title: Decreased anticoagulant response to tissue factor pathway inhibitor type 1 in plasmas from patients with lupus anticoagulants.
abstract: Inhibition of tissue factor pathway inhibitor type 1 (TFPI) is one of the mechanisms by which lupus anticoagulants (LA) may upregulate tissue factor (TF) activity. We wanted to examine whether purified immunoglobulin G (IgG) from patients with LA may interfere with the ability of TFPI to inhibit ex vivo TF-induced thrombin generation. The endogenous thrombin potential (ETP) in pooled normal plasma (PNP) supplemented with IgG from either patients with LA or controls was determined in the absence or presence of recombinant TFPI (rTFPI). In the presence of a heparin neutralizer, the ETP was also determined in plasmas from patients with LA and controls before and after heparin injection in order to quantify the anticoagulant effect of heparin-releasable TFPI in vivo. Compared with IgG from controls (n = 14), IgG from patients with LA (n = 28) induced a wide range of enhancing or inhibitory effects on the ETP in PNP. The response to rTFPI in PNP with IgG from patients with LA correlated inversely with thrombin generation (r(s) = 0.637, P = 0.0003). Correspondingly, the relative inhibition of ETP in postheparin plasmas was smaller for patients (n = 11) than for controls (n = 9) (32% vs. 68%, P = 0.007). Our findings support the hypothesis that TFPI anticoagulant activity is inhibited in some patients with LA.
authors.affiliation: Department of Haematology, Ullevål University Hospital, Oslo, Norway. sigurdli@ulrik.uio.no
authors.forename: Sigurd
authors.initials: S
authors.lastname: Liestøl
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Sandset
authors.forename: Eva Marie
authors.initials: EM
authors.lastname: Jacobsen
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mowinckel
authors.forename: Finn
authors.initials: F
authors.lastname: Wisløff
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D016736:Antiphospholipid Syndrome / Q000097:blood*; D001777:Blood Coagulation / Q000187:drug effects; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism* / Q000494:pharmacology; D008074:Lipoproteins / Q000097:blood / Q000494:pharmacology*; D016682:Lupus Coagulation Inhibitor / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013917:Thrombin / Q000378:metabolism*; D013918:Thrombin Time; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D007074:Immunoglobulin G; D008074:Lipoproteins; D016682:Lupus Coagulation Inhibitor; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D013917:Thrombin