PAI‐1 5G/5G genotype is an independent risk of intracranial hemorrhage in post‐lysis stroke patients

Abstract

Objective: Thrombolysis by recombinant tissue plasminogen activator (rt-PA) is the main pharmacological therapy in acute ischemic stroke (IS); however, it is only effective in a subset of patients. Here we aimed to investigate the role of plasminogen activator inhibitor-1 (PAI-1), an effective inhibitor of t-PA, and its major polymorphism (PAI-1 4G/5G) in therapy outcome. Methods: Study population included 131 consecutive IS patients who all underwent thrombolysis. Blood samples were taken on admission, 1 and 24 h after rt-PA infusion. PAI-1 activity and antigen levels were measured from all blood samples and the PAI-1 4G/5G polymorphism was determined. Clinical data including NIHSS were registered on admission and day 1. ASPECTS was assessed using CT images taken before and 24 h after thrombolysis. Intracranial hemorrhage (ICH) was classified according to ECASS II. Long-term outcome was defined 90 days post-event by the modified Rankin Scale (mRS). Results: PAI-1 activity levels dropped transiently after thrombolysis, while PAI-1 antigen levels remained unchanged. PAI-1 4G/5G polymorphism had no effect on PAI-1 levels and did not influence stroke severity. PAI-1 activity/antigen levels as measured on admission were significantly elevated in patients with worse 24 h ASPECTS (<7). Logistic regression analysis including age, sex, NIHSS on admission, BMI, history of arterial hypertension, and hyperlipidemia conferred a significant, independent risk for developing ICH in the presence of 5G/5G genotype (OR:4.75, 95%CI:1.18-19.06). PAI-1 levels and PAI-1 4G/5G polymorphism had no influence on long-term outcomes. Interpretation: PAI-1 5G/ 5G genotype is associated with a significant risk for developing ICH in post-lysis stroke patients.

Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis

“…Interestingly, here we show that with the exception of plasminogen levels at admission, there is no direct relation between thrombus size and the investigated fibrinolysis parameters at admission or 24 h later. In a previous study by our group involving 131 AIS patients, we found that PAI-activity and antigen levels before thrombolysis, 1 hour and 24 hours after thrombolysis showed no association with short‐term or long‐term functional outcomes [ 29 ], thus levels of this marker were not measured in this cohort. In this patient cohort, plasminogen levels were significantly lower in case of higher CBS (smaller thrombi) that might be a result of significantly higher incorporation of plasminogen to thrombi and as a consequence, the consumption of the protein.…”

Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

“…Moreover, in approximately 6-8% of patients, therapy-associated bleeding complications will take place, which potentially leads to worsening of symptoms and might be fatal in approximately 1% of thrombolysed patients [6]. The outcome and safety of thrombolysis is likely to depend on factors influencing or regulating fibrinolysis, but the exact pathomechanism is largely unknown [7][8][9][10].…”

The Role of Biomarkers in Atherothrombotic Stroke—A Systematic Review

“…However, another study showed that the PAI-1 5G/5G genotype is associated with an increased risk of hemorrhage after rt-PA treatment. Furthermore, PAI-1 levels were increased significantly in patients who had ASPECTS scores below 7 points [39].…”