistic basis. In all these situations, therapeutic doses of LMWH, or UFH in case of renal insufficiency with monitoring of anti-Xa activity, are proposed.In conclusion, intensification of heparin treatment should be considered in the context of COVID-19 on the basis of clinical and biological criteria of severity, especially in severely ill ventilated patients, for whom the diagnosis of pulmonary embolism cannot be easily confirmed.

Management of Intraprocedural Anticoagulation in Patients on Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Catheter Ablation for Atrial Fibrillation: Understanding the Gaps in Evidence.

Catheter ablation has gained a prominent role in the management of atrial fibrillation (AF), with recent data providing positive evidence on hard outcomes, including hospitalization and mortality. Ablation, however, exposes the patient to a rather unique situation, combining risks for both major bleeding and thromboembolic events. In this setting, the critical importance of rigorous anticoagulation during the procedure has been underlined, and the latest international guidelines now recommend performing AF catheter ablation with uninterrupted non-vitamin K antagonist oral anticoagulants (NOACs) and concomitant administration of unfractionated heparin adjusted to achieve and maintain a target activated clotting time of ≥300 seconds. Whereas observational studies and randomized controlled trials support the safety and efficacy of uninterrupted NOAC strategy for AF catheter ablation, recent experiences have questioned this point, showing a greater unfractionated heparin requirement in NOAC-treated patients compared with vitamin K antagonists-treated patients to achieve the target activated clotting time. Important gaps in evidence regarding optimal intraprocedural anticoagulation management need to be acknowledged. A thorough appreciation of the physiology of anticoagulation during AF catheter ablation and the relevant differences between vitamin K antagonists and NOACs is required, while also understanding the limitations of activated clotting time measurement with regard to accurate intraprocedural anticogulation monitoring. This review aims to provide a critical look at this relatively ignored aspect of AF catheter ablation, especially pitfalls in NOAC monitoring, and to identify gaps in knowledge that need to be addressed in the near future.

Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra® ): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP).

INTRODUCTION: Emicizumab (Hemlibra® ) recently became available and requires an adaptation for managing bleeding, suspected bleeding and emergency or scheduled invasive procedures in haemophilia A patients with inhibitor. This implicates a multidisciplinary approach and redaction of recommendations for care that must be regularly adapted to the available data. AIM: The following text aims to provide a guide for the management of people with haemophilia A with inhibitor treated with emicizumab in case of bleeding or invasives procedures. METHODS: The French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia (CRH), in collaboration with the French Working Group on Perioperative Haemostasis (GIHP) have been working together to make proposals for the management of these situations. RESULTS: Haemostatic treatment and other medications should be given stepwise, according to the severity and location of the bleeding or the risk of bleeding of the procedure as well as the haemostatic response obtained at each step in order to ensure an optimal benefit/risk ratio. CONCLUSION: The lack of data means that it is only possible to issue proposals rather than recommendations.

Prospective analysis of serious cardiorespiratory events in children during ophthalmic artery chemotherapy for retinoblastoma under a deep standardized anesthesia.

BACKGROUND AND OBJECTIVE: Serious adverse cardiorespiratory events complicate super selective ophthalmic artery chemotherapy for retinoblastoma in anesthetized children. Their mechanism remains unclear but may be attributed to an autonomic nervous reflex induced by the catheter close to the ophthalmic artery. Inadequate depth of anesthesia during catheter stimulation might be an aggravating factor. Thus, we tested whether deep general anesthesia reduced the incidence of serious cardiorespiratory events. METHODS: Children were prospectively included in this observational study. Standardized deep general anesthesia with sevoflurane, rocuronium, and sufentanil was administered. Sevoflurane MAC was kept between 1.5 and 1.7 and additional sufentanil administered. Serious cardiorespiratory event criteria were predefined and included arterial hypotension, bradycardia, and severe decrease in lung compliance. They were recorded and the factors influencing their occurrence were investigated. RESULTS: One hundred fifteen procedures were performed on 32 children. The median MAC of sevoflurane was 1.5 and median BIS value was 44. Serious cardiorespiratory events occurred in 20% of procedures and were mainly severe decrease in lung compliance (83% of events). All of them required active treatment. One procedure was aborted due to cardiorespiratory compromise and required an epinephrine infusion. All severe decreases in lung compliance occurred within 2 minutes after catheter insertion in the ophthalmic artery. No recorded demographic and endovascular characteristics were associated with serious cardiorespiratory events. CONCLUSION: Serious cardiorespiratory events occur commonly during super selective ophthalmic artery chemotherapy. Standardized deep anesthesia with analgesia did not appear to be protective. No predictive factors were identified, but these events systematically arose within 2 minutes after ophthalmic artery catheter insertion. Anesthetists and neuroradiologists should be prepared to manage these serious complications and parents should be informed of the risks.

Evaluation of recombinant factor VIIa, tranexamic acid and desmopressin to reduce prasugrel-related bleeding: A randomised, placebo-controlled study in a rabbit model.

BACKGROUND: Prasugrel is a thienopyridine that inhibits platelet aggregation more rapidly and effectively than clopidogrel, with an increased bleeding risk. OBJECTIVE: The current study aimed to evaluate the efficacy of three nonspecific haemostatic drugs - recombinant activated factor VII (rFVIIa), tranexamic acid and desmopressin (DDAVP) - to limit blood loss after administration of prasugrel in a rabbit model of bleeding while also evaluating any prothrombotic effects. DESIGN: Randomised, placebo-controlled study. SETTING: Faculty of Medicine, University of Geneva, Switzerland, in 2013. ANIMALS: Anaesthetised and artificially ventilated rabbits (n=56). INTERVENTIONS: Animals were randomly allocated to one of five groups: control (placebo-placebo), prasugrel-placebo, rFVIIa (prasugrel-rFVIIa 150 µg kg), tranexamic acid (prasugrel-tranexamic acid 20 mg kg) or DDAVP (prasugrel-DDAVP 1 µg kg). Two hours after an oral prasugrel loading dose (4 mg kg), a stenosis and an injury were inflicted on the carotid artery to induce cyclic flow reductions (CFRs) due to thrombosis. Haemostatic drugs were administered during the ensuing observation period. MAIN OUTCOME MEASURES: Standardised hepatosplenic sections were performed to evaluate the primary endpoint of blood loss, monitored for 15 min. Ear-immersion bleeding time and incidence of CFRs were secondary endpoints. RESULTS: Prasugrel decreased ADP-induced platelet aggregation (light transmission method) from 66 ±â€Š4% (mean ±â€ŠSD) to 41 ±â€Š7% (P < 0.001) and doubled blood loss: 10.7 g (10.1 to12.7) [median (interquartile range)] vs. 20.0 g (17.0 to 24.4), P = 0.003 in the control and prasugrel-placebo groups, respectively. rFVIIa, tranexamic acid and DDAVP reduced neither hepatosplenic blood loss [19.7 g (14.0 to 27.6), 25.2 g (22.6 to 28.7) and 22.9 g (16.8 to 28.8), respectively] nor bleeding time compared with placebo. Regarding safety, rVIIa induced three or more CFRs in 5/12 rabbits, vs. 0/12 in the prasugrel-placebo group (P = 0.037), whereas tranexamic acid and DDAVP did not increase them. CONCLUSION: The three studied haemostatic drugs rFVIIa, tranexamic acid and DDAVP failed to reduce prasugrel-related bleeding in this model. rFVIIa-treated rabbits were more prone to arterial thrombotic events. TRIAL REGISTRATION: NA.

Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study.

AIMS: Patients receiving direct oral anticoagulants (DOACs) frequently undergo elective invasive procedures. Their management is challenging. We aimed to determine the optimal duration of DOAC discontinuation that ensures a minimal anticoagulant effect during the procedure. METHODS AND RESULTS: This prospective multicentre study included 422 DOAC-treated patients requiring an invasive procedure. Pre-procedural DOAC concentration ([DOAC]) and routine haemostasis assays were performed to determine i/the proportion of patients who achieved a minimal pre-procedural [DOAC] (≤30 ng/mL) according to the duration of DOAC discontinuation, ii/the predictors of minimal [DOAC] and, iii/the ability of routine assays to predict minimal [DOAC]. Lastly, we assessed the predictors of peri-procedural bleeding events. The duration of DOAC discontinuation ranged from 1 to 218 h and pre-procedural [DOAC] from ≤30 to 527 ng/mL. After a 49-72-h discontinuation, 95% of the [DOAC] were ≤30 ng/mL. A 72-h discontinuation predicted concentrations ≤30 ng/mL with 91% specificity. In multivariable analysis, duration of DOAC discontinuation, creatinine clearance <50 mL/min and antiarrhythmics were independent predictors of minimal pre-procedural [DOAC] (concordance statistic 0.869; 95% confidence interval: 0.829-0.912). Conversely, routine haemostasis assays were poor predictors. Last, creatinine clearance <50 mL/min, antiplatelets and high-bleeding risk procedures were predictors of bleeding events. CONCLUSION: A last DOAC intake 3 days before a procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment, especially in dabigatran-treated patients, and antiarrhythmics in anti-Xa-treated patients should result in a longer DOAC interruption. In situations requiring testing, routine assays should not replace DOAC concentration measurement.

Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions.

RATIONALE: Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures. OBJECTIVE: To investigate the time course of HMW multimers changes in models and patients with instantaneous induction/reversal of pathological high shear and its related bedside assessment. METHODS AND RESULTS: We investigated the time course of the induction/recovery of HMW multimers defects under instantaneous changes in shear stress in an aortic stenosis rabbit model and in patients undergoing implantation of a continuous flow left ventricular assist device. We further investigated the recovery of HMW multimers and monitored these changes with PFA-CADP in aortic stenosis patients undergoing transcatheter aortic valve implantation or balloon valvuloplasty. Experiments in the aortic stenosis rabbit model and in left ventricular assist device patients demonstrated that induction/recovery of HMW multimers occurs within 5 minutes. Transcatheter aortic valve implantation patients experienced an acute decrease in shear stress and a recovery of HMW multimers within minutes of implantation which was sustained overtime. In patients with residual high shear or with residual aortic regurgitation, no recovery of HMW multimers was observed. PFA-CADP profiles mimicked HMW multimers recovery both in transcatheter aortic valve implantation patients without aortic regurgitation (correction) and transcatheter aortic valve implantation patients with aortic regurgitation or balloon valvuloplasty patients (no correction). CONCLUSIONS: These results demonstrate that variations in von Willebrand factor multimeric pattern are highly dynamic, occurring within minutes after changes in blood flow. It also demonstrates that PFA-CADP can evaluate in real time the results of transcatheter aortic valve procedures.

Correction of prasugrel-related bleeding by prophylactic transfusion of human platelets in a rabbit model.

BACKGROUND: Prasugrel provides rapid and intense inhibition of platelet aggregation combined with an increased risk of bleeding. We evaluated the efficacy and safety of platelet transfusion to reduce blood loss after a prasugrel loading dose in a rabbit model. STUDY DESIGN AND METHODS: Thirty-five rabbits were randomized into five groups: "control" (saline plus physiological buffer), "no-transfusion" (prasugrel plus physiological buffer), "platelet low dose" (prasugrel loading dose plus transfusion with a platelet count increase <80 × 109 /L), "platelet intermediate dose" (prasugrel loading dose plus transfusion with a platelet count increase 80-120 × 109 /L), and "platelet high dose" (prasugrel loading dose plus transfusion with a platelet count increase ≥120 × 109 /L). Naïve, washed human platelets in physiological buffer were transfused before bleeding was induced. Sequentially, a stenosis and an injury were carried out on the carotid artery to induce cyclic thrombotic occlusions. Ultimately, liver sections were performed to evaluate the primary endpoint of blood loss monitored for 15 minutes. RESULTS: Blood loss in the "control" group was 3.16 g/kg (inerquartile range [IQR] [2.87-4.89]) and was increased in the "no-transfusion" group to 6.15 g/kg (IQR [4.79-9.15]; p < 0.02). There was a gradual trend across the three transfusion groups toward less bleeding, and the highest dose of platelet transfusion significantly decreased prasugrel-induced blood loss (3.05 g/kg; IQR [2.55-3.56]; p = 0.006). Platelet aggregation was significantly but only partially restored in the latter group. Regarding safety, platelet transfusion was not associated with an increase in thrombotic events regardless of the dose. CONCLUSIONS: In this animal model, platelet transfusion aiming for a platelet count increase of at least 120 × 109 /L was necessary to correct prasugrel-related bleeding.

The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation: An in-vitro study.

BACKGROUND: Management of ticagrelor-induced bleeding is challenging, as no antidote is currently available. Platelet transfusion, usually proposed to reverse antiplatelet drugs, has been suggested to be ineffective but few data are available. OBJECTIVE: To assess the efficacy of platelet supplementation to restore platelet aggregation inhibited by ticagrelor. DESIGN: In vitro study. SETTING: Blood samples were obtained from the French Blood Bank Institute. PARTICIPANTS: Healthy blood donors. INTERVENTIONS: Whole blood from healthy donors was spiked with ticagrelor or aspirin (used as a positive control). MAIN OUTCOME MEASURES: Platelet aggregation was investigated with impedance aggregometry on whole blood [expressed in ohms (V)] and light transmission aggregometry (expressed in %) on platelet-rich plasma using ADP or arachidonic acid as agonists for ticagrelor or aspirin, respectively. Platelet supplementation was defined as the addition of washed platelet suspension increasing at least 60% of whole blood platelet count. RESULTS: Ticagrelor (3.25 mM) inhibited ADP-induced platelet aggregation compared with control either in whole blood (2 vs. 13 V, P < 0.05) or in platelet-rich plasma (15 vs. 75% P < 0.05). Aspirin (25 mM) inhibited arachidonic acid-induced aggregation (1 vs. 7.5 V, P < 0.05 in whole blood and 5 vs. 77.5%, P = 0.01 in platelet-rich plasma). Platelet supplementation completely restored arachidonic acid-induced platelet aggregation in whole blood (10 vs. 1 V, P = 0.008) and platelet-rich plasma (73 vs. 5%, P < 0.01) in aspirin-treated samples, whereas it failed to correct ADP-induced aggregation (2 vs. 2 V in whole blood and 13.5 vs. 15% in platelet-rich plasma, P > 0.05) in ticagrelor-treated samples. We also report a case of a ticagrelor-treated patient in whom platelet transfusion failed to restore ADP-induced platelet aggregation. CONCLUSION: Platelet supplementation restored platelet aggregation in aspirin-spiked but not in ticagrelor-spiked samples. These results do not support the use of platelet transfusion to reverse the effects of ticagrelor.