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Plasma clot properties in patients with a mild-to-moderate bleeding tendency of unknown cause

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Abstract

In a large proportion of patients with mild bleeding disorders (MBDs) no diagnosis can be established by routine coagulation tests. We investigated whether alterations in plasma clot properties account for MBDs of unknown cause. Ninety-five patients with MBDs of unknown origin and 98 age- and sex-matched healthy controls were investigated. Furthermore, data of 25 patients with a deficiency of factor VIII were analyzed. Plasma clot characteristics in the absence and presence of recombinant tissue plasminogen activator (rtPA) represented by the lag phase, rate of protofibril formation (Vmax), fibrin structure (ΔAbs), time to peak (TTP), half lysis time (t50 and area under the curve (AUC) were measured in turbidometric clot formation and lysis assays. In the fibrinolysis assay, Vmax was lower in patients than in healthy controls. No differences in the other parameters of clot formation and lysis were detected between the groups. There was no clear association of plasma clot properties with the clinical severity of bleeding in patients with MBDs. Patients with known decreased factor VIII levels also showed a lower Vmax. Fibrinogen levels were positively associated with each of the assessed parameters in both groups, with the strongest association with ΔAbs, indicating altered fibrin structure. Factor VIII activity correlated with altered clot characteristics similar to fibrinogen, especially in patients, with the strongest positive correlation to Vmax. This cohort of patients with MBDs of unknown origin showed a lower rate of fibrin formation in the fibrinolysis assay, but otherwise similar plasma clot properties compared to healthy controls.

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Acknowledgments

This study was conducted in collaboration with the MedUni Wien Biobank. J. Gebhart has received financial support of the Bayer Hemophilia Clinical Training Award (http://www.bayer-hemophilia-awards.com). We thank CSL Behring for the financial support of the study by an unrestricted grant.

Conflict of interest

The authors declare that they have no competing interests.

Statement of informed consent

Informed consent was obtained from all individuals (patients and healthy controls) for being included in the study.

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Authors and Affiliations

  1. Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University Vienna, Vienna, Austria

    J. Gebhart, C. Laczkovics, F. Posch, C. Ay, S. E. Reitter-Pfoertner & I. Pabinger

  2. Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria

    H. Haslacher

  3. Clinical Research Center, Vascular Biology, Thrombosis and Hemostasis Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary

    L. Muszbek

  4. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA

    A. S. Wolberg

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  1. J. Gebhart
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  2. C. Laczkovics
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  3. F. Posch
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  4. C. Ay
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  5. S. E. Reitter-Pfoertner
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  6. H. Haslacher
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  7. L. Muszbek
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  8. A. S. Wolberg
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  9. I. Pabinger
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Correspondence to I. Pabinger.

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Gebhart, J., Laczkovics, C., Posch, F. et al. Plasma clot properties in patients with a mild-to-moderate bleeding tendency of unknown cause. Ann Hematol 94, 1301–1310 (2015). https://doi.org/10.1007/s00277-015-2399-7

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  • DOI: https://doi.org/10.1007/s00277-015-2399-7

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