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Lindahl, Tomas
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Publications (10 of 153) Show all publications
Holm, J., Szabó, Z., Alehagen, U., Lindahl, T. & Cederholm, I. (2018). Copeptin Release in Cardiac Surgery: A New Biomarker to Identify Risk Patients?. Journal of Cardiothoracic and Vascular Anesthesia, 32(1), 245-250
Open this publication in new window or tab >>Copeptin Release in Cardiac Surgery: A New Biomarker to Identify Risk Patients?
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2018 (English)In: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 32, no 1, p. 245-250Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To describe the dynamics of copeptin in open cardiac surgery during the perioperative course.

DESIGN: Prospective cohort study.

SETTING: Single tertiary hospital.

PARTICIPANTS: Twenty patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB).

INTERVENTIONS: No intervention.

MEASUREMENTS AND MAIN RESULTS: Copeptin concentrations were measured pre-, peri-, and postoperatively until day 6 after surgery. Patients were analyzed as a whole cohort (n = 20) and in a restricted "normal cohort" consisting of patients with normal preoperative copeptin concentration (<10 pmol/L) and perioperative uneventful course (n = 11). In the whole cohort, preoperative copeptin concentration was 7.0 pmol/L (interquartile range: 3.1-11 pmol/L). All patients had an early rise of copeptin, with 80% having peak copeptin concentration at weaning from CPB or upon arrival in the intensive care unit. Patients in the "normal cohort" had copeptin concentration at weaning from CPB of 194 pmol/L (98-275), postoperative day 1, 27 pmol/L (18-31); and day 3, 8.9 pmol/L (6.3-12).

CONCLUSIONS: Regardless of cardiac surgical procedure and perioperative course, all patients had an early significant rise of copeptin concentrations, generally peaking at weaning from CBP or upon arrival in the intensive care unit. Among patients with normal copeptin concentration preoperatively and uneventful course, the postoperative copeptin concentrations decreased to normal values within 3-to-4 days after cardiac surgery. Furthermore, the restricted "normal cohort" generally tended to display lower levels of copeptin concentration postoperatively. Further studies may evaluate whether copeptin can be a tool in identifying risk patients in cardiac surgery.

Place, publisher, year, edition, pages
Saunders Elsevier, 2018
Keywords
cardiac surgery, copeptin, kinetics, perioperative care
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-144019 (URN)10.1053/j.jvca.2017.06.011 (DOI)000424730300032 ()29102258 (PubMedID)2-s2.0-85033433737 (Scopus ID)
Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-03-08Bibliographically approved
Alfredsson, J., Swahn, E., Gustafsson, K. M., Janzon, M., Jonasson, L., Logander, E., . . . Lindahl, T. (2018). Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction.. Platelets, 1-7
Open this publication in new window or tab >>Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction.
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2018 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, p. 1-7Article in journal (Refereed) Epub ahead of print
Abstract [en]

There is a large inter-individual variation in response to clopidogrel treatment, and previous studies have indicated higher risk of thrombotic events in those with high residual platelet reactivity (HPR). Less is known about individual variation over time. The aim of this prospective cohort study was to investigate intra-individual variation in platelet reactivity. Platelet aggregation in whole blood was assessed in 77 patients, at 3 days, 8 days and 6 months after admission for acute myocardial infarction and loading dose of clopidogrel. All patients were treated with aspirin and clopidogrel through 6-month follow-up. We found a significant increase in median ADP-stimulated aggregation from third to eighth day (195 vs. 250 AU*min, p-value = 0.001) but not from day 8 to 6 months (250 vs. 223 AU*min, p-value = 0.666). There was no significant change in the overall rate of HPR (15.6% vs 20.8%, p-value 0.503) or low platelet reactivity (LPR) (37.7% vs 33.8%, p-value = 0.609) from day 8 to 6-month follow-up. In contrast, more than one in four changed HPR status, 15.6% from non-HPR to HPR and 10.4% HPR to non-HPR. A shift in LPR status appeared even more frequent, occurring in about one of three patients. In spite of similar median aggregation and rate of HPR during 6-month follow-up, about one in four of the patients changed HPR status and one in three changed LPR status. This may be important information for a concept of risk stratification based on a single aggregation value early after an acute coronary syndromes.

Keywords
High residual platelet reactivity, myocardial infarction, platelet
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-149564 (URN)10.1080/09537104.2018.1479519 (DOI)29869923 (PubMedID)
Available from: 2018-07-06 Created: 2018-07-06 Last updated: 2018-08-06
Tunströmer, K., Faxälv, L., Boknäs, N. & Lindahl, T. L. (2018). Quantification of Platelet Contractile Movements during Thrombus Formation. Thrombosis and Haemostasis, 118(09), 1600-1611
Open this publication in new window or tab >>Quantification of Platelet Contractile Movements during Thrombus Formation
2018 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 118, no 09, p. 1600-1611Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
New York: Georg Thieme Verlag KG, 2018
Keywords
flow chambers, thrombosis, platelet aggregation, platelet contraction, fluorescence microscopy
National Category
Medical Image Processing
Identifiers
urn:nbn:se:liu:diva-150961 (URN)10.1055/s-0038-1668151 (DOI)000444575200013 ()30112750 (PubMedID)
Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2018-10-04Bibliographically approved
Lindahl, T., Ramström, S., Boknäs, N. & Faxälv, L. (2016). Caveats in studies of the physiological role of polyphosphates in coagulation. Biochemical Society Transactions, 44, 35-39
Open this publication in new window or tab >>Caveats in studies of the physiological role of polyphosphates in coagulation
2016 (English)In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 44, p. 35-39Article in journal (Refereed) Published
Abstract [en]

Platelet-derived polyphosphates (polyP), stored in dense granule and released upon platelet activation, have been claimed to enhance thrombin activation of coagulation factor XI (FXI) and to activate FXII directly. The latter claim is controversial and principal results leading to these conclusions are probably influenced by methodological problems. It is important to consider that low-grade contact activation is initiated by all surfaces and is greatly amplified by the presence of phospholipids simulating the procoagulant membranes of activated platelets. Thus, proper use of inhibitors of the contact pathway and a careful choice of materials for plates and tubes is important to avoid artefacts. The use of phosphatases used to degrade polyP has an important drawback as it also degrades the secondary activators ADP and ATP, which are released from activated platelets. In addition, the use of positively charged inhibitors, such as polymyxin B, to inhibit polyP in platelet-rich plasma and blood is problematic, as polymyxin B also slows coagulation in the absence of polyP. In conclusion we hope awareness of the above caveats may improve research on the physiological roles of polyP in coagulation. © 2016 Authors; published by Portland Press Limited.

Place, publisher, year, edition, pages
Portland Press Ltd, 2016
Keywords
Blood; Coagulation; Contact activation; Phosphatase; Platelets; Polyphosphate
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126155 (URN)10.1042/BST20150220 (DOI)26862185 (PubMedID)2-s2.0-84957871941 (Scopus ID)
Note

Funding Agencies|20140410, Hjärt-Lungfonden; K2013-65X-15060-10-3, Hjärt-Lungfonden

Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2017-11-30
Claesson, K., Lindahl, T. & Faxälv, L. (2016). Counting the platelets: a robust and sensitive quantification method for thrombus formation. Thrombosis and Haemostasis, 115(6), 1178-1190
Open this publication in new window or tab >>Counting the platelets: a robust and sensitive quantification method for thrombus formation
2016 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 115, no 6, p. 1178-1190Article in journal (Refereed) Published
Abstract [en]

Flow chambers are common tools used for studying thrombus formation in vitro. However, the use of such devices is not standardised and there is a large diversity among the flow chamber systems currently used, and also in the methods used for quantifying the thrombus development. It was the study objective to evaluate a new method for analysis and quantification of platelet thrombus formation that can facilitate comparison of results between research groups. Whole blood was drawn over a collagen patch in commercial Ibid or in-house constructed PDMS flow chambers. Five percent of the platelets were fluorescently labelled and z-stack time-lapse images were captured during thrombus formation. Images were processed in a Python script in which the number of platelets and their respective x-, y- and z-positions were obtained. For comparison with existing methods the platelets were also labelled and quantified using fluorescence intensity and thrombus volume estimations by confocal microscopy. The presented method was found less sensitive to microscope and image adjustments and provides more details on thrombus development dynamics than the methods for measuring fluorescence intensity and thrombus volume estimation. The platelet count method produced comparable results with commercial and PDMS flow chambers, and could also obtain information regarding the stability of each detected platelet in the thrombus. In conclusion, quantification of thrombus formation by platelet count is a sensitive and robust method that enables measurement of platelet accumulation and platelet stability in an absolute scale that could be used for comparisons between research groups.

Place, publisher, year, edition, pages
SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN, 2016
Keywords
Platelet aggregation; microfluidics; thrombosis; fluorescence microscopy; computer-assisted image processing
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-130073 (URN)10.1160/TH15-10-0799 (DOI)000377237400011 ()26842994 (PubMedID)
Note

Funding Agencies|Swedish Research Council [K2015-79X-22644-01-3]; Linkoping University

Available from: 2016-07-06 Created: 2016-07-06 Last updated: 2018-09-06
Chaireti, R., Lindahl, T., Bystrom, B., Bremme, K. & Larsson, A. (2016). Inflammatory and endothelial markers during the menstrual cycle. Scandinavian Journal of Clinical and Laboratory Investigation, 76(3), 190-194
Open this publication in new window or tab >>Inflammatory and endothelial markers during the menstrual cycle
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2016 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 3, p. 190-194Article in journal (Refereed) Published
Abstract [en]

Background The menstrual cycle exhibits a pattern of repeated inflammatory activity. The present study aims to evaluate inflammatory and endothelial markers during the two phases of a menstrual cycle. Methods The study cohort consisted of 102 women with regular menstrual cycles. Inflammatory and endothelial markers (interleukin-6 [IL-6], pentraxin-3 [PTX-3], hs-C reactive protein [hs-CRP], sE-selectin, sP-selectin, intracellular and vascular cell adhesion molecules [ICAM-1 and VCAM-1] and cathepsins L, B and S) were measured during the early follicular and the late luteal phase of a normal menstrual cycle. Results Pentraxin-3 (PTX-3) and hs-CRP were significantly higher during the follicular phase compared to the luteal phase (p &lt; 0.001 respectively p = 0.025). The other inflammatory and endothelial markers, with the exception of cathepsin B, were higher, albeit not significantly, during the follicular phase. Conclusions Inflammatory activity, expressed mainly by members of the pentraxin family, is higher during the early follicular compared to the luteal phase. This could be associated to menstruation but the exact mechanisms behind this pattern are unclear and might involve the ovarian hormones or an effect on hepatocytes.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2016
Keywords
menstrual cycle; Inflammation; pentraxin
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127556 (URN)10.3109/00365513.2015.1129670 (DOI)000372195200002 ()26963835 (PubMedID)
Available from: 2016-05-04 Created: 2016-05-03 Last updated: 2017-11-30
Ramström, S., Södergren, A., Tynngård, N. & Lindahl, T. (2016). Platelet Function Determined by Flow Cytometry: New Perspectives?. Seminars in Thrombosis and Hemostasis, 42(3), 268-281
Open this publication in new window or tab >>Platelet Function Determined by Flow Cytometry: New Perspectives?
2016 (English)In: Seminars in Thrombosis and Hemostasis, ISSN 0094-6176, E-ISSN 1098-9064, Vol. 42, no 3, p. 268-281Article in journal (Refereed) Published
Abstract [en]

Flow cytometry enables studies of several different aspects of platelet function in response to a variety of platelet agonists. This can be done using only a small volume of whole blood, and also in blood with low platelet counts. These properties, together with the increasing number of flow cytometers available in hospitals worldwide, make flow cytometry an interesting option for laboratories interested in studies of platelet function in different clinical settings. This review focuses on practical issues regarding the use of flow cytometry for platelet function testing. It provides an overview of available activation markers, platelet agonists, and experimental setup issues. The review summarizes previous experience and factors important to consider to perform high-quality platelet function testing by flow cytometry. It also discusses its current use and possibilities and challenges for future use of flow cytometry in clinical settings

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
blood platelets; flow cytometry; platelet activation; platelet function testing
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126156 (URN)10.1055/s-0035-1570082 (DOI)000373139300011 ()26886398 (PubMedID)
Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2017-11-30Bibliographically approved
Zdolsek, J., Bergek, C., Lindahl, T. & Hahn, R. (2015). Colloid osmotic pressure and extravasation of plasma proteins following infusion of Ringers acetate and hydroxyethyl starch 130/0.4. Acta Anaesthesiologica Scandinavica, 59(10), 1303-1310
Open this publication in new window or tab >>Colloid osmotic pressure and extravasation of plasma proteins following infusion of Ringers acetate and hydroxyethyl starch 130/0.4
2015 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no 10, p. 1303-1310Article in journal (Refereed) Published
Abstract [en]

BackgroundDuring fluid infusion therapy, plasma proteins are diluted and leak from the intravascular space, which alters the colloid osmotic pressure (COP) and potentially affects coagulation. We hypothesised that acetated Ringers and starch solution, alone or in combination, influence these mechanisms differently. Materials and methodsOn different occasions, 10 male volunteers were infused with 20ml/kg acetated Ringers and 10ml/kg 6% hyroxyethyl starch 130/0.4 (Voluven((R))) alone or in combination (first with starch solution followed by Ringers solution). Blood samples were collected every 30-min for measurements of COP, blood haemoglobin, platelets, and plasma concentrations of albumin, immunoglobulins (IgG and IgM), coagulation factor VII (FVII), fibrinogen, cystatin C, activated partial thromboplastin time (APTT) and prothrombin international normalised ratio (PT-INR). Changes were compared with the haemoglobin-derived plasma dilution. ResultsThe COP increased by 8.4% (SD 3) with starch and decreased by 26.2% (7.9) with Ringers. These infusions diluted the plasma by 23.4% (5.3) and 18.7% (4.9) respectively. The COP changes in the combined experiment followed the same pattern as the individual infusions. Albumin and IgG changes in excess of the plasma dilution were very subtle. The intravascular contents of the IgM and platelets decreased, whereas FVII, fibrinogen and cystatin C increased. PT-INR increased by 1/3 of the plasma dilution, whereas changes in APTT did not correlate with the plasma dilution. ConclusionsThe starch increased COP and only minor capillary leak occurred in healthy volunteers. The fluid-induced plasma dilution correlated with mild impairment of the extrinsic coagulation pathway but not of the intrinsic pathway.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122412 (URN)10.1111/aas.12558 (DOI)000362589100010 ()26079310 (PubMedID)
Note

Funding Agencies|Stockholm City Council [20070421]; Ostergotland County Council [156791]

Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2017-12-01
Connolly-Andersen, A.-M., Sundberg, E., Ahlm, C., Hultdin, J., Baudin, M., Larsson, J., . . . Nilsson, S. (2015). Increased Thrombopoiesis and Platelet Activation in Hantavirus-Infected Patients. Journal of Infectious Diseases, 212(7), 1061-1069
Open this publication in new window or tab >>Increased Thrombopoiesis and Platelet Activation in Hantavirus-Infected Patients
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2015 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 212, no 7, p. 1061-1069Article in journal (Refereed) Published
Abstract [en]

Background. Thrombocytopenia is a common finding during viral hemorrhagic fever, which includes hemorrhagic fever with renal syndrome (HFRS). The 2 main causes for thrombocytopenia are impaired thrombopoiesis and/or increased peripheral destruction of platelets. In addition, there is an increased intravascular coagulation risk during HFRS, which could be due to platelet activation. Methods. Thrombopoiesis was determined by quantification of platelet counts, thrombopoietin, immature platelet fraction, and mean platelet volume during HFRS. The in vivo platelet activation was determined by quantification of soluble P-selectin (sP-selectin) and glycoprotein VI (sGPVI). The function of circulating platelets was determined by ex vivo stimulation followed by flow cytometry analysis of platelet surface-bound fibrinogen and P-selectin exposure. Intravascular coagulation during disease was determined by scoring for disseminated intravascular coagulation (DIC) and recording thromboembolic complications. Results. The levels of thrombopoietin, immature platelet fraction, and mean platelet volume all indicate increased thrombopoiesis during HFRS. Circulating platelets had reduced ex vivo function during disease compared to follow-up. Most interestingly, we observed significantly increased in vivo platelet activation in HFRS patients with intravascular coagulation (DIC and thromboembolic complications) as shown by sP-selectin and sGPVI levels. Conclusions. HFRS patients have increased thrombopoiesis and platelet activation, which contributes to intravascular coagulation.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS INC, 2015
Keywords
disseminated intravascular coagulation; hantavirus; hemorrhagic fever with renal syndrome; platelets; thrombosis; viral hemorrhagic fever
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122665 (URN)10.1093/infdis/jiv161 (DOI)000363191300007 ()25762786 (PubMedID)
Note

Funding Agencies|Medical Faculty of Umea University; County Council of Vasterbotten [216851, 243061, 238461, 321411]; County Councils of Northern Sweden [296301]

Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2017-12-01
Alfredsson, J., Lindahl, T. L., Gustafsson, K. M., Janzon, M., Jonasson, L., Logander, E., . . . Swahn, E. (2015). 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).. Thrombosis Research, 136(2), 335-340
Open this publication in new window or tab >>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).
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2015 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 2, p. 335-340Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Pergamon Press, 2015
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-119644 (URN)10.1016/j.thromres.2015.05.021 (DOI)000363953000026 ()26033398 (PubMedID)
Note

Funding agencies: Linkoping University; County Council of Ostergotland

Available from: 2015-06-24 Created: 2015-06-23 Last updated: 2017-12-04
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