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Carboxypeptidase U (CPU, TAFIa, CPB2) Generation in Acute Ischemic Stroke Patients Undergoing Thrombolysis and Endovascular Thrombectomy

1University of Antwerp, Laboratory of Medical Biochemistry, Wilrijk, Antwerp, Belgium, 2Institut de Recherches Internationales Servier (I.R.I.S.), Cardiovascular and Metabolic Diseases Center for Therapeutic Innovation, Suresnes, France, 3Hospital de Bellvitge, Department of Neurology, Hospitalet de Llobregat-Barcelona, Spain, 4Vall d'Hebron University Hospital, Stroke Unit, Department of Neurology, Barcelona, Spain, 5Universitat Autónoma de Barcelona, Departament de Medicina, Barcelona, Spain

Abstract Number: PB0737

Meeting: ISTH 2020 Congress

Theme: Fibrinolysis and Proteolysis » Fibrinolytic Factors and Inhibitors

Background: Procarboxypeptidase U is activated by thrombin(-thrombomodulin) or plasmin into carboxypeptidase U (CPU, TAFIa, CPB2), a potent antifibrinolytic enzyme and an appealing target for the treatment of acute ischemic stroke (AIS). The kinetics of the total active and inactivated CPU (CPU+CPUi) have been studied in AIS; however, the kinetics of CPU generation and the influence of endovascular thrombectomy (EVT) on the CPU system are unknown.

Aims: Studying CPU generation in AIS patients receiving thrombolysis with or without EVT.

Methods: 37 AIS patients with documented cerebral artery occlusion and treated with rtPA (N=20) or rtPA+EVT (N=17) were included in this study which was conducted according to the tenets of the declaration of Helsinki revised in Fortaleza. CPU generation was studied by measurement of CPU activity and CPU+CPUi antigen levels. Blood samples were collected at baseline and at several time points over 24h after thrombolysis initiation.

Results: Demographic characteristics were similar in both groups (mean age: 77.8 ± 17 y.o.). Occlusions were mainly distal in the rtPA group and proximal in the rtPA+EVT group. CPU and CPU+CPUi levels were highly variable in both groups. Levels increased upon rtPA administration (Figure 1A-B) and reached peak values at the end of thrombolysis. Then, CPU activity decreased rapidly to baseline level within 3h, while CPU+CPUi levels remained elevated until 7h after thrombolysis induction. CPU activity and CPU+CPUi levels tended to be higher in the rtPA+EVT cohort compared to the rtPA cohort.

Conclusions: CPU was rapidly generated during thrombolysis and decreased immediately after the end of rtPA infusion. Conversely, CPU+CPUi levels remained elevated for several hours. This underlines the complementarity of both measurements to assess the dynamics of the CPU system during AIS. Whether the trend towards higher CPU levels during EVT is due to larger thrombus size or to the procedure itself remains to be investigated.


[Median (interquartile Range, IQR) CPU activity and CPU+CPUi antigen in plasma of AIS patients undergoing thrombolysis +/-EVT.]

To cite this abstract in AMA style:

Mertens JC, Blanc-Guillemaud V, Claesen K, Leenaerts D, Tyl B, Cardona P, Hendriks D, Molina CA. Carboxypeptidase U (CPU, TAFIa, CPB2) Generation in Acute Ischemic Stroke Patients Undergoing Thrombolysis and Endovascular Thrombectomy [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/carboxypeptidase-u-cpu-tafia-cpb2-generation-in-acute-ischemic-stroke-patients-undergoing-thrombolysis-and-endovascular-thrombectomy/. Accessed September 29, 2023.

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