Greater Fibrinolysis Resistance but No Greater Platelet Aggregation in Critically Ill COVID-19 Patients.

BACKGROUND: The hemostatic balance in patients with coronavirus disease 2019 (COVID-19) seems to be shifted toward a hypercoagulable state. The aim of the current study was to assess the associated coagulation alterations by point-of-care-diagnostics, focusing on details of clot formation and lysis in these severely affected patients. METHODS: The authors' prospective monocentric observational study included critically ill patients diagnosed with COVID-19. Demographics and biochemical data were recorded. To assess the comprehensive hemostatic profile of this patient population, aggregometric (Multiplate) and viscoelastometric (CloPro) measures were performed in the intensive care unit of a university hospital at a single occasion. Coagulation analysis and assessment of coagulation factors were performed. Data were compared to healthy controls. RESULTS: In total, 27 patients (21 male; mean age, 60 yr) were included. Impedance aggregometry displayed no greater platelet aggregability in COVID-19 in comparison with healthy controls (area under the curve [AUC] in adenosine diphosphate test, 68 ± 37 U vs. 91 ± 29 U [-27 (Hodges-Lehmann 95% CI, -48 to -1); P = 0.043]; AUC in arachidonic acid test, 102 ± 54 U vs. 115 ± 26 U [-21 (Hodges-Lehmann 95% CI, -51 to 21); P = 0.374]; AUC in thrombin receptor activating peptide 6 test, 114 ± 61 U vs. 144 ± 31 U [-31 (Hodges-Lehmann 95% CI, -69 to -7); P = 0.113]). Comparing the thromboelastometric results of COVID-19 patients to healthy controls, the authors observed significant differences in maximum clot firmness in fibrin contribution to maximum clot firmness assay (37 ± 11 mm vs. 15 ± 4 mm [21 (Hodges-Lehmann 95% CI, 17 to 26); P < 0.001]) and lysis time in extrinsic activation and activation of fibrinolysis by tissue plasminogen activator assay (530 ± 327 s vs. 211 ± 80 s [238 (Hodges-Lehmann 95% CI, 160 to 326); P < 0.001]). CONCLUSIONS: Thromboelastometry in COVID-19 patients revealed greater fibrinolysis resistance. The authors did not find a greater platelet aggregability based on impedance aggregometric tests. These findings may contribute to our understanding of the hypercoagulable state of critically ill patients with COVID-19.

Reduced Platelet Activity in Patients with Acute Intracranial Hemorrhage.

BACKGROUND: Acquired platelet dysfunction is a common element of trauma-induced coagulopathy and has been linked to increased mortality. The aim of the study was to describe the prevalence of platelet dysfunction in patients with acute intracranial bleeding. METHODS: Patients diagnosed with acute intracranial bleeding were screened for eligibility. Patients with an urgent need for craniotomy were enrolled in this prospective monocentric study. Platelet function analyses using multiple electrode aggregometry (TRAPtest, ASPItest and ADPtest) and conventional coagulation tests were performed. The area under the aggregation curves of the ASPItest and ADPtest were defined as primary outcome variables. RESULTS: Seventy-seven patients were screened for eligibility, and 49 patients were ultimately enrolled in the study. In 14 patients (29%), clinically relevant platelet dysfunction was observed. Of those, 8 patients were treated with antiaggregatory medication at the time of study inclusion. Six patients (12%) were diagnosed with acute acquired platelet dysfunction. CONCLUSIONS: Decreased platelet function was present in nearly one-third of patients with acute intracranial bleeding. Hemotherapy algorithms for the treatment of coagulopathy in this cohort should incorporate aggregometric measures to enable rapid goal-directed therapy.

Activation of Platelets and Occurrence of Cerebral Vasospasm and Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage in a Prospective Pilot-Trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) often leads to poor outcome. The aim of the study was to assess platelet function in patients after SAH. METHODS: In this prospective observational study in patients suffering from SAH, platelet count and aggregability were assessed by multiple electrode aggregometry (MEA) over 14 days. RESULTS: In 12 of 18 patients, cerebral vasospasms (CVS) were diagnosed; of those, five developed delayed cerebral ischemia (DCI). We observed a significant increase in the platelet count compared to baseline from day 8 onwards (p < 0.037) and, in patients with CVS and DCI, a significant difference in outcome classified by the mRS (p = 0.047). Repeated measures ANOVA determined no differences in platelet aggregability in patients with or without CVS/DCI. CONCLUSIONS: Besides an increase in platelet count, we detected no increase in platelet aggregability. Nevertheless, patients after SAH may have increased platelet aggregability, which is not reflected by MEA.

Impact of Intraoperative Cell Salvage on Blood Coagulation Factor Concentrations in Patients Undergoing Cardiac Surgery.

BACKGROUND: Cardiothoracic surgery is associated with major blood loss and allogeneic transfusion of red blood cell concentrates. To minimize allogeneic red blood cell (RBC) transfusion, intraoperative cell salvage has been effectively used for years. The objective of this study was to evaluate the impact of cell salvage on blood coagulation factors. METHODS: We enrolled 30 patients scheduled for cardiac surgery in a prospective single-center observational cohort study at an academic hospital. Blood samples from the cell salvage system were obtained from both the reservoir and the processed red blood cell concentrate. Coagulation factors, fibrinogen, antithrombin and von Willebrand activity, and antigen were assessed before and after cell salvage. Statistical analysis was performed using Wilcoxon matched-pairs signed rank test. RESULTS: Our results revealed a significant decrease of fibrinogen (P < .001), coagulation factors II (P = .004), factors VII, X, and XIII (P < .001), and all other measured coagulation factor concentrations/activities in the processed red blood cell concentrate, when compared to the concentrations/activities of the reservoir. CONCLUSIONS: The results of the present study revealed a significant reduction of coagulation factor concentrations/activities by the washing process. Therefore, physicians need to consider adequate management of coagulation in patients with major blood loss and the need of large volumes of RBC transfusion.

Evaluation of the C-MAC Miller Video Laryngoscope Sizes 0 and 1 During Tracheal Intubation of Infants Less Than 10 kg.

STUDY OBJECTIVE: Video laryngoscopy has primarily been developed to assist in difficult airways. Using video laryngoscopy in pediatric airway management is an up-and-coming topic. The aim of the presented study was to compare the intubation conditions obtained when using the C-MAC video laryngoscope with Miller blades sizes 0 and 1 for standard direct laryngoscopy and indirect laryngoscopy in children weighing less than 10 kg. DESIGN: This was a prospective study. SETTING: The study was performed in a university hospital. PATIENTS: Following ethical approval, 86 infants weighing less than 10 kg and undergoing surgery under general anesthesia were studied prospectively. INTERVENTION: Indirect and direct laryngoscopy either with C-MAC Miller blade size 0 or size 1. MEASUREMENTS: First, direct laryngoscopy was performed, and the best obtained view was graded without looking at the video monitor. A second investigator blinded to the view obtained under direct laryngoscopy graded the laryngeal view on the video monitor. Time to intubation, intubation conditions, and intubation attempts were recorded. RESULTS: In infants less than 10 kg, intubation conditions were excellent. There were no significant differences between the use of Miller blade 0 or 1 in reference to Cormack-Lehane grade, time to intubation, time to best view, or intubation attempts. Comparing direct and indirect intubation conditions using either Miller blade 0 or 1 revealed that the use of indirect laryngoscopy provided a significantly better view (P < 0.05) of the vocal cords. In 3 infants weighing more than 8 kg, the Miller blade 0 was described as too short and narrow for intubation. CONCLUSIONS: Both devices allowed for an excellent visualization of the vocal cords.

[Hyperfibrinolysis after Resuscitation due to Acute Pulmonary Artery Embolism]. / Hyperfibrinolyse nach Reanimation bei akuter Lungenarterienembolie.

In an 81-year-old patient, acute hemodynamic instability requiring resuscitation occurred during an elective transurethral prostate resection. The procedure was ended prematurely and after ROSC a CT diagnosis was carried out, which confirmed the suspected diagnosis of fulminant pulmonary embolism. Anticoagulant therapy with heparin was initiated. About two hours after admission to the intensive care unit, hemorrhage requiring massive transfusion developed, which according to viscoelastometric diagnostics was most likely due to fulminant hyperfibrinolysis. This case report describes the pathophysiology of so-called post-cardiac arrest coagulopathy and discusses the use of antifibrinolytic therapy in patients with thrombotic complications such as pulmonary artery embolism.

Fast Interpretation of Thromboelastometry and Aggregometry in Patients Suffering from Chronic Liver Disease.

BACKGROUND: Collective specific variegated alterations in the hemostatic system cast doubt on the uncritical usage of standard hemotherapy algorithms in patients with chronic liver disease. The aims of the present study were to examine the applicability of commonly used early viscoelastic parameters in this particular collective and to develop first-time thresholds for the early detection of clinically relevant platelet dysfunction. METHODS: Patients suffering from advanced chronic liver disease were enrolled in this prospective single-centre study and consecutively allocated to Group 1 (MELD (Model for End-Stage Liver Disease) score 6 - 11) or Group 2 (MELD score > 16). We performed conventional laboratory coagulation analyses, as well as viscoelastometry (ROTEM®, EXTEM test, and FIBTEM test) and aggregometry (Multiplate®, ASPItest, and ADPtest), in each patient to analyze their hemostatic capacity. We analyzed the association between the A10 values (clot firmness 10 minutes after the initiation of clot building) in the EXTEM and FIBTEM tests and the corresponding Maximum Clot Firmness (MCF) values and performed receiver operating characteristic (ROC) curve analyses to investigate the ability of early parameters from the ASPItest and ADPtest (Aggregation Units (AU) 1 minute (T1), 2 minutes (T2) and 3 minutes (T3) after induction of platelet aggregation) of the Multiplate® system to predict clinically relevant platelet dysfunction. RESULTS: In the complete study collective (n = 50) and in Group 1 and Group 2 (each n = 25), A10 values correlated highly significantly with corresponding MCF values. The bias between the A10 and the MCF values was 5.1 ± 2.4 mm and 1.2 ± 1.1 mm for the EXTEM test and FIBTEM test, respectively. The highest sensitivity and specificity values for the prediction of clinically relevant platelet dysfunction at measuring point T3 were analyzed to be the values 54.9 AU/min in the ASPItest and 50.1 AU/min in the ADPtest. CONCLUSIONS: The results of the study indicate that the basic principle of using the A10 values as so-called early vis-coelastic parameters for the estimation of MCF values is legitimate. The presumably divergent bias between the A10 and MCF values necessitates the development of collective specific thresholds in hemotherapy algorithms for coagulopathic patients suffering from advanced chronic liver disease.

Live Confocal Visualization of FXIII Activity.

In addition to its important functions in angiogenesis, wound healing, bone biology, immunology, pregnancy, and adipogenesis, transglutaminase factor XIII is an outstanding determinant of clot characteristics. Factor XIII mediates clot stability by covalent cross-linking of fibrin-fibrils and inhibition of fibrinolysis. For decades it was assumed that factor XIII mediates the formation of a 3-dimensional net structure of the clot. It was the aim of our experiment to prove this thesis.

Patient Blood Management is Associated With a Substantial Reduction of Red Blood Cell Utilization and Safe for Patient's Outcome: A Prospective, Multicenter Cohort Study With a Noninferiority Design.

OBJECTIVE: To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patient's safety. BACKGROUND: The World Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available. METHODS: In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization. RESULTS: A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P < 0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P < 0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21 ±â€Š0.05 to 1.00 ±â€Š0.05 (relative change by 17%, P < 0.001). CONCLUSIONS: The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patient's safety. Further studies should elucidate which PBM measures are most clinically and cost effective. TRIAL REGISTRATION: PBM-Study ClinicalTrials.gov, NCT01820949.

Cost-Effectiveness of POC Coagulation Testing Using Multiple Electrode Aggregometry.

BACKGROUND: The economic effects of Point-of-Care (POC) coagulation testing including Multiple Electrode Aggregometry (MEA) with the Multiplate device have not been examined. METHODS: A health economic model with associated clinical endpoints was developed to calculate the effectiveness and estimated costs of coagulation analyses based on standard laboratory testing (SLT) or POC testing offering the possibility to assess platelet dysfunction using aggregometric measures. Cost estimates included pre- and perioperative costs of hemotherapy, intra- and post-operative coagulation testing costs, and hospitalization costs, including the costs of transfusion-related complications. RESULTS: Our model calculation using a simulated true-to-life cohort of 10,000 cardiac surgery patients assigned to each testing alternative demonstrated that there were 950 fewer patients in the POC branch who required any transfusion of red blood cells. The subsequent numbers of massive transfusions and patients with transfusion-related complications were reduced with the POC testing by 284 and 126, respectively. The average expected total cost in the POC branch was 288 Euro lower for every treated patient than that in the SLT branch. CONCLUSIONS: Incorporating aggregometric analyses using MEA into hemotherapy algorithms improved medical outcomes in cardiac surgery patients in the presented health economic model. There was an overall better economic outcome associated with POC testing compared with SLT testing despite the higher costs of testing.

Thoracic epidural anesthesia with ropivacaine does not compromise the tolerance of acute normovolemic anemia in pigs.

BACKGROUND: The initial treatment of an acute blood loss with acellular fluids leads to the dilution of the red cell mass remaining in the vasculature, that is, to acute normovolemic anemia. Whether the compensation and, thus, the tolerance of acute anemia, are affected by sympathetic block induced by thoracic epidural anesthesia has not yet been investigated. METHODS: Eighteen anesthetized and mechanically ventilated pigs were instrumented with thoracic epidural catheters and randomly assigned to receive an epidural injection of either 5-ml ropivacaine 0.2% (n = 9) aiming for a Th5-Th10 block or saline (n = 9) followed by continuous epidural infusion of 5 ml/h of either fluid. Subsequently, acute normovolemic anemia was induced by replacement of whole blood with 6% hydroxyethyl starch solution until a "critical" limitation of oxygen transport capacity was reached as indicated by a sudden decrease in oxygen consumption. The critical hemoglobin concentration quantified at this time point was the primary endpoint; secondary endpoints were hemodynamic and oxygen transport parameters. RESULTS: Thoracic epidural anesthesia elicited only a moderate decrease in mean arterial pressure and cardiac index and a transient decrease in oxygen extraction ratio. During progressive anemia, the compensatory increases in cardiac index and oxygen extraction ratio were not compromised by thoracic epidural anesthesia. Critical hemoglobin concentration was reached at identical levels in both groups (ropivacaine group: 2.5 ± 0.6 g/dl, saline group: 2.5 ± 0.6 g/dl). CONCLUSION: Thoracic epidural anesthesia with ropivacaine 0.2% does not decrease the tolerance to acute normovolemic anemia in healthy pigs. The hemodynamic compensation of acute anemia is fully preserved despite sympathetic block, and the critical hemoglobin concentration remains unaffected.

[Update on point-of-care-based coagulation treatment : Systems, reagents, device-specific treatment algorithms]. / Update der Point-of-care-basierten Gerinnungstherapie : Systeme, Reagenzien, gerätespezifische Behandlungsalgorithmen.

Viscoelastic test (VET) procedures suitable for point-of-care (POC) testing are in widespread clinical use. Due to the expanded range of available devices and in particular due to the development of new test approaches and methods, the authors believe that an update of the current treatment algorithms is necessary. The aim of this article is to provide an overview of the currently available VET devices and the associated reagents. In addition, two treatment algorithms for the VET devices most commonly used in German-speaking countries are presented.

[Recommendations for the specialist further training of nursing personnel on intensive care units in the treatment of abdominal aortic aneurysms: results of a modified Delphi procedure with experts]. / Empfehlungen zur Fachweiterbildung von Pflegefachpersonen der Intensivstation bei der Behandlung des Bauchaortenaneurysmas: Ergebnisse eines modifizierten Delphi-Verfahrens mit Expert:innen.

INTRODUCTION: The medical development in the previous 15 years and the changes in treatment reality of the comprehensive elective treatment of abdominal aortic aneurysms necessitate a re-evaluation of the quality assurance guidelines of the Federal Joint Committee in Germany (QBAA-RL). In the current version this requires a specialist further training quota for nursing personnel in intensive care wards of 50%. The quota was determined in 2008 based on expert opinions, although a direct empirical evidence base for this does not exist. METHODS: Representatives from the fields of patient representation, physicians, nursing personnel and other relevant interface areas were invited to participate in a modified Delphi procedure. Following a comprehensive narrative literature search, a survey and focus group discussions with national and international experts, a total of three anonymized online-based voting rounds were carried out for which previously determined key statements were assessed with a 4­point Likert scale (totally disagree up to totally agree). In addition, the expert panel had also defined a recommendation for a minimum quota for the specialist training of nursing personnel on intensive care wards in the treatment of abdominal aortic aneurysms, whereby an a priori agreement of 80% of the participants was defined as the consensus limit. RESULTS: Overall, 37 experts participated in the discussions and three successive voting rounds (participation rate 89%). The panel confirmed the necessity of a re-evaluation of the guideline recommendations and recommended the introduction of a shift-related minimum quota of 30% of the full-time equivalent of nursing personnel on intensive care wards and the introduction of structured promotional programs for long-term elevation of the quota. CONCLUSION: In this national Delphi procedure with medical and nursing experts as well as representatives of patients, the fundamental benefits and needs of professional specialist qualifications in the field of intensive care medicine were confirmed. The corresponding minimum quota for specialist further training of intensive care nursing personnel should generally apply without limitations to specific groups. The expert panel stipulates a shift-related minimum quota for intensive care nursing personnel with specialist training of 30% of the nursing personnel on intensive care wards and the obligatory introduction of structured and transparent promotion programs for the long-term enhancement.

Perioperative coagulation management during cardiac surgery.

PURPOSE OF REVIEW: Cardiac surgery patients commonly present bleeding complications that negatively influence patient's clinical outcome. Therefore, fast and detailed diagnoses as well as early and specific therapy of perioperative coagulopathy are of high clinical relevance. The so-called point-of-care (POC) methods for coagulation analyses are increasingly used in perioperative care. It is the purpose of this review to present modern aspects of coagulation management, discuss the effect of the implementation of POC methods in perioperative care, and present substantial components of hemotherapy algorithms to manage coagulopathy in cardiac surgery patients. RECENT FINDINGS: Recent studies suggest that implementation of point-of-care testing in hemotherapy algorithms which inclose stepwise therapeutic escalation may reduce perioperative blood loss and the transfusion rate of allogenic blood products. This should improve patient's clinical outcome and reduce costs. SUMMARY: Prospective randomized multicenter studies are needed to confirm the hypothesis that algorithm-based specific hemotherapy in conjunction with POC testing minimizes patient's exposure to blood products and improves clinical outcome.

[Perioperative point-of-care coagulation testing--recently published studies]. / Point-of-Care-Testing--Aktuelle Studien zum Stellenwert der Point-of-Care-Gerinnungsdiagnostik im perioperativen Bereich.

Point-of-care (POC) devices are increasingly being used at the bedside in perioperative patient management of hemostatic function. Aggregometric methods can be utilized in preoperative screening of thrombocytopathia and are qualified to describe the efficacy of antiplatelet therapy. Published data about the value of point-of-care diagnostic gives partially conflicting results.Current prospective randomized studies indicate that implementation of hemostatic treatment algorithms based on viscoelastic and aggregometric POC-analysis may reduce transfusion rate of allogenic blood products, improve clinical outcome and reduce cost of hemostatic treatment.

[Management of extended blood loss and massive transfusion]. / Deklaration von Helsinki zur Patientensicherheit in der Anästhesiologie--Teil 5: Management des Blutungsnotfalls und der Massivtransfusion.

In patients suffering from massive bleeding, transfusion of allogenic blood products (red blood cells, fresh frozen plasma and platelets) and the application of other hemostatic therapy in form of coagulation factor concentrates represent therapeutic approaches to optimize hemostasis and to restore and assure tissue oxygenation. In accordance to the "Helsinki declaration on patient safety" of the European Society of Anaesthesiology, this review article describes a clinical practice guideline for the treatment of patients requiring massive transfusion that was implemented at the University hospital Frankfurt in 2013. Our guideline may be used as a template for other institutions.

Reduction of Fresh Frozen Plasma Requirements by Perioperative Point-of-Care Coagulation Management with Early Calculated Goal-Directed Therapy.

BACKGROUND: Massive bleeding and transfusion of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets are associated with increased morbidity, mortality and costs. PATIENTS AND METHODS: We analysed the transfusion requirements after implementation of point-of-care (POC) coagulation management algorithms based on early, calculated, goal-directed therapy with fibrinogen concentrate and prothrombin complex concentrate (PCC) in different perioperative settings (trauma surgery, visceral and transplant surgery (VTS), cardiovascular surgery (CVS) and general and surgical intensive care medicine) at 3 different hospitals (AUVA Trauma Centre Salzburg, University Hospital Innsbruck and University Hospital Essen) in 2 different countries (Austria and Germany). RESULTS: In all institutions, the implementation of POC coagulation management algorithms was associated with a reduction in the transfusion requirements for FFP by about 90% (Salzburg 94%, Innsbruck 88% and Essen 93%). Furthermore, PRBC transfusion was reduced by 8.4-62%. The incidence of intraoperative massive transfusion (≥10 U PRBC) could be more than halved in VTS and CVS (2.56 vs. 0.88%; p < 0.0001 and 2.50 vs. 1.06%; p = 0.0007, respectively). Platelet transfusion could be reduced by 21-72%, except in CVS where it increased by 115% due to a 5-fold increase in patients with dual antiplatelet therapy (2.7 vs. 13.7%; p < 0.0001). CONCLUSIONS: The implementation of perioperative POC coagulation management algorithms based on early, calculated, goal-directed therapy with fibrinogen concentrate and PCC is associated with a reduction in the transfusion requirements for FFP, PRBC and platelets as well as with a reduced incidence of massive transfusion. Thus, the limited blood resources can be used more efficiently.

Potential of whole blood coagulation reconstitution by desmopressin and fibrinogen under conditions of hypothermia and acidosis--an in vitro study using rotation thrombelastometry.

BACKGROUND: Desmopressin (DDAVP) and fibrinogen improve platelet function and clot stability. We investigated the influence of DDAVP and fibrinogen on whole blood coagulation in an in vitro model of hypothermia and acidosis. METHODS: After IRB approval and written consent blood samples were taken from 10 healthy volunteers. Samples were prepared with hydrochloric acid to maintain--beside normal pH--reduced pH (∼7.2) and severely reduced pH (∼7.0), and were assigned to four treatment groups: addition of either isotonic saline for compensation of dilutional effects (ISO), desmopressin (DDAVP+), fibrinogen (FIB+), or both substances (DDAVP+FIB+). Baseline was ISO at 37°C and normal pH. Remaining samples were incubated for 30 min and measured at 32°. Rotation thrombelastometry (ROTEM) after extrinsically activation and fibrin polymerization was tested. Repeated measures ANOVA were performed (p < 0.05). RESULTS: Hypothermia and acidosis synergistically impaired whole blood coagulation. DDAVP+ normalized maximum clot firmness (MCF) at normal pH. Coagulation time (CT) was not affected. FIB+ normalized MCF at pH 7.35 and pH 7.2. CT was normalized independently of pH. DDAVP+FIB+ did not show additional effects to FIB+. Fibrin polymerization was increased by FIB+ and DDAVP+FIB+ independently of pH. DDAVP+ did not alter fibrin polymerization. CONCLUSION: DDAVP and fibrinogen increased whole blood coagulation under hypothermia. Acidosis diminished this effect. Thus, acidosis should be corrected first and then both substances could be used for bridging until normothermia can be achieved. In combination, the effects of fibrinogen were overwhelming DDAVP effects. Thus, combined administration did not show any benefit compared to fibrinogen administration alone.

Tranexamic acid partially improves platelet function in patients treated with dual antiplatelet therapy.

BACKGROUND: Although the impact of tranexamic acid on platelet function remains controversial, tranexamic acid is part of clinical algorithms for the management of platelet dysfunction. The goal of our prospective, observational study was to examine the effects of tranexamic acid on platelet function in patients treated with dual antiplatelet therapy compared to those who ceased antiplatelet therapy for at least 7 days. METHODS: Forty patients scheduled for cardiac surgery were enrolled in this study. Group 1 consisted of 20 patients who ceased antiplatelet therapy with aspirin and clopidogrel at least 7 days before surgery. Group 2 consisted of 20 patients who were treated with aspirin and clopidogrel until the day before surgery. Using the Multiplate device (Dynabyte, Munich, Germany), multiple electrode aggregometry (MEA) was performed following platelet stimulation with thrombin receptor activating peptide-6 (TRAP-6), arachidonic acid or ADP on blood collected 20 min before and after application of 2 g tranexamic acid. RESULTS: Compared with group 1, platelet aggregation was statistically significantly reduced in ASPItest and ADPtest in group 2, whereas there were no significant differences in the TRAPtest. In group 1, platelet aggregation did not differ significantly before and after tranexamic acid treatment. In contrast, in group 2, we observed a significant increase in arachidonic acid-induced [295 (280/470) arbitrary aggregation units × min [AU*min; median (25th/75th percentile) vs. 214 (83/409) AU*min, P = 0.01] and ADP-induced platelet aggregation [560 AU*min (400/760 AU*min) vs. 470 AU*min (282/550 AU*min), P = 0.013], whereas platelet aggregation following stimulation with TRAP-6 did not change significantly [980 (877/1009) AU*min, median (25th/75th percentile) after tranexamic acid vs. 867 (835/961) AU*min before tranexamic acid, P = 0.464]. CONCLUSION: The results of this study indicate that tranexamic acid potentially corrects defects in arachidonic acid-induced and ADP-induced platelet aggregation imposed by dual antiplatelet therapy. However, platelet aggregation in response to arachidonic acid or ADP in the blood of patients who have not received aspirin and clopidogrel is unaffected by tranexamic acid. These results support the use of tranexamic acid to partially reverse platelet aggregation dysfunction due to antiplatelet therapy.

Interaction of heparin and protamine in presence of overdosage: in vitro study.

BACKGROUND: Heparin is used for anticoagulation during cardiopulmonary bypass. After weaning from bypass, protamine is administered to neutralize the effects of heparin and thus reestablish hemostasis. Rotational thrombelastometry has been shown to discriminate between heparin and other impairing effects on coagulation. We analyzed the interaction of heparin and protamine under different conditions of overdosage in an in-vitro trial. METHODS: Blood samples were taken from 17 healthy volunteers, separated, and spiked in vitro with heparin, protamine for heparin neutralization, an overdosage of protamine, and two dosages of re-heparinization to evaluate heparin effects under the condition of protamine overdosage. All samples were analyzed in a standard ROTEM rotational thromboelastometry device after intrinsic activation with and without addition of heparinase. Coagulation time, maximum clot firmness, and clot formation time were recorded. RESULTS: Heparin led to prolongation of coagulation and clot formation times in the test without heparinase. Adequate protamine addition normalized the test, and overdosage of protamine led to significant prolongation of both times. Addition of heparin in the presence of protamine overdosage normalized these parameters. CONCLUSION: We reconfirmed that the ROTEM device enables discrimination of the effects heparin and protamine on coagulation and detection of the coagulation-impairing effects of protamine overdosage. Furthermore, we were able to show a positive effect on coagulation times by heparin in the presence of protamine overdosage. Because this was an in-vitro study, these findings need to be confirmed in vivo, requiring further research.