Recombinant ADAMTS13 for Hereditary Thrombotic Thrombocytopenic Purpura.

A 27-year-old patient with a history of severe obstetrical complications and arterial thrombosis received a diagnosis of hereditary thrombotic thrombocytopenic purpura (TTP) due to severe ADAMTS13 deficiency when she presented with an acute episode in the 30th week of her second pregnancy. When the acute episode of hereditary TTP became plasma-refractory and fetal death was imminent, weekly injections of recombinant ADAMTS13 at a dose of 40 U per kilogram of body weight were initiated. The patient's platelet count normalized, and the growth of the fetus stabilized. At 37 weeks 1 day of gestation, a small-for-gestational-age boy was delivered by cesarean section. At the time of this report, the patient and her son were well, and she continued to receive injections of recombinant ADAMTS13 every 2 weeks. (Funded by the Swiss National Science Foundation.).

Thromboprophylaxis with argatroban in critically ill patients with sepsis: a review.

During sepsis, an initial prothrombotic shift takes place, in which coagulatory acute-phase proteins are increased, while anticoagulatory factors and platelet count decrease. Further on, the fibrinolytic system becomes impaired, which contributes to disease severity. At a later stage in sepsis, coagulation factors may become depleted, and sepsis patients may shift into a hypo-coagulable state with an increased bleeding risk. During the pro-coagulatory shift, critically ill patients have an increased thrombosis risk that ranges from developing micro-thromboses that impair organ function to life-threatening thromboembolic events. Here, thrombin plays a key role in coagulation as well as in inflammation. For thromboprophylaxis, low molecular weight heparins (LMWH) and unfractionated heparins (UFHs) are recommended. Nevertheless, there are conditions such as heparin resistance or heparin-induced thrombocytopenia (HIT), wherein heparin becomes ineffective or even puts the patient at an increased prothrombotic risk. In these cases, argatroban, a direct thrombin inhibitor (DTI), might be a potential alternative anticoagulatory strategy. Yet, caution is advised with regard to dosing of argatroban especially in sepsis. Therefore, the starting dose of argatroban is recommended to be low and should be titrated to the targeted anticoagulation level and be closely monitored in the further course of treatment. The authors of this review recommend using DTIs such as argatroban as an alternative anticoagulant in critically ill patients suffering from sepsis or COVID-19 with suspected or confirmed HIT, HIT-like conditions, impaired fibrinolysis, in patients on extracorporeal circuits and patients with heparin resistance, when closely monitored.

Accuracy of a Single, Heparin-Calibrated Anti-Xa Assay for the Measurement of Rivaroxaban, Apixaban, and Edoxaban Drug Concentrations: A Prospective Cross-Sectional Study.

Background: Applying a single anti-Xa assay, calibrated to unfractionated heparin to measure rivaroxaban, apixaban, and edoxaban would simplify laboratory procedures and save healthcare costs. Aim: We hypothesized that a heparin-calibrated anti-Xa assay would accurately measure rivaroxaban, apixaban, and edoxaban drug concentrations and correctly predict clinically relevant drug levels. Methods: This analysis is part of the Simple-Xa study, a prospective multicenter cross-sectional study conducted in clinical practice. Patients treated with rivaroxaban, apixaban, or edoxaban were included. Anti-Xa activity was measured using the Siemens INNOVANCE® Heparin assay. Drug concentrations were determined using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cut-off levels were determined in a derivation dataset (50% of patients) and sensitivities and specificities were calculated in a verification dataset (50% of patients). Results: Overall, 845 patients were available for analysis. Correlation coefficients (r s ) between the heparin-calibrated anti-Xa assay and drug concentrations were 0.97 (95% CI 0.97, 0.98) for rivaroxaban, 0.96 (0.96, 0.97) for apixaban, and 0.96 (0.94, 0.99) for edoxaban. The area under the receiver operating characteristics curve (ROC) was 0.99 for all clinically relevant drug concentrations. In the verification dataset, the sensitivity was 94.2% (95% CI 90.8-96.6) for 30 µg L-1, 95.8% (92.4-98.0) for 50 µg L-1, and 98.7% (95.5-99.9) for 100 µg L-1. Specificities were 86.3% (79.2-91.7), 89.8% (84.5-93.7), and 88.7% (84.2-92.2), respectively. Conclusion: In a large prospective study in clinical practice, a strong correlation of heparin-calibrated anti-Xa measurements with LC-MS/MS results was observed and clinically relevant drug concentrations were predicted correctly.

The Angiostrongylus vasorum Excretory/Secretory and Surface Proteome Contains Putative Modulators of the Host Coagulation.

Angiostrongylus vasorum is a cardiopulmonary nematode of canids and is, among others, associated with bleeding disorders in dogs. The pathogenesis of such coagulopathies remains unclear. A deep proteomic characterization of sex specific A. vasorum excretory/secretory proteins (ESP) and of cuticular surface proteins was performed, and the effect of ESP on host coagulation and fibrinolysis was evaluated in vitro. Proteins were quantified by liquid chromatography coupled to mass spectrometry and functionally characterized through gene ontology and pathway enrichment analysis. In total, 1069 ESP (944 from female and 959 from male specimens) and 1195 surface proteins (705 and 1135, respectively) were identified. Among these were putative modulators of host coagulation, e.g., von Willebrand factor type D domain protein orthologues as well as several proteases, including serine type proteases, protease inhibitors and proteasome subunits. The effect of ESP on dog coagulation and fibrinolysis was evaluated on canine endothelial cells and by rotational thromboelastometry (ROTEM). After stimulation with ESP, tissue factor and serpin E1 transcript expression increased. ROTEM revealed minimal interaction of ESP with dog blood and ESP did not influence the onset of fibrinolysis, leading to the conclusion that Angiostrongylus vasorum ESP and surface proteins are not solely responsible for bleeding in dogs and that the interaction with the host's vascular hemostasis is limited. It is likely that coagulopathies in A. vasorum infected dogs are the result of a multifactorial response of the host to this parasitic infection.

Management of bleeding events and invasive procedures in patients with haemophilia A without inhibitors treated with emicizumab.

INTRODUCTION: Emicizumab (Hemlibra®, Hoffmann-La Roche, Switzerland) is now available for haemophilia A patients with or without factor VIII inhibitors. Management of bleeding events and replacement therapy for invasive procedures have to be adapted. OBJECTIVE: To provide a practical guidance for the management of breakthrough bleeding events and elective or urgent surgery in adult and paediatric patients with haemophilia A without inhibitors treated with emicizumab. METHODS: Based on the available literature and the experiences collected from adult and paediatric patients treated in Switzerland, the Working Party on Haemostasis of the Swiss Society of Haematology and the Swiss Haemophilia Network worked together to reach a consensus on the management of bleeding events and invasive procedures. RESULTS AND CONCLUSION: Minor bleeding events and invasive procedures associated with low bleeding risk can be treated without factor replacement therapy in most cases, whereas major bleeding events and high-risk surgery require additional factor VIII replacement at usual doses, at least for the first days. Emicizumab treatment should be continued throughout the procedure and during the postoperative period. Elective major surgery should be planned according to emicizumab dosing for patients with a once-a-month posology. Of note, so far only few data are available on the management of major bleeds and surgery in patients with haemophilia A treated with emicizumab and this practical guidance will have to be regularly updated with growing experience.  .

Efficacy of a new pathogen-reduced cryoprecipitate stored 5 days after thawing to correct dilutional coagulopathy in vitro.

BACKGROUND: Fibrinogen supplementation during bleeding restores clot strength and hemostasis. Cryoprecipitate, a concentrated source of fibrinogen, has prolonged preparation time for thawing, a short shelf life resulting in frequent wastage, and infectious disease risk. This in vitro study investigated the efficacy of a new pathogen-reduced cryoprecipitate thawed and stored at room temperature for 5 days (PR Cryo) to treat dilutional hypofibrinogenemia, compared to immediately thawed standard cryoprecipitate (Cryo) or fibrinogen concentrate (FC). STUDY DESIGN AND METHODS: Ten phlebotomy specimens from healthy volunteers were diluted 1:1 with crystalloid and supplemented with PR Cryo and Cryo (at a dose replicating transfusion of two pooled doses [10 units]) and FC at a dose replicating 50 mg/kg. Changes in clot firmness (thromboelastometry) and in coagulation factor activity were assessed at baseline, after dilution, and after supplementation. RESULTS: Clinical dosing was used, as described above, and consequently the FC dose contained 24% and 36% more fibrinogen versus PR Cryo and Cryo, respectively. At baseline, subjects had a median FIBTEM maximum clot firmness of 13.5 mm, versus 6.5 mm after 50% dilution (p = 0.005). After supplementation with PR Cryo, a median FIBTEM maximum clot firmness of 13 mm was observed versus 9.0 mm for Cryo (p = 0.005) or 16.5 mm for FC (p = 0.005). Median factor XIII was higher after PR Cryo (64.8%) versus Cryo (48.3%) (p = 0.005). Fibrinogen activity was higher after FC (269.0 mg/dL) versus PR Cryo (187.0 mg/dL; p = 0.005) or Cryo (193.5 mg/dL; p = 0.005); the difference between PR Cryo and Cryo supplementation (p = 0.445) was not significant. CONCLUSION: PR Cryo used 5 days after thawing effectively restores clot strength after in vitro dilution.

Comparison of the efficacy of two human fibrinogen concentrates to treat dilutional coagulopathy in vitro.

Both congenital and acquired fibrinogen deficiency can be safely treated with administration of fibrinogen concentrate. The aim of this study was to test the efficacy of a new fibrinogen product (Fibryga) compared to a licensed product (Haemocomplettan) in an in vitro model of dilutional coagulopathy. Ten blood specimens from healthy volunteers were diluted 1:1 with balanced crystalloid solution and subsequently supplemented with each fibrinogen concentrate at a dose replicating in vivo supplementation (50 mg kg-1). Changes in clot firmness (FIBTEM and EXTEM assay), as well as changes in the fibrinogen antigen level, fibrinogen activity, factor XIII level and fibronectin levels were assessed at baseline, after dilution and after adding fibrinogen concentrate. There was no significant difference between the drugs in their in vitro ability to improve clot firmness in the FIBTEM assay (Fibryga: mean MCF 14.4 mm (SD 3.4 mm) vs. Haemocomplettan: MCF 14.1 mm (2.4); p = .584). Fibryga led to significantly higher clot firmness in EXTEM MCF: 56.7 mm (3.8) vs. 53.7 mm (3.7); p < .001). Distinct differences between FXIII levels (significantly higher in Fibryga; mean 40.9% (6.2%) vs. 31.0% (6.2%); p < .001) and fibronectin levels (significantly higher in Haemocomplettan; mean 0.008 g L-1 (SD 0.002 g L-1) vs. 0.002 g L-1 (SD 0.002 g L-1; p < .001) were observed between products. This is the first study to demonstrate that Fibryga and Haemocomplettan have similar efficacy in improving clot firmness in a dilutional hypofibrinogenemia model in vitro.

Influence of cryoprecipitate, Factor XIII, and fibrinogen concentrate on hyperfibrinolysis.

BACKGROUND: Hyperfibrinolysis is a potentially life-threatening condition associated with poor clot integrity and excessive bleeding. Although antifibrinolytics are an effective treatment, more liberal use of these drugs may lead to a prothrombotic risk, and an earlier and potentially safer treatment option would be desirable. Hyperfibrinolysis has been shown to be attenuated by in vitro supplementation of purified human Factor (F)XIII concentrate. Cryoprecipitate represents an alternative source of FXIII and the only approved source of concentrated FXIII in some countries. The aim of this study was to investigate whether cryoprecipitate, FXIII, and fibrinogen concentrate mitigate hyperfibrinolysis. STUDY DESIGN AND METHODS: Ten citrate blood specimens from healthy subjects were spiked with tissue plasminogen activator (t-PA) and subsequently supplemented with cryoprecipitate, FXIII, fibrinogen concentrate, and ɛ-aminocaproic acid (EACA). Thromboelastometry tests were performed at baseline, after t-PA, and after supplementation. Hyperfibrinolysis was assessed using the clot lysis index at 60 minutes (LI60; reciprocal of maximum lysis). RESULTS: The LI60 was significantly improved (fibrinolysis attenuated) after cryoprecipitate supplementation compared to t-PA alone and compared to FXIII and fibrinogen concentrate. Hyperfibrinolysis was only fully reversed using EACA. In addition, cryoprecipitate demonstrated the least variability in the attenuation of hyperfibrinolysis among 10 healthy subjects, compared to FXIII and fibrinogen concentrate. CONCLUSION: This is the first study to show that cryoprecipitate is able to significantly mitigate hyperfibrinolysis in an in vitro model. Further investigations are warranted to determine whether cryoprecipitate may have a previously unrecognized benefit and should be administered earlier in resuscitation protocols.

Impact of rivaroxaban on point-of-care assays.

BACKGROUND: Point-of-care testing (POCT) is regularly used to assess haemostasis in various clinical settings. The impact of rivaroxaban on those POCT is still elusive. We aimed to study the effects of rivaroxaban on most commonly used POCT assays. METHODS: Blood samples were taken before, 3h, and 24h after administration of 20mg rivaroxaban to 20 healthy volunteers as part of a prospective, multicenter validation study (clinicaltrials.govNCT01710267). Blood samples were analysed with thromboelastometry (ROTEM®), two platelet function assays (INNOVANCE® PFA-200 and Multiplate®), and the CoaguChek® XS. Rivaroxaban plasma levels were determined using liquid chromatography-mass spectrometry. RESULTS: Rivaroxaban significantly modified some thromboelastometry parameters (CT INTEM: mean difference 56.1s, 95% CI: 41.8, 70.3; CT EXTEM: 47.5s, 95% CI: 37.8, 57.1; CT HEPTEM: 50.1s, 95% CI: 34.7, 65.6), and CoaguChek® XS parameters (prothrombin time: mean difference 3.8s, 95% CI: 3.3, 4.2; INR: 0.32, 95% CI: 0.27, 0.38; prothrombin ratio: -36.1%, 95% CI: -32.3, -39.9). CT EXTEM and INR showed a moderate correlation with rivaroxaban plasma levels (r=0.83; 95% CI 0.69, 0.9 and r=0.83; 95% CI 0.70, 0.91, respectively) and a high sensitivity to detect rivaroxaban treatment at peak levels (0.95; 95% CI: 0.76, 1.0 and 0.90, 95% CI 0.70, 0.99, respectively). CONCLUSIONS: Rivaroxaban 20mg treatment significantly alters ROTEM® and CoaguChek® XS parameters. Even though POCT do not allow precise quantification of rivaroxaban plasma concentration, CT EXTEM and CoaguChek XS detect the presence of rivaroxaban at peak level with a high sensitivity.

Is viscoelastic coagulation monitoring with ROTEM or TEG validated?

Recent years have seen increasing worldwide interest in the use of viscoelastic coagulation monitoring tests, performed using devices such as ROTEM and TEG. The use of such tests to guide haemostatic therapy may help reduce transfusion of allogeneic blood products in bleeding patients and is supported in European guidelines for managing trauma and severe perioperative bleeding. In addition, viscoelastic tests form the basis of numerous published treatment algorithms. However, some publications have stated that viscoelastic tests are not validated. A specific definition of the term validation is lacking and regulatory requirements of the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have been fulfilled by ROTEM and TEG assays. Viscoelastic tests have been used in pivotal clinical trials, and they are approved for use in most of the world's countries. Provided that locally approved indications are adhered to, the regulatory framework for clinicians to use viscoelastic tests in routine clinical practice is in place.

A brief review of 50 years of perioperative thrombosis and hemostasis management.

Perioperative thrombosis and hemostasis management has changed dramatically over the past 50 years. From two anticoagulants and one anti-aggregant, the number of currently available drugs has recently increased several-fold, leaving clinicians with the problem of choosing the optimal agent. Individualized preoperative assessment of bleeding risk based on bleeding history and testing limited to high-risk patients is an emerging concept. Based on the identification of risk factors for venous thromboembolism (VTE), pharmacologic and non-pharmacologic strategies for perioperative VTE prophylaxis have had a major impact on patient outcome. For patients undergoing surgery who are treated with anticoagulants and anti-aggregants, "bridging" strategies have been proposed. Bleeding management strategies have shifted focus from replacing lost blood volume to new approaches aimed at preventing blood loss, reducing the potential complications of blood loss, and preventing the transfusion of blood products. For some areas of perioperative thrombosis and hemostasis management, randomized controlled trial (RCT) data are emerging, but the database remains insufficient to date. Clearly, more RCTs need to be published for perioperative thrombosis and hemostasis management to become an evidence-based approach.

FIBTEM PLUS provides an improved thromboelastometry test for measurement of fibrin-based clot quality in cardiac surgery patients.

BACKGROUND: The viscoelastic functional fibrinogen (FF) and FIBTEM assays measure the contribution of fibrin to clot strength. Inhibition of platelet function is a necessary precondition for these tests to work. We investigated a novel test for measuring fibrin-based clotting, FIBTEM PLUS, in cardiac surgery and compared it with FF and FIBTEM. METHODS: A prospective, observational study was performed which included 30 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Blood samples were drawn at the beginning of surgery (pre-CPB), approximately 20 minutes before weaning from CPB and 5 minutes after heparin neutralization. FF, FIBTEM, and FIBTEM PLUS tests were performed in duplicate for all blood samples. Additional coagulation parameters, including platelet count, plasma fibrinogen levels, factor XIII activity, and heparin concentration, were also recorded for each sample. RESULTS: At all time points, the lowest mean maximum clot firmness (MCF) was observed with FIBTEM PLUS, although a statistically significant difference between FIBTEM and FIBTEM PLUS was observed only at baseline (mean values 22 vs 19 mm, P = 0.01; FF value for comparison: 27.7 mm). FF maximum amplitude (MA) values were significantly higher than FIBTEM MCF and FIBTEM PLUS MCF pre-CPB, during CPB and after heparin neutralization (P ≤ 0.001 for FF MA versus FIBTEM MCF and for FF MA versus FIBTEM PLUS MCF at all time points). The difference between FIBTEM MCF and FIBTEM PLUS MCF correlated with platelet count (r = 0.46;P < 0.001), whereas differences between FF MA and FIBTEM MCF, or FF MA and FIBTEM PLUS MCF did not (r = -0.07, P = 0.51; r = 0.16, P = 0.12, respectively). Differences between the assays were unrelated to heparin levels, which decreased considerably after protamine administration compared with heparin levels recorded before weaning from CPB (decrease from 2.1 to 0.1 U/mL and from 2.8 to 0.2 U/mL for anti-factor IIa and anti-factor Xa, respectively). Agreement between duplicate measurements was similar with FIBTEM and FIBTEM PLUS assays and lower with FF. Significant positive correlations were found between MCF or MA and fibrinogen concentration (all P < 0.001); the highest correlation was with FIBTEM PLUS MCF (r = 0.70). CONCLUSION: The FIBTEM PLUS assay produces precise results. At baseline, it provides greater inhibition of platelets than FIBTEM, but there is no meaningful difference between FIBTEM PLUS and FIBTEM in patients with low platelet counts.

Variability between laboratories performing coagulation tests with identical platforms: a nationwide evaluation study.

BACKGROUND: While the assessment of analytical precision within medical laboratories has received much attention in scientific enquiry, the degree of as well as the sources causing variation between them remains incompletely understood. In this study, we quantified the variance components when performing coagulation tests with identical analytical platforms in different laboratories and computed intraclass correlations coefficients (ICC) for each coagulation test. METHODS: Data from eight laboratories measuring fibrinogen twice in twenty healthy subjects with one out of 3 different platforms and single measurements of prothrombin time (PT), and coagulation factors II, V, VII, VIII, IX, X, XI and XIII were analysed. By platform, the variance components of (i) the subjects, (ii) the laboratory and the technician and (iii) the total variance were obtained for fibrinogen as well as (i) and (iii) for the remaining factors using ANOVA. RESULTS: The variability for fibrinogen measurements within a laboratory ranged from 0.02 to 0.04, the variability between laboratories ranged from 0.006 to 0.097. The ICC for fibrinogen ranged from 0.37 to 0.66 and from 0.19 to 0.80 for PT between the platforms. For the remaining factors the ICC's ranged from 0.04 (FII) to 0.93 (FVIII). CONCLUSIONS: Variance components that could be attributed to technicians or laboratory procedures were substantial, led to disappointingly low intraclass correlation coefficients for several factors and were pronounced for some of the platforms. Our findings call for sustained efforts to raise the level of standardization of structures and procedures involved in the quantification of coagulation factors.

Perioperative diclofenac application during video-assisted thoracic surgery pleurodesis modulates early inflammatory and fibrinolytic processes in an experimental model.

BACKGROUND/PURPOSE: It has been substantiated that the quality of pleurodesis is reduced when non-steroidal anti-inflammatory drugs (NSAIDs) are used perioperatively. The effects of NSAID administration on the early inflammatory and fibrinolytic processes after mechanical pleurodesis were investigated in an established pig model. METHODS: Left-sided mechanical pleural abrasion was performed on 24 pigs assigned to either an NSAID or a control group. Pleural fluid and blood samples were analysed over a 24-hour period. Histological evaluation of neutrophil influx at the site of pleural abrasion was performed. RESULTS: The volume of pleural effusion was significantly decreased in the diclofenac group at 10 and 24 h, and the protein content was significantly lower. The diclofenac group at 24 h had a diminished total number of white blood cells and a reduced content of transforming growth factor-ß. Moreover, the diclofenac group had a reduced percentage of neutrophils at 6 h. Significantly increased levels of D-dimers and tissue plasminogen activator were measured at 6 h and of interleukin-10 at 24 h. Neutrophils at the site of pleural abrasion were significantly reduced. CONCLUSIONS: Systemic application of diclofenac led to a local enhancement of fibrinolysis and attenuation of pro-inflammatory and fibrotic processes necessary for adhesion formation in our model.

[The new Anticoagulants - Relevant Facts for the GP]. / Die neuen Antikoagulantien - Was muss der Praktiker wissen?

Goal of this article is to select three molecules from all the candidates currently under clincial development and to present and comapre their characteristics. Dabigatran is a direct thrombin (FIIa) inhibitor, whereas Rivaroxaban and Apixaban are direct factor Xa (FXa) inhibitors. All three represent small molecules thatreversibly, rapidly and directly bind to their target, the active center of the respective activated coagulation factor. Phase III data have been published for venous thromboembolism prophylaxis for each of these three drugs. Interestingly, VTE prophylaxis is initiated postoperatively with these products. Rivaroxaban currently holds the only accepted indication in Switzerland. For the indications VTE, atrial fibrillation and acute coronary syndrome promising phase III data have been or are in the process of being published. Monitoring is not necessary for any of these three new anticoagulants.

Immunomodulatory drugs increase endothelial tissue factor expression in vitro.

INTRODUCTION: Immunomodulatory compounds such as thalidomide (THL) and lenalidomide (LEN) represent treatment options for multiple myeloma. Venous thromboembolism is a potential complication of immunomodulatory treatment in myeloma patients. The optimal thromboprophylactic strategy to prevent this drug-induced hypercoagulable state is debated. It is the aim of this study to investigate i) the effect of immunomodulatory treatment on endothelial cell tissue factor (TF) expression and function, ii) the regulation of the observed TF activity, and iii) the modulating effect of low molecular weight heparin and aspirin on TF activity in vitro. MATERIALS AND METHODS: These aims were addressed in an in vitro culture model, human umbilical vein endothelial cells, using TF activity and antigen assays as well flow cytometry, real time PCR and electron microscopy. RESULTS: At THL and LEN concentrations resembling those observed in myeloma patients in vivo and in the presence of tumor necrosis factor-α (TNFα) we observed significantly increased TF activity in human umbilical vein endothelial cells in vitro. Concordant changes were detected for tissue factor mRNA and TF whole cell antigen. Dalteparin and a mixture of monoclonal anti-TF antibodies inhibited TF activity by 100% and more than 80% respectively, while aspirin's inhibitory effect was only approximately 30%. In the presence of TNFα we detected the generation of endothelial cell-derived microparticles which expressed TF activity. CONCLUSIONS: Our in vitro data support the hypothesis that THL and LEN induce a hypercoagulable state through increased endothelial TF expression.

In vitro factor XIII supplementation increases clot firmness in Rotation Thromboelastometry (ROTEM).

Factor XIII (F XIII) is an essential parameter for final clot stability. The purpose of this study was to determine the impact of the addition of factor (F)XIII on clot stability as assessed by Rotation Thromboelastometry (ROTEM). In 90 intensive care patients ROTEM measurements were performed after in vitro addition of F XIII 0.32 IU, 0.63 IU, 1.25 IU and compared to diluent controls (DC; aqua injectabile) resulting in approximate F XIII concentrations of 150, 300 and 600%. Baseline measurements without any additions were also performed. The following ROTEM parameters were measured in FIBTEM and EXTEM tests: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), maximum lysis (ML), maximum clot elasticity (MCE) and alpha-angle (alphaA). Additionally, laboratory values for FXIII, fibrinogen (FBG), platelets and haematocrit were contemporaneously determined. In the perioperative patient population mean FBG concentration was elevated at 5.2 g/l and mean FXIII concentration was low at 62%. The addition of FXIII led to a FBG concentration-dependent increase in MCF both in FIBTEM and EXTEM. Mean increases in MCF (FXIII vs. DC) of approximately 7 mm and 6 mm were observed in FIBTEM and EXTEM, respectively. F XIII addition also led to decreased CFT, increased alphaA, and reduced ML in FIBTEM and EXTEM. In vitro supplementation of FXIII to supraphysiologic levels increases maximum clot firmness, accelerates clot formation and increases clot stability in EXTEM and FIBTEM as assayed by ROTEM in perioperative patients with high fibrinogen and low FXIII levels.