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
