From the Departments of Internal Medicine (T.G., U.G.) and Neurology
(M.S.) and the Laboratory of Thrombosis Research (T.G., A.H., J.H.B.),
University Hospital, Bern, Switzerland.
Correspondence to Matthias Sturzenegger, MD, Department of Neurology, University Hospital, CH-3010 Bern, Switzerland. E-mail matthias.sturzenegger{at}insel.ch
Background and
Purpose—Cerebrovascular events (CVE) in patients with
prosthetic heart valves (PHV) have remained a severe and
frequent complication despite oral anticoagulation with or without
aspirin. We studied the possible pathophysiological
involvement of platelet-derived microparticles (PMP) as a
contributing factor for the increased incidence of CVE in patients
with PHV.
Methods—We compared in a retrospective, case-control study the
clinical outcome after the implantation of the PHV with several
different independent morphological and functional methods, including
simultaneous transcranial Doppler
monitoring of both middle cerebral arteries, PMP detection by flow
cytometry with use of platelet-specific antibodies, coagulation
markers, and determination of the procoagulant activity by Russell's
viper venom time, a phospholipid-dependent coagulation assay.
Results—Eight of 26 patients with PHV had 9 CVE during 136
person-years of observation. Transcranial Doppler
monitoring revealed an increased frequency of
microembolic signals recorded over a 30-minute
period in patients with CVE (75±25; median, 55; range, 27 to 248)
compared with those without CVE (23±12; median, 7; range, 0 to 153;
P<0.05) or with control subjects (0;
P<0.001). Flow cytometry analysis showed
increased levels of PMP in patients with compared to those without CVE
(4.1±0.6% versus 2.4±0.4% of all fluorescence-positive
events gated; P<0.05). Increased procoagulant activity
was documented by the shortened Russell's viper venom time expressed
as an increased level of platelet equivalents per microliter of
plasma in patients compared with control subjects (+24.7±14.9%;
P<0.01). Subgroup analysis revealed that
patients with CVE had a higher excess of platelet equivalents per
microliter of plasma than patients without CVE in relation to the
controls (+68.7±36.7%; P<0.05). Mildly elevated
thrombin–antithrombin III complexes (2.9±0.7; median, 2.3; normal,
<2.0 µg/L) suggested incompletely suppressed thrombin formation, and
fibrin generation (fibrinopeptide A) was in the upper
normal range (2.1±0.2; median, 1.8; normal, <2.0 ng/mL), despite
adequate anticoagulation (INR=3.6±0.1).
Conclusions—Our data show increased microembolic
signals, platelet microparticles, and procoagulant activity in
symptomatic patients with PHV and provide a potential
pathophysiological explanation of CVE.
© 1998 American Heart Association, Inc.
Original Contributions
Mechanisms of Cerebrovascular Events as Assessed by Procoagulant Activity, Cerebral Microemboli, and Platelet Microparticles in Patients With Prosthetic Heart Valves
Key Words: cerebral embolism • coagulation • heart valve prosthesis • platelets • procoagulant
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