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Cystatin C and creatinine as markers of bleeding and mortality during oral anticoagulant treatment
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.ORCID-id: 0000-0003-4423-4135
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.ORCID-id: 0000-0002-0350-2132
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
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2012 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Ort, förlag, år, upplaga, sidor
2012. , s. 88
Nyckelord [en]
Oral anticoagulants, warfarin, mortality, bleeding, biomarkers
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
medicin
Identifikatorer
URN: urn:nbn:se:umu:diva-53424ISBN: 978-91-7459-380-8 (tryckt)OAI: oai:DiVA.org:umu-53424DiVA, id: diva2:512016
Tillgänglig från: 2012-03-26 Skapad: 2012-03-26 Senast uppdaterad: 2021-11-15Bibliografiskt granskad
Ingår i avhandling
1. Determinants of adverse events during oral anticoagulant treatment
Öppna denna publikation i ny flik eller fönster >>Determinants of adverse events during oral anticoagulant treatment
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Treament with oral anticoagulation is highly effective in reducing the burden of thromboembolic complications in several clinical conditions. The number of patients receiving oral anticoagulation is growing steadily. InSwedenabout 1.5 percent of the population receives treatment. Although the treatment is highly effective in preventing thromboembolic complications, it is also associated with a substantial increase in the risk of bleeding. In clinical practice every physician has to balance the potential benefit of treatment against the risk of bleeding complications in the individual patient.

To aid in this decision making, risk scores addressing the likelihood of thromboembolic events, as well as the risk of bleeding complications, have been developed. These scores are imperfect and, to some degree limited by the fact that the risk factors predictive of thromboembolic events are also often associated with bleeding complications. The addition of biomarkers has the potential to increase the predictive ability of risk scores and further enhance the net benefit of oral anticoagulant treatment in the individual patient. In this thesis several potential biomarkers for thromoboembolic and haemorrhagic complications of anticoagulant therapy have been investigated in a longitudinal cohort study of 719 patients with a median follow-up time of 4.2 years.

Thrombomodulin is a key component in the generation of activated protein C and hence, a coagulation inhibitor. Conversely, it is also a key component in the inhibition of fibrinolysis by activation of trombin-activated fibrinolysis inhibitor. In warfarin-treated patients we demonstrate that thrombomodulin predicts an increased risk of bleeding complications, but not cardiovascular events. Thus, thrombomodulin has potential as a biomarker specifically for bleeding complications.

Von Willebrand factor plays a central and intricate role in the aggregation of platelets and low levels of VWF have been associated with bleeding as a manifestation of von Willebrand’s disease. In our study we noted that high levels of von Willebrand factor predict an increased risk of cardiovascular as well as all-cause mortality, possibly as an expression of endothelial dysfunction. We also noted that high levels of WVF seem to be associated with serious bleeding complications.

Decreased renal function is usually measured by an increase in the levels of creatinine and cystatin C, or a decrease in the calculated glomerular filtration rate. A decrease in kidney function is regarded as a marker of an increased risk of bleeding complications. We investigated all the mentioned markers of kidney function and no association with bleeding complications became apparent. However, a clear association between a decrease in kidney function and mortality was noted. Our findings indicate that the emphasis on impaired kidney function as a risk marker needs to be shifted from bleeding complications toward thromboembolic events.

Fibrinolysis is important in containing coagulation and several constituents of the fibrinolytic pathway have been shown to predict cardiovascular events and mortality. We found that fibrinolytic factors seem to predict cardiovascular events in patients with oral anticoagulation and that D-dimer also predicts bleeding complications.

In conclusion, we have found several biomarkers which exhibit different predictive abilities in patients with oral anticoagulation. It is likely that biomarkers, either alone, in combination, or as ancillary components of risk scores, can contribute to improved risk stratification in patients with oral anticoagulation.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2012. s. 88
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1483
Nyckelord
Oral anticoagulants, warfarin, mortality, bleeding, biomarkers
Nationell ämneskategori
Hematologi
Forskningsämne
medicin
Identifikatorer
urn:nbn:se:umu:diva-53431 (URN)978-91-7459-380-8 (ISBN)
Disputation
2012-04-27, Forumsalen, Campus, Skellefteå, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2012-04-05 Skapad: 2012-03-26 Senast uppdaterad: 2021-11-15Bibliografiskt granskad

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Lind, MarcusBoman, KurtSlunga Järvholm, LisbethJansson, Jan-Håkan

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Lind, MarcusBoman, KurtSlunga Järvholm, LisbethJansson, Jan-Håkan
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