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Abnormalities in coagulum lysis and structure are associated with deep venous thrombosis
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The present study aimed to investigate the relationship between deep venous thrombosis (DVT) and fibrinolytic susceptibility of plasma coagulum, including the possible role of this property in laboratory diagnosis. From 276 patients consecutively admitted to hospital for suspected deep venous thrombosis (DVT), 75 patients and 47 controls were selected. With certainty, the patients and controls either had or did not have DVT. Fibrinolytic susceptibility was assayed by reacting plasma with thromboplastin and tissue plasminogen activator and recording a nephelometric signal. Coagulation time (CT), coagulum lysis time (CLT) and maximal increase in coagulum light scatter (CLS) were determined. Increase in D-dimer levels caused by coagulum lysis was also determined. This was viewed as a fibrinogen measure. CL T and CLS were interpreted as measures of fibrinolytic susceptibility and coagulum structure, respectively. CL T and CLS for patients and controls differed, p<0.025 and p<0.001, respectively. Compared to 5% for controls, 24% and 43% of the patients showed CL T and CLS outside the reference range. High fibrinogen levels could not explain the findings, since these were normal in most patients with abnormal CL T and CLS. Abnormal coagulum lysis and abnormal coagulum structure were thus found to be associated with DVT. Possible laboratory diagnostic role of CL T and CLS was investigated with bivariate reference ranges that excluded 5% and 0.3%. These ranges excluded significantly (p<0.0001) more patients, 47% and 27%, respectively. Tests for abnormal fibrinolytic susceptibility and coagulum structure may thus have a role in laboratory diagnosis of thrombotic disorders.

Keyword [en]
Clot lysis, fibrin gel network, fibrinolysis, thrombosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-81002OAI: oai:DiVA.org:liu-81002DiVA: diva2:549797
Available from: 2012-09-05 Created: 2012-09-05 Last updated: 2012-09-05Bibliographically approved
In thesis
1. Real-time analysis of blood coagulation and fibrinolysis: new rheological and optical sensing techniques for diagnosis of haemostatic disorders.
Open this publication in new window or tab >>Real-time analysis of blood coagulation and fibrinolysis: new rheological and optical sensing techniques for diagnosis of haemostatic disorders.
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The haemostatic system has a dual paradoxical function in the body. It should arrest bleeding whenever needed, but also keep the blood flowing in the circulatory system without any obstructing blood clots. The system is complex with maoy intertwined processes that interact to produce a fine-tuned regulation of the performance. In case of malfunction in this regulation there may be an excessive coagulation ability, thrombophilia, or bleeding tendency, haemophilia. These are common disorders in the Western societies and may be lethal. The long-term airo of this work is therefore to improve the laboratory diagnosis of haemostatic disorders, for thrombophilia in particular. To achieve this goal a global approach has been chosen, meaning that the environment in which a blood sample is analysed should mimic the physiology of the haemostatic system to better elucidate the overall situation in a particular individual. A first attempt to assess the susceptibility for tissue plasminogen activator induced lysis and coagulum structure in plasma as markers for deep vein thrombosis showed promising results with 47% abnormals among the DVT patients included in the study. To improve this assay new sensing techniques were needed, since one of the most important conditions included in a global assay is analysis of whole blood, i.e. blood with all types of blood cells present. Whole blood is opaque and excludes the traditional optical methods that have been used for coagulation analysis. Several candidate techniques have been identified and surface plasmon resonance (SPR), quartz crystal microbalance-dissipation (QCM-D), and free oscillation rheometry (FOR) have been evaluated for haemostatic studies in this thesis. SPR is an optical surface sensitive technique that has showed promising results for measurements in blood plasma during coagulation and fibrinolysis and for whole blood coagulation. The SPR responses were sensitive to treatments with heparin and oral anticoagulants, which are substances used to treat thrombosis. QCM-D that is sensitive to mass deposition and viscoelastic changes in the sample at the quartz crystal surface has been tested in combination with SPR and provided new information about the viscoelastic properties of the coagulum, although with similar sensing depth as SPR. The idea of combined sensing techniques was reconsidered and resulted in a combination of SPR and FOR for siroultaneous real-time measurements in a blood sample. FOR is bulk sensitive and probes rheological changes in the sample. The combination was applied in studies of plasma and whole blood coagulation as well as plasma fibrinolysis. Coagulation studies including chemical surface modifications by using thiol-based self-assembled monolayers were also attempted. Finally, the FOR/SPR combination was found to be sensitive to inhibition of platelet aggregation and blood cell shape changes iroplying that studies on the cellular component of the blood is possible. In conclusion, the combination of FOR and SPR is a promising sensing system for an improved global assay for haemostatic disorders.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2001. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 663
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25656 (URN)10032 (Local ID)91-7219-764-1 (ISBN)10032 (Archive number)10032 (OAI)
Public defence
2001-03-16, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-05Bibliographically approved

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Hansson, Kenny M.Lindahl, Tomas L.

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