Editor—In order to meet the current challenges in anaesthesiology, intensive care, and emergency medicine, highly specialised technologies are increasingly and urgently required. Recent years have seen major innovations, especially in the fields of bleeding diagnostics and individualised coagulation management. In the last 20 yr, point-of-care viscoelastic testing (VET) has become an integral part of goal-directed haemostatic therapy for bleeding patients in trauma, cardiac surgery, transplantation, and postpartum haemorrhage. 1 Gonzalez E. Moore E.E. Moore H.B. et al. Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg. 2016; 263: 1051-1059 Google Scholar , 2 Agarwal S. Abdelmotieleb M. Viscoelastic testing in cardiac surgery. Transfusion. 2020; 60: S52-S60 Google Scholar , 3 Khanna P. Sinha C. Singh A.K. Kumar A. Sarkar S. The role of point of care thromboelastography (TEG) and thromboelastometry (ROTEM) in management of Primary postpartum haemorrhage: a meta-analysis and systematic review. Saudi J Anaesth. 2023; 17: 23-32 Google Scholar , 4 Park S.Y. Viscoelastic coagulation test for liver transplantation. Anesth Pain Med (Seoul). 2020; 15: 143-151 Google Scholar Viscoelastic testing has gradually replaced standard coagulation tests such as prothrombin time and activated partial thromboplastin time in identifying and monitoring coagulopathy. 5 Weber C.F. Görlinger K. Meininger D. et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology. 2012; 117: 531-547 Google Scholar Moreover, VET-guided haemostatic therapy has been shown to reduce allogeneic blood product transfusion, and in certain indications mortality. 1 Gonzalez E. Moore E.E. Moore H.B. et al. Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg. 2016; 263: 1051-1059 Google Scholar ,5 Weber C.F. Görlinger K. Meininger D. et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology. 2012; 117: 531-547 Google Scholar Such data have given rise to the development of haemostatic treatment algorithms for bleeding patients, which have subsequently found their way into guidelines and recommendations issued by various societies. 6 Kietaibl S. Ahmed A. Afshari A. et al. Management of severe peri-operative bleeding: guidelines from the European society of anaesthesiology and intensive care: second update 2022. Eur J Anaesthesiol. 2023; 40: 226-304 Google Scholar ,7 Rossaint R. Afshari A. Bouillon B. et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023; 27: 80 Google Scholar

BACKGROUND:Thrombophilia testing is controversial, not least because of its high cost. Because comprehensive valid testing requires standardized blood collection close by the specialized laboratory, and interpretation of findings together with clinical data, often only part of the necessary laboratory analyses can be performed in remote central laboratories. Restrictive indications for testing, as have been recommended by previous reviews on the topic, have been based on incomplete analytics, studies with small case numbers, or short observation periods, and on an inappropriate, simple risk stratification for venous thromboembolism (VTE), further subdivided into provoked and unprovoked events.METHODS:The authors reviewed four electronic databases for all peer-reviewed and in-press articles about thrombophilia, VTE, obstetric complications, and arterial thrombosis. After confirmation for relevance to the topic, 201 articles were accepted for inclusion in this article. This review summarizes the studies relevant to the evaluation of thrombophilic conditions, and their combination with each other and with clinical risk factors, to stratify individual risk for thromboembolism and obstetric complications.RESULTS:Thrombophilia testing requires highly skilled personnel for laboratory analysis and interpretation. Clinical conditions that influence the results as well as special preanalytical, analytical, and postanalytical aspects must be considered if valid results are to be obtained. Tests involved include the natural anticoagulants antithrombin, protein C, and protein S; the procoagulants fibrinogen (dysfibrinogen), prothrombin (mutation G20210A), factor V (Leiden mutation), factor VIII/von Willebrand factor/blood group ABO, factor IX, and factor XI; the anti-phospholipid antibodies to detect an antiphospholipid syndrome and potentially additional uncertain thrombophilic conditions. The risks of thrombophilic conditions and clinical risk factors for VTE are cumulative or even supra-additive. Scores from thrombophilic conditions and other genetic and nongenetic risk factors permit estimation of risk for first and recurrent VTE. Therapeutic strategies can be derived from this risk stratification.CONCLUSIONS:Thrombophilia testing is indicated when the results have potential to influence the type and duration of treatment. Indications include certain patients after VTE; or patients without previous VTE but with positive family history regarding VTE or thrombophilia before major surgery, pregnancy, combined oral contraceptives, or hormone replacement therapy. Whether or not thrombophilia is present should help determine anticoagulation, hormonal contraception, or hormone replacement.

Abstract Objectives Assessing urgency in ectopic pregnancies (ECP) remains controversial since the disorder covers a large clinical spectrum. Severe conditions such as acute abdomen or hemodynamic instability are mostly related to intra-abdominal blood loss diagnosed as free fluid (FF) on transvaginal sonography (TVS). The aims of the current study were to investigate the value of FF and to assess other potentially predictive parameters for judging urgency. Methods Retrospective cohort analysis on prospectively collected cases of proven ECP (n = 343). Demographics, clinical and laboratory parameters, and findings on TVS and laparoscopy (LSC) were extracted from the digital patient file. FF on TVS and free blood (FB) in LSC were evaluated. Low urgency was defined as FB (LSC) < 100 ml and high urgency as FB (LSC) ≥ 300 ml. The best subset of variables for the prediction of FB was selected and predictors of urgency were evaluated using receiver operator characteristic (ROC) curves. Results Clinical symptoms, age, β-HCG, hemoglobin (HB) preoperative, and FF were examined in multivariate analysis for the cutoff values of 100 ml and 300 ml. FF was the only independent predictor for low and high urgency; HB preoperative was only significant for high urgency offering marginal improvement. ROC analysis revealed FF as an excellent discriminatory parameter for defining low (AUC 0.837, 95% CI 0.794–0.879) and high urgency (AUC 0.902, 95 % CI 0.860–0.945). Conclusion Single assessment of FF on TVS is most valuable for judging urgency. However, the exact cutoff values for a low- and high-risk situation must still be defined.

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.).

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.

Factor XIII (FXIII) is the final factor in the coagulation cascade. It converts soluble fibrin monomers into a stable fibrin clot, prevents premature degradation of fibrin, participates in wound healing, and helps prevent the loss of the endothelial barrier function. FXIII deficiency is believed to be rare, and this may explain why clinicians do not routinely take it into consideration. Congenital FXIII deficiency is a rare disease with a reported prevalence of 1 per million. However, the prevalence of acquired FXIII deficiency is much higher. Acquired forms have been described in patients with decreased hepatic or bone marrow synthesis, overconsumption and increased degradation by autoantibodies. This review offers guidance on how to suspect and diagnose FXIII deficiency in both the preoperative consultation and different surgical settings. We also analyze current scientific evidence in order to clarify when and why this clinical situation should be suspected, and how it may be treated. (Cite this article as: Guilabert P, Asmis L, Cortina V, Barret JP, Colomina MJ. Factor XIII and surgical bleeding. Minerva Anestesiol 2022;88:156-65. DOI: 10.23736/S0375-9393.22.15772-X)

BackgroundApplying a single anti-Xa assay, calibrated to unfractionated heparin to measure rivaroxaban, apixaban, and edoxaban would simplify laboratory procedures and save healthcare costs. AimWe hypothesized that a heparin-calibrated anti-Xa assay would accurately measure rivaroxaban, apixaban, and edoxaban drug concentrations and correctly predict clinically relevant drug levels. MethodsThis 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(R) 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). ResultsOverall, 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 mu g L-1, 95.8% (92.4-98.0) for 50 mu g L-1, and 98.7% (95.5-99.9) for 100 mu g L-1. Specificities were 86.3% (79.2-91.7), 89.8% (84.5-93.7), and 88.7% (84.2-92.2), respectively. ConclusionIn 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.

TransfusionVolume 61, Issue 3 p. 991-992 LETTER TO THE EDITOR Response to Wirtz et al: The impact of blood product ratio and procoagulant therapy on the development of thromboembolic events in severely injured hemorrhaging trauma patients Thorsten Haas, Corresponding Author thorsten.haas@kispi.uzh.ch orcid.org/0000-0002-9520-8693 Department of Pediatric Anesthesia, Zurich University Childrenʼs Hospital, Zurich, Switzerland Correspondence Thorsten Haas, Anesthesiology, University Childrenʼs Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland. Email: thorsten.haas@kispi.uzh.chSearch for more papers by this authorJeannie Callum, orcid.org/0000-0001-6133-0677 Transfusion Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaSearch for more papers by this authorOliver Grottke, Anesthesiology, RWTH Aachen University Hospital, Aachen, GermanySearch for more papers by this authorLars M. Asmis, Center of Perioperative Hemostasis, Zurich, SwitzerlandSearch for more papers by this authorMelissa M. Cushing, orcid.org/0000-0001-8042-1494 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USASearch for more papers by this author Thorsten Haas, Corresponding Author thorsten.haas@kispi.uzh.ch orcid.org/0000-0002-9520-8693 Department of Pediatric Anesthesia, Zurich University Childrenʼs Hospital, Zurich, Switzerland Correspondence Thorsten Haas, Anesthesiology, University Childrenʼs Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland. Email: thorsten.haas@kispi.uzh.chSearch for more papers by this authorJeannie Callum, orcid.org/0000-0001-6133-0677 Transfusion Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaSearch for more papers by this authorOliver Grottke, Anesthesiology, RWTH Aachen University Hospital, Aachen, GermanySearch for more papers by this authorLars M. Asmis, Center of Perioperative Hemostasis, Zurich, SwitzerlandSearch for more papers by this authorMelissa M. Cushing, orcid.org/0000-0001-8042-1494 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USASearch for more papers by this author First published: 14 March 2021 https://doi.org/10.1111/trf.16241 This letter was not supported in the form of grants, equipment, or drugs. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume61, Issue3March 2021Pages 991-992 RelatedInformation

Les thromboembolies veineuses représentent l’une des principales causes de morbidité et mortalité maternelles. Cet article présente les principes essentiels pour l’évaluation du risque et des recommandations pour la prise en charge de situations cliniques fréquentes.

Venöse Thromboembolien stellen eine der wichtigsten Ursachen mütterlicher Morbidität und Mortalität dar. Dieser Artikel legt wichtige Prinzipien der Risikoabschätzung und Empfehlungen zum Management häufiger klinischer Situationen dar.

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.

Based on the available literature and published recommendations from international societies, the Working Party on Hemostasis (Swiss Society of Hematology) has prepared recommendations for pharmacological thromboprophylaxis in COVID-19 patients in the acute setting.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect that occurs in 0.1–5% of heparin treated patients. Management of acute HIT currently involves (1) cessation of heparin exposure, and (2) inhibition of coagulation with an anticoagulant other than heparin. Several anticoagulants can be considered for the treatment of HIT. Anticoagulant monitoring, management of drug-induced adverse events including bleeding, and therapeutic dosing schedules in selected clinical settings represent challenges to the clinician treating HIT patients. Moreover, the fact that not all registered anticoagulants are approved for HIT in Switzerland further complicates the management of HIT. The present recommendations on the anticoagulant treatment of HIT in Switzerland have been elaborated by a panel of Swiss experts belonging to the Working Party Hemostasis (WPH) of the Swiss Society of Hematology (SGH-SSH). They are intended to support clinicians in their decision making when treating HIT patients.

INTRODUCTION: Emicizumab (Hemlibra (R), 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.

Although the viscoelastic testing (VET) method was first described by Hartert more than seven decades ago, its application as point-of-care (POC) instrumentation in the surgical and trauma settings is relatively recent. Short turnaround times and delivery of results in real time provide clinicians with a relevant and rapid global assessment of hemostasis. Recent advances have further simplified and parsed out the multiple components of hemostasis and clotting to assess for large alterations in clotting factors, inhibitors, fibrinogen, and fibrinolysis. As such, many have reported the use of various VET variables in managing perioperative bleeding and have developed transfusion protocols for specific blood products and pharmacological intervention based on these testing results.2–6 A summary of the VET method is discussed in previous articles within this supplementary edition. This article specifically focuses on the use of VET in the context of platelet function tests (PFTs), and its advantages and limitations compared to other PFT in various clinical settings.

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.

BACKGROUNDFibrinogen 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 METHODSTen 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.RESULTSClinical 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.CONCLUSIONPR Cryo used 5 days after thawing effectively restores clot strength after in vitro dilution.

Abstract 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.

Platelet quality in different platelet concentrates (PCs) has been the subject of several studies. Nonetheless, there is a lack of robust data on the correlation and agreement among platelet function tests as a prerequisite for the association of PC functionality in vitro with platelet function in vivo post PC transfusion. The purpose of our study was to correlate a larger panel of platelet function assays in PCs and to assess whether the methods agree sufficiently and can be used interchangeably. Twelve apheresis platelet concentrates in plasma (APC), 16 pooled platelet concentrates in plasma (PPC), and 12 PPC in T-sol (PPCA) were examined on days 1 and 4 after production. PCs were tested for platelet count, light transmission aggregation (LTA) induced by ADP, collagen, or TRAP; platelet ATP release induced by collagen; and spontaneous and ADP and TRAP-induced increase in CD62P and PAC1 expression measured by flow cytometry. All tests were performed in undiluted platelet-rich plasma, recalcified and mixed with an inhibitor of factor Xa and thrombin. Most platelet function parameters correlated significantly with each other, but agreement among methods was insufficient. A proper inverse correlation was observed between ADP-induced LTA and spontaneous platelet activation assessed by CD62P expression (r=-0.61, p<0.0001). Spontaneous CD62P correlated also significantly with spontaneous PAC1 (r=0.69, p<0.0001) and inversely with TRAP-induced CD62P expression (r=-0.86, p<0.0001). We found significant correlations among all flow cytometric assays measuring platelet CD62P and PAC1 expression induced by ADP or TRAP. Subsequent Bland Altman analysis revealed insufficient agreement between methods. With one exception (collagen-induced LTA compared with TRAP-induced LTA, percentage error=16%) the limits of agreement expressed as percentage error exceeded the chosen acceptable difference of 30%.In APC, platelet count was 41% and 44% higher, respectively, than in PPC and PPCA (p<0.0001). Spontaneous CD62P and PAC1 expression were significantly greater, and ADP-induced aggregation and agonist-induced increase in CD62P and PAC1 were significantly lower in PPCA compared to APC and PPC on day 4 of storage. ADP and TRAP-induced CD62P and PAC1 activatability fell significantly during storage between day 1 and day 4 in APC and PPCA, but not in PPC. In conclusion, different platelet function tests capture different aspects of platelet function and do not correlate and agree sufficiently to be used interchangeably.

Essentials Accurate determination of anticoagulant plasma concentration is important in clinical practice. We studied the accuracy and consistency of anti‐Xa assays for rivaroxaban in a multicentre study. In a range between 50 and 200 μg L−1, anti‐Xa activity correlated well with plasma concentrations. The clinical value might be limited by overestimation and intra‐ and inter‐individual variation.