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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-8-14
pubmed:abstractText
Antiphospholipid antibodies (aPA) frequently interfere with the protein C pathway. This manifests as acquired activated protein C (APC) resistance in the absence of factor V Leiden and has been proposed as a putative mechanism for the pathogenesis of the antiphospholipid syndrome (APS). We have developed a Russell's viper venom test, performed with and without activation of endogenous protein C, which is sensitive to aPA-associated APC resistance. Results were reported as the endogenous APC ratio (EAPCr); the ratio of the two clotting times normalized against pooled normal plasma. Forty-four patients with aPA, anticardiolipin and/or lupus anticoagulant, including 34 with a history of thrombosis or pregnancy morbidity; a control group of aPA-negative patients; and 26 healthy normals were studied. EAPCr (mean, SD) was significantly higher in APS patients (1.94, 0.58) than normals (0.98, 0.12) or controls (1.14, 0.19; P < 0.00001). Elevated EAPCr (> 1.22) occurred in 91% of aPA-positive patients, predominantly due to resistance to APC (87%) rather than prolonged basal clotting times alone (15%). Significant correlation was observed between the EAPCr value and dilute Russell's viper venom time (rs = 0.44, P = 0.003), IgG anticardiolipin (rs = 0.54, P = 0.002), protein S (r = -0.46, P = 0.01) and activated partial thromboplastin time-based APC resistance (r = -0.61, P = 0.001). There was no significant relationship between EAPCr and protein C concentration, anti-beta2-glycoprotein-I (anti-beta2GPI) or IgM anticardiolipin. Purified aPA IgG caused a dose-dependent increase in APC resistance when added to normal plasma. We conclude that aPA-associated acquired APC resistance is a common feature of APS and may be independent of anti-beta2GPI.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0957-5235
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
477-83
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Detection of acquired resistance to activated protein C associated with antiphospholipid antibodies using a novel clotting assay.
pubmed:affiliation
Department of Haematology, University College London, UK. chris.gardner@uchevaluation.co.uk
pubmed:publicationType
Journal Article