Hemostatic disturbances in acute ischemic stroke

Background: Stroke is the 2nd most common cause of death after ischemic heart disease. About 85% of all strokes are caused by a thrombus or an embolus in the cerebral circulation. Stroke causes major handicap with impaired quality of life for the patients and their families and a large costs to society. Modern treatment of ischemic stroke includes thrombolytic and antithrombotic agents, but despite this treatment many patients do suffer a new ischemic stroke.

Overall aim: To study hemostasis with emphasis on global hemostatic methods and try to identify subgroups of ischemic stroke with a more activated hemostasis, thus at risk of cerebrovascular complications.

Paper I and II: 32 patients were recruited from the Stroke units at Danderyd Hospital and at Karolinska University Hospital. Blood samples was collected in the acute phase and in the convalescence of ischemic stroke. TAFI (an attenuator of fibrinolysis), Overall Hemostatic Potential (OHP; a global marker of hemostasis assessing both coagulation and fibrinolysis) and inflammatory markers were determined in plasma. We found an impaired fibrinolysis with increased levels of TAFI and a decreased fibrinolytic capacity assessed by the OHP-method (paper I). Furthermore, the fibrin network formed was found to be less permeable in ischemic stroke patients (n=20) as compared to controls, both in the acute phase and after two months. In addition, the network was more resistant to fibrinolysis (paper II) as measured by our global method of fibrinolysis.

Paper III and IV: 209 patients with ischemic stroke (67%) or transient ischemic attack (TIA) (33%) were recruited from the Stroke units at Danderyd Hospital and at the Southern Hospital in Stockholm. Thrombin generation was measured by the Calibrated automated Thrombogram (CAT) and platelet activity was assessed by flowcytometric measurements of platelet-derived microparticles (PMPs) in plasma. Peak thrombin concentrations were found to be elevated both in the acute phase of the event and at one month (paper III). In addition, an increase in PMPs was present in the acute phase and at one month. They exposed tissue factor and P-selectin on their surfaces and these molecules may contribute to the activation of hemostasis in acute ischemic stroke (paper IV).

Conclusion: Manifest ischemic stroke and TIA are conditions associated with an imbalance between coagulation and fibrinolysis, and elevated plasma levels of platelet-derived microparticles. Global methods of hemostasis may be useful in the evaluation of the hemostatic balance in ischemic stroke and a discrimination between high and low risk patients might be possible with standardized global assays in the future.

List of scientific papers

I. Thrombin activatable fibrinolysis inhibitor and its relationship to fibrinolysis and inflammation during the acute and convalescent phase of ischemic stroke. Rooth E, Wallen NH, Antovic A, von Arbin M, Kaponides G, Wahlgren N, Margareta Blombäck, Antovic JP. Blood Coagulation and Fibrinolysis. 2007 Jun 18 (4): 365-70.
https://doi.org/10.1097/MBC.0b013e3281139c34

II. Decreased fibrin network permeability and impaired fibrinolysis in the acute and convalescent phase of ischemic stroke. Rooth E, Wallen NH, Blombäck M, He S. Thrombosis Research. 2011 Jan; 127(1): 51-6.
https://doi.org/10.1016/j.thromres.2010.09.011

III. Elevated thrombin generation in acute ischemic stroke and transient ischemic attack. Rooth E, Sobocinski-Doliwa P, Antovic J, Frykman V, von Arbin M, Rosenqvist M, Wallén NH. [Submitted]

IV. Tissue factor and P-selectin expression on platelet-derived microparticles in patients with acute ischemic stroke or transient ischemic attack. Rooth E, Mobarrez F, Sobocinski-Doliwa P, Antovic J, Frykman V, von Arbin M, Rosenqvist M, Wallén NH. [Manuscript]