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


CONCLUSIONS
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.
Pönitz
Volker
V
Department of Internal Medicine, Stavanger University Hospital, POB 8100, 4068, Stavanger, Norway. volker.poenitz@lyse.net
Pritchard
David
D
Grundt
Heidi
H
Nilsen
Dennis Winston T
DW
D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015956:Factor XIIa / Q000032:analysis / Q000187:drug effects*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D000077785:Tenecteplase; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D015956:Factor XIIa; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase