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Tynngård, Nahreen
Publications (10 of 26) Show all publications
Hashem, R., Tynngård, N., Lundmark, K. & Falk, L. (2019). Microcystic adnexal carcinoma originating in a nevus sebaceous: a case report of a 16-year-old boy. Acta Dermato-Venereologica, 99
Open this publication in new window or tab >>Microcystic adnexal carcinoma originating in a nevus sebaceous: a case report of a 16-year-old boy
2019 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 99Article in journal (Refereed) Accepted
Place, publisher, year, edition, pages
Uppsala, Sweden: Society for the Publication of Acta Dermato - Venereologica, 2019
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-160353 (URN)10.2340/00015555-3272 (DOI)31386165 (PubMedID)
Available from: 2019-09-19 Created: 2019-09-19 Last updated: 2019-11-28Bibliographically approved
Kander, T., Larsson, A., Taune, V., Schott, U. & Tynngård, N. (2016). Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study. PLoS ONE, 11(3), e0151202
Open this publication in new window or tab >>Assessment of Haemostasis in Disseminated Intravascular Coagulation by Use of Point-of-Care Assays and Routine Coagulation Tests, in Critically Ill Patients; A Prospective Observational Study
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, p. e0151202-Article in journal (Refereed) Published
Abstract [en]

Background Disseminated intravascular coagulopathy (DIC) relates to the consumption of coagulation factors and platelets with bleeding and micro thrombosis events. Aim The aim of this study was to compare haemostasis parameters in critically ill patients with DIC versus patients without DIC, and in survivors versus non-survivors over time. Correlations between the DIC-score, the degree of organ failure and the haemostasis were assessed. Method Patients admitted to the intensive care unit with a condition known to be associated with DIC and with an expected length of stay of >3 days were included. Routine laboratory tests, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration and D-dimer were measured. Coagulation and platelet function were assessed with two point-of-care devices; Multiplate and ROTEM. DIC scores were calculated according to the International Society on Thrombosis and Haemostasis and Japanese Association for Acute Medicine. Results Blood was sampled on days 0-1, 2-3 and 4-10 from 136 patients with mixed diagnoses during 290 sampling events. The point-of-care assays indicated a hypocoagulative response (decreased platelet aggregation and reduced clot strength) in patients with DIC and, over time, in non-survivors compared to survivors. Patients with DIC as well as non-survivors had decreased fibrinolysis as shown by ROTEM. DIC scores were higher in non-survivors than in survivors. Conclusions Patients with DIC displayed signs of a hypocoagulative response and impaired fibrinolysis, which was also evident over time in non-survivors. Patients with DIC had a higher mortality rate than non-DIC patients, and DIC scores were higher in non-survivors than in survivors.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127049 (URN)10.1371/journal.pone.0151202 (DOI)000371992300110 ()26959974 (PubMedID)
Available from: 2016-04-13 Created: 2016-04-13 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
Södergren, A., Tynngård, N., Berlin, G. & Ramström, S. (2016). Responsiveness of platelets during storage studied with flow cytometry - formation of platelet subpopulations and LAMP-1 as new markers for the platelet storage lesion. Vox Sanguinis, 110(2), 116-125
Open this publication in new window or tab >>Responsiveness of platelets during storage studied with flow cytometry - formation of platelet subpopulations and LAMP-1 as new markers for the platelet storage lesion
2016 (English)In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 110, no 2, p. 116-125Article in journal (Refereed) Published
Abstract [en]

Background and ObjectivesStorage lesions may prevent transfused platelets to respond to agonists and arrest bleeding. The aim of this study was to evaluate and quantify the capacity of platelet activation during storage using flow cytometry and new markers of platelet activation. Materials and MethodsActivation responses of platelets prepared by apheresis were measured on days 1, 5, 7 and 12. In addition, comparisons were made for platelet concentrates stored until swirling was affected. Lysosome-associated membrane protein-1 (LAMP-1), P-selectin and phosphatidylserine (PS) exposure were assessed by flow cytometry on platelets in different subpopulations in resting state or following stimulation with platelet agonists (cross-linked collagen-related peptide (CRP-XL), PAR1- and PAR4-activating peptides). ResultsThe ability to form subpopulations upon activation was significantly decreased already at day 5 for some agonist combinations. The agonist-induced exposure of PS and LAMP-1 also gradually decreased with time. Spontaneous exposure of P-selectin and PS increased with time, while spontaneous LAMP-1 exposure was unchanged. In addition, agonist-induced LAMP-1 expression clearly discriminated platelet concentrates with reduced swirling from those with retained swirling. This suggests that LAMP-1 could be a good marker to capture changes in activation capacity in stored platelets. ConclusionThe platelet activation potential seen as LAMP-1 exposure and fragmentation into platelet subpopulations is potential sensitive markers for the platelet storage lesion.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
Keywords
apheresis; haemostasis; platelet concentrates; platelet function; platelet transfusion
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126141 (URN)10.1111/vox.12324 (DOI)000370657500002 ()26389538 (PubMedID)
Note

Funding Agencies|Region Ostergotland; Linkoping University through the LiU Research Fellows program

Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2018-10-25
Sandgren, P., Berlin, G. & Tynngård, N. (2016). Treatment of platelet concentrates with ultraviolet C light for pathogen reduction increases cytokine accumulation. Transfusion, 56(6), 1377-1383
Open this publication in new window or tab >>Treatment of platelet concentrates with ultraviolet C light for pathogen reduction increases cytokine accumulation
2016 (English)In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 56, no 6, p. 1377-1383Article in journal (Refereed) Published
Abstract [en]

BACKGROUNDPathogen reduction technologies use photoactive substances in combination with ultraviolet (UV) light to inactivate pathogens. A new method uses only UVC light for pathogen reduction. This study assesses the effects of UVC light treatment on cytokine release in platelet (PLT) concentrates (PCs). STUDY DESIGN AND METHODSA PC with 35% plasma and 65% PLT additive solution (SSP+) was prepared from five buffy coats. Three such PCs were pooled and divided into 3 units. One unit was used as a nonirradiated control, the second was a gamma-irradiated control, and the third unit was treated with UVC light technology. Ten units of each type were investigated. Cytokine release was analyzed on Days 1, 5, and 7 of storage. Correlation between cytokines, PLT surface markers, and hemostatic properties was investigated. RESULTSSwirling was well preserved and pH was above the reference limit of 6.4 during storage of PLTs in all groups. Cytokine levels increased during storage in all groups but to a larger degree in PCs treated with UVC light. Only weak correlation was found between cytokines and PLT surface markers (ramp;lt;0.5). However, several cytokines showed strong correlation (ramp;gt;0.6) with the PLTs ability to promote clot retraction. CONCLUSIONUVC treatment resulted in increased release from PLT alpha granules as evident by a higher cytokine release compared to nonirradiated and gamma-irradiated PCs. The clinical relevance of these findings needs to be further evaluated.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:liu:diva-130296 (URN)10.1111/trf.13601 (DOI)000378553200048 ()27080102 (PubMedID)
Note

Funding Agencies|Region Ostergotland; Linkoping Medical Society; MacoPharma

Available from: 2016-07-31 Created: 2016-07-28 Last updated: 2018-01-10
Larsson, A., Tynngård, N., Kander, T., Bonnevier, J. & Schott, U. (2015). Comparison of point-of-care hemostatic assays, routine coagulation tests, and outcome scores in critically ill patients. Journal of critical care, 30(5), 1032-1038
Open this publication in new window or tab >>Comparison of point-of-care hemostatic assays, routine coagulation tests, and outcome scores in critically ill patients
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2015 (English)In: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 30, no 5, p. 1032-1038Article in journal (Refereed) Published
Abstract [en]

Purpose: The purposes of the study are to compare point-of-care (POC) hemostatic devices in critically ill patients with routine laboratory tests and intensive care unit (ICU) outcome scoring assessments and to describe the time course of these variables in relation to mortality rate. Materials and methods: Patients admitted to the ICU with a prognosis of more than 3 days of stay were included. The POC devices, Multiplate platelet aggregometry, rotational thromboelastometry, and ReoRox viscoelastic tests, were used. All variables were compared between survivors and nonsurvivors. Point-of-care results were compared to prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen concentration, and Sequential Organ Failure Assessment score and Simplified Acute Physiology Score 3. Results: Blood was sampled on days 0 to 1, 2 to 3, and 4 to 10 from 114 patients with mixed diagnoses during 237 sampling events. Nonsurvivors showed POC and laboratory signs of hypocoagulation and decreased fibrinolysis over time compared to survivors. ReoRox detected differences between survivors and nonsurvivors better than ROTEM and Multiplate. Conclusions: All POC and routine laboratory tests showed a hypocoagulative response in nonsurvivors compared to survivors. ReoRox was better than ROTEM and Multiplate at detecting differences between surviving and nonsurviving ICU patients. However, Simplified Acute Physiology Score 3 showed the best association to mortality outcome.

Place, publisher, year, edition, pages
W B SAUNDERS CO-ELSEVIER INC, 2015
Keywords
Aggregation; Coagulopathy; Platelets; Thromboelastography; Survival
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122052 (URN)10.1016/j.jcrc.2015.06.014 (DOI)000360558500029 ()26190696 (PubMedID)
Available from: 2015-12-18 Created: 2015-10-19 Last updated: 2017-12-01
Tynngård, N., Trinks, M. & Berlin, G. (2015). In vitro function of platelets treated with ultraviolet C light for pathogen inactivation: a comparative study with nonirradiated and gamma-irradiated platelets. Transfusion, 55(6), 1169-1177
Open this publication in new window or tab >>In vitro function of platelets treated with ultraviolet C light for pathogen inactivation: a comparative study with nonirradiated and gamma-irradiated platelets
2015 (English)In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 55, no 6, p. 1169-1177Article in journal (Refereed) Published
Abstract [en]

BackgroundDuring storage of platelet concentrates (PCs) replication of contaminating pathogens might occur, which can be prevented by various pathogen inactivation (PI) methods using photoactive substances in combination with ultraviolet (UV) light. A new method uses only UVC light for PI without photoactive substances. This study evaluates the in vitro function, including hemostatic properties (clot formation and elasticity), of platelets (PLTs) treated with UVC light. Study Design and MethodsA PC with 35% plasma and 65% PLT additive solution (SSP+) was prepared from five buffy coats. Three PCs were pooled and divided into 3units. One unit was used as a nonirradiated control, the second was a gamma-irradiated control, and the third unit was treated with UVC light. In vitro variables including analysis of coagulation by free oscillation rheometry were analyzed on Days 1, 5, and 7 of storage. Ten units in each group were investigated. ResultsSwirling was well preserved, and the pH level was higher than the reference limit (6.4) during storage of PLTs in all groups. Glycolysis and PLT activation were higher for UVC-treated PLTs but the clot-forming capacity was unaffected. However, immediately after UVC treatment, the clot elastic properties were slightly affected. Hypotonic shock response decreased immediately after UVC treatment but recovered partly during the storage period. ConclusionUVC treatment affected the in vitro properties, but PLT quality and storage stability were well preserved for up to 7 days, and the in vitro hemostatic capacity of UVC-treated PLTs was only minimally altered. The clinical relevance of these changes needs to be evaluated in controlled trials.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:liu:diva-120238 (URN)10.1111/trf.12963 (DOI)000356366300024 ()25524519 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland; Linkoping Medical Society

Available from: 2015-07-21 Created: 2015-07-20 Last updated: 2018-01-11
Thomas, O., Lybeck, E., Strandberg, K., Tynngård, N. & Schott, U. (2015). Monitoring Low Molecular Weight Heparins at Therapeutic Levels: Dose-Responses of, and Correlations and Differences between aPTT, Anti-Factor Xa and Thrombin Generation Assays. PLoS ONE, 10(1), Article ID e0116835.
Open this publication in new window or tab >>Monitoring Low Molecular Weight Heparins at Therapeutic Levels: Dose-Responses of, and Correlations and Differences between aPTT, Anti-Factor Xa and Thrombin Generation Assays
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 1, article id e0116835Article in journal (Refereed) Published
Abstract [en]

Background Low molecular weight heparins (LMWHs) are used to prevent and treat thrombosis. Tests for monitoring LMWHs include anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT) and thrombin generation. Anti-FXa is the current gold standard despite LMWHs varying affinities for FXa and thrombin. Aim To examine the effects of two different LMWHs on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests concordance. Method Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU)/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR) and Hemochron Jr (HCJ)) and an optical plasma method using two different reagents (ActinFSL and PTT-Automat). Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP) was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents. Results Methods mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11) and 69s (SD 14) for enoxaparin and between 101s (SD 21) and 140s (SD 28) for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (R(s)0.62-0.87), whereas the other aPTT methods had similar correlation coefficients (R(s)0.80-0.92). Conclusions aPTT displays a linear dose-respone to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXas present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWHs.

Place, publisher, year, edition, pages
Public Library of Science, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114992 (URN)10.1371/journal.pone.0116835 (DOI)000348821400018 ()25625201 (PubMedID)
Note

Funding Agencies|Medical Faculty, University of Lund; Regional medical research grant, Region Skane ALF

Available from: 2015-03-09 Created: 2015-03-06 Last updated: 2017-12-04
Tynngård, N., Wallstedt, M., Södergren, A. L., Faxälv, L. & Ramström, S. (2015). Platelet adhesion changes during storage studied with a novel method using flow cytometry and protein-coated beads. Platelets, 26(2), 177-185
Open this publication in new window or tab >>Platelet adhesion changes during storage studied with a novel method using flow cytometry and protein-coated beads
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2015 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 26, no 2, p. 177-185Article in journal (Refereed) Published
Abstract [en]

The aim of the present study was to set up and evaluate a novel method for studies of platelet adhesion and activation in blood and platelet suspensions such as platelet concentrate (PC) samples using protein-coated polystyrene beads and flow cytometry. To demonstrate its usefulness, we studied PCs during storage. PCs were prepared by aphaeresis technique (n = 7). Metabolic variables and platelet function was measured on day 1, 5, 7 and 12 of storage. Spontaneous and TRAP-6-induced adhesion to fibrinogen- and collagen-coated beads was analyzed by flow cytometry. P-selectin and phosphatidyl serine (PS) expression was assessed on platelets bound to beads as well as on non-adherent platelets. Platelet adhesion to fibrinogen beads had increased by day 12 and adhesion to collagen beads at day 7 of storage (p < 0.05). TRAP-6 stimulation significantly increased the platelet adhesion to fibrinogen beads (p < 0.05) as well as the P-selectin and PS exposure on platelets bound to beads (p < 0.01) during the first 7 days of storage, but by day 12, significant changes were no longer induced by TRAP-6 stimulation. We demonstrate that our adhesion assay using protein-coated polystyrene beads can be used to assess the adhesion properties of platelets during storage without the addition of red blood cells. Therefore it may offer a useful tool for future studies of platelet adhesive capacity in transfusion medicine and other settings.

National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-111533 (URN)10.3109/09537104.2014.891728 (DOI)000351740700012 ()24679340 (PubMedID)
Available from: 2014-10-22 Created: 2014-10-22 Last updated: 2018-01-11Bibliographically approved
Thomas, O., Larsson, A., Tynngård, N. & Schott, U. (2015). Thromboelastometry versus free-oscillation rheometry and enoxaparin versus tinzaparin: an in-vitro study comparing two viscoelastic haemostatic tests dose-responses to two low molecular weight heparins at the time of withdrawing epidural catheters from ten patients after major surgery. BMC Anesthesiology, 15
Open this publication in new window or tab >>Thromboelastometry versus free-oscillation rheometry and enoxaparin versus tinzaparin: an in-vitro study comparing two viscoelastic haemostatic tests dose-responses to two low molecular weight heparins at the time of withdrawing epidural catheters from ten patients after major surgery
2015 (English)In: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 15Article in journal (Refereed) Published
Abstract [en]

Background: Monitoring low molecular weight heparins (LMWHs) in the perioperative period is prudent in patients at high risk of coagulative complications, especially when the patient has an epidural catheter requiring withdrawal, which is associated with the risk of spinal haematoma. The aim of this study was to evaluate the in vitro dose-responses of two different LMWHs on two different viscoelastic haemostatic tests, using blood sampled from patients with normal routine coagulation parameters, on the day after major surgery when their epidural catheters were due to be withdrawn. Methods: Enoxaparin or tinzaparin were added in vitro to blood from ten patients who had undergone oesophageal resection, to obtain plasma concentrations of approximately 0, 0.5, 1.0 and 1.5 IU/mL. Coagulation was monitored using thromboelastometry (ROTEM (R)) using the InTEM (R) activating reagent; and free oscillation rheometry (FOR: ReoRox (R)), activated using thromboplastin. Clot initiation was measured using ROTEM-CT, ReoRox-COT1 and ReoRox-COT2. Clot propagation was measured using ROTEM-CFT, ROTEM-Alpha Angle and ReoRox-Slope. Clot stability was measured using ROTEM-MCF and ReoRox-Gmax, and clot lysis was measured using ROTEM-ML and ReoRox-ClotSR. Results: Clot initiation time assessed by thromboelastometry and FOR was prolonged by increasing concentrations of both LMWHs (P &lt; 0.01). Equivalent doses of tinzaparin in international units (anti FXa units) per millilitre prolonged clot initiation more than enoxaparin (P &lt; 0.05). There was significant inter-individual variation - the ranges of CT and COT1 at LMWH-concentrations of 0 and 1.5 IU/mL overlapped. None of the tests reflecting clot formation rate or stability showed a dose-response to either LMWH but clot lysis showed a tentative negative dose-response to the LMWHs. Conclusions: Clot initiation times dose-dependent prolongation by LMWHs in this study agrees with previous research, as does tinzaparins stronger anti-coagulative effect than enoxaparin at equivalent levels of anti-FXa activity. This casts doubt on the validity of using anti-FXa assays alone to guide dosage of LMWHs. The significant inter-individual variation in dose-response suggests that the relationship between dose and effect in the postoperative period is complicated. While both ROTEM and FOR may have some role in postoperative monitoring, more research is needed before any conclusion can be made about their clinical usefulness.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2015
Keywords
Coagulation; Factor Xa; Thromboelastometry; Free-oscillation rheometry; Low molecular weight heparin; Postoperative; Enoxaparin; Tinzaparin; Epidural haematoma; Spinal haematoma
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-123800 (URN)10.1186/s12871-015-0145-2 (DOI)000365587500002 ()26603039 (PubMedID)
Note

Funding Agencies|ISEX-ALF

Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2017-11-30
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