ABSTRACT
Antiphospholipid antibodies may interfere with the PC pathway, displaying a resistance to the activated PC (resistant phenotype). This effect was evaluated by the APCR and the ProCG systems in 36 lupus anticoagulant samples, yielding abnormal results in 47% of APCR(original), 17% of APCR(modified), and 22% of ProCG test. ProCG values correlated with APCR(original) but not with APCR(modified). Most of lupus anticoagulants affecting the PC pathway showed abnormal APCR(original) results but not abnormal ProCG values. The different behavior between both systems may be due to the heterogeneity of the antibodies or could be attributed to the fact that, in the ProCG, a PC activator is added, while the APCR employs already activated exogenous PC.
Subject(s)
Antibodies, Antiphospholipid/pharmacology , Protein C/metabolism , Activated Protein C Resistance/blood , Activated Protein C Resistance/genetics , Female , Humans , Lupus Coagulation Inhibitor/pharmacology , Male , Phenotype , Predictive Value of Tests , Protein C/drug effects , Reagent Kits, DiagnosticABSTRACT
BACKGROUND AND OBJECTIVES: The development of neutralizing anti-factor VIII antibodies (a-fVIII) is a major clinical complication. Lupus anticoagulant (LA) might affect detection of a-fVIII, since both inhibitors may act on the same coagulation pathway. Our aim was to accomplish unequivocal detection and titration of a-fVIII even in the presence of LA. DESIGN AND METHODS: We evaluated a-fVIII activity by a chromogenic substrate (CS) method in samples with a-fVIII (n=6), LA (n=12) and presumably both LA+a-fVIII (n=5). The inhibition index before (Ii) and after incubation at 37 C (Ii(37)) was estimated. We also performed factor VIII assays (one-stage and CS) and titration methods (Bethesda and CS) in parallel. RESULTS: Inhibition in the a-fVIII group (Ii=5-3200) was potentiated by incubation (Ii(37)=27-5200) as it was in LA+a-fVIII (Ii=9-21; Ii(37)=50-903). LA samples showed no or meaningless inhibitory effect (Ii=0-7; Ii(37)=0-4) or a-fVIII activity (0.00-0.06 CSU/ml) by the CS method; on the contrary, very low to moderate (0.52-7.00 BU/ml) a-fVIII activity was recorded by the Bethesda method. The two titration methods did not correlate (p>0.100) in the presence of LA, or LA+a-fVIII. Differences between factor VIII:C and factor VIIIcs were significant only in LA samples (p=0.005); however, patients with residual factor VIII activity from the LA+a-fVIII group also showed higher factor VIIIcs values than factor VIII:C ones. INTERPRETATION AND CONCLUSIONS: Results indicate the possibility of detecting and titrating a-fVIII without interference of LA by the CS method. This marks a difference with respect to the Bethesda method, in which a measurable effect can be expected in the presence of a strong LA.
Subject(s)
Autoantibodies/blood , Chromogenic Compounds , Factor VIII/immunology , Isoantibodies/blood , Humans , Lupus Coagulation Inhibitor/blood , Lupus Coagulation Inhibitor/pharmacology , TitrimetryABSTRACT
El anticoagulante lúpico es un inhibidor de la coagulación sanguínea adquirido espontáneamente que interfiere con la activación de la protrombina por el complejo activador. Este inhibidor, una inmunoglobulina, aparece más comúnmente en el plasma de pacientes con desórdenes autoinmunes incluyendo el lupus eritematoso sistémico, pero también ha sido asociado con enfermedades no relacionadas directamente con el sistema inmune y en pacientes sin ninguna enfermedad demostrable. Los pacientes con este "anticoagulante" usulamente están libres de sangrado a pesar de las anormalidades en su coagulación. Paradójicamente, han sido reportados episodios de trombosis venosa profunda, trombosis arterial u oclusión cerebrovascular, embolismo pulmonar y trombosis en la circulación renal. El mecanismo de estas asociaciones es desconocido, pero su comprensión será necesaria para un mejor diagnóstico y tratamiento de esta nueva entidad