| 1. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 2. |
- Karlsson, Anna, et al.
(författare)
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The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy - the TABANETOC trial : study protocol for a randomized clinical multicenter trial
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 581-585
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis.Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT.Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured.Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0–1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants.Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.
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| 3. |
- Karlsson, Anna, 1985-, et al.
(författare)
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The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy – the TABANETOC trial: study protocol for a randomized clinical multicenter trial
- 2024
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Ingår i: Acta Oncologica. - Uppsala : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 581-585
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis.Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT.Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured.Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0–1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants.Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.
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| 4. |
- Albrektsson, Tomas, 1945, et al.
(författare)
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Histologic investigations on 33 retrieved Nobelpharma implants.
- 1993
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Ingår i: Clinical materials. - 0267-6605. ; 12:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Thirty Nobelpharma implants were retrieved from 17 patients despite a remaining clinical stability, after between 1 and 16 years of clinical function. The reasons for implant removal were bone resorption in combination with soft tissue disorders, psychological causes, implant fracture and post mortem cases. When measured at the cortical passage, there was an average of 84.9% direct bone-to-implant contact and 81.8% average surface bone area in individual threads as evaluated in a computerized morphometric system at the light microscopic level.
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| 5. |
- Alehagen, Urban, et al.
(författare)
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Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure.
- 2010
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Ingår i: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. - 1473-5733. ; 21:1, s. 62-9
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.
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| 6. |
- Alfredsson, Joakim, et al.
(författare)
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Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel : Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).
- 2015
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Ingår i: Thrombosis Research. - : Pergamon Press. - 0049-3848 .- 1879-2472. ; 136:2, s. 335-340
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.
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| 7. |
- Boknäs, Niklas, et al.
(författare)
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Contact activation : important to consider when measuring the contribution of tissue factor-bearing microparticles to thrombin generation using phospholipid-containing reagents
- 2014
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Ingår i: Journal of Thrombosis and Haemostasis. - : John Wiley & Sons. - 1538-7933 .- 1538-7836. ; 12:4, s. 515-518
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Tidskriftsartikel (refereegranskat)abstract
- Background: A commercial MP reagent containing phospholipids is used for thrombin generation (TG) measurements to estimate the procoagulant activity of microparticles (MPs). Previous reports have shown that contact activation affects TG when TF levels are low, and that addition of phospholipids might augment this effect.Objectives: To quantify the impact of contact activation on TG in the presence of phospholipids and low/no TF, as is the case using a commercially available MP-reagent. Methods Thrombin generation was analyzed using MP- or platelet-rich plasma (PRP)-reagent in the presence and absence of corn trypsin inhibitor and anti-TF antibodies, respectively. To quantify the impact of different experimental parameters on contact activation, microparticle-depleted plasma was analyzed in the presence of different concentrations of phospholipids, TF and/or contact activating agents (kaolin).Results: Even with low contact activating blood collection tubes, substantial thrombin generation was observed with the MP-reagent, but this was completely inhibited by addition of corn trypsin inhibitor. Control experiments illustrate that the phospholipids in the reagent play a major role in enhancing TG initiated by FXIIa. Even with the PRP-reagent, which is recommended for determining the content of phospholipids from MPs, TG was partly dependent on contact activation.Conclusions: Contact activation plays a major role in TG when using reagents/samples containing phospholipids but little or no tissue factor. This needs to be considered and accounted for in future clinical studies using TG to assess the procoagulant activity of MPs.
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| 8. |
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| 9. |
- Chaireti, Roza, et al.
(författare)
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Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event
- 2014
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 134:2, s. 455-461
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Tidskriftsartikel (refereegranskat)abstract
- Background: In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding.Aims: To evaluate the haemostatic potential in patients with liver disease.Methods: We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n=47), Budd-Chiari syndrome (BCS, n=15) and cirrhosis (n=24) and compared the results to those obtained from healthy controls (n=21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared with an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence]/[marker measured in the absence of thrombomodulin].Results: There were no differences between patients with BCS, patients on warfarin treatment and controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared with controls [p=0.006 for endogenous thrombin potential (ETP) and p<0.001 for peak thrombin. P<0.001 for both ratios ETP and peak] and patients with non-cirrhotic PVT (p=0.001, p=0.006, p<0.001, p<0.001 for ETP, peak, ratio ETP, ratio peak). The patients with cirrhotic PVT exhibited higher ETP (p=0.044) and peak (p=0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP ratio: p=0.001, peak ratio: p=0.001).Conclusions: Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer treatment with anticoagulants in this group.
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| 10. |
- Chaireti, Roza, et al.
(författare)
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Thrombin generation and D-dimer concentrations in a patient cohort investigated for venous thromboembolism. Relations to venous thrombosis, factor V Leiden and prothrombin G20210A. The LIST study.
- 2009
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 124:2, s. 178-84
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The present study evaluated possible relations between various markers of thrombin generation, D-dimer and venous thromboembolism in outpatients with and without the FV Leiden and the protrombin mutations. PATIENTS AND METHODS: Our cohort consisted of 98 patients with the FV Leiden and 15 with the prothrombin mutation and an equal number of age- and gender-matched controls. All subjects were investigated due to suspicion of venous thromboembolism and the diagnosis was objectively confirmed or refuted. RESULTS: We compared the D-dimer values and the thrombin generation markers among different patient groups (with/without thromboembolism, with/without genetic factors, gender-linked). The only statistically significant difference noted was prolonged time both for the initiation and termination of thrombin generation in patients with thrombosis. This applied to controls and to patients heterozygous for the FV Leiden. Additionally, the D-dimer values were elevated in patients with the FV Leiden. No difference was found among the patients with prothrombin mutation and their controls. DISCUSSION: Multi-variant analysis indicated that the difference in D-dimer between FV Leiden patients and controls was due to the greater number of patients with confirmed thrombosis in the former group, a finding supported by an independent prospective study on postoperative thrombosis. Neither D-dimer concentration nor thrombin generation depend on FV Leiden. The total amount of thrombin generated was not related to diagnosis. The prolonged thrombin generation noted in controls and FV Leiden heterozygotes with thrombosis may point out different thrombin generation profiles in different patient populations and requires further studies.
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| 11. |
- Chaireti, Roza, et al.
(författare)
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Thrombin generation and levels of factor VII activity measured in the presence of rabbit and human thromboplastins in patients with mild factor VII deficiency – effects of mutations in factor VII
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background/Aim: It is known that spontaneous prolonged prothrombin time-international normalized ratio may be caused by deficiency of factor VII (FVII). The activity of FVII in the presence of thromboplastins of different origin is affected by the presence of specific mutations in the F7 gene. The present study aims to evaluate patients with mild FVII deficiency and somewhat discrepant FVII activity depending on the use of human or rabbit thromboplastin in relation to mutations in the FVII gene and markers of thrombin generation.Patients and methods: A cohort of 10 patients with mild deficiency of FVII and discrepant FVII activity was investigated. The median ratio of the FVII activity in the presence of human/rabbit thromboplastin was 1.4. All but 1 patient had mild to no bleeding symptoms. A genetic analysis of the F7 gene was performed. Thrombin generation was measured by the calibrated automated thrombogram in platelet poor plasma in the presence of human recombinant and different dilutions of rabbit thromboplastin and compared with thrombin generation in healthy controls (n=12). Thrombin generation was measured in 9 patients as 1 was treated with warfarin at the time of the blood sampling.Results: Six previously described mutations were found. Two of those (FVII Padua and FVII Shinjo) are known to affect the results for FVII activity dependent on the species origin of the thromboplastin. Nine out of 10 patients had one mutation in common (Arg353Gln), which however does not affect the binding site of FVII to tissue factor. Lagtime and ttpeak increased with decreasing concentrations of thromboplastin and total and maximum thrombin concentrations increased with increasing thromboplastin concentrations in the patients with FVII deficiency. ETP in patients with FVII deficiency was 86% of ETP in controls.Discussion: The Arg353Gln mutation was very common, however it does not appear to affect the reactivity towards thromboplastins of different origins. Although ETP was higher in the healthy controls, thrombin generation in FVII deficient patients was enough to sustain normal haemostasis. The expected thrombin generation patterns with increasing thromboplastin concentrations were confirmed for the patients in this study.
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| 12. |
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| 13. |
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| 14. |
- Ekblad, Tobias, 1979-, et al.
(författare)
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Patterned Hydrogels for Controlled Platelet Adhesion from Whole Blood and Plasma
- 2010
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Ingår i: Advanced Functional Materials. - : John Wiley & Sons. - 1616-301X .- 1616-3028. ; 20:15, s. 2396-2403
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Tidskriftsartikel (refereegranskat)abstract
- This work describes the preparation and properties of hydrogel surface chemistries enabling controlled and well-defined cell adhesion. The hydrogels may be prepared directly on plastic substrates, such as polystyrene slides or dishes, using a quick and experimentally simple photopolymerization process, compatible with photolithographic and microfluidic patterning methods. The intended application for these materials is as substrates for diagnostic cell adhesion assays, particularly for the analysis of human platelet function. The adsorption of fibrinogen and other platelet promoting molecules is shown to be completely inhibited by the hydrogel, provided that the film thickness is sufficient (>5 nm). This allows the hydrogel to be used as a matrix for presenting selected bioactive ligands without risking interference from nonspecifically adsorbed platelet adhesion factors, even in undiluted whole blood and blood plasma. This concept is demonstrated by preparing patterns of proteins on hydrogel surfaces, resulting in highly controlled platelet adhesion. Further insights into the protein immobilization and platelet adhesion processes are provided by studies using imaging surface plasmon resonance. The hydrogel surfaces used in this work appear to provide an ideal platform for cell adhesion studies of platelets, and potentially also for other cell types.
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| 15. |
- Erlinge, David, et al.
(författare)
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Prasugrel 5-mg in the very elderly attenuates platelet inhibition but maintains non-inferiority to prasugrel 10-mg in non-elderly patients: The GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients.
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 62:7, s. 577-583
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We assessed pharmacodynamic (PD) response for the reduced prasugrel 5-mg maintenance dose in very elderly (≥75y; VE) patients. BACKGROUND: In TRITON-TIMI 38, prasugrel 10-mg reduced ischemic events versus clopidogrel 75-mg, but increased bleeding in VE patients. METHODS: We examined PD and active-metabolite pharmacokinetics with prasugrel 5-mg and 10-mg and clopidogrel 75-mg in a three-period (12 days each), blinded, cross-over study in VE (n=73, mean 79±3y) or non-elderly (≥45-<65y, NE) (n=82, 56±5y) stable coronary artery disease (CAD) patients on background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow(®) P2Y12 (VN-P2Y12), and VASP. The primary comparison was non-inferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5-mg in VE versus the 75th percentile for prasugrel 10-mg in NE, using a prespecified one-sided 97.5% confidence interval for the difference <15%. RESULTS: Prasugrel 5-mg in VE met the primary pharmacodynamic non-inferiority criterion versus prasugrel 10-mg in NE. For prasugrel 5-mg, MPA was significantly lower (mean±SD, 57±14%) than clopidogrel (63±14%) (p<0.001) in VE, but higher than prasugrel 10-mg in NE (46±12%) (p<0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5-mg resulted in fewer VE poor responders versus clopidogrel. Rates of mild bleeding were higher with prasugrel 10-mg, but similar for prasugrel 5-mg versus clopidogrel 75-mg. CONCLUSIONS: In aspirin-treated stable CAD patients, prasugrel 5-mg in VE attenuated platelet inhibition while meeting prespecified non-inferiority criterion versus prasugrel 10-mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75-mg in VE.
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| 16. |
- Faxälv, Lars, et al.
(författare)
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Activation of blood coagulation at charged supported lipid membranes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this work was to investigate the relationship between surface charge of phospholipid membranes and coagulation. Also, we wanted to demonstrate that coagulation at phospholipid membranes could successfully be studied in the method for imaging of coagulation.Analytical procedure: Supported phospholipid membranes were formed from palmitoyl-oleoyl-glycero-3-ethylphosphocholine (POEPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1- palmitoyl-2-oleoyl-sn-glycero-3-[phospho-L-serine] (POPS) on silicon substrates. The surface charge of the phospholipid membranes was controlled by using different compositions of POPS (negative net charge), POPC (weak negative net charge) and POEPC (positive net charge). Imaging of coagulation experiments were performed on all phospholipid membrane coated surfaces as well as the clean silicon substrate. The experiments were performed in platelet-free plasma (PFP) diluted 50:50 with phosphate-buffered saline (PBS).Results: Comparing the negatively charged SiO2 surface with the negatively charged POPS (30%)/POPC(70%) we found an interesting difference. Although both surfaces activated coagulation rapidly, the POPS surface facilitated a faster propagation of coagulation from the surface than the SiO2 surface. It was also found that in order for the phospholipid membranes to exert procoagulant properties, the POPS content in the membrane had to exceed ~6 %. It was also found that positively charged phospholipid membranes did not induce activation of coagulation.Conclusions: The work in this paper demonstrated that the coagulation process at phospholipid membranes can be studied in a straightforward manner using the imaging of coagulation setup. Furthermore, we speculate that the negatively charged phospholipid membranes but not the SiO2 surface can support the binding of coagulation factor complexes, thus facilitating a faster propagation of coagulation. The fact that the POPS content must exceed ~ 6% to fully exert procoagulant properties was also a very interesting result, especially since platelets, when activated, become procoagulant by increasing their negatively charged phosphatidylserine exposure from ~0 % to maximally ~10 %.
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| 17. |
- Faxälv, Lars, et al.
(författare)
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Blood compatibility of photografted hydrogel coatings
- 2010
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Ingår i: ACTA BIOMATERIALIA. - : Elsevier Science B.V. Amsterdam. - 1742-7061. ; 6:7, s. 2599-2608
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this work we have evaluated the haemocompatibility of different surface modifications, intended for biomaterials and biosensor applications. Polystyrene slides were coated with thin hydrogel films by self-initiated photografting of four different monomers. The hydrogel surface modifications were thoroughly characterized and tested for their protein resistance and ability to facilitate platelet adhesion and activation of the coagulation system. There was very little protein adsorption from human plasma on the hydrogels formed from poly(ethylene glycol) methacrylate (PEGMA) and 2-hydroxyethyl methacrylate (HEMA). Platelet adhesion tests performed under both static and flow conditions showed that these coatings also demonstrated very high resistance towards platelet adhesion. A small amount of platelets were found to adhere to hydrogels formed from ethylene glycol methyl ether methacrylate (EGMEMA) and 2-carboxyethyl methacrylate (CEA). The polystyrene substrates themselves facilitated large amounts of platelet adhesion under both static and flow conditions. Utilizing a novel setup for imaging of coagulation, it was shown that none of the hydrogel surfaces activated the coagulation system to any great extent. We suggest that this simple fabrication method can be used to produce hydrogel coatings with unusually high blood compatibility, suitable for demanding biomaterials applications.
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| 18. |
- Faxälv, Lars, et al.
(författare)
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Imaging of blood plasma coagulation and its propagation at surfaces.
- 2008
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Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 85:4, s. 1129-34
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Tidskriftsartikel (refereegranskat)abstract
- A new method utilizing image capture and processing was developed for the analysis of blood plasma coagulation at surfaces. The coagulation was detected in a cuvette by time-lapse image capture of light scattering from the developing fibrin network. By image processing and computer analysis of the captured image data, both early detection of coagulation at the surface and the propagation phase of coagulation could be measured in the same experiment. It is possible to use both platelet-rich plasma (PRP) and platelet-free plasma (PFP) with the method, and thereby study the platelet contribution to both surface coagulation and propagation of coagulation. Two well-known model surfaces, hydrophilic and hydrophobic glass, were used in combination with PRP and PFP to illustrate the method. Hydrophilic glass activated coagulation significantly faster (PRP: 7.0 +/- 1.7 min, PFP: 5.9 +/- 1.2 min, n= 16) than hydrophobic glass (PRP: 50 +/- 14 min, PFP: 65 +/- 32 min, n = 16) in both PRP and PFP. Hydrophilic surfaces showed a faster initial propagation of coagulation adjacent to the surface (mean velocity: 0.14 +/- 0.05 mm/ minute) compared with the propagation observed further out from the surface (mean velocity: 0.05 +/- 0.01 mm/min). The method is very flexible and can be suitable for screening hemocompatibility of biomaterials.
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| 19. |
- Faxälv, Lars, et al.
(författare)
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The role of coagulation factor XII in propagation of coagulation
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The physiological relevance and function of coagulation factor XII (FXII), the first zymogen in the intrinsic pathway, has for a long time been a matter of debate. The aim of this study was to shed some light on the role of factor XII in thrombus formation with a focus on its effect during the propagation phase of coagulation. In order to study propagation of coagulation we utilized a new imaging method to measure propagation rates from an activating surface in both platelet-free plasma and platelet-rich plasma. The most essential results revealed that both FXII and its substrate FXI are located on the surface of activated platelets. The surface of preexisting clots does not support coagulation in a FXII dependent manner. However, we found strong evidence for an accelerated propagation of tissue factor initiated coagulation when contact activation of FXII simultaneously occurred in the proximity. In vivo sources for contact activation may be exposed subendothelial collagen as well as soluble and cell derived poly-anions. If such in vivo contact activation of FXII occurs, even though moderate, it could contribute to in vivo thrombus growth rate and thus be of pathophysiological importance.
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| 20. |
- Ferrandis, Maria-José, et al.
(författare)
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Ruling out cardiac failure : Cost-benefit analysis of a sequential testing strategy with NT-proBNP before echocardiography
- 2013
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Ingår i: Upsala Journal of Medical Sciences. - : Informa Healthcare. - 0300-9734 .- 2000-1967. ; 118:2, s. 75-79
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To estimate the possible economic benefit of a sequential testing strategy with NT-proBNP to reduce the number of echocardiographies.Methods. Retrospective study in a third-party payer perspective. The costs were calculated from three Swedish counties: Blekinge, Östergötland, and Uppland. Two cut-off levels of NT-proBNP were used: 400 and 300 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies.Results. The estimated costs for NT-proBNP tests and echocardiographies per county were reduced by 33%–36% with the 400 pg/mL cut-off and by 28%–29% with the 300 pg/mL cut-off. This corresponded to a yearly cost reduction of approximately €2–5 million per million inhabitants in these counties.Conclusion. The use of NT-proBNP as a screening test could substantially reduce the number of echocardiographies in the diagnostic work-up of patients with suspected cardiac failure, as well as the associated costs.
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| 21. |
- Grenegård, Magnus, et al.
(författare)
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The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine
- 2008
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:27, s. 18493-18504
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Tidskriftsartikel (refereegranskat)abstract
- Human platelets express protease-activated receptor 1 (PAR1) and PAR4 but limited data indicate for differences in signal transduction. We studied the involvement of PAR1 and PAR4 in the cross-talk between thrombin and epinephrine. The results show that epinephrine acted via alpha(2A)-adrenergic receptors to provoke aggregation, secretion, and Ca(2+) mobilization in aspirin-treated platelets pre-stimulated with subthreshold concentrations of thrombin. Incubating platelets with antibodies against PAR4 or the PAR4-specific inhibitor pepducin P4pal-i1 abolished the aggregation. Furthermore, platelets pre-exposed to the PAR4-activating peptide AYPGKF, but not to the PAR1-activating peptide SFLLRN, were aggregated by epinephrine, whereas both AYPGKF and SFLLRN synergized with epinephrine in the absence of aspirin. The roles of released ATP and ADP were elucidated by using antagonists of the purinergic receptors P2X(1), P2Y(1), and P2Y(12) (i.e. NF449, MRS2159, MRS2179, and cangrelor). Intriguingly, ATP, but not ADP, was required for the epinephrine/thrombin-induced aggregation. In Western blot analysis, a low concentration of AYPGKF, but not SFLLRN, stimulated phosphorylation of Akt on serine 473. Moreover, the phosphatidyl inositide 3-kinase inhibitor LY294002 antagonized the effect of epinephrine combined with thrombin or AYPGKF. Thus, in aspirin-treated platelets, PAR4, but not PAR1, interacts synergistically with alpha(2A)-adrenergic receptors, and the PI3-kinase/Akt pathway is involved in this cross-talk. Furthermore, in PAR4-pretreated platelets, epinephrine caused dense granule secretion, and subsequent signaling from the ATP-gated P2X(1)-receptor and the alpha(2A)-adrenergic receptor induced aggregation. These results suggest a new mechanism that has ATP as a key element and circumvents the action of aspirin on epinephrine-facilitated PAR4-mediated platelet activation.
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| 22. |
- Hansson, Kenny M., et al.
(författare)
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Abnormalities in coagulum lysis and structure are associated with deep venous thrombosis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The present study aimed to investigate the relationship between deep venous thrombosis (DVT) and fibrinolytic susceptibility of plasma coagulum, including the possible role of this property in laboratory diagnosis. From 276 patients consecutively admitted to hospital for suspected deep venous thrombosis (DVT), 75 patients and 47 controls were selected. With certainty, the patients and controls either had or did not have DVT. Fibrinolytic susceptibility was assayed by reacting plasma with thromboplastin and tissue plasminogen activator and recording a nephelometric signal. Coagulation time (CT), coagulum lysis time (CLT) and maximal increase in coagulum light scatter (CLS) were determined. Increase in D-dimer levels caused by coagulum lysis was also determined. This was viewed as a fibrinogen measure. CL T and CLS were interpreted as measures of fibrinolytic susceptibility and coagulum structure, respectively. CL T and CLS for patients and controls differed, p<0.025 and p<0.001, respectively. Compared to 5% for controls, 24% and 43% of the patients showed CL T and CLS outside the reference range. High fibrinogen levels could not explain the findings, since these were normal in most patients with abnormal CL T and CLS. Abnormal coagulum lysis and abnormal coagulum structure were thus found to be associated with DVT. Possible laboratory diagnostic role of CL T and CLS was investigated with bivariate reference ranges that excluded 5% and 0.3%. These ranges excluded significantly (p<0.0001) more patients, 47% and 27%, respectively. Tests for abnormal fibrinolytic susceptibility and coagulum structure may thus have a role in laboratory diagnosis of thrombotic disorders.
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| 23. |
- Hansson, Kenny M., et al.
(författare)
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Surface plasmon resonance and free oscillation rheometry in combination : A new approach forstudies on haemostasis and biomaterials
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In haemostasis and biomaterial research it is important to be able to study biological processes at surfaces and in the bulk. Surface plasmon resonance (SPR) is sensitive to changes at surface and free oscillation rheometry (FOR) probes the bulk. The present work demonstrates the usefulness of the combination of the techniques for simultaneous real-time measurements on coagulation and fibrinolysis of blood plasma, as well as coagulation of whole blood. SFLLRN stimulated coagulation of native whole blood presented a higher SPR signal with a different appearance than for plasma coagulation, while the FOR signals corresponding to plasma and whole blood coagulation were similar. This result indicated that the SPR technique was more sensitive to cell-surface interactions than to fibrin formation in whole blood, while the FOR technique were equally sensitive to coagulation in whole blood and plasma. Spontaneous coagulation of native whole blood in contact with methyland hydroxyl-terminated self-assembled monolayers on gold and gold surfaces regenerated after coagulation by degradation of adsorbed proteins with trypsin and SOS were also studied. The regenerated gold surfaces displayed the shortest coagulation times, although the contact-activation of blood coagulation was found to be low. The methylated and hydroxylated surfaces were comparable in terms of coagulation activation, while the hydroxylated surfaces presented FOR signals that indicated difficulties for the coagulum to attach to the surface. The combination of SPR and FOR may be suited for studies of cell-surface interactions, and may find applications in studies of blood cell defects in patients and testing of medical substances.
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| 24. |
- Harris, L. F., et al.
(författare)
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A fully integrated microfluidic device for point of care monitoring of antithrombotics
- 2016
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Ingår i: Analytical Methods. - : ROYAL SOC CHEMISTRY. - 1759-9660 .- 1759-9679. ; 8:35, s. 6500-6505
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Tidskriftsartikel (refereegranskat)abstract
- The simplicity and efficiency of point of care diagnostics have revolutionised patient care. Current methods for measuring hypercoagulability often require trained technicians, large blood volumes, and result in long turnaround times. Standard testing for hypercoagulable disorders is performed in the central laboratory using automated coagulation analysers. However the trend is moving towards the development and implementation of point of care testing, as a result of the ever increasing number of patients on antithrombotic therapy. We present a novel microfluidic device and assay for monitoring the effect of two anticoagulants, unfractionated heparin (UFH) and low molecular weight heparin (LMWH). The assay is based on the anti-Xa assay principle but uses fluorescence detection. Our device is a disposable laminate microfluidic strip, fabricated from the cyclic polyolefin (COP), Zeonor (R), which is extremely suitable for application to fluorescent device platforms. We present data on the execution of the anti-Xa assay in this microfluidic format, demonstrating that the assay can be used to measure both UFH and LMWH in human plasma samples from 0 to 1 U mL(-1), with a rapid result obtained within 30-60 seconds.
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| 25. |
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| 26. |
- Hillarp, Andreas, et al.
(författare)
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Mer samstämmiga laboratorieresultat efter övergången till INR. Skillnaderna mellan sjukhus- och primärvårdslaboratorier utjämnade
- 2002
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Ingår i: Läkartidningen. - 0023-7205. ; 99:50, s. 70-5073
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Tidskriftsartikel (refereegranskat)abstract
- In 1999 a new and simplified procedure for calibration of the Owren prothrombin time (Owren PT) assay was introduced in Sweden by the national external quality assessment scheme (Equalis). The new protocol allowed local calibration by means of lyophilised national plasma calibrators and expression of results as an international normalised ratio (INR). A two-year follow-up involving analysis of data from all laboratories that have returned results to Equalis is reported. There was a significant reduction in both between-laboratory and within-laboratory variation after the introduction of the new calibration procedure. For the larger hospital laboratories analysing external controls with INR>2, the mean coefficient of variation (CV) was reduced from 9.1% to 5.6% (P<0.0001). The corresponding results from smaller laboratories in the primary health care units showed a similar decrease in CV from 8.8% to 6.3% (P<0.0001). This study shows that the Owren PT assay is well suited for INR calibration employing calibrant plasmas.
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| 27. |
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| 28. |
- Kimenai, Dorien M., et al.
(författare)
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Sex differences in investigations and outcomes among patients with type 2 myocardial infarction
- 2021
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Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 107:18, s. 1480-1486
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Type 2 myocardial infarction (MI) is a heterogenous condition and whether there are differences between women and men is unknown. We evaluated sex differences in clinical characteristics, investigations and outcomes in patients with type 2 MI.Methods: In the Swedish Web based system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we compared patients admitted to coronary care units with a diagnosis of type 1 or type 2 MI. Sex-stratified Cox regression models evaluated the association with all-cause death in men and women separately.Results: We included 57 264 (median age 73 years, 65% men) and 6485 (median age 78 years, 50% men) patients with type 1 and type 2 MI, respectively. No differences were observed in the proportion of men and women with type 2 MI who underwent echocardiography and coronary angiography, but women were less likely than men to have left ventricular (LV) impairment and obstructive coronary artery disease (CAD). Compared with type 1 MI, patients with type 2 MI had higher risk of death regardless of sex (men: adjusted HR 1.55 (95% CI 1.44 to 1.67); women: adjusted HR 1.34 (95% CI 1.24 to 1.45)). In those with type 2 MI, the risk of death was lower for women than men (adjusted HR 0.85 (95% CI 0.76 to 0.92) (men, reference)).Conclusions: Type 2 MI occurred in men and women equally and we found no evidence of sex bias in the selection of patients for cardiac investigations. Patients with type 2 MI had worse outcomes, but women were less likely to have obstructive CAD or severe LV impairment and were more likely to survive than men.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Lindahl, Tomas L, et al.
(författare)
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Methods for evaluation of platelet function.
- 2009
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Ingår i: Transfusion and apheresis science. - : Elsevier BV. - 1473-0502 .- 1878-1683. ; 41:2, s. 121-125
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Tidskriftsartikel (refereegranskat)abstract
- There are a multitude of platelet function tests available, reflecting the complex nature of the platelet in haemostasis. No simple single test will ever cover all aspects of platelet function. Some tests focus on the aggregation of platelets, for example aggregometry, other on the swelling in response to hypotonic solutions, i.e. the well-known hypotonic shock response, or adhesion or coagulation and clot retraction, for example thromboelastography. In general there is a lack of clinical studies showing a predictive value of analysis of platelet concentrates.
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| 33. |
- Nylander, Martina, et al.
(författare)
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The periodontal pathogen Porphyromonas gingivalis sensitises human blood platelets to epinephrine
- 2008
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Ingår i: Platelets. - : Taylor & Francis. - 1369-1635 .- 0953-7104. ; 19:5, s. 352-358
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies indicate connections between periodontitis and atherothrombosis, and the periodontal pathogen Porphyromonas gingivalis has been found within atherosclerotic lesions. P. gingivalis-derived proteases, designated gingipains activate human platelets, probably through a "thrombin-like" activity on protease-activated receptors (PARs). However, the potential interplay between P. gingivalis and other physiological platelet activators has not been investigated. The aim of this study was to elucidate consequences and mechanisms in the interaction between P. gingivalis and the stress hormone epinephrine. By measuring changes in light transmission through platelet suspensions, we found that P. gingivalis provoked aggregation, whereas epinephrine alone never had any effect. Intriguingly, pre-treatment of platelets with a low, sub-threshold number of P. gingivalis (i.e. a density that did not directly provoke platelet aggregation) resulted in a marked aggregation response when epinephrine was added. This synergistic action was not inhibited by the cyclooxygenas inhibitor aspirin. Furthermore, fura-2-measurements revealed that epinephrine caused an intracellular Ca(2+) mobilization in P. gingivalis pre-treated platelets, whereas epinephrine alone had no effect. Inhibition of the arg-specific gingipains, but not the lys-specific gingipains, abolished the aggregation and the Ca(2+) response provoked by epinephrine. Similar results were achieved by separate blockage of platelet alpha(2)-adrenergic receptors and PARs. In conclusion, the present study shows that a sub-threshold number of P. gingivalis sensitizes platelets to epinephrine. We suggest that P. gingivalis-derived arg-specific gingipains activates a small number of PARs on the surface of the platelets. This leads to an unexpected Ca(2+) mobilization and a marked aggregation response when epinephrine subsequently binds to the alpha(2)-adrenergic receptor. The present results are consistent with a direct connection between periodontitis and stress, and describe a novel mechanism that may contribute to pathological platelet activation.
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| 34. |
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| 35. |
- Ramström, Sofia, et al.
(författare)
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Coagulation of whole blood ex vivo : role of tissue factor, factor XI and factor XII for platelet-dependent coagulation amplification
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Activated platelets play an important part both in the formation of the platelet plug aud as a catalytic surface for the plasma coagulation factors. We have earlier shown that activation of platelets in whole blood collected without anticoagulauts shortens the clotting time by approximately 50%. Here, we examine the involvement of TF, factor XII and factor XI in this platelet-dependent coagulation acceleration.Addition of an antibody against tissue factor did not prolong the clotting times for blood samples with platelet activators such as TRAP-6 or a collagen related peptide (CRP), nor for samples with only buffer added. Addition of com trypsin inhibitor (CTI) to inhibit fXIIa prolonged the clotting times by 21% for samples with eRP added. In samples with only buffer or with TRAP-6, en prolonged the clotting times by around 50%. Simultaneous addition of en and anti-TF did not cause any fnrther prolongation.Addition of a polyclonal antibody against factor XI caused a more marked prolongation of the clotting times, especially for TRAP-6 and buffer containing samples, but also for CRP.Only small amounts of thrombin-anti-thrombin (TAT) complexes were found in fresh blood samples directly after blood sampling, same amounts as described for blood down directly into tubes with anticoagulants. We cannot exclude the possibility that these small amounts could activate factor XI on the platelet surface, but that cannot explain the shortened clotting times and increased amounts of TAT found in samples with CRP added. The nature of this platelet-dependent coagulation amplification will be addressed in coming studies.
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| 36. |
- Sahaf, Bita, et al.
(författare)
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Direct Evidence for Thioredoxin in Platelets : Studies on its release into human plasma
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Thioredoxin is a multifunctional protein involved in protecting cells against oxidative stress, and it acts as a co-cytokine and chemotactic factor during an immune response. Mechanisms behind thioredoxin release and transport in the blood are unknown, although the presence of thioredoxin in extracellular fluids is indisputable. We investigated the role of circulatory thioredoxin. We have previously found that release of selenoprotein thioredoxin reductase to the blood is induced by oxidative stress, and thioredoxin reductase is present in plasma (Söderberg, Sabaf, and Rosén, Cancer Res. 60, 2281; 2000). Both thioredoxin and protein disulfide isomerase are substrates for thioredoxin reductase, and both are exposed on the surface oflymphocytes and monocytes. Plasma thioredoxin level is elevated by oxidative stress, a condition often seen in burn patients and HIV carriers. Three of our present findings demonstrate that platelets contain thioredoxin and that circulatory thioredoxin is transported primarily in platelets in healthy blood donors. First, thioredoxin, but not thioredoxin reductase was detected in platelets by deconvolution fluorescence microscopy. Second, plasma thioredoxin concentration was sensitive to thrombocytolysis: a significant decrease in thioredoxin was seen in plasma samples (n = 20) pretreated with the platelet degranulation inhibitors theophylline, adenosine, dipyridamol, acetylsalicylic acid, and apyrase (thioredoxin decreased from 28 down to 8 ng/ml; p < 0.0001). Release of thioredoxin from platelets was induced by the thioloxidant diamide but not by platelet degranulation caused by thrombin, a thrombin peptide (SFLLRN) and collagen, ADP, or PMA-ionophore. Third, in thrombocytopenic and thrombocytemic patients, plasma levels of thioredoxin, but not ß- thromboglobulin, were strongly correlated with platelet numbers (correlation coefficient, r = 0.7). Summarizing, we found direct evidence that thioredoxin is present in platelets and is liberated by oxidative stress (diamide). This suggests that platelets are essential for prompt delivery of this cellular reducing agent to sites of injury, where it can activate coagulation factors and subsequently reduce or balance reactive oxygen species released by inflammatory macrophages.
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| 37. |
- Szymanowski, Aleksander, et al.
(författare)
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Soluble markers of apoptosis in myocardial infarction patients during acute phase and 6-month follow up
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- ObjectivesThe aim of the study was to investigate circulating markers of apoptosis in the acute phase and at follow8up in patients with ST8elevation myocardial infarction (STEMI) or non8ST8elevation myocardial infarction (NSTEMI).BackgroundMyocardial cell death during acute MI results from necrosis, apoptosis and autophagy. An elevated rate of apoptosis can continue for several days after the acute event, contributing to an increased final infarct size. Moreover, a lower but still increased apoptosis can continue for months resulting in left ventricular (LV) dysfunction and heart failure. Few studies have analysed markers of apoptosis longitudinally in MI patients. Also, it is not known whether STEMI and NSTEMI patients differ in regard to these markers. MethodsThis study is a prespecified substudy of the APACHE trial. We included 61 STEMI and 40 NSTEMI patients. Blood samples for analysis of soluble tumor necrosis factor receptor (sTNFR) 1, sTNFR2, sFas, sFas ligand (sFasL) and IL86 were collected at baseline prior to PCI, at 3 days and at 6 months. High sensitivity troponin T (hsTnT) was measured at 688 hours and echocardiography was performed at 283 days after admission to hospital.ResultsSTEMI compared to NSTEMI patients showed very similar temporal patterns for each of the markers of apoptosis analyzed. Levels of sTNFRs increased from baseline to day 3 and the absolute increase as well as day 3 levels correlated significantly with TnT. At 6 months, sTNFR1 had returned to baseline whereas levels of sTNFR2 were still elevated. Soluble Fas and sFasL did not change from baseline to day 3, and both markers were significantly lower in the acute phase compared to 6 months. Indeed, sFas at day 3 correlated negatively with TnT. At all time points, plasma sTNFRs were significantly higher in patients with reduced LV function, whereas no such associations with sFas or sFasL was observed. ConclusionsThe TNF and Fas/FasL pathways of apoptosis, as reflected by soluble markers, show markedly different temporal changes after an acute MI, indicating diverse roles of these two systems. STEMI compared to NSTEMI patients showed very similar temporal patterns for all the analyzed markers, suggesting apoptosis to be equally involved in myocardial damage of either infarct type.
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| 38. |
- Tunströmer, Kjersti, 1986-, et al.
(författare)
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Quantification of Platelet Contractile Movements during Thrombus Formation
- 2018
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Ingår i: Thrombosis and Haemostasis. - New York : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 118:09, s. 1600-1611
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Tidskriftsartikel (refereegranskat)abstract
- Imaging methods based on time-lapse microscopy are important tools for studying the dynamic events that shape thrombus formation upon vascular injury. However, there is a lack of methods to translate the vast amount of visual data generated in such experiments into quantitative variables describing platelet movements that can be subjected to systematic analysis. In this study, we developed experimental and computational protocols allowing for a detailed mathematical analysis of platelet movements within a developing thrombus. We used a flow chamber-based model of thrombosis wherein a collagen strip was used to initiate platelet adhesion and activation. Combining the use of a platelet staining protocol, designed to enable identification of individual platelets, and image processing, we tracked the movements of a large number of individual platelets during thrombus formation and consolidation. These data were then processed to generate aggregate measures describing the heterogeneous movements of platelets in different areas of the thrombus and at different time points. Applying this model and its potential, to a comparative analysis on a panel of platelet inhibitors, we found that total platelet intra-thrombus movements are only slightly reduced by blocking the interactions between glycoproteins IIb/IIIa and Ib and their ligands or by inhibiting thromboxane synthesis or P2Y12 signalling. In contrast, whereas 30 to 40% of the platelets movements (for the CD42a-labelled platelets) and 20% (for the pro-coagulant platelets), within a thrombus, are contractile, i.e., towards the centre of the thrombus, this contractile component is almost totally abolished in the presence of agents inhibiting these pathways.
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| 39. |
- Tynngård, Nahreen, et al.
(författare)
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Assays of different aspects of haemostasis : what do they measure?
- 2015
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Ingår i: Thrombosis Journal. - : BioMed Central (BMC). - 1477-9560. ; 13
-
Forskningsöversikt (refereegranskat)abstract
- Haemostasis is a complex process affected by many factors including both cellular and plasma components. It is a multistep process starting with platelet adhesion to damaged endothelium and ending in clot fibrinolysis. There are several methods available to study different aspects of haemostasis including adhesion, aggregation, coagulation and fibrinolysis. This review describes the different methods, what aspects of haemostasis they measure and their limitations. Methods discussed include methods to study adhesion (e.g. PFA-100, cone and platelet(let) analyzer and perfusion chambers) and aggregation (e.g. Multiplate, VerifyNow and Plateletworks). Furthermore the principles behind viscoelastic haemostatic assays are presented as well as methods that can analyse aspects of haemostasis in plasma or platelet-rich-plasma samples (thrombin generation, overall haemostasis potential and Thrombodynamics Analyzer).
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| 40. |
- Tynngård, Nahreen, et al.
(författare)
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Effects of different blood components on clot retraction analysed by measuring elasticity with a free oscillating rheometer
- 2006
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 17:8, s. 545-554
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Tidskriftsartikel (refereegranskat)abstract
- Free oscillation rheometry (FOR) using the ReoRox® 4 instrument makes it possible, at bedside, to study the coagulation process in blood over time and gives information on clotting time and coagulum elastic properties. In order to find out how various factors influence the FOR analysis we studied the coagulation process and change of elasticity over time in non-anticoagulated and citrated blood samples, plasma samples with various platelet concentrations (0-200 109/l) and blood samples with various haematocrit (0-40%). Blood samples supplemented with fibrinogen were analysed to elucidate the importance of fibrinogen on elasticity. The importance of the GPIIb/IIIa receptor on platelets was investigated by comparing the elasticity development in blood samples in presence and absence of a GPIIb/IIIa receptor inhibitor, abciximab. Anticoagulation with citrate did not have major influence on the viscoelastic properties of the coagulum. Increasing number of platelets and increasing fibrinogen concentration resulted in higher elasticity while increasing haematocrit gave lower elasticity. Blood samples with GPIIb/IIIa receptor inhibitor had very low elasticity indicating the importance of functional GPIIb/IIIa receptors. In conclusion we consider FOR to be a useful method to study the elastic properties of the coagulum. Various factors such as the number of red blood cells and platelets as well as the fibrinogen concentration should be taken into consideration when evaluating the results. The ReoRox® 4 instrument had excellent measuring range and unusually small artefactual effects on clot elasticity induced by the instrument in comparison with published results on other instruments.
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| 41. |
- Tynngård, Nahreen, et al.
(författare)
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Effects of intercept pathogen inactivation on platelet function as analysed by free oscillation rheometry
- 2008
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Ingår i: Transfusion and apheresis science. - : Elsevier BV. - 1473-0502 .- 1878-1683. ; 38:1, s. 85-88
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Intercept Blood System, using InterSol as additive solution, is used for inactivation of contaminating pathogens in PCs, thus reducing the risk for transfusion transmitted infection and making it possible to prolong the storage period. This study aimed at investigating the ability of Intercept treated platelets to induce clot formation, as measured by coagulation time using free oscillation rheometry (FOR), and to compare with that of platelets in concentrates with the additive solution T-Sol or plasma. Methods: Seventy-four single-donor platelet units were diluted in InterSol (n = 27) or T-Sol (n = 47) to a mean plasma concentration of 38%. The Intercept treatment was performed by addition of amotosalen HCl to the InterSol PCs followed by UVA irradiation and treatment with a compound adsorption device (CAD). Forty-six units were collected and stored in 100% plasma for comparison. Clotting time was measured by FOR in fresh PCs (within 26 h after collection) after stimulation by a platelet activator. Soluble P-selectin was analysed as a marker of platelet activation in the Intercept and T-Sol PCs. Results: The clotting time was shorter for Intercept treated platelets compared to platelets in T-Sol and plasma (p < 0.05). There was no difference in clotting time between T-Sol and plasma PCs. Soluble P-selectin was higher for Intercept platelets than platelets in T-Sol (p < 0.05). Conclusions: The platelets treated with the Intercept procedure had good clot promoting capacity.
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| 42. |
- Tynngård, Nahreen, et al.
(författare)
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Free oscillation rheometry detects changes in clot properties in pregnancy and thrombocytopaenia
- 2008
-
Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 19:5, s. 373-378
-
Tidskriftsartikel (refereegranskat)abstract
- Improved methods are needed to identify patients at risk for thrombotic or bleeding events. Free oscillation rheometry (FOR) is a technique that offers information on coagulation, based on contributions of all blood components, by measurement of clotting time and changes in clot elasticity. This is the first study that evaluates FOR parameters in subjects likely to represent hypercoagulability (pregnant women) and hypocoagulability (thrombocytopenic patients). Clotting time and blood clot elasticity were measured by FOR in blood samples obtained from women in different pregnancy trimesters (n = 58), in thrombocytopenic patients before and after a platelet transfusion (n = 20) and in healthy blood donors (n = 60). The clotting time was shorter and the clot elasticity higher in pregnant women compared to the non-pregnant female blood donors. The elasticity was higher in late pregnancy compared to early pregnancy. Compared to the blood donors, the thrombocytopenic patients had lower elasticity, which was increased by a platelet transfusion, but there was no difference in clotting time. The results suggest that FOR can provide new information on the haemostatic status of patients at risk of thrombotic or bleeding events as well as information on the haemostatic effect of a platelet transfusion.
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| 43. |
- Tynngård, Nahreen, et al.
(författare)
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The effect of gamma irradiation on the quality of apheresis platelets during storage for 7 days
- 2008
-
Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 48:8, s. 1669-1675
-
Tidskriftsartikel (refereegranskat)abstract
- Background:This study compares the quality of gamma-irradiated versus nonirradiated platelet (PLT) concentrates (PCs) during storage for 7 days as assessed by various in vitro methods. A new technique, free oscillation rheometry (FOR), which measures clotting time and coagulum elasticity, was also used to evaluate the PLT function. Study design and methods: Single-donor PLTs were collected by apheresis technique (n = 20). The PLTs from each donor were divided into two PCs, one gamma-irradiated with 25 Gy and the other used as a nonirradiated control. Blood gases, metabolic variables, and swirling were analyzed from Day 0. Samples taken on Days 1, 5, and 7 were also analyzed for hypotonic shock response (HSR), P-selectin, and glycoprotein (GP)Ib expression by flow cytometry and coagulation by FOR. Results: Swirling, HSR, and the percentage of GPIb-expressing cells were well maintained for 7 days of storage. pH was always within accepted range (6.4-7.4). Glucose decreased and lactate increased during the storage period (p < 0.05). P-selectin expression increased during storage (p < 0.05). The FOR clotting time remained constant, whereas the build-up of elasticity was slower after storage (p < 0.05). No difference was found between irradiated and nonirradiated PCs. Conclusion: The results indicate a well-preserved quality of gamma-irradiated apheresis PLTs during storage for 7 days as assessed by in vitro methods, with no difference compared to nonirradiated PLTs.
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| 44. |
- Welinder, Karen Gjesing, et al.
(författare)
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Biochemical Foundations of Health and Energy Conservation in Hibernating Free-Ranging Subadult Brown Bear Ursus arctos
- 2016
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Ingår i: Journal of Biological Chemistry. - Rockville, USA : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 291:43, s. 22509-22523
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Tidskriftsartikel (refereegranskat)abstract
- Brown bears (Ursus arctos) hibernate for 5-7 months without eating, drinking, urinating and defecating at a metabolic rate of only 25% of the summer activity rate. Nonetheless, they emerge healthy and alert in spring. We quantified the biochemical adaptations for hibernation by comparing the proteome, metabolome, and hematologic features of blood from hibernating and active free-ranging subadult brown bears with a focus on conservation of health and energy. We found that total plasma protein concentration increased during hibernation, even though the concentrations of most individual plasma proteins decreased, as did the white blood cell types. Strikingly, antimicrobial defense proteins increased in concentration. Central functions in hibernation involving the coagulation response and protease inhibition, as well as lipid transport and metabolism, were upheld by increased levels of very few key or broad-specificity proteins. The changes in coagulation factor levels matched the changes in activity measurements. A dramatic 45-fold increase in sex-hormone-binding-globulin SHBG levels during hibernation draws, for the first time, attention to its significant but unknown role in maintaining hibernation physiology. We propose that energy for the costly protein synthesis is reduced by three mechanisms, (i) dehydration, which increases protein concentration without de novo synthesis; (ii) reduced protein degradation rates due to a 6 °C reduction in body temperature, and decreased protease activity; and (iii) a marked redistribution of energy resources only increasing de novo synthesis of few key proteins. This comprehensive global data identified novel biochemical strategies for bear adaptations to the extreme condition of hibernation, and have implications for our understanding of physiology in general.
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| 45. |
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