CLINICAL STUDIES
The presence of infection-related antiphospholipid antibodies in infective endocarditis determines a major risk factor for embolic events
Leon Iri Kupferwasser, MD*,
Gerd Hafner, MD ,
Susanne Mohr-Kahaly, MD*,
Raimund Erbel, MD, FACC ,
J.ürgen Meyer, MD, FACC* and
Harald Darius, MD, FACC*
* II. Medical Clinic, Mainz University, Mainz, Germany
Institute of Clinical Chemistry, Mainz University, Mainz, Germany
Division of Cardiology, Essen University, Essen, Germany
Manuscript received July 16, 1998;
revised manuscript received November 23, 1998,
accepted January 5, 1999.
Reprint requests and correspondence: Dr. Leon Iri Kupferwasser, Adult Infectious Diseases, Harbor-UCLA Medical Center, Building RB-2, 1000 West Carson Street, Torrance, California 90509
kupferwasser{at}humc.edu
OBJECTIVES
The impact of infection-associated antiphospholipid antibodies (APA) on endothelial cell activation, blood coagulation and fibrinolysis was evaluated in patients with infective endocarditis with and without major embolic events.
BACKGROUND
An embolic event is a common and severe complication of infective endocarditis. Despite the fact that APAs are known to be associated with infectious diseases, their pathogenic role in infective endocarditis has not been clearly defined.
METHODS
The relationship among the occurrence of major embolic events, echocardiographic vegetation size, endothelial cell activation, thrombin generation, fibrinolysis and APA was examined in 91 patients with definite infective endocarditis, including 26 patients with embolic events and 65 control subjects without embolic events.
RESULTS
Overall, 14.3% of patients exhibited elevated APA levels. Embolic events occurred more frequently in patients with elevated levels of APA than in patients without (61.5% vs. 23.1%; p = 0.008). Patients with elevated levels of APA showed higher levels of prothrombin-fragment F1+2 (p = 0.005), plasminogen-activator inhibitor 1 (p = 0.0002), von Willebrand factor (p = 0.002) and lower levels of activated protein C (p = 0.001) than patients with normal levels of APA. Thrombin generation and endothelial cell activation were both positively correlated with levels of APA. The occurrence of elevated APA levels was frequently associated with structural valve abnormalities (p = 0.01) and vegetations >1.3 cm (p = 0.002).
CONCLUSIONS
Infection-associated elevated APA levels in patients with infective endocarditis are related to endothelial cell activation, thrombin generation and impairment of fibrinolysis. This may contribute to the increased risk for major embolic events in these patients.
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Abbreviations and Acronyms
| | ACA | = anticardiolipin antibodies | | APA | = antiphospholipid antibodies | | APA(+) | = elevated levels of antiphospholipid antibodies | | APA(–) | = normal levels of antiphospholipid antibodies | | aPC | = activated protein C | | aPTT | = activated prothrombin time | | F1+2 | = prothrombin fragment 1+2 | | LAC | = lupus anticoagulant | | PAI-1 | = plasminogen activator inhibitor-1 | | SD | = standard deviation | | vWF | = von Willebrand factor |
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