| 1. |
- Aradi, Daniel, et al.
(författare)
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Platelet function testing in acute cardiac care - is there a role for prediction or prevention of stent thrombosis and bleeding?
- 2015
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 113:2, s. 221-230
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Tidskriftsartikel (refereegranskat)abstract
- The role of platelet function testing in acute coronary syndrome patients undergoing percutaneous coronary intervention remains controversial despite the fact that high platelet reactivity is an independent predictor of stent thrombosis and emerging evidence suggests also a link between low platelet reactivity and bleeding. In this expert opinion paper, the Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association and the Working Group on Thrombosis of the European Society of Cardiology aim to provide an overview of current evidence in this area and recommendations for practicing clinicians.
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| 2. |
- Axelman, Elena, et al.
(författare)
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Novel peptides that inhibit heparanase activation of the coagulation system
- 2014
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 112:3, s. 466-477
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Tidskriftsartikel (refereegranskat)abstract
- Heparanase is implicated in cell invasion, tumour metastasis and angiogenesis. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (IF). We describe new peptides derived from the solvent accessible surface of TF pathway inhibitor 2 (TFPI-2) that inhibit the heparanase procoagulant activity. Peptides were evaluated in vitro by measuring activated coagulation factor X levels and co-immunoprecipitation. Heparanase protein and/or lipopolysaccharide (LPS) were injected intra-peritoneally and inhibitory peptides were injected subcutaneously in mouse models. Plasma was analysed by ELISA for thrombin-antithrombin complex (TAT), D-dimer as markers of coagulation activation, and interleukin 6 as marker of sepsis severity. Peptides 5, 6, 7, 21 and 22, at the length of 11-14 amino acids, inhibited heparanase procoagulant activity but did not affect IF activity. Injection of newly identified peptides 5, 6 and 7 significantly decreased or abolished TAT plasma levels when heparanase or LPS were pre-injected, and inhibited clot formation in an inferior vena cava thrombosis model. To conclude, the solvent accessible surface of TFPI-2 first Kunitz domain is involved in TF/heparanase complex inhibition. The newly identified peptides potentially attenuate activation of the coagulation system induced by heparanase or LPS without predisposing to significant bleeding tendency.
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| 3. |
- Badimon, Lina, et al.
(författare)
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Antithrombotic therapy in obesity
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:4, s. 681-688
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Tidskriftsartikel (refereegranskat)abstract
- Clinical management of obese subjects to reduce their risk of suffering cardiovascular events is complex. Obese patients typically require preventive strategies, life-style modifications, and multi-drug therapy to address obesity-induced co-morbidities. Data regarding the effects of excess weight on the pharmacokinetics of most drugs is scarce as these individuals are often excluded from clinical trials. However, the physiological alterations observed in obese patients and their lower response to some antiplatelet agents and anticoagulants have suggested that dosage regimes need to be adjusted for these subjects. In this review we will briefly discuss platelet alterations that can contribute to increased thrombotic risk, analyse existing data regarding the effects of obesity on drug pharmacokinetics focusing on antiplatelet agents and anticoagulants, and we will describe the beneficial effects of weight loss on thrombosis.
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| 4. |
- Becker, Richard C., et al.
(författare)
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Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome
- 2010
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 104:5, s. 976-983
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Tidskriftsartikel (refereegranskat)abstract
- Apixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acute coronary syndrome (ACS) Apixaban's effect on D dimer and prothrombin fragment 12 (F1 2) (coagulation activity biomarkers) was determined in a randomised, double blinded, placebo controlled phase 2 study Patients (n=1,715) with either ST segment elevation or non ST segment elevation ACS received either placebo or apixaban 2 5 mg twice daily 10 mg once daily, 10 mg twice daily or 20 mg once daily for six months Samples were obtained at baseline (before study drug administration), week 3 and week 26 Apixaban plasma concentrations were measured directly by liquid chromatography/mass spectometry and anti Xa activity was determined using apixaban as a reference standard D dimer and F 1 2 were measured using ELISA based methods Most patients had elevated D dimer and Fl 2 levels at baseline Both coagulation activity biomarkers decreased by week 3 in all treatment groups but to a greater degree with apixaban than placebo (p<0 001) In a multivariable analysis, apixaban was independently associated with a change in biomarkers over time (p<0 0001) While the overall decrease did not differ significantly among the three highest apixaban doses, Fl 2 was suppressed more rapidly by the 10 mg once daily than the 2 5 mg twice daily dose (p<0 05) There was a strong and direct relationship between apixaban plasma concentrations and anti Xa apixaban levels, and an inverse relationship for both measures with coagulation activity biomarkers In conclusion the oral direct factor Xa inhibitor apixaban significantly reduced coagulation activity biomarkers among patients with ACS The 10 mg once daily dose reduced thrombin generation (F 1 2) and fibrin formation (D dimer) more rapidly and robustly than the 25 mg twice daily dose The effect on both D dimer and F 12 was apixaban concentration and factor Xa inhibition dependent durable and provided general guidance for dose selection in phase 3 investigation.
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| 5. |
- Bergqvist, David, et al.
(författare)
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Evaluation of the duration of thromboembolic prophylaxis after high-risk orthopaedic surgery : The ETHOS observational study
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 270-279
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Tidskriftsartikel (refereegranskat)abstract
- Real-life data on post-discharge venous thromboembolism (VTE) prophylaxis practices and treatments are lacking. We assessed post-operative VTE prophylaxis prescribed and received in a prospective registry, compared with the 2004 American College of Chest Physicians (ACCP) guidelines in high-risk orthopaedic surgery patients. Consecutive patients undergoing total hip arthroplasty (THA), hip fracture surgery (HFS), or knee arthroplasty (KA) were enrolled at discharge from 161 centres in 17 European countries if they had received in-hospital VTE prophylaxis that was considered in accordance with the ACCP guidelines by the treating physician. Data on prescribed and actual prophylaxis were obtained from hospital charts and patient post-discharge diaries. Post-operative prophylaxis prescribed and actual prophylaxis received were considered adherent or adequate, respectively, if recommended therapies were used for ≥28 days (HFS and THA) or ≥10 days (KA). Among 4,388 patients, 69.9% were prescribed ACCP-adherent VTE prophylaxis (THA: 1,411/2,217 [63.6%]; HFS: 701/1,112 [63.0%]; KA: 955/1,059 [90.2%]). Actual prophylaxis received was described in 3,939 patients with an available diary after discharge (non-evaluability rate of 10%). Mean actual durations of pharmacological prophylaxis from surgery were: 28.4 ± 13.7 (THA), 29.3 ± 13.9 (HFS), and 28.7 ± 14.1 days (KA). ACCP-adequate VTE prophylaxis was received by 66.5% of patients (60.9% THA, 55.4% HFS, and 88.7% KA). Prophylaxis inadequacies were mainly due to inadequate prescription, non-recommended prophylaxis prescription at discharge, or too short prophylaxis prescribed. In high-risk orthopaedic surgery patients with hospital-initiated prophylaxis, there is a gap between ACCP recommendations, prescribed and actual prophylaxis received, mainly due to inadequate prescription at discharge.
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| 6. |
- Bergqvist, David, et al.
(författare)
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Post-discharge compliance to venous thromboembolism prophylaxis in high-risk orthopaedic surgery : Results from the ETHOS registry
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 280-287
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) risk persists for several weeks following high-risk orthopaedic surgery (HROS). The ETHOS registry evaluated post-operative VTE prophylaxis prescribed, and actual VTE prophylaxis received, compared with the 2004 American College of Chest Physicians (ACCP) guidelines in HROS patients. We performed a subanalysis of ETHOS to assess patient compliance with ACCP-adherent prophylaxis after discharge and the factors predicting poor compliance. Consecutive patients undergoing hip fracture surgery, total hip arthroplasty, or knee arthroplasty were enrolled at discharge from 161 centres in 17 European countries if they had received adequate in-hospital VTE prophylaxis. Data on prescribed and actual prophylaxis received were obtained from hospital charts and patient post-discharge diaries. Good compliance was defined as percentage treatment intake ≥80% with no more than two consecutive days without treatment. A total of 3,484 patients (79.4%) received ACCP-adherent anticoagulant prescription at discharge and 2,999 (86.0%) had an evaluable patient diary. In total, 87.7% of evaluable patients were compliant with prescribed treatment after discharge. The most common reason for non-compliance (33.4%) was "drug was not bought". Injection of treatment was not a barrier to good compliance. Main factors affecting compliance related to purchase of and access to treatment, patient education, the person responsible for administering injections, country, and type of hospital ward at discharge. Within our study population, patient compliance with ACCP-adherent thromboprophylaxis prescribed at discharge was good. Improvements in patient education and prescribing practices at discharge may be important in further raising compliance levels in high-risk orthopaedic surgery patients.
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| 7. |
- Bikdeli, Behnood, et al.
(författare)
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Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction : Rationale and Methodology
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:2, s. 348-361
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Tidskriftsartikel (refereegranskat)abstract
- Background Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed.Objective To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin.Methods We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin.Results From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin).Conclusion We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results..
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| 8. |
- Braun, Oscar, et al.
(författare)
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Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:6, s. 1223-1231
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Tidskriftsartikel (refereegranskat)abstract
- Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow (R) P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PR!) after 14 days of maintenance dosing. Clopi-, dogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but notABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.
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| 9. |
- Braun, Oscar, et al.
(författare)
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Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease
- 2008
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 100:4, s. 626-633
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Tidskriftsartikel (refereegranskat)abstract
- Prasugrel, a novel P2Y(12) ADP-receptor antagonist, has been reported to achieve greater inhibition of platelet aggregation compared to clopidogrel as assessed by light transmission aggregometry. It was the objective of this study to investigate the effect of prasugrel on alternative markers of platelet activation in comparison to a high loading dose and the approved maintenance dose of clopidogrel. One hundred ten aspirin-treated patients with stable coronary artery disease were randomized to a loading dose (LD, day 1)/ maintenance dose (MD, days 2-29) of prasugrel 60 mg/10 mg or clopidogrel 600 mg/75 mg. Platelet activation markers were analyzed by whole blood flow cytometry pre-dose and at 2 and 24 hours after LD and pre-dose at 14 and 29 days. After stimulation with 20 muM ADP, 2 hours after LD, significantly lower expression of activated GPIIb/IIIa (4.3 vs. 21.8 [mean fluorescent intensity (MFI)], p < 0.001) and P-selectin (2.0 vs. 11.7 MFI, p < 0.001) along with decreased formation of platelet-monocyte aggregates (16.4% vs. 29.6% positive cells, p < 0.001) was observed with prasugrel versus clopidogrel. All these effects were maintained through 24 hours and during the MD period. In conclusion, prasugrel 60 mg LD and 10 mg MD inhibit several markers of platelet activation and the formation of platelet-monocyte aggregates more effectively than a 600 mg LD and 75 mg MD of clopidogrel. Attenuated platelet aggregation and reduced expression of platelet pro-coagulant and pro-inflammatory markers with prasugrel suggest the potential to reduce cardiovascular events both in the acute setting and in long-term treatment.
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| 10. |
- Bukkems, Laura H., et al.
(författare)
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Association between Sports Participation, Factor VIII Levels and Bleeding in Hemophilia A
- 2023
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 123:03, s. 317-325
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLittle is known on how sports participation affects bleeding risk in hemophilia. This study aimed to examine associations between sports participation, factor VIII (FVIII) levels and bleeding in persons with hemophilia A.MethodsIn this observational, prospective, single-center study, persons with hemophilia A who regularly participated in sports were followed for 12 months. The associations of patient characteristics, FVIII levels, and type/frequency of sports participation with bleeding were analyzed by repeated time-to-event modelling.ResultsOne hundred and twelve persons (median age: 24 years [interquartile range:16-34], 49% severe, 49% on prophylaxis) were included. During follow-up, 70 bleeds of which 20 sports-induced were observed. FVIII levels were inversely correlated with the bleeding hazard; a 50% reduction of the baseline bleeding hazard was observed at FVIII levels of 3.1 and a 90% reduction at 28.0 IU/dL. The bleeding hazard did not correlate with sports participation. In addition, severe hemophilia, prestudy annual bleeding rate, and presence of arthropathy showed a positive association with the bleeding hazard.ConclusionsThis analysis showed that FVIII levels were an important determinant of the bleeding hazard, but sports participation was not. This observation most likely reflects the presence of adequate FVIII levels during sports participation in our study. Persons with severe hemophilia A exhibited a higher bleeding hazard at a similar FVIII levels than nonsevere, suggesting that the time spent at lower FVIII levels impacts overall bleeding hazard. These data may be used to counsel persons with hemophilia regarding sports participation and the necessity of adequate prophylaxis.
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