TH open : companion journal to thrombosis and haemostasis最新文献

{"title":"Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors","authors":"Shuichi Okamoto, N. Suzuki, Atsuo Suzuki, Sachiko Suzuki, S. Tamura, Mochihito Suzuki, N. Takahashi, T. Kojima, T. Kanematsu, Tetsuhito Kojima, H. Kiyoi, N. Ishiguro, T. Matsushita","doi":"10.1055/s-0039-3401001","DOIUrl":"https://doi.org/10.1055/s-0039-3401001","url":null,"abstract":"Abstract We managed perioperative hemostasis for a 72-year-old man with hemophilia A and low inhibitor titers (3 BU/mL), who underwent osteosynthesis for supracondylar fracture of the left humerus. He was treated perioperatively using the combination of high doses of factor VIII (FVIII) with recombinant human Factor VIII Fc fusion protein (rFVIIIFc), followed by emicizumab. On the day of surgery (day 0), he was administered bolus infusion of 150 IU/kg rFVIIIFc, followed by continuous infusion at a dose of 4 IU/kg/h. Emicizumab, 3 mg/kg, was injected subcutaneously once a week, on days 5, 12, 19, and 26. Inhibitors were detected on day 6 at a titer of 4 BU/mL and FVIII:C decreased to below assay sensitivity limits on day 10. The rate of increase in inhibitor titers was high, with inhibitors increasing to 343.4 BU/mL on day 14. The transition of thrombin production by thrombin generation assay (TGA) showed temporary decrease in thrombin production on day 7, although it was restored by day 10, i.e., five days after commencement of emicizumab therapy. Rotational thromboelastometry displayed consistent results with TGA, showing that clotting time was prolonged and the alpha angle decreased to less than measurable levels on day 6, although they were improved by day 10. There were no bleeding-related events or other adverse events throughout the perioperative period. In conclusion, emicizumab was effective for the management of perioperative hemostasis after development of an anamnestic response in a patient with hemophilia A with inhibitors. Combination therapy with high doses of FVIII followed by emicizumab could be a workable alternative for patients with hemophilia A with inhibitors.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"102 1","pages":"e364 - e366"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80626545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Treatment of Cancer-Associated Thrombosis: Beyond HOKUSAI","authors":"I. Mahé, I. Elalamy, G. Gerotziafas, P. Girard","doi":"10.1055/s-0039-3400276","DOIUrl":"https://doi.org/10.1055/s-0039-3400276","url":null,"abstract":"[This corrects the article DOI: 10.1055/s-0039-1696659.].","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"1995 1","pages":"e348 - e349"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82430997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reliability and Feasibility of the Self-Administered ISTH-Bleeding Assessment Tool","authors":"M. Punt, M. Blaauwgeers, M. Timmer, P. Welsing, R. Schutgens, K. V. van Galen","doi":"10.1055/s-0039-3400483","DOIUrl":"https://doi.org/10.1055/s-0039-3400483","url":null,"abstract":"Abstract Introduction Standardized bleeding assessment tools (BATs), such as the International Society for Thrombosis and Hemostasis (ISTH)-BAT, are screening instruments used during the diagnostic workup of suspected bleeding disorders. A self-administered ISTH-BAT (self-BAT) would enhance screening and save time during an outpatient clinic visit. Aim This study was aimed to investigate the reliability and feasibility of the self-BAT. Methods The electronic self-BAT was created from the ISTH-BAT and paper-version of self-BAT and optimized by patients and physicians. Patients with a (suspected) congenital platelet defect (CPD), who had previously undergone physician-administered ISTH-BAT assessment, were invited to complete the self-BAT. Optimal self-BAT cut-off values to detect a bleeding tendency, as defined by the ISTH-BAT, were evaluated by receiver operator characteristic (ROC) curve analysis to reach a sensitivity ≥95%. Reliability was tested by assessing sensitivity, specificity, and intraclass correlation (ICC). Feasibility was evaluated on comprehension and length of self-BAT. Results Both versions of the BAT were completed by 156 patients. Optimal cut-off values for self-BAT to define a bleeding tendency were found to be identical to those of the ISTH-BAT. Normal/abnormal scores of the ISTH-BAT and self-BAT were agreed in 88.5% (138/156, 95% confidence interval [CI]: 0.83–0.93) of patients. The sensitivity and specificity of the self-BAT to detect a bleeding tendency were 96.9 and 48.1%, respectively. The ICC was 0.73. Self-BAT questions were graded by 96.8% (151/156) as “very easy,” “easy,” and “satisfactory” and questionnaire length as “exactly right” by 91% (142/156) of patients. Conclusion In patients with a (suspected) CPD, the self-BAT is sufficiently reliable and feasible to detect a bleeding tendency, which supports its use as a screening tool.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"40 1","pages":"e350 - e355"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78088920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermediate-High Risk Pulmonary Embolism","authors":"Rosa Mirambeaux, F. León, B. Bikdeli, R. Morillo, D. Barrios, E. Mercedes, L. Moores, V. Tapson, R. Yusen, D. Jiménez","doi":"10.1055/s-0039-3401003","DOIUrl":"https://doi.org/10.1055/s-0039-3401003","url":null,"abstract":"Abstract Limited information exists about the prevalence, management, and outcomes of intermediate-high risk patients with acute pulmonary embolism (PE). In a prospective cohort study, we evaluated consecutive patients with intermediate-high risk PE at a large, tertiary, academic medical center between January 1, 2015 and March 31, 2019. Adjudicated outcomes included PE-related mortality and a complicated course through 30 days after initiation of PE treatment. Repeat systolic blood pressure (SBP), heart rate (HR), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) measurements, and echocardiography were performed within 48 hours after diagnosis. Among 1,015 normotensive patients with acute PE, 97 (9.6%) had intermediate-high risk PE. A 30-day complicated course and 30-day PE-related mortality occurred in 23 (24%) and 7 patients (7.2%) with intermediate-high risk PE. Seventeen (18%) intermediate-high risk patients received reperfusion therapy. Within 48 hours after initiation of anticoagulation, normalization of SBP, HR, cTnI, BNP, and echocardiography occurred in 82, 86, 78, 72, and 33% of survivors with intermediate-high risk PE who did not receive immediate thrombolysis. A complicated course between day 2 and day 30 after PE diagnosis for the patients who normalized SBP, HR, cTnI, BNP, and echocardiography measured at 48 hours occurred in 2.9, 1.4, 4.5, 3.3, and 14.3%, respectively. Intermediate-high risk PE occurs in approximately one-tenth of patients with acute symptomatic PE, and is associated with high morbidity and mortality. Normalization of HR 48 hours after diagnosis might identify a group of patients with a very low risk of deterioration during the first month of follow-up.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"34 1","pages":"e356 - e363"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83839226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Hypoxic Environment Attenuates Exercise-Induced Procoagulant Changes Due to Decreased Platelet Activation.","authors":"Cécile H Kicken,&nbsp;Lisa N van der Vorm,&nbsp;Suzanne Zwaveling,&nbsp;Evi Schoenmaker,&nbsp;Jasper A Remijn,&nbsp;Dana Huskens,&nbsp;Bas de Laat","doi":"10.1055/s-0039-1692991","DOIUrl":"https://doi.org/10.1055/s-0039-1692991","url":null,"abstract":"<p><p><b>Introduction</b>  Although physical exercise is protective against cardiovascular disease, it can also provoke sudden cardiac death (exercise paradox). Epidemiological studies suggest that systemic hypoxia at high altitude is a risk factor for venous thromboembolism. Forthcoming, this study investigated the effect of repeated exercise at high altitude on blood coagulation, platelet function, and fibrinolysis. <b>Methods</b>  Six trained male volunteers were recruited. Participants ascended from sea level to 3,375 m altitude. They performed four exercise tests at 65 to 80% of their heart-rate reserve during 2 hours: one time at sea level and three times on consecutive days at 3,375 m altitude. Thrombin generation (TG) was measured in whole blood (WB) and platelet-rich and platelet-poor plasma. Coagulation factor levels were measured. Platelet activation was measured as αIIbβ3 activation and P-selectin expression. Fibrinolysis was studied using a clot-lysis assay. <b>Results</b>  Normoxic exercise increased plasma peak TG through increased factor VIII (FVIII), and increased von Willebrand factor (VWF) and active VWF levels. Platelet granule release potential was slightly decreased. After repetitive hypoxic exercise, the increase in (active) VWF tapered, and there was no more distinct exercise-related increase in peak. Platelet aggregation potential and platelet-dependent TG decreased at high altitude. There were no effects on fibrinolysis upon exercise and/or hypoxia. <b>Conclusion</b>  Strenuous exercise induces a procoagulant state that is mediated by the endothelium, by increasing VWF and secondarily raising FVIII levels. After repetitive exercise, the amplitude of the endothelial response to exercise diminishes. A hypoxic environment appears to further attenuate the procoagulant changes by decreasing platelet activation and platelet-dependent TG.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"3 3","pages":"e216-e226"},"PeriodicalIF":0.0,"publicationDate":"2019-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0039-1692991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Deficiency of Intrinsic Coagulation Factors XI and XII on Ex Vivo Thrombus Formation and Clot Lysis","authors":"J. Govers-Riemslag, Joke Konings, J. Cosemans, Johanna P. van Geffen, B. de Laat, J. Heemskerk, Y. Dargaud, H. ten Cate","doi":"10.1055/s-0039-1693485","DOIUrl":"https://doi.org/10.1055/s-0039-1693485","url":null,"abstract":"Abstract The contributions of coagulation factor XI (FXI) and FXII to human clot formation is not fully known. Patients with deficiency in FXI have a variable mild bleeding risk, whereas FXII deficiency is not associated with bleeding. These phenotypes make FXII and FXI attractive target proteins in anticoagulant therapy. Here, we studied the mechanisms of fibrin clot formation, stability, and fibrinolytic degradation in patients with severe FXI or FXII deficiency. Thrombin generation was triggered in platelet-poor (PPP) and platelet-rich plasma (PRP) with the biological FXII trigger sulfatides. Intrinsic and extrinsic thrombus formation and degradation in whole blood were determined with rotational thromboelastometry (ROTEM). Clot formation under flow was assessed by perfusion of whole blood over collagen microspots with(out) tissue factor (TF). Thrombin generation and clot formation were delayed in FXII- and FXI-deficient patients triggered with sulfatides. In FXI-deficient plasma, this delay was more pronounced in PRP compared to PPP. In whole blood of FXII-deficient patients, clots were smaller but resistance to fibrinolysis was normal. In whole blood of FXI-deficient patients, clot formation was normal but the time to complete fibrinolysis was prolonged. In flow chamber experiments triggered with collagen/TF, platelet coverage was reduced in severe compared with moderate FXI deficiency, and fibrin formation was impaired. We conclude that quantitative defects in FXII and FXI have a substantial impact on contact activation-triggered coagulation. Furthermore, FXI deficiency has a dose-dependent suppressing effect on flow-mediated and platelet/TF-dependent clot formation. These last data highlight the contribution of particularly FXI to hemostasis.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"23 1","pages":"e273 - e285"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81295042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The (Fab)ulous Destiny of Idarucizumab: Highlighting Its Interference with Urine Protein Immunofixation","authors":"N. Gendron, H. Flament, E. Litvinova, Sofia Ortuno, N. Ajzenberg, D. Faille","doi":"10.1055/s-0039-1697642","DOIUrl":"https://doi.org/10.1055/s-0039-1697642","url":null,"abstract":"Abstract Idarucizumab is a humanized antigen binding fragment (Fab) of a recombinant anti-dabigatran monoclonal antibody (IgG1-kappa) that allows rapid and sustained reversal of dabigatran-induced anticoagulation in case of bleeding or urgent surgery. Herein, we report a very unusual case of dabigatran reversal by idarucizumab in a 79-year-old woman with acute kidney failure admitted to a hospital in a context of hemoptysis. Three repeated injections were necessary because of massive dabigatran overdose and high rebounds of dabigatran plasma concentration. Idarucizumab was found on urine immunofixation up to 6 days after the last injection where it reacted with anti-kappa light chain antibody, but not with anti-gamma heavy chain antibody. Physicians should be aware of the increased half-life of idarucizumab in this context of acute kidney impairment and of its interference with urine immunofixation because it could lead to false-positive results and misdiagnosis of a paraprotein.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"33 1","pages":"e306 - e308"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80659882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the PAR-1 Antagonist Vorapaxar on Platelet Activation and Coagulation Biomarkers in Patients with Stable Coronary Artery Disease","authors":"R. Olie, P. V. D. van der Meijden, H. Spronk, R. van Oerle, S. Barvik, V. Bonarjee, H. ten Cate, D. Nilsen","doi":"10.1055/s-0039-1695710","DOIUrl":"https://doi.org/10.1055/s-0039-1695710","url":null,"abstract":".","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"5 1","pages":"e259 - e262"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80673096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cartridge-Based Thromboelastography Can Be Used to Monitor and Quantify the Activity of Unfractionated and Low-Molecular-Weight Heparins","authors":"J. Dias, C. Lopez-Espina, M. Panigada, H. Dalton, J. Hartmann, Hardean E. Achneck","doi":"10.1055/s-0039-1696658","DOIUrl":"https://doi.org/10.1055/s-0039-1696658","url":null,"abstract":"Abstract Thromboelastography is increasingly utilized in the management of bleeding and thrombotic complications where heparin management remains a cornerstone. This study assessed the feasibility of the cartridge-based TEG® 6s system (Haemonetics Corp., Braintree, Massachusetts, United States) to monitor and quantify the effect of unfractionated and low-molecular-weight heparin (UFH and LMWH). Blood samples from healthy donors were spiked with UFH (n = 23; 0–1.0 IU/mL) or LMWH (enoxaparin; n = 22; 0–1.5 IU/mL). Functional fibrinogen maximum amplitude (CFF.MA), RapidTEG activated clotting time (CRT.ACT), and kaolin and kaolin with heparinase reaction time (CK.R and CKH.R) were evaluated for their correlation with heparin concentrations, as well as the combination parameters ΔCK.R − CKH.R, ratio CK.R/CKH.R, and ratio CKH.R/CK.R. Nonlinear mixed-effect modelling was used to study the relationship between concentrations and parameters, and Bayesian classification modelling for the prediction of therapeutic ranges. CK.R and CRT.ACT strongly correlated with the activity of LMWH and UFH (p < 0.001). Using combination parameters, heparin activity could be accurately quantified in the range of 0.05 to 0.8 IU/mL for UFH and 0.1 to 1.5 IU/mL for LMWH. CRT.ACT was able to quantify heparin activity at higher concentrations but was only different from the reference range (p < 0.05) at >0.5 IU/mL for UFH and >1.5 IU/mL for LMWH. Combination parameters classified blood samples into subtherapeutic, therapeutic, and supratherapeutic heparin ranges, with an accuracy of >90% for UFH, and >78% for LMWH. This study suggests that TEG 6s can effectively monitor and quantify heparin activity for LMWH and UFH. Additionally, combination parameters can be used to classify blood samples into therapeutic ranges based on heparin activity.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"75 1","pages":"e295 - e305"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89531450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Factor XII Autoantibodies in Patients with Recurrent Pregnancy Loss Recognize the Second Epidermal Growth Factor–Like Domain","authors":"Yoshihiro Sato, T. Sugi, R. Sakai","doi":"10.1055/s-0039-1695709","DOIUrl":"https://doi.org/10.1055/s-0039-1695709","url":null,"abstract":"Summary Background Factor XII (FXII) deficiency and autoantibodies that bind to FXII (anti-FXII) have been described in patients with adverse pregnancy outcomes, including recurrent pregnancy loss. It has been reported that FXII functions not only as a coagulation protein but also as a growth factor. Objectives We studied the association between anti-FXII and the epidermal growth factor (EGF) system in patients with recurrent pregnancy loss. Patients/Methods We used synthetic peptides that span the second EGF-like domain in the heavy chain of FXII (EGF2) in inhibition and direct binding studies to determine if anti-FXII antibodies recognize EGF2. Furthermore, we examined whether anti-FXII antibodies, which recognize EGF2, also recognize recombinant EGF and heparin-binding EGF-like growth factor (HB-EGF). Results Among 100 patients with recurrent pregnancy loss, the plasma of 23 patients (23.0%) recognized the synthetic peptide ASQ41, which covers EGF2. Among the 23 anti-ASQ41-positive patients, plasma samples from 13 patients (56.5%) recognized the 22-residue segment C-terminal half of ASQ41. Among the 23 anti-ASQ41-positive patients, the plasma of 17 patients (73.9%) recognized recombinant human EGF. Affinity-purified anti-FXII antibodies, which recognize ASQ41, also recognized recombinant EGF family proteins such as EGF and HB-EGF. Conclusions The autoantibodies in patients with recurrent pregnancy loss recognized the EGF2 domain in FXII and other proteins of the EGF family. Since proteins in the EGF family play an important role in normal pregnancy, autoantibody-associated disruption of the EGF system may cause pregnancy loss.","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"1 1","pages":"e263 - e272"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76046169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}