Thromb Haemost 2021; 121(05): 584-593
DOI: 10.1055/s-0040-1721146
Coagulation and Fibrinolysis

High Thrombin Generation after Acute Ischemic Stroke or Transient Ischemic Attack Is Associated with a Reduced Risk of Recurrence: An Observational Cohort Study

Annika Lundström
1  Division of Neurology, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
,
Elisabeth Änggårdh-Rooth
1  Division of Neurology, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
,
Fariborz Mobarrez
2  Department of Medical Sciences, Uppsala University, Uppsala, Sweden
,
Charlotte Thålin
3  Division of Internal Medicine, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
,
Bruna Gigante
4  Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
5  Division of Cardiovascular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
,
Ann Charlotte Laska
1  Division of Neurology, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
,
Håkan Wallén
4  Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
› Author Affiliations
Funding This work was partly funded by the Swedish Stroke Association, Karolinska Institutet Coagulation Fund, and the Stockholm Regional Fund for Research, Development, and Education, which is gratefully acknowledged.

Abstract

Thrombin is increasingly recognized to be of importance for cardiovascular disease. The aim of this study was to investigate the prognostic value of thrombin generation variables in a cohort of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Thrombin generation potential measured by calibrated automated thrombogram (CAT) and prothrombin fragment F1 + 2 was determined in the acute and convalescent phases for a cohort of 190 patients with AIS/TIA. Microvesicle (MV)-induced thrombin generation potential was determined for a subset of patients using modified CAT. Primary outcome was a composite of fatal and nonfatal AIS or myocardial infarction as documented in Swedish registers during a total follow-up of 986 patient-years. Hazard ratios (HRs) were calculated using Cox regression based on variable median split. Peak thrombin and endogenous thrombin potential (ETP) above median in the acute phase were associated with a reduced risk of primary outcome after adjustment for cardiovascular risk factors, HR: 0.50 (0.27–0.92), p = 0.026 and HR: 0.53 (0.28–0.99), p = 0.048, respectively. F1 + 2 was lower in patients than in healthy controls but not associated with outcome. MV-induced peak thrombin above median in the acute phase was associated with recurrent AIS, unadjusted HR: 2.65 (1.03–6.44), p = 0.044. Contrary to expectation, high thrombin generation potential is associated with a reduced risk of recurrent ischemic event in patients with AIS/TIA. Low ETP/peak thrombin combined with high MV-induced peak thrombin can potentially identify patients at high risk of recurrence.

Supplementary Material



Publication History

Received: 10 June 2020

Accepted: 15 October 2020

Publication Date:
12 December 2020 (online)

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