Daniel Dirkmann

Hypothermia and acidosis synergistically impair coagulation in human whole blood.

BACKGROUND:Hypothermia and acidosis were reported to influence coagulopathy in different clinical settings. We evaluated whole blood coagulation to determine the effects of hypothermia and/or acidosis on hemostasis. METHODS:Whole blood samples (3.000 &mgr;L) from 10 healthy volunteers (2 female, 8 male) were acidified by adding 40 &mgr;L of hydrochloric acid of increasing molarity to achieve a blood pH (&agr;-stat) between 7.0 and 7.37, and coagulation was analyzed by rotational thromboelastometry after an incubation period of 30 min using both intrinsically (InTEM ™) and extrinsically (ExTEM ™) activated assays. To assess temperature-dependent effects, all tests were performed at blood/thromboelastometer temperatures of 30, 33, 36, and 39°C, respectively. An additional extrinsically activated test with addition of cytochalasin D was performed to examine clot formation without platelet contribution. RESULTS:Hypothermia at a normal pH produced an increased coagulation time [ExTEM: 65 s ± 3.6 (36°C) vs 85 ± 4 (30°C), P < 0.001; coagulation time, InTEM: 181 s ± 10 (36°C) vs 226 ± 9, P < 0.001] and clot formation time [ExTEM: 105 s ± 5 (36°C) vs 187 ± 6 (30°C), P < 0.001]; clot formation time [InTEM: 101 s ± 5 (36°C) vs 175 ± 7, P < 0.001], as well as decreased &agr; angle [ExTEM: 65.6 ± 1.8 (36°C) vs 58 ± 1.1, P < 0.01, P < 0.01; InTEM: 70.5 ± 1.8 (36°C) vs 60.2 ± 1.5, P < 0.001]. Maximum clot firmness was significantly impaired only in InTEM assays [56.9 mm ± 0.9 (36°C) vs 52.7 ± 0.9, P < 0.05]. In contrast, acidosis per se had no significant effects during normothermia. Acidosis amplified the effects of hypothermia, and synergistically impaired clotting times, &agr; angle, and decreased maximum clot firmness, again in both extrinsically and intrinsically activated assays. Formation of a fibrin clot tested after abolition of platelet function by cytochalasin D was not impaired. Clot lysis decreased under hypothermic and/or acidotic conditions, but increased with hyperthermia. CONCLUSIONS:In this in vitro study, hypothermia produced coagulation changes that were worsened by acidosis whereas acidosis without hypothermia has no significant effect on coagulation, as studied by thromboelastometry. This effect was mediated by the inhibition of coagulation factors and platelet function. Thus, thromboelastometry performed at 37°C overestimated integrity of coagulation during hypothermia in particular in combination with acidosis.

Perioperative Coagulation Management and Control of Platelet Transfusion by Point-of-Care Platelet Function Analysis

About one third of all blood components transfused intraoperatively is used in cardiac surgery, whereas mortality of cardiosurgical patients correlates nearly linear with the number of transfused units of packed red blood cells. Acquired platelet function disorders play a major role in perioperative bleeding in cardiac surgery. Therefore, the use of point-of-care-suitable platelet function analyzers seems to be reasonable in this field. Methods: Platelet function analyzer PFA-100®, rotational thrombelastometry (ROTEM®), and multiple platelet function analyzer (Multiplate®) are in principle applicable for point-of-care testing. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. Results: Perioperative use of platelet function analyzers is helpful in prediction of blood loss in cardiac surgery. Perioperative usage of blood components and their respective costs can be reduced by an appropriate coagulation management. Conclusion: Algorithms for perioperative coagulation management based on point-of-care testing permit a fast diagnostic and goal-directed therapy of coagulation and functional platelet disorders. The possibility to reduce the mortality of patients and the overall cost for hospital stay is subject of further studies.

Potential value of transfusion protocols in cardiac surgery

Purpose of review On the one hand, cardiac and aortic surgery is associated with a high rate of allogeneic blood transfusion. On the other hand, both bleeding and allogeneic blood transfusion is associated with increased morbidity, mortality, and hospital costs in cardiac and aortic surgery. This article reviews the current literature between 1995 and 2012 dealing with transfusion protocols in cardiovascular surgery. The 16 studies fitting these search criteria have evaluated the impact of the implementation of ROTEM/TEG based coagulation management algorithms on transfusion requirement and outcome in overall 8507 cardiovascular surgical patients. Recent findings The use of point-of-care (POC) transfusion and coagulation management algorithms based on viscoelastic tests such as thromboelastometry (ROTEM) and thrombelastography (TEG) in combination with POC platelet function tests such as whole blood impedance aggregometry (Multiplate) have been shown to be associated with reduced allogeneic blood transfusion requirements, reduced incidence of thrombotic/thromboembolic and transfusion-related adverse events, and improved outcomes in cardiac surgery. Summary Implementation of POC algorithms including a comprehensive bundle of POC diagnostics (thromboelastometry and whole blood impedance aggregometry) in combination with first-line therapy using immediately available specific coagulation factor concentrates (fibrinogen and prothrombin complex concentrate) and defining strict indications, calculated dosages, and clear sequences for each haemostatic intervention seems to be complex but most effective in reducing perioperative transfusion requirements and has been shown to be associated with a decreased incidence of thrombotic/thromboembolic events, transfusion-related adverse events, as well as with improved patients’ outcomes including 6-month mortality.

Factor XIII and tranexamic acid but not recombinant factor VIIa attenuate tissue plasminogen activator-induced hyperfibrinolysis in human whole blood.

BACKGROUND: Hyperfibrinolysis is a pathological state that often results in depletion of coagulation factors and platelets and can contribute to bleeding. Factor XIII (FXIII) and thrombin activatable fibrinolysis inhibitor have key roles in protecting clots against fibrinolysis. We tested the hypotheses that FXIII concentrate, prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), and tranexamic acid (TA) inhibit fibrinolysis to different degrees, and that platelets contribute to antifibrinolysis. METHODS: Hyperfibrinolysis was induced by addition of recombinant tissue plasminogen activator (r-tPA) (final concentration: 100 ng · mL−1) to citrated whole blood obtained from 13 healthy volunteers. To assess inhibition of fibrinolysis, we added to the assays FXIII-A2B2 (0.42 U · mL−1), PCC (0.42 U · mL−1), rFVIIa (final concentration: 1.6 &mgr;g · mL−1), TA (final concentration: 0.33 mg · mL−1), or saline. Coagulation was analyzed by rotational thromboelastometry (ROTEM®) using the clot lysis index (CLI) after 45 and 60 minutes in extrinsically activated assays, with (FIBTEM®) and without (EXTEM®) inhibition of platelet function by cytochalasin D. RESULTS: After r-tPA–evoked fibrinolysis (CLI45: median 78%; 72/85.5, 25th/75th percentile), FXIII (90%; 82.5/96, P = 0.025), PCC (89%; 74/91, P = 0.0465), and TA (94%; 92/96, P = 0.001) but not rFVIIa (79%; 72/86.5, P = 1.0) significantly attenuated the decrease in CLI. Similarly, CLI60 increased only with FXIII (66%; 33/90.5, P = 0.017) and TA (90%; 89/92, P = 0.001) compared with r-tPA alone (21%; 7/59). After abolition of platelet function by cytochalasin D, only TA (95%; 89/97.5, P = 0.0025) and PCC (84%; 70.5/90, P = 0.0305) but not FXIII or rFVIIa significantly increased CLI45 and CLI60 (TA: 89%; 84.5/96, P = 0.01 and PCC: 55%; 29.5/60, P = 0.0405) compared with r-tPA alone (CLI45: 59%; 40.5/72.5 and CLI60: 10%; 0/30). CONCLUSION: In thromboelastometric assays using whole blood, only TA, FXIII, and PCC significantly inhibited r-tPA–evoked hyperfibrinolysis whereas rFVIIa had no effect. We also found that the effects of exogenous FXIII were dependent on the presence of functional platelets.

Coagulation management with factor concentrates in liver transplantation: a single‐center experience

Allogeneic blood products transfusion during liver transplantation (LT) can be associated with increased morbidity and mortality. Data on thromboelastometry (ROTEM)‐guided coagulation management with coagulation factor concentrates (CFCs)—fibrinogen concentrate and/or prothrombin complex concentrate (PCC)—are sparse. We aimed to retrospectively evaluate the safety events observed with this approach in our clinic.

[Platelet function analysis with point-of-care methods].

BACKGROUND More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance. METHODS Platelet function analyzer (PFA-100), multiple platelet function analyzer (Multiplate), and rotational thrombelastometry (ROTEM) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. RESULTS PFA-100 enables a sensitive detection of von Willebrands syndrome. Multiplate is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction. CONCLUSION Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.ZusammenfassungHintergrund:Immer mehr Patienten werden heutzutage mit Thrombozytenaggregationshemmern behandelt. Dabei ist eine suffiziente Blockade der Thrombozytenaggregation einerseits von entscheidender Bedeutung für die Effektivität einer Herzinfarkt- oder Schlaganfallprophylaxe, insbesondere bei Patienten mit medikamentenbeschichteten Stents. Andererseits kann diese Medikation aber auch perioperativ zu einem wesentlich erhöhten Blutungsrisiko führen. Für beide Situationen ist eine Kontrolle der Effektivität der Therapie bzw. eine Beurteilung der Beeinträchtigung des Hämostasesystems von entscheidender Bedeutung.Methodik:Mit dem Platelet Function Analyzer (PFA-100®), dem Multiple Platelet Function Analyzer (Multiplate®) und der Rotationsthrombelastometrie (ROTEM®) stehen zurzeit leicht zu bedienende und verlässliche Point-of-Care-(POC-)taugliche Geräte zur Verfügung, die jedoch unterschiedliche Aspekte der Thrombozytenfunktion untersuchen und auch unterschiedliche Limitationen aufweisen. Daher hängt die Auswahl des richtigen Testsystems von der jeweiligen Fragestellung ab.Ergebnisse:Der PFA-100® ermöglicht einen sensitiven Nachweis eines Von-Willebrand-Syndroms. Der Multi plate®-Analyzer eignet sich zur Kontrolle der Effektivität einer Therapie mit Thrombozytenaggregationshemmern, wie z.B. Acetylsalicylsäure, Clopidogrel und Glykoprotein-IIb/IIIa-Rezeptor-Antagonisten. Die ROTEM®-Analyse ermöglicht eine ganzheitliche Beurteilung des Hämostasesystems und erfasst dabei insbesondere eine Hyperfibrinolyse, Heparineffekte und die Fibrinogen-Thrombozyten-Interaktion.Schlussfolgerung:Aufgrund ihrer einfachen Handhabbarkeit sind die beschriebenen POC-Geräte sowohl für den Einsatz im Operationssaal oder auf der Intensivstation als auch im Herzkatheterlabor oder in der kardiologischen Praxis geeignet. Sie ermöglichen dort eine schnelle Erfassung der Thrombozytenfunktion und eine individuell gesteuerte Therapie.AbstractBackground:More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance.Methods:Platelet function analyzer (PFA-100®), multiple platelet function analyzer (Multiplate®), and rotational thrombelastometry (ROTEM®) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question.Results:PFA-100® enables a sensitive detection of von Willebrands syndrome. Multiplate® is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM® analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM® analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction.Conclusion:Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.

Assessment of early thromboelastometric variables from extrinsically activated assays with and without aprotinin for rapid detection of fibrinolysis.

BACKGROUND:Although thromboelastometry (ROTEM®) and thrombelastography can be used for bedside diagnosis of fibrinolysis, the time needed for detection is often prolonged. Since untreated fibrinolysis can result in consumption of coagulation factors and bleeding, early diagnosis and decision making are desirable. Accordingly, we assessed ROTEM variables from extrinsically activated assays with (APTEM®) and without (EXTEM®) addition of aprotinin for their ability to rapidly identify fibrinolysis. Specifically, we tested the hypotheses that prolonged clotting time, clot formation time, low clot firmness (at 5, 10, 15, and 20 minutes, designated A5, A10, A15, and A20, respectively), low maximum clot firmness (MCF) in EXTEM assays, and differences in these variables from parallel APTEM and EXTEM assays (designated as &Dgr;variables) predict fibrinolysis. METHODS:Data from 411 thromboelastometric measurements (obtained from 352 patients) with fibrinolysis and from 2537 measurements without fibrinolysis (obtained from 1605 patients) were assessed and analyzed using receiver operating characteristics. Data were analyzed as a pooled fibrinolysis cohort, and subanalyses were performed from sets assigned to categories of fibrinolysis related to the timing of thrombus lysis (i.e., a decrease of clot firmness to <15% of MCF within 30, 45, and 60 minutes, respectively). A lower 95% confidence limit of the area under the receiver operating characteristic curve (AUC [SE] <0.6) was considered a failure to substantially improve detection of increased fibrinolysis. AUCs were compared to identify the variable providing the best predictive association with fibrinolysis. As a secondary end point, optimum cutoff values at the point estimate corresponding to the greatest Youden index were calculated along with the respective sensitivities and specificities. RESULTS:In the pooled cohort, clot formation time (AUC: 0.652 [0.016]), &agr;-angle (AUC: 0.675 [0.015]), A5 (AUC: 0.718 [0.013]), A10 (AUC: 0.734 [0.0.13]), A15 (AUC: 0.752 [0.013]), A20 (AUC: 0.771 [0.013]), and MCF (AUC: 0.799 [0.012]) predicted fibrinolysis. Fibrinolysis was also predicted by &Dgr;A15 (AUC: 0.675 [0.016]), &Dgr;A20 (AUC: 0.719 [0.015]), and &Dgr;MCF (AUC: 0.812 [0.013]). AUCs increased in a time-related fashion. The ability to predict subsequent fibrinolysis based on thromboelastometry was higher when it occurred early rather than later during testing. However, for prediction of late fibrinolysis, only MCF (AUC: 0.655 [0.025]) appears to be potentially clinically useful. CONCLUSIONS:Low early values of clot firmness in extrinsically activated thromboelastometric assays are associated with fibrinolysis and improve its early detection. Additional assays with aprotinin fail to improve the early diagnosis of fibrinolysis compared with assays without aprotinin.

Recombinant tissue-type plasminogen activator-evoked hyperfibrinolysis is enhanced by acidosis and inhibited by hypothermia but still can be blocked by tranexamic acid.

BACKGROUND Hypothermia and acidosis have been suggested as key initiators of trauma-induced coagulopathy, and severe bleeding caused by hyperfibrinolysis (HF) predicts mortality. We tested in vitro (1) whether clinically relevant grades of hypothermia, acidosis, and their combination impact on recombinant tissue-type plasminogen activator (r-tPA)–evoked HF and assessed (2) the efficacy of tranexamic acid (TA) in inhibiting fibrinolysis under such conditions. METHODS To assess the effects of r-tPA–evoked HF, venous blood (3,000 &mgr;L) from healthy volunteers was incubated with r-tPA (final concentration, 100 ng/mL) or saline (control) for 30 minutes at the final measurement temperature. Before thromboelastometric measurements, samples were acidified (addition of 40 &mgr;L of 0.5 or 1N hydrochloric acid, respectively) to achieve a pH (alpha-stat) of approximately 7.1 or 6.9, respectively. To assess effects of hypothermia, tests were performed at blood/thromboelastometer temperatures of 33°C and 37°C, respectively. Coagulation was analyzed using rotational thromboelastometry (ROTEM), particularly assessing the Clot Lysis Index (CLI) after 45 minutes (CLI45) in extrinsically activated assays (EXTEM). RESULTS Addition of r-tPA evoked fibrinolysis (CLI45: median, 64; 25th/75th percentile, 48/80) compared with saline controls (CLI45: median, 93; 25th/75th percentile, 91/96). Moderate acidosis (pH [mean ± SD], 7.12 ± 0.03) did not affect r-tPA–induced fibrinolysis. However, severe acidosis (pH, 6.91 ± 0.02) significantly aggravated r-tPA–induced fibrinolysis (CLI45: median, 49; 25th/75th percentile, 26/71; p = 0.0039) compared with fibrinolysis with normal pH and normothermia (median, 77; 25th/75th percentile, 65.5/83). In contrast, hypothermia (33°C) at normal pH (median ± SD, 7.37 ± 0.02) markedly mitigated fibrinolysis (CLI45: median, 94; 25th/75th percentile, 88/96; p = 0.0156) compared with normothermia (CLI45: median, 64; 25th/75th percentile, 48/80). TA (final concentration, 0.33 mg/mL) abolished r-tPA–evoked fibrinolysis even during severe acidosis (CLI45: median, 92; 25th/75th percentile, 86.5/94; p = 0.0039). CONCLUSION Severe acidosis significantly increases r-tPA–evoked fibrinolysis, whereas hypothermia markedly mitigates HF. The latter finding may imply that rapid rewarming of trauma patients might aggravate fibrinolysis. TA reliably abolished fibrinolysis also under these conditions, supporting its role in trauma-induced coagulopathy.

Messung der Thrombozytenfunktion mit Point-of-Care-Methoden

BACKGROUND More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance. METHODS Platelet function analyzer (PFA-100), multiple platelet function analyzer (Multiplate), and rotational thrombelastometry (ROTEM) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. RESULTS PFA-100 enables a sensitive detection of von Willebrands syndrome. Multiplate is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction. CONCLUSION Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.ZusammenfassungHintergrund:Immer mehr Patienten werden heutzutage mit Thrombozytenaggregationshemmern behandelt. Dabei ist eine suffiziente Blockade der Thrombozytenaggregation einerseits von entscheidender Bedeutung für die Effektivität einer Herzinfarkt- oder Schlaganfallprophylaxe, insbesondere bei Patienten mit medikamentenbeschichteten Stents. Andererseits kann diese Medikation aber auch perioperativ zu einem wesentlich erhöhten Blutungsrisiko führen. Für beide Situationen ist eine Kontrolle der Effektivität der Therapie bzw. eine Beurteilung der Beeinträchtigung des Hämostasesystems von entscheidender Bedeutung.Methodik:Mit dem Platelet Function Analyzer (PFA-100®), dem Multiple Platelet Function Analyzer (Multiplate®) und der Rotationsthrombelastometrie (ROTEM®) stehen zurzeit leicht zu bedienende und verlässliche Point-of-Care-(POC-)taugliche Geräte zur Verfügung, die jedoch unterschiedliche Aspekte der Thrombozytenfunktion untersuchen und auch unterschiedliche Limitationen aufweisen. Daher hängt die Auswahl des richtigen Testsystems von der jeweiligen Fragestellung ab.Ergebnisse:Der PFA-100® ermöglicht einen sensitiven Nachweis eines Von-Willebrand-Syndroms. Der Multi plate®-Analyzer eignet sich zur Kontrolle der Effektivität einer Therapie mit Thrombozytenaggregationshemmern, wie z.B. Acetylsalicylsäure, Clopidogrel und Glykoprotein-IIb/IIIa-Rezeptor-Antagonisten. Die ROTEM®-Analyse ermöglicht eine ganzheitliche Beurteilung des Hämostasesystems und erfasst dabei insbesondere eine Hyperfibrinolyse, Heparineffekte und die Fibrinogen-Thrombozyten-Interaktion.Schlussfolgerung:Aufgrund ihrer einfachen Handhabbarkeit sind die beschriebenen POC-Geräte sowohl für den Einsatz im Operationssaal oder auf der Intensivstation als auch im Herzkatheterlabor oder in der kardiologischen Praxis geeignet. Sie ermöglichen dort eine schnelle Erfassung der Thrombozytenfunktion und eine individuell gesteuerte Therapie.AbstractBackground:More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance.Methods:Platelet function analyzer (PFA-100®), multiple platelet function analyzer (Multiplate®), and rotational thrombelastometry (ROTEM®) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question.Results:PFA-100® enables a sensitive detection of von Willebrands syndrome. Multiplate® is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM® analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM® analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction.Conclusion:Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.

Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.

Background:Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex’s impact on a panel of coagulation assays. Methods:Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Results:Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (−7%, P = 0.009; −7.8%, P < 0.0001; −6.9%, P < 0.0001; and −4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Conclusion:Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.