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1.
  • Ariens, Robert, et al. (author)
  • Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress
  • 2020
  • In: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS. - : Wiley. - 2475-0379. ; 4:5, s. 680-713
  • Research review (peer-reviewed)abstract
    • The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education.
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  • Bartoli-Abdou, J. K., et al. (author)
  • Associations between illness beliefs, medication beliefs, anticoagulation-related quality of life, and INR control: Insights from the Switching Study
  • 2018
  • In: Research and Practice in Thrombosis and Haemostasis. - : Elsevier BV. - 2475-0379. ; 2:3, s. 497-507
  • Journal article (peer-reviewed)abstract
    • Background: Anticoagulation control with vitamin--K antagonists (VKAs) in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) can be measured using time in therapeutic range (TTR), where TTR >65% is considered good and low TTR may be associated with low adherence. Methods: This cross--sectional observational study compared illness beliefs, treatment beliefs, and treatment satisfaction of patients with TTR >75% and TTR<50% using validated tools to determine their association with TTR. Adults requiring chronic VKA therapy were recruited from 2 hospital anticoagulation clinics in London, UK. Results: 311 patients with TTR >75% and 214 with TTR<50% were recruited. TTR >75% patients had been taking warfarin on average over 2 years longer than TTR <50% patients (P<.001). Statistically significant differences in beliefs were found in all subscales other than in treatment control, general harm, and general overuse. Cluster analysis determined there were 4 distinct clusters of beliefs among patients. Multivariate binary logistic regression found VTE patients were least likely to have poor TTR (OR = 0.49; 95% CI 0.29, 0.77). Patients in the "cautious of therapy and fearful of illness" cluster were most likely to have low TTR (OR = 4.75; 95% CI 2.75, 8.77). Conclusion: Illness perceptions, medication beliefs and treatment satisfaction were associated with INR control. VTE patients and those who were accepting of both illness and treatment were most likely to have optimal INR control.
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  • Boknäs, Niklas, 1979-, et al. (author)
  • Platelet function testing at low platelet counts : When can you trust your analysis?
  • 2019
  • In: Research and Practice in Thrombosis and Haemostasis. - : Wiley-Blackwell. - 2475-0379. ; 3:2, s. 285-290
  • Journal article (peer-reviewed)abstract
    • Background: Although flow cytometry is often brought forward as a preferable method in the setting of thrombocytopenia, the relative effects of low sample counts on results from flow cytometry-based platelet function testing (FC-PFT) in comparison with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) has not been reported.Objectives: To compare the effects of different sample platelet counts (10, 50, 100, and 200x10(9)L(-1)) on platelet activation measured with FC-PFT, LTA, and MEA using the same anticoagulant and agonist concentrations as for the commercial MEA test.Methods: Platelets were stimulated with two commonly used platelet agonists (ADP [6.5 mu molL(-1)] and PAR1-AP [TRAP, 32 mu molL(-1)]). The specified sample platelet counts were obtained by combining platelet-rich and platelet poor hirudinized plasma in different proportions with or without red blood cells.Results: For FC, P-selectin exposure and PAC-1 binding was reduced at 10x10(9)L(-1) after stimulation with PAR1-AP (by approximately 20% and 50%, respectively), but remained relatively unchanged when ADP was used as agonist (n=9). The platelet count-dependent effects observed with PAR1-AP were eliminated when samples were pre-incubated with apyrase, implying that reduced purinergic signaling was the main underlying factor (n=5). Both aggregometry-based PFTs showed a 50% reduction at 50x10(9)L(-1) and more than 80% reduction at 10x10(9)L(-1), irrespective of agonist used (n=7).Conclusions: Although FC-PFT is generally preferable to aggregometry-based PFTs in situations with low sample platelet counts, a careful optimization of experimental parameters is still required in order to eliminate platelet count-related effects.
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  • Chowdary, Pratima, et al. (author)
  • Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc : Data on safety and effectiveness from phase 3 pivotal studies
  • 2022
  • In: Research and Practice in Thrombosis and Haemostasis. - : Wiley. - 2475-0379. ; 6:5
  • Journal article (peer-reviewed)abstract
    • Background Surgical procedures impose hemostatic risk to people with hemophilia, which may be minimized by optimal factor (F) replacement therapy. Methods This analysis evaluates the efficacy and safety of extended half-life factor replacement recombinant FVIII and FIX Fc fusion proteins (rFVIIIFc and rFIXFc) during surgery in phase 3 pivotal (A-LONG/Kids A-LONG and B-LONG/Kids B-LONG) and extension (ASPIRE and B-YOND) studies. Dosing regimens were determined by investigators. Injection frequency, dosing, blood loss, transfusions, and hemostatic response were assessed. Results Forty-five major (n = 31 subjects) and 90 minor (n = 70 subjects) procedures were performed in hemophilia A; 35 major (n = 22) and 62 minor (n = 37) procedures were performed in hemophilia B. Unilateral knee arthroplasty was the most common major orthopedic procedure (hemophilia A: n = 15/34; hemophilia B: n = 8/24). On the day of surgery, median total dose in adults/adolescents was 81 IU/kg for rFVIIIFc and 144 IU/kg for rFIXFc; most major procedures required <= 2 injections (including loading dose). Through days 1-14, most major procedures had <= 1 injection/day. Hemostasis was rated excellent (rFVIIIFc: n = 39/42; rFIXFc: n = 29/33) or good (n = 3/42; n = 4/33) in evaluable major surgeries, with blood loss comparable with subjects without hemophilia. Most minor procedures in adults/adolescents required one injection on the day of surgery, including median loading dose of 51 IU/kg (rFVIIIFc) and 80 IU/kg (rFIXFc). No major treatment-related safety concerns were identified. No subjects developed inhibitors or serious vascular thromboembolic events. Conclusions rFVIIIFc and rFIXFc were efficacious and well tolerated for the management of perioperative hemostasis across a wide spectrum of major and minor surgeries in hemophilia.
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  • Edfors, Fredrik, et al. (author)
  • Proteomics in thrombosis research
  • 2022
  • In: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS. - : Wiley. - 2475-0379. ; 6:3
  • Journal article (peer-reviewed)abstract
    • A State of the Art lecture titled "Proteomics in Thrombosis Research" was presented at the ISTH Congress in 2021. In clinical practice, there is a need for improved plasma biomarker-based tools for diagnosis and risk prediction of venous thromboembolism (VTE). Analysis of blood, to identify plasma proteins with potential utility for such tools, could enable an individualized approach to treatment and prevention. Technological advances to study the plasma proteome on a large scale allows broad screening for the identification of novel plasma biomarkers, both by targeted and nontargeted proteomics methods. However, assay limitations need to be considered when interpreting results, with orthogonal validation required before conclusions are drawn. Here, we review and provide perspectives on the application of affinity-and mass spectrometry-based methods for the identification and analysis of plasma protein biomarkers, with potential application in the field of VTE. We also provide a future perspective on discovery strategies and emerging technologies for targeted proteomics in thrombosis research. Finally, we summarize relevant new data on this topic, presented during the 2021 ISTH Congress.
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  • Fager Ferrari, Marcus, et al. (author)
  • Evaluation of the Sialidase Inhibitor Oseltamivir in GNE-associated Thrombocytopenia
  • 2021
  • In: Research and practice in thrombosis and haemostasis. - 2475-0379. ; 5:S2, s. 644-645
  • Conference paper (peer-reviewed)abstract
    • Background: GNE encodes UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the rate limiting enzyme of sialic acid biosynthesis. Biallelic variants in GNE have recently been associated with severe isolated macrothrombocytopenia, attributed to an increased clearance of desialylated platelets. Interestingly, treatment with the sialidase inhibitor oseltamivir has been reported to increase platelet counts in conditions such as immune thrombocytopenia (ITP) and influenza. We present a case of a 17-year-old boy (the proband) with severe congenital macrothrombocytopenia (platelet counts < 10 x 109/L). Whole genome sequencing revealed two previously undescribed compound heterozygous variants in GNE (c.416_426del, p.Ile139Argfs*4 and c.1352G>A, p.Arg451Gln). The proband was otherwise healthy, with no signs of GNE myopathy. ​​​​ Aims: To investigate the consequences of the identified variants in GNE and evaluate the effect of oseltamivir in GNE-associated thrombocytopenia. Methods: Sialylation of platelets, granulocytes, lymphocytes and monocytes was determined by flow cytometry in the proband and healthy controls (n = 5), using Sambucus nigra lectin (SNA) and Maackia amurensis lectin II (MAL II). Platelet sialylation was reassessed in the proband following treatment with oseltamivir (75 mg twice daily, off-label use). Informed consent was obtained from all participants. The study was approved by the regional ethical committee. Results: Sialylation of platelets and leukocytes was markedly decreased in the proband compared with the healthy controls, consistent with a deleterious effect of the compound heterozygous variants in GNE (Figure 1). Platelet sialylation was persistently decreased after 18 days of treatment with oseltamivir, and no clinically significant elevation of the platelet counts could be observed (Figure 1, Figure 2).
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  • Glise Sandblad, Katarina, 1982, et al. (author)
  • Pulmonary embolism and deep vein thrombosis-comorbidities and temporary provoking factors in a register-based study of 1.48 million people.
  • 2022
  • In: Research and practice in thrombosis and haemostasis. - : Elsevier BV. - 2475-0379. ; 6:4
  • Journal article (peer-reviewed)abstract
    • Knowledge on differences in patients who present with deep vein thrombosis (DVT) and those with pulmonary embolism (PE) is incomplete.To determine comorbidities and temporary provoking factors in patients with a first-time PE or DVT.This was a nationwide Swedish registry-based, retrospective, case-control study including 298172 patients with first-time venous thromboembolism (VTE) and 1185079 controls matched for age, sex, and county of residence, free of VTE at the time of matching.Patients with PE were older than those with DVT (mean age, 69 vs 66years) and included slightly more women (PE, 53.4% vs DVT, 52.1%). After multivariable adjustment for comorbidities (within 7years) and temporary provoking factors (within 3months), heart failure (PE: adjusted odds ratio [aOR], 2.64 [99% confidence interval [CI], 2.55-2.73]; DVT: aOR, 1.66 [99% CI, 1.60-1.72]), ischemic heart disease (PE: aOR, 1.51 [99% CI, 1.47-1.56]; DVT: aOR, 1.01 [99% CI, 0.98-1.04]), and chronic obstructive pulmonary disease (PE: aOR, 2.51 [99% CI, 2.40-2.63]; DVT, 1.54 [99% CI, 1.47-1.62]) were among diseases that showed higher odds ratios in patients with PE than in those with DVT, compared with controls. Comorbidities registered within 6months were associated with higher aORs than those within 7years. The highest population attributable risks for PE were for cancer (13.0%) and heart failure (11.7%).Cardiopulmonary diseases, particularly with recent onset, imply a higher risk for PE, whereas orthopedic surgery and lower-extremity fractures carry a higher risk of DVT.
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  • Labarque, Veerle, et al. (author)
  • F8/F9 variants in the population-based PedNet Registry cohort compared with locus-specific genetic databases of the European Association for Haemophilia and Allied Disorders and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project.
  • 2023
  • In: Research and practice in thrombosis and haemostasis. - : Elsevier BV. - 2475-0379. ; 7:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Hemophilia A and B are caused by variants in the factor (F) VIII or FIX gene. Selective reporting may influence the distribution of variants reported in genetic databases.OBJECTIVES: To compare the spectrum of F8 and F9 variants in an international population-based pediatric cohort (PedNet Registry) with the spectrum found in the European Association for Haemophilia and Allied Disorders (EAHAD) and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project (CHAMP/CHBMP) databases. METHODS: All patients registered in the PedNet Registry on January 1, 2021 were included in this study. As comparators, data from patients with severe hemophilia included in the CHAMP/CHBMP registry (US center data) and EAHAD were used.RESULTS: Genetic information was available for 1941 patients. Intron 22 inversion was present in 52% of patients with severe hemophilia A; frameshift (36%), missense (28%), and nonsense (20%) were the most frequent variants in patients with severe hemophilia A who were inversion-negative. The most frequent variants in severe hemophilia B were missense (48%). In nonsevere disease, most variants were missense variants (moderate hemophilia A: 91%; mild hemophilia A: 95%, moderate and mild hemophilia B: 86% each). Comparison with the databases demonstrated a higher proportion of missense variants associated with severe hemophilia B in EAHAD (68%) than in PedNet (48%) and CHBMP (46%).CONCLUSION: The PedNet population-based cohort provides an alternative to the established databases, which collect data by selective reporting, as it is a well-maintained database covering the full spectrum of pathogenic F8 and F9 variants, and indicates the number of patients affected by each particular variant.
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  • Manderstedt, Eric, et al. (author)
  • Detection of mosaics in hemophilia A by deep Ion Torrent sequencing and droplet digital PCR
  • 2020
  • In: Research and practice in thrombosis and haemostasis. - : Wiley. - 2475-0379. ; 4:7, s. 1121-1130
  • Journal article (peer-reviewed)abstract
    • Background: The occurrence of mosaicism in hemophilia A (HA) has been investigated in several studies using different detection methods. Objectives: To characterize and compare the ability of AmpliSeq/Ion Torrent sequencing and droplet digital polymerase chain reaction (ddPCR) for mosaic detection in HA. Methods: Ion Torrent sequencing and ddPCR were used to analyze 20 healthy males and 16 mothers of sporadic HA patients. Results: An error-rate map over all coding positions and all positions reported as mutated in the F8-specific mutation database was produced. The sequencing produced a mean read depth of >1500X where >97% of positions were covered by >100 reads. Higher error frequencies were observed in positions with A or T as reference allele and in positions surrounded on both sides with C or G. Seventeen of 9319 positions had a mean substitution error frequency >1%. The ability to identify low-level mosaicism was determined primarily by read depth and error rate of each specific position. Limit of detection (LOD) was <1% for 97% of positions with substitutions and 90% of indel positions. The positions with LOD >1% require repeated testing and mononucleotide repeats with more than four repeat units need an alternative analysis strategy. Mosaicism was detected in 1 of 16 mothers and confirmed using ddPCR. Conclusions: Deep sequencing using an AmpliSeq/Ion Torrent strategy allows for simultaneous identification of disease-causing mutations in patients and mosaicism in mothers. ddPCR has high sensitivity but is hampered by the need for mutationspecific design.
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  • Manderstedt, Eric, et al. (author)
  • Detection of mosaics in hemophilia A by deep Ion Torrent sequencing and droplet digital PCR
  • 2020
  • In: Research and practice in thrombosis and haemostasis. - : Elsevier BV. - 2475-0379. ; 4:7, s. 1121-1130
  • Journal article (peer-reviewed)abstract
    • Background: The occurrence of mosaicism in hemophilia A (HA) has been investigated in several studies using different detection methods. Objectives: To characterize and compare the ability of AmpliSeq/Ion Torrent sequencing and droplet digital polymerase chain reaction (ddPCR) for mosaic detection in HA. Methods: Ion Torrent sequencing and ddPCR were used to analyze 20 healthy males and 16 mothers of sporadic HA patients. Results: An error-rate map over all coding positions and all positions reported as mutated in the F8-specific mutation database was produced. The sequencing produced a mean read depth of >1500X where >97% of positions were covered by >100 reads. Higher error frequencies were observed in positions with A or T as reference allele and in positions surrounded on both sides with C or G. Seventeen of 9319 positions had a mean substitution error frequency >1%. The ability to identify low-level mosaicism was determined primarily by read depth and error rate of each specific position. Limit of detection (LOD) was <1% for 97% of positions with substitutions and 90% of indel positions. The positions with LOD >1% require repeated testing and mononucleotide repeats with more than four repeat units need an alternative analysis strategy. Mosaicism was detected in 1 of 16 mothers and confirmed using ddPCR. Conclusions: Deep sequencing using an AmpliSeq/Ion Torrent strategy allows for simultaneous identification of disease-causing mutations in patients and mosaicism in mothers. ddPCR has high sensitivity but is hampered by the need for mutationspecific design.
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  • Manderstedt, Eric, et al. (author)
  • Genetic variation of the blood coagulation regulator tissue factor pathway inhibitor and venous thromboembolism among middle-aged and older adults: A population-based cohort study
  • 2022
  • In: Research and practice in thrombosis and haemostasis. - : Elsevier BV. - 2475-0379. ; 6:7
  • Journal article (peer-reviewed)abstract
    • Background: Tissue factor is the main initiator of blood coagulation, and tissue factor pathway inhibitor (TFPI) is the primary inhibitor of the initiation of blood coagulation. The genetic variation of TFPI and the relation to venous thromboembolism (VTE), that is, venous thrombosis and pulmonary embolism, remains to be clarified. This exome sequencing study aimed to determine the molecular epidemiology of the TFPI gene and the relation to VTE in a large population-based cohort of middle-aged and older adults. Methods: The exomes of TFPI were analyzed for variants in 28,794 subjects without previous VTE (born 1923–1950, 60% women), who participated in the Malmö Diet and Cancer Study (1991–1996). Patients were followed until the first event of VTE, death, or 2018. Qualifying variants were defined as loss-of-function or nonbenign (PolyPhen-2) missense variants with minor allele frequency less than 0.1%. Results: No common variant was associated with VTE. Nine rare variants (two loss-of-function and seven nonbenign missense) were classified as qualifying and included in collapsing analysis. Prevalence of qualifying variants was 0.09%. Five individuals with VTE compared to 17 individuals without VTE carried one qualifying variant. Cox multivariate regression analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking and alcohol consumption, rs6025, rs1799963, and ancestry showed a hazard ratio of 2.9 (95% CI, 1.2–7.1) for rare qualifying variants. Conclusion: Rare qualifying TFPI variants were associated with VTE, suggesting that rare variants in TFPI contribute to the development of VTE. The qualifying TFPI gene variants were very rare, suggesting a constrained gene. © 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).
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  • Pedersen, Annie, 1981, et al. (author)
  • Fibrinogen concentrations predict long-term cognitive outcome in young ischemic stroke patients
  • 2018
  • In: Research and Practice in Thrombosis and Haemostasis. - : Elsevier BV. - 2475-0379. ; 2:2, s. 339-346
  • Journal article (peer-reviewed)abstract
    • Background: Cognitive impairment is frequent after stroke, and young patients may live with this consequence for a long time. Predictors of cognitive outcomes after stroke represent a current gap of knowledge. Objectives: To investigate levels of three hemostatic biomarkers as predictors of long-term cognitive function after stroke. Methods: This longitudinal study included consecutively recruited patients with ischemic stroke at 18-69 years (n = 268). Blood was collected 3 months after index stroke and analyzed for plasma concentrations of fibrinogen, von Willebrand factor (VWF) and tissue-type plasminogen activator (t-PA) antigen. Cognitive function 7 years after index stroke was assessed by the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS). Participants with stroke <50 years of age were also examined by the Trail Making Test A and B (n = 41). Associations between biomarker concentrations and cognitive scales were assessed in the whole group and in participants with stroke <50 years of age. Results: The hemostatic biomarkers fibrinogen, VWF and t-PA, were all correlated to total BNIS score, but these associations did not withstand adjustment for confounding factors in the whole group. However, in patients <50 years, we found an independent association between fibrinogen concentrations and total BNIS score (beta(std) = -.27, 95% confidence interval [CI], -0.47 to -0.07) and to performance on the Trail Making Test A (beta(std) = 31, 95% CI, 0.03-0.58). No such association was seen for the Trail Making Test B. Conclusion: High convalescent fibrinogen concentrations were associated with worse long-term cognitive outcomes in ischemic stroke <50 years of age. We propose further investigations of fibrinogen in relation to cognitive function in stroke in the young.
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  • Shannon, Oonagh (author)
  • The role of platelets in sepsis
  • 2021
  • In: Research and practice in thrombosis and haemostasis. - : Elsevier BV. - 2475-0379. ; 5:1, s. 27-37
  • Journal article (peer-reviewed)abstract
    • A State of the Art lecture titled “The role of platelets in sepsis” was presented at the ISTH congress in 2020. Sepsis is a life-threatening organ dysfunction caused by a dysregulated and multifaceted host response to infection. Platelets play a significant role in the coordinated immune response to infection and therefore in the inflammation and coagulation dysfunction that contributes to organ damage in sepsis. Thrombocytopenia has a high incidence in sepsis, and it is a marker of poor prognosis. The genesis of thrombocytopenia is likely multifactorial, and unraveling the involved molecular mechanisms will allow development of biomarkers of platelet function in sepsis. Such platelet biomarkers can facilitate study of antiplatelet interventions as immunomodulatory treatment in sepsis. Finally, relevant new data on this topic presented during the 2020 ISTH virtual congress are reviewed.
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  • Singh, Sukhi, 1990, et al. (author)
  • Adrenaline enhances in vitro platelet activation and aggregation in blood samples from ticagrelor-treated patients
  • 2018
  • In: Research and Practice in Thrombosis and Haemostasis. - : John Wiley & Sons. - 2475-0379. ; 2:4, s. 718-725
  • Journal article (peer-reviewed)abstract
    • Background: Temporarily improved platelet reactivity may reduce the bleeding in patients on antiplatelet therapy who have ongoing bleeding or who are in need of acute surgery. Adrenaline can bind to adrenergic alpha(2A)-receptors on platelets and potentially enhance platelet reactivity.Objective: To assess if adrenaline can improve adenosine diphosphate (ADP)-induced platelet aggregation and activation in blood samples from patients on dual antiplatelet therapy with acetylsalicylic acid (ASA) and the ADP-receptor antagonist ticagrelor.Methods: Blood samples were collected from a total of forty acute coronary syndrome patients on dual antiplatelet therapy with ASA and ticagrelor. ADP-induced platelet aggregation (by impedance aggregometry) and activation (by flow cytometry) were assessed before and after supplementation with adrenaline and/or platelet concentrate.Results: Adrenaline supplementation (770 nmol L-1) increased median ADP-induced aggregation from 15 (25-75th percentiles: 10-20) to 26 (18-38) aggregation units. The effect was independent of concomitant platelet supplementation. Adrenaline also increased ADP-induced platelet activation: from 40% (36-54%) to 83% (74-88%) platelets with active fibrinogen receptor (binding PAC-1) and from 13% (7-21%) to 35% (18-50%) P-selectin-expressing platelets.Conclusions: Adrenaline potentiated ADP-induced platelet aggregation and activation in blood samples from ticagrelor-treated patients. Adrenaline infusion may be a new method to enhance platelet function in ticagrelor-treated patients who are in need of acute surgery or have ongoing bleeding. In vivo studies are needed to confirm the present results.
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  • Sjöland, Helen, 1959, et al. (author)
  • Pulmonary embolism and deep venous thrombosis after COVID-19: long-term risk in a population-based cohort study
  • 2023
  • In: Research and Practice in Thrombosis and Haemostasis. - 2475-0379. ; 7:5
  • Journal article (peer-reviewed)abstract
    • Background: Venous thromboembolism (VTE) (pulmonary embolism [PE] or deep venous thrombosis [DVT]) is common during acute COVID-19. Long-term excess risk has not yet been established. Objectives: To study long-term VTE risk after COVID-19. Methods: Swedish citizens aged 18 to 84 years hospitalized and/or testing positive for COVID-19 between January 1, 2020, and September 11, 2021 (exposed), stratified by initial hospitalization, were compared to matched (1:5), nonexposed, population-derived subjects without COVID-19. Outcomes were incident VTE, PE, or DVT recorded within 60, 60 to <180, and & GE;180 days. Cox regression was used for evalu-ation, and a model adjusted for age, sex, comorbidities, and socioeconomic markers was developed to control for confounders. Results: Among exposed patients, 48,861 were hospitalized for COVID-19 (mean age, 60.6 years) and 894,121 were without hospitalization (mean age, 41.4 years). Among patients hospitalized for COVID-19, fully adjusted hazard ratios during 60 to <180 days were 6.05 (95% CI, 4.80-7.62) for PE and 3.97 (CI, 2.96-5.33) for DVT compared with that for nonexposed patients with corresponding estimates among those with COVID-19 without hospitalization 1.17 (CI, 1.01-1.35) and 0.99 (CI, 0.86-1.15), based on 475 and 2311 VTE events, respectively. Long-term (& GE;180 days) hazard ratios in patients hospitalized for COVID-19 were 2.01 (CI, 1.51-2.68) for PE and 1.46 (CI, 1.05-2.01) for DVT, while nonhospitalized patients had similar risk as nonexposed patients, based on 467 and 2030 VTE events, respectively. Conclusion: Patients hospitalized for COVID-19 retained an elevated excess risk of VTE, mainly PE, after 180 days, while long-term risk of VTE in individuals with COVID-19 without hospitalization was similar to that in the nonexposed patients.
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  • Steen Carlsson, Katarina, et al. (author)
  • High use of pain, depression, and anxiety drugs in hemophilia: more than 3000 people with hemophilia in an 11-year Nordic registry study
  • 2023
  • In: Research and Practice in Thrombosis and Haemostasis. - : Elsevier BV. - 2475-0379. ; 7:2
  • Journal article (peer-reviewed)abstract
    • Background: Pain is a common feature of hemophilia, but prevalence of depression and anxiety is less studied. Registry data on prescription drugs can provide an objective measure of the magnitude of these complications. Objectives: To identify treatment patterns of prescribed pain, antidepressant, and antianxiety medications compared with those of matched controls in 4 Nordic countries. Methods: The MIND study (NCT03276130) analyzed longitudinal individual-level national data during 2007-2017. People with hemophilia (PwH) were identified from National Health Data Registers by diagnosis or factor replacement treatment and compared with population controls. Three subgroups were defined by the use of factor concentrates and sex (moderate-to-high factor consumption (factor VIII [FVIII] use of ≥40 IU/kg/week or FIX use of ≥10 IU/kg/week), low factor consumption, and women including carriers). Results: Data of 3246 PwH, representing 30,184 person-years, were analyzed. PwH (including children and adults) used more pain, depression, and anxiety medications compared with controls. This was most accentuated in the moderate-to-high factor consumption group and notably also observed in men with low factor consumption and women including carriers, usually representing a milder phenotype. A higher opioid use was observed across all age groups: 4- to 6-fold higher in the moderate-to-high factor consumption group and 2- to 4-fold higher in the low factor consumption group. Conclusion: The consistent higher use of pain, depression, and anxiety medications among PwH compared with population controls, regardless of age, sex, or factor consumption, in broad national data suggests a need for improved bleed protection and hemophilia care for all severities including mild hemophilia.
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