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Knutson, Folke
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Publications (10 of 20) Show all publications
Mogensen, S., Lubenow, N., Nilsson, P., Engquist, H., Knutson, F., Enblad, P., . . . Frykholm, P. (2017). An evaluation of the mixed pediatric unit for blood loss replacement in pediatric craniofacial surgery. Pediatric Anaesthesia, 27(7), 711-717
Open this publication in new window or tab >>An evaluation of the mixed pediatric unit for blood loss replacement in pediatric craniofacial surgery
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2017 (English)In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 27, no 7, p. 711-717Article in journal (Refereed) Published
Abstract [en]

Background: Surgical correction for craniosynostosis is often associated with significant perioperative hemorrhage. We implemented a transfusion strategy with a strict protocol including transfusion triggers, frequent assessment of coagulation tests, and the use of a novel transfusion unit, the mixed pediatric unit. Aim: The aim of the study was to evaluate if the applied transfusion strategy could reduce total blood loss and number of blood donors. Methods: Children <1 year old admitted for craniosynostosis surgery were included for the study. On the day before surgery, an adult red blood cell unit was mixed with plasma and split into two mixed pediatric units-one intended for intraoperative use and the other saved for the postoperative period. A series of blood samples were obtained for standard coagulation parameters as well as thromboelastography to evaluate potential coagulopathy. Estimated blood loss, the number of additional standard packed red cell units opened in the first 24 h after surgery, the volume of fluid administered, and the total transfusion volumes were compared to a historical control group with similar age and characteristics. Results: Nineteen infants were included in the study group, and were compared to 21 historical controls. There was a significant reduction of intraoperative transfusion volume. Twelve patients were transfused postoperatively, but in 8 of these additional exposure to packed red cell donor blood was avoided by using the saved mixed pediatric unit. In the historical controls, a total of 10 packed red cell units were used in nine patients postoperatively. No additional transfusions of plasma, platelets, fibrinogen, or tranexamic acid were needed in either group, and the coagulation parameters including thromboelastography remained within their respective normal ranges in the study group. Conclusion: For craniofacial surgery in infants, moderate perioperative blood loss and avoidance of coagulopathy is possible when a multifactorial approach is implemented. In this setting, intraoperative, but not total perioperative blood loss was reduced with the studied protocol. The study indicates that there may be a role for mixed pediatric units to reduce exposure to multiple donors although the reduction in total donor exposure was not significant.

Keywords
craniosynostosis, blood loss, surgical, postoperative hemorrhage, blood transfusion, blood coagulation tests, thromboelastography, infants
National Category
Anesthesiology and Intensive Care Pediatrics
Identifiers
urn:nbn:se:uu:diva-330012 (URN)10.1111/pan.13140 (DOI)000405081500007 ()28436074 (PubMedID)
Available from: 2017-10-11 Created: 2017-10-11 Last updated: 2017-10-11Bibliographically approved
Lieshout-Krikke, R. W., Domanovic, D., de Kort, W., Mayr, W., Liumbruno, G. M., Pupella, S., . . . Follea, G. (2017). Selection strategies for newly registered blood donors in European countries. Blood Transfusion, 15(6), 495-501
Open this publication in new window or tab >>Selection strategies for newly registered blood donors in European countries
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2017 (English)In: Blood Transfusion, ISSN 1723-2007, Vol. 15, no 6, p. 495-501Article in journal (Refereed) Published
Abstract [en]

Background: Two selection strategies for newly-registered blood donors are available: a singlevisit selection called the standard selection procedure (SSP), and a two-stage selection named predonation and donation screening (PDS). This study reviews the selection strategies for newly-registered donors currently applied in European countries.

Material and methods: We collected data on donor selection procedures, blood donation, laboratory screening and HIV, HCV and HBV positive donors/donations from 2010 to 2013 in 30 European countries by using questionnaires. We grouped the countries according to the applied selection strategy, and for each country, we calculated the 4-year prevalence of confirmed positive results indicating the presence of overall and recent HIV, HCV and HBV infections among first-time and repeat donations and among newly-registered donors.

Results: Most of the 24 countries (80%) apply the SSP strategy for selection of newly-registered donors. Twenty-two countries (73.3%) employ a nucleic acid amplification testing in addition to the mandatory serological screening. The survey confirms a higher overall prevalence of HIV, HCV and HBV infections among first-time donations and newly-registered donors than among repeat donations. In contrast, the prevalence of recently acquired HIV and HCV infections was lower among first-time donations and newly-registered donors than among repeat donations, but higher for recent HBV infections (6.7/105 vs 2.6/105 in the SSP setting and 4.3/105 vs 0.5/105 in one country using PDS). The relatively low numbers of infected donors selected by PDS impeded accurate assessment of the prevalence of recent infections in first-time donations.

Discussion: The data from European countries provide inconclusive evidence that applying PDS reduces the risk of donations being made in the diagnostic window of first-time donors. The impact of PDS on the risk of window-period donations and blood donor management needs further investigation.

Keywords
donors, infectious diseases, screening, selection
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-340170 (URN)10.2450/2016.0107-16 (DOI)000413802600003 ()27723449 (PubMedID)
Available from: 2018-01-30 Created: 2018-01-30 Last updated: 2018-01-30Bibliographically approved
Strandberg, G., Sellberg, F., Sommar, P., Ronaghi, M., Lubenow, N., Knutson, F. & Berglund, D. (2017). Standardizing the freeze-thaw preparation of growth factors from platelet lysate. Transfusion, 57(4), 1058-1065
Open this publication in new window or tab >>Standardizing the freeze-thaw preparation of growth factors from platelet lysate
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2017 (English)In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 57, no 4, p. 1058-1065Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Over the past decades, the focus on the regenerative properties of platelets (PLTs) has intensified and many PLT-derived growth factors are readily used in medical settings. A general lack of standardization in the preparation of these growth factors remains, however, and this study therefore examines the dynamics of growth factors throughout the freeze-thaw procedure.

STUDY DESIGN AND METHODS: Plateletpheresis (PA) and PLT-poor plasma (PPP) samples were collected from 10 healthy donors. PA was lysed to produce PLT lysate (PL) for 1, 3, 5, 10, and 30 freeze-thaw cycles. The resulting growth factor and cytokine concentrations from PPP, PA, and PL of different cycles were analyzed and compared using enzyme-linked immunosorbent assay and multiplex bead assays.

RESULTS: PL produced by the freeze-thaw procedure resulted in approximately four-to 10-fold enrichment of transforming growth factor-b1, epidermal growth factor, PLT-derived growth factor (PDGF)-AB/BB, PLT factor-4, and fibroblast growth factor-2. The increase in concentrations plateaued at Cycles 3 and 5 and in some cases declined with further cycles. The concentrations of insulin-like growth factor-1, hepatocyte growth factor, vascular endothelial growth factor, and bone morphogenetic protein-2 in PL were essentially comparable to those in PPP.

CONCLUSION: Using the freeze-thaw method, optimal preparation of PL with regard to the concentration of growth factors was achieved at Cycles 3 to 5. Based on our findings, the clinical significance of using a greater number of cycles is likely limited.

Place, publisher, year, edition, pages
WILEY, 2017
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-328740 (URN)10.1111/trf.13998 (DOI)000402864500029 ()28182293 (PubMedID)
Available from: 2017-08-30 Created: 2017-08-30 Last updated: 2017-08-30Bibliographically approved
Sellberg, F., Berglund, E., Ronaghi, M., Strandberg, G., Löf, H., Sommar, P., . . . Berglund, D. (2016). Composition of growth factors and cytokines in lysates obtained from fresh versus stored pathogen-inactivated platelet units. Transfusion and apheresis science, 55(3), 333-337
Open this publication in new window or tab >>Composition of growth factors and cytokines in lysates obtained from fresh versus stored pathogen-inactivated platelet units
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2016 (English)In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 55, no 3, p. 333-337Article in journal (Refereed) Published
Abstract [en]

Background: Platelet lysate is a readily available source of growth factors, and other mediators, which has been used in a variety of clinical applications. However, the product remains poorly standardized and the present investigation evaluates the composition of platelet lysate obtained from either fresh or stored pathogen-inactivated platelet units.

Materials and Methods: Platelet pooled units (n = 10) were obtained from healthy blood donors and tested according to standard procedures. All units were pathogen inactivated using amotosalen hydrochloride and UVA exposure. Platelet lysate was subsequently produced at two separate time-points, either from fresh platelet units or after 5 days of storage, by repeated freeze-thaw cycles. The following mediators were determined at each time point: EGF, FGF-2, VEGF, IGF-1, PDGF-AB/BB, BMP-2, PF4, TGF-beta isoform 1, IL-1(i, IL-2, IL-6, IL-10, IL-12p70, 1L-17A, TNF-alpha, and IFN-gamma.

Results: The concentration of growth factors and cytokines was affected by time in storage. Notably, TGF-beta, PDGF-AB/BB, and PF4 showed an increase of 27.2% (p < 0.0001), 29.5% (p = 0.04) and 8.2% (p = 0.0004), respectively. A decrease was seen in the levels of IGF-1 and FGF-2 with 22% (p = 0.041) and 11% (p = 0.01), respectively. Cytokines were present only in very low concentrations and all other growth factors remained stable with time in storage.

Conclusion: The composition of mediators in platelet lysate obtained from pathogen inactivated platelet units differs when produced from fresh and stored platelet units, respectively. This underscores the need for further standardization and optimization of this important product, which potentially may influence the clinical effects.

Keywords
Platelet lysate, Pathogen-inactivation, Growth factor, Cytokine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-314425 (URN)10.1016/j.transci.2016.08.004 (DOI)000390964500014 ()
Available from: 2017-02-02 Created: 2017-02-02 Last updated: 2017-11-29Bibliographically approved
Sellberg, F., Ronaghi, M., Knutson, F. & Berglund, D. (2016). Inflammatory cytokines in serum samples of healthy blood donors [Letter to the editor]. Transfusion and apheresis science, 55(2), 246-247
Open this publication in new window or tab >>Inflammatory cytokines in serum samples of healthy blood donors
2016 (English)In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 55, no 2, p. 246-247Article in journal, Letter (Refereed) Published
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-313620 (URN)10.1016/j.transci.2016.07.020 (DOI)000386744900019 ()27475802 (PubMedID)
Available from: 2017-01-23 Created: 2017-01-23 Last updated: 2017-11-29Bibliographically approved
Knutson, F., Saxner, A. J., Lejskog, K. & Löf, H. (2016). Ten Years of Experience With a Pathogen-reduction Technique In Platelets and Low Levels of Adverse Events. Paper presented at AABB Annual Meeting, OCT 22-25, 2016, Orlando, FL. Transfusion, 56, 194A-194A
Open this publication in new window or tab >>Ten Years of Experience With a Pathogen-reduction Technique In Platelets and Low Levels of Adverse Events
2016 (English)In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 56, p. 194A-194AArticle in journal, Meeting abstract (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-309836 (URN)000384646400539 ()
Conference
AABB Annual Meeting, OCT 22-25, 2016, Orlando, FL
Available from: 2016-12-08 Created: 2016-12-07 Last updated: 2017-11-29Bibliographically approved
Knutson, F., Osselaer, J., Pierelli, L., Lozano, M., Cid, J., Tardivel, R., . . . Corash, L. (2015). A prospective, active haemovigilance study with combined cohort analysis of 19 175 transfusions of platelet components prepared with amotosalen-UVA photochemical treatment. Vox Sanguinis, 109(4), 343-352
Open this publication in new window or tab >>A prospective, active haemovigilance study with combined cohort analysis of 19 175 transfusions of platelet components prepared with amotosalen-UVA photochemical treatment
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2015 (English)In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 109, no 4, p. 343-352Article in journal (Refereed) Published
Abstract [en]

Background and Objectives A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT (TM) Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated platelet components (PCT-PLT) administered across a broad patient population. Materials and Methods This open-label, observational haemovigilance programme of PCT-PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post-transfusion and for serious adverse events (SAEs) up to 7 days post-transfusion. All adverse events were assessed for severity (Grade 0-4), and causal relationship to PCT-PLT transfusion. Results Over the course of 7 years in the study centres, 4067 patients received 19 175 PCT-PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per-transfusion basis, 123 (0.6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0.4%) and urticaria (41, 0.2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0.1%). No case of transfusion-related acute lung injury, transfusion-associated graft-versus-host disease, transfusion-transmitted infection or death was attributed to the transfusion of PCT-PLT. Conclusion This longitudinal haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components.

Keywords
amotosalen, haemovigilance, INTERCEPT, pathogen inactivation, platelets, safety
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-271041 (URN)10.1111/vox.12287 (DOI)000365413400006 ()25981525 (PubMedID)
Available from: 2016-01-05 Created: 2016-01-05 Last updated: 2017-12-01Bibliographically approved
Stenwall, P.-A., Bergström, M., Seiron, P., Sellberg, F., Olsson, T., Knutson, F. & Berglund, D. (2015). Improving the anti-inflammatory effect of serum eye drops using allogeneic serum permissive for regulatory T cell induction. Acta Ophthalmologica, 93(7), 654-657
Open this publication in new window or tab >>Improving the anti-inflammatory effect of serum eye drops using allogeneic serum permissive for regulatory T cell induction
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2015 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 7, p. 654-657Article in journal (Refereed) Published
Abstract [en]

PurposeTo investigate the cytokine composition and anti-inflammatory effects of allogeneic serum preparations for improved use as serum eye drops. MethodsSerum of 15 healthy blood donors was extensively screened for cytokines, including IL-1, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-15, 1L-17A, E and F, IL-21, IL-22, IL-23, IL-27, IL-28A, IL-31, IL-33, granulocyte macrophage colony-stimulating factor (GM-CSF), chemokine ligand 20 (CCL20), tumour necrosis factor (TNF)- and TNF-, interferon (IFN)- and transforming growth factor (TGF)-. The levels of cytokines were assessed before and after heat-induced inactivation. Individual serum preparations were tested for their anti-inflammatory effect using an invitro test to differentiate effector T lymphocytes into anti-inflammatory regulatory T cells. ResultsThe anti-inflammatory cytokine TGF- was readily detected in the serum of all blood donors and was only modestly affected by heat-induced inactivation. Serum containing high amounts of TGF- was more effective at inducing anti-inflammatory regulatory T cells. The serum of one healthy blood donor displayed high levels of inflammatory cytokines. ConclusionWe propose that serum used as eye drops is screened for its cytokine content, making it possible to correlate the composition to the clinical outcome. Based on the findings in this study, tailored serum eye drops produced from allogeneic donors may provide increased anti-inflammatory effects. This may be superior to autologous serum eye drops, which in many cases are retrieved from patients with inflammatory diseases.

Keywords
allogeneic serum eye drops, cytokines, dry eye, regulatory T cells, TGF-beta
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-267654 (URN)10.1111/aos.12801 (DOI)000363890500031 ()26178796 (PubMedID)
Funder
Magnus Bergvall Foundation
Available from: 2015-11-27 Created: 2015-11-25 Last updated: 2018-01-10Bibliographically approved
Melki, V., Tano, E., Hakansson, L. D., Tran, P.-K., Knutson, F., Malinski, T. & Borowiec, J. (2014). Effect of Glyceryl Trinitrate on Staphylococcus aureus Growth and Leukocyte Activation during Simulated Extracorporeal Circulation. The thoracic and cardiovascular surgeon, 62(5), 402-408
Open this publication in new window or tab >>Effect of Glyceryl Trinitrate on Staphylococcus aureus Growth and Leukocyte Activation during Simulated Extracorporeal Circulation
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2014 (English)In: The thoracic and cardiovascular surgeon, ISSN 0171-6425, E-ISSN 1439-1902, Vol. 62, no 5, p. 402-408Article in journal (Refereed) Published
Abstract [en]

Background Previously, nitric oxide has been shown to possess antimicrobial effects. In this study, we aim to test the effect of glyceryl trinitrate (GTN) on Staphylococcus aureus growth during simulated extracorporeal circulation (SECC) and also to examine the effect of S. aureus, alone and in combination with GTN, on activation markers of the innate immune system during SECC. Methods In an in vitro system of SECC, we measured GTN-induced changes in markers of leukocyte activation in whole blood caused by S. aureus infestation, as well as the effect of GTN on S. aureus growth. Results GTN had no effect on S. aureus growth after 240 minutes SECC. Staphylococcus aureus reduced the expression of granulocyte Fc gamma-receptor CD32 but stimulated the expression of monocyte CD32. Staphylococcus aureus stimulated expression of some leukocyte adhesion key proteins, activation marker CD66b, lipopolysaccharide-receptor CD14, and C3b-receptor CD35. Staphylococcus aureus and GTN addition induced significant increases in monocyte CD63 (lysosomal granule protein) levels. Conclusion GTN does not affect S. aureus growth during SECC and has no effect on SECC-induced leukocyte activation.

Keywords
glyceryl trinitrate, Staphylococcus aureus, simulated extracorporeal circulation, postoperative infection, cardiac surgery
National Category
Surgery Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-232653 (URN)10.1055/s-0033-1363296 (DOI)000340748500005 ()
Available from: 2014-09-24 Created: 2014-09-22 Last updated: 2017-12-05Bibliographically approved
Hron, G., Knutson, F., Thiele, T., Althaus, K., Busemann, C., Friesecke, S., . . . Lubenow, N. (2013). Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill patients despite a positive PF4/heparin-antibody test. Upsala Journal of Medical Sciences, 118(4), 279-284
Open this publication in new window or tab >>Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill patients despite a positive PF4/heparin-antibody test
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2013 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 279-284Article in journal (Refereed) Published
Abstract [en]

Thrombocytopenia can cause diagnostic challenges in patients who have received heparin. Heparin-induced thrombocytopenia (HIT) is often considered in the differential diagnosis, and a positive screening can be mistaken as confirmation of the disorder. We present two patients who both received low-molecular-weight heparin for several days. In the first patient, clinical judgment rejected the suspicion of HIT despite a positive screening assay, and treatment for the alternative diagnosis of post-transfusion purpura was correctly initiated. In the second patient, the inaccurate diagnosis HIT was pursued due to a positive screening assay, while the alternative diagnosis of drug-dependent thrombocytopenia caused by piperacillin/tazobactam was rejected. This resulted in re-exposure to piperacillin/tazobactam which caused a second episode of severe thrombocytopenia. A positive screening assay for platelet factor 4/heparin-antibody should be verified by a functional assay, especially in patients with low pretest probability for HIT.

Keywords
Drug-induced thrombocytopenia, heparin-induced thrombocytopenia, HIT, piperacillin-induced thrombocytopenia, post-transfusions purpura, PTP
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-210569 (URN)10.3109/03009734.2013.838811 (DOI)000325527300012 ()
Available from: 2013-11-13 Created: 2013-11-11 Last updated: 2017-12-06Bibliographically approved
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