Background
Envenomation by the European adder, Vipera berus berus (Vbb), is a medical emergency. The overall in vivo haemostatic effects of pro- and anticoagulant components in Vbb venom, and the downstream effects of cellular injury and systemic inflammation, are unclear.
Objectives
To longitudinally describe the global coagulation status of dogs after Vbb envenomation and compare to healthy controls. A secondary aim was to investigate differences between dogs treated with and without antivenom.
Methods
Citrated plasma was collected at presentation, 12 hours (h), 24 h, 36 h and 15 days after bite from 28 dogs envenomated by Vbb, and from 28 healthy controls at a single timepoint. Thrombin generation (initiated with and without exogenous phospholipids and tissue factor), thrombin-antithrombin (TAT)-complexes and the procoagulant activity of phosphatidylserine (PS)-expressing extracellular vesicles (EVs), expressed as PS-equivalents, were measured.
Results
At presentation the envenomated dogs were hypercoagulable compared to controls, measured as increased thrombin generation, TAT-complexes and PS-equivalents. The hypercoagulability decreased gradually but compared to controls thrombin generation and PS-equivalents were still increased at day 15. The discrepancy in peak thrombin between envenomated dogs and controls was greater when the measurement was phospholipid-dependent, indicating that PS-positive EVs contribute to hypercoagulability. Lag time was shorter in non-antivenom treated dogs, compared to antivenom treated dogs <24 h after envenomation.
Conclusions
Hypercoagulability was measured in dogs up to 15 days after Vbb envenomation. Dogs treated with antivenom may be less hypercoagulable than their non-antivenom treated counterparts. Thrombin generation is a promising diagnostic and monitoring tool for Vbb envenomation.
Rognes, Ingrid Nygren; Hellum, Marit; Ottestad, William; Bache, Kristi Grønvold; Eken, Torsten & Henriksson, Carola Elisabeth
(2021).
Extracellular vesicle-associated procoagulant activity is highest the first 3 hours after trauma and thereafter declines substantially: A prospective observational pilot study.
Journal of Trauma and Acute Care Surgery.
ISSN 2163-0755.
91(4),
s. 681–691.
doi: 10.1097/TA.0000000000003333.
Fulltekst i vitenarkivVis sammendrag
Background: Trauma patients have high concentrations of circulating extracellular vesicles (EVs) following injury, but the functional role of EVs in this setting is only partly deciphered. We aimed to describe in detail EV-associated procoagulant activity in individual trauma patients during the first 12 hours after injury to explore their putative function and relate findings to relevant trauma characteristics and outcome.
Methods: In a prospective observational study of 33 convenience recruited trauma patients, citrated plasma samples were obtained at trauma center admission and 2, 4, 6, and 8 hours thereafter. We measured thrombin generation from isolated EVs and the procoagulant activity of phosphatidylserine (PS)-exposing EVs. Correlation and multivariable linear regression analyses were used to explore associations between EV-associated procoagulant activity and trauma characteristics as well as outcome measures.
Results: EV-associated procoagulant activity was highest in the first 3 hours after injury. EV-associated thrombin generation normalized within 7 to 12 hours of injury, whereas the procoagulant activity of PS-exposing EVs declined to a level right above that of healthy volunteers. Increased EV-associated procoagulant activity at admission was associated with higher New Injury Severity Score, lower admission base excess, higher admission international normalized ratio, prolonged admission activated partial thromboplastin time, higher Sequential Organ Failure Assessment score at day 0, and fewer ventilator-free days.
Conclusion: Our data suggest that EVs have a transient hypercoagulable function and may play a role in the early phase of hemostasis after injury. The role of EVs in trauma-induced coagulopathy and posttraumatic thrombosis should be studied bearing in mind this novel temporal pattern.
Level of evidence: Prognostic/epidemiologic, level V.
Garabet, Lamya Samir Noori; Ghanima, Waleed Khalid; Hellum, Marit Synnøve; Sandset, Per Morten; Bussel, James B. & Tran, Hoa Thi Tuyet
[Vis alle 7 forfattere av denne artikkelen](2019).
Increased microvesicle-associated thrombin generation in patients with immune thrombocytopenia after initiation of thrombopoietin receptor agonists.
Platelets.
ISSN 0953-7104.
doi: 10.1080/09537104.2019.1639655.
Aass, Hans Christian Dalsbotten; Hellum, Marit Synnøve; Siebke, Anne-Marie; Brandtzæg, Petter; Berg, Jens Petter & Øvstebø, Reidun
[Vis alle 7 forfattere av denne artikkelen](2018).
Whole-blood incubation with the Neisseria meningitidis lpxL1 mutant induces less pro-inflammatory cytokines than the wild type, and IL-10 reduces the MyD88-dependent cytokines.
Innate Immunity.
ISSN 1753-4259.
24(2),
s. 101–111.
doi: 10.1177/1753425917749299.
Fulltekst i vitenarkiv
Hellum, Marit Synnøve; Lie, Maria Isabel Lopes Romao Franc; Øvstebø, Reidun; Hauge, Truls & Henriksson, Carola
(2017).
The effect of corn trypsin inhibitor, anti-tissue factor pathway inhibitor antibodies and phospholipids on microvesicle-associated thrombin generation in patients with pancreatic cancer and healthy controls.
PLOS ONE.
ISSN 1932-6203.
12(9).
doi: 10.1371/journal.pone.0184579.
Fulltekst i vitenarkiv
Hellum, Marit Synnøve; Siebke, Anne-Marie; Berg, Jens Petter; Brandtzæg, Petter; Øvstebø, Reidun & Henriksson, Carola
(2017).
The Neisseria meningitidis lpxL1 mutant induces less tissue factor expression and activity in primary human monocytes and
monocyte-derived microvesicles than the wild type meningococcus.
Innate Immunity.
ISSN 1753-4259.
23(2),
s. 196–205.
doi: 10.1177/1753425916684201.
Øvstebø, Reidun; Hellum, Marit Synnøve; Aass, Hans Christian; Siebke, Anne-Marie; Brandtzæg, Petter & Mollnes, Tom Eirik
[Vis alle 7 forfattere av denne artikkelen](2014).
Microparticle-associated tissue factor activity is reduced by inhibition of the complement protein 5 in Neisseria meningitidis-exposed whole blood.
Innate Immunity.
ISSN 1753-4259.
20(5),
s. 552–560.
doi: 10.1177/1753425913502099.
Iversen, Nina; Sletten, Marit; Hellum, Marit Synnøve; Skogstad, Marie Jeanette; Chollet, Maria Eugenia & Skarpen, Ellen
[Vis alle 11 forfattere av denne artikkelen](2019).
Functional characterization of FV deficiency in Norway: Effects of F5 mutations on secretion, endoplasmic reticulum stress, apoptosis, and activated protein C sensitivity.