Effect of long-acting thromboxane receptor antagonist (BMS 180,291) on experimental antiphospholipid syndrome.
Antiphospholipid syndrome (APS) is characterized by recurrent thromboembolic phenomena, recurrent fetal loss and thrombocytopenia associated with high titers of IgG anticardiolipin antibodies and/or lupus anticoagulant. There is an increased platelet aggregation in these patients and thus aspirin was found to be effective in abrogating some of the clinical findings. The purpose of this study was to employ the experimentally induced APS in mice infused with anticardiolipin antibodies, to study the effect of a thromboxane receptor antagonist (BMS, 180, 291) on the various overt manifestations of APS. Experimental APS was induced in pregnant female mice by iv infusion of a pathogenic anticardiolipin antibody (CAM). The mice were then treated daily with 300 micrograms/mouse of BMS. The study group and the untreated group were killed on day 17 of pregnancy. Live and absorbed fetuses and the mean weight of the placentae, fetuses and platelet counts were recorded. BMS treated mice had a significant reduction in fetal resorption rate from 45% to 19.8% and an increase in mean placental and embryo weights (182 vs 104, 1043 vs 721 mg, respectively). In parallel, an increase in platelet count (from 597,100 to 1075,000 platelets/mm3) and decrease in activated thromboplastin time (95 to 44s) was seen. It seems that thromboxane receptor antagonist may be effective in abrogating the diverse manifestations seen in APLS. Increased platelet aggregation may be one of the pathogenetic mechanisms in APS.
Department of Medicine B, Sheba Medical Center Tel-Hashomer, Israel.
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Shoenfeld
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D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000187:drug effects / Q000473:pathology; D005260:Female; D005327:Fetal Resorption / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D010080:Oxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D010314:Partial Thromboplastin Time; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011247:Pregnancy; D011422:Propionates / Q000494:pharmacology* / Q000627:therapeutic use; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*
D017153:Antibodies, Anticardiolipin; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010080:Oxazoles; D011422:Propionates; D017482:Receptors, Thromboxane; C078904:ifetroban