The aims of this study are to determine the level of activity of the hemostatic system (in vivo thrombin generation) in patients who have suffered a previous ischemic stroke. We will measure the plasma level of the prothrombin activation fragment Fl+2, in a representative subset of patients in the Warfarin Aspirin Recurrent Stroke Study (WARSS - NINDS 5 R0l NS2837I). In that study, patients who have suffered a """"""""cryptogenic"""""""" (embolic) stroke are assigned to either antithrombotic or antiplatelet therapy. The treatment arms consist of warfarin to maintain INR between 1.4 and 2.8, or aspirin at 325 mg/day. For this substudy of WARSS, we hypothesize that Patients with previous embolic stroke will have a higher level of Fl+2 than patients with other types of ischemic stroke. We will determine whether prothrombin fragment Fl+2 is lowered to a greater extent by warfarin than by aspirin in the embolic """"""""cryptogenic"""""""" group of patients as compared to patients in the other stroke groups (atherothrombotic, tandem arterial pathology, small vessel/lacunar). In addition to prothrombin fragment Fl+2 and INR, we will measure serum fibrinogen, albumin/globulin ratios and complete blood counts. To determine whether the relationships between the various parameters are stable over time, plasma samples will be obtained every six months for 2.5 years. Our proposed studies provide the opportunity to answer the following questions: (a) is there a particular group of patients that have a higher level of prothrombin generation?; (b) is there a particular subgroup of patients who are resistant to warfarin-induced thrombin generation?; (c) if warfarin is effective in preventing secondary stroke at the target INR, what is the relation between INR and Fl+2?; and (d) are these relationships stable over time?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS033765-03
Application #
2519964
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Program Officer
Marler, John R
Project Start
1995-09-01
Project End
1998-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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Ay, Hakan; Oliveira-Filho, Jamary; Buonanno, Ferdinando S et al. (2002) 'Footprints' of transient ischemic attacks: a diffusion-weighted MRI study. Cerebrovasc Dis 14:177-86
Ay, H; Buonanno, F S; Abraham, S A et al. (1998) An electrocardiographic criterion for diagnosis of patent foramen ovale associated with ischemic stroke. Stroke 29:1393-7