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Specific types of activated Factor XII increase following thrombolytic therapy with tenecteplase

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Abstract

Background

Activated Factor XII (XIIa) is believed to participate in a number of pathophysiological processes including inflammation, thrombosis and fibrinolysis. Increasing XIIa levels following thrombolytic therapy have previously been reported. In contrast to other thrombolytics, tenecteplase (TNK-tpa) does not show paradoxical thrombin activation, indicating a lower procoagulant effect of this fibrin-selective thrombolytic agent. Recent research has demonstrated that in-vivo XIIa exists in a number of different types, and the aim of this study was to investigate plasma variations of different types of XIIa following thrombolytic treatment with TNK-tpa.

Methods

Citrated blood samples were obtained from 34 patients admitted with acute ST-elevation myocardial infarction (STEMI) treated with TNK-tpa. Samples were taken immediately prior to treatment, 30–90 min after and 4 days post-treatment. XIIa measurements were performed using 2 ELISA assays designed to preferentially measure different types of XIIa; XIIaA and XIIaR. Both assays utilised a monoclonal antibody 2/215, which is highly specific for XIIa, as the solid phase capture antibody. The assay for XIIaA used a conjugate based on a polyclonal antibody against the entire XIIa molecule, whilst the assay for XIIaR incorporated a reagent to release otherwise unavailable XIIa and used a conjugate based on a monoclonal antibody against β-XIIa.

Results

Changes in plasma XIIaA concentration as a result of therapy were more evident than changes in XIIaR concentration. XIIaA showed a significant increase from 67.1 (49.0–84.4) pM to 97.8 (75.5–133.1) pM [median and 25 and 75% percentiles] in the 30–90 min sample (P < 0.001), returning to pre-intervention levels 61.5 (47.5–81.0) pM by day 4. In contrast, no significant change in XIIaR concentration was observed following thrombolytic therapy with TNK-tpa.

Conclusion

In patients admitted with STEMI, thrombolytic therapy with TNK-tpa resulted in a significant short-lasting increase in specific types of XIIa (namely XIIaA), whereas other types of XIIa (XIIaR) were largely unaffected by this intervention.

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Authors and Affiliations

  1. Department of Internal Medicine, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway

    Volker Pönitz, Heidi Grundt & Dennis Winston T. Nilsen

  2. The University of Bergen, Bergen, Norway

    Volker Pönitz, Heidi Grundt & Dennis Winston T. Nilsen

  3. Axis-Shield Diagnostics, Dundee, UK

    David Pritchard

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  1. Volker Pönitz
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  2. David Pritchard
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  3. Heidi Grundt
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  4. Dennis Winston T. Nilsen
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Correspondence to Volker Pönitz.

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Pönitz, V., Pritchard, D., Grundt, H. et al. Specific types of activated Factor XII increase following thrombolytic therapy with tenecteplase. J Thromb Thrombolysis 22, 199–203 (2006). https://doi.org/10.1007/s11239-006-9031-6

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  • DOI: https://doi.org/10.1007/s11239-006-9031-6

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