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

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 beta-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.

• Authors: Volker Pönitz, David Pritchard, Heidi Grundt, Dennis Winston T Nilsen
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 22 Issue 3 Pg. 199-203 (Dec 2006) ISSN: 0929-5305 [Print] Netherlands
• PMID: 17111198 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Fibrinolytic Agents
• Factor XIIa
• Tissue Plasminogen Activator
• Tenecteplase

Topics

• Aged
• Enzyme-Linked Immunosorbent Assay (methods)
• Factor XIIa (analysis, drug effects)
• Female
• Fibrinolytic Agents (pharmacology)
• Humans
• Male
• Middle Aged
• Myocardial Infarction (blood, drug therapy)
• Tenecteplase
• Thrombolytic Therapy
• Tissue Plasminogen Activator (pharmacology)