Document Detail

Acquired protein C dysfunction but not decreased activity of thrombomodulin is a possible marker of thrombophilia in patients with lupus anticoagulant.
MedLine Citation:
PMID:  7822946     Owner:  NLM     Status:  MEDLINE    
Lupus anticoagulants (LAs) are acquired antiphospholipid antibodies, and the occurrence of LA is associated with an increased risk of developing thrombosis. In a population of 46 patients with LA with or without LA-associated thrombophilia, it was analyzed whether the concentration of LA could be correlated to the individual thrombotic risk in patients with LA. No significant difference was found in the concentrations of LA measured by routinely used functional and immunologic assays in patients with LA with thrombophilia when compared with patients with LA without thrombophilia. Inhibition of thrombomodulin (TM) activity by LA has been postulated to be one of the major pathogenic mechanisms causing thrombophilia in LA. Therefore the inhibition of endothelial cell-dependent TM activity by LA was analyzed by using a protein C (PC) activation assay. Reduced rates of PC activation were found in only 2 out of the 46 cases, ruling out that inhibition of TM activity is a common phenomenon in patients with LA. However, anionic phospholipids are necessary to ascertain the anticoagulant activity of activated PC (APC). To prove the hypothesis that the anticoagulant activity of APC is inhibited by LA, the anticoagulant response of purified APC added to LA-containing plasma was measured through the amount of factor VIII inactivation. Thirteen out of 14 patients with recurrent thrombotic events and 10 out of 19 patients with one single episode of thrombosis showed an APC response outside the mean--2 SD range of normal human controls. In contrast, among 13 patients with LA without symptoms, only one showed an abnormal APC response. From these data it is concluded that LA inhibits the APC anticoagulant activity and that this type of acquired APC dysfunction may contribute to the pathogenesis of LA-associated thrombophilia. Moreover, the APC anticoagulant response assay may prove to be a useful marker to identify patients with LA with a high thrombotic risk.
B Pötzsch; H Kawamura; K T Preissner; M Schmidt; C Seelig; G Müller-Berghaus
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of laboratory and clinical medicine     Volume:  125     ISSN:  0022-2143     ISO Abbreviation:  J. Lab. Clin. Med.     Publication Date:  1995 Jan 
Date Detail:
Created Date:  1995-02-15     Completed Date:  1995-02-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375375     Medline TA:  J Lab Clin Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  56-65     Citation Subset:  AIM; IM    
Hemostasis Research Unit, Max-Planck-Institut für Physiologische und Klinische Forschung, Kerckhoff-Klinik, Bad Nauheim, Germany.
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MeSH Terms
Blood Coagulation Tests
Disease Susceptibility
Endothelium, Vascular / cytology,  metabolism
Factor VIII / metabolism
Lupus Coagulation Inhibitor / blood*
Middle Aged
Protein C / physiology*
Thrombomodulin / antagonists & inhibitors,  metabolism*
Thrombosis / etiology*
Reg. No./Substance:
0/Lupus Coagulation Inhibitor; 0/Protein C; 0/Thrombomodulin; 9001-27-8/Factor VIII
Comment In:
J Lab Clin Med. 1995 Jan;125(1):16-7   [PMID:  7822942 ]

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