Studies on phospholipid antibodies, APC-resistance and associated mutation in the coagulation factor V gene.
The influence of antibodies against phospholipids (PLa) on APC response was investigated in 155 women with a history of thromboembolism and/or repeated foetal losses. PLa were determined as antibodies against cardiolipin (CLa) and phosphatidyl serine (PSa) and as lupus anticoagulant (LA) tested by dilute Russell's Viper Venom time and by the Textarin/Ecarin ratio. APC-response was studied by a clotting (aPTT-based) and by an amidolytic (factor IXa-X-based) assay. A reduced response to APC (APC-resistance) was found in 49% of 65 PLa-positive and in 13% of 90 PLa-negative samples (chi 2 = 23.9; p < 0.5 x 10(-4)). It was more common in the samples with LA, as compared to CLa+PSa positive (58% vs. 30%, not significant). The presence of the mutation causing Arg506-Gln substitution in coagulation factor V was investigated in 84 samples. The occurrence of the mutation in APC-resistant patients with CLa+PSa or with LA in one of the two assays was similar to those without PLa (84% and 100%, respectively). In the absence of APC resistance, the occurrence of the mutation was similar in the samples with and without PLa (14% vs. 11%). Samples with LA, determined by both tests used, comprised a special group where the frequency of the mutation in the APC resistant samples was significantly reduced (p < 0.01). In the latter samples, the pathogenic mechanism of APC resistance may be connected with the influence on phospholipid membranes.
Bokarewa
M I
MI
Department of Laboratory Medicine/Blood Coagulation Research, Karolinska Institute, Stockholm, Sweden.
Bremme
K
K
Falk
G
G
Sten-Linder
M
M
Egberg
N
N
Blombäck
M
M
D000026:Abortion, Habitual / Q000209:etiology; D000293:Adolescent; D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000032:analysis; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000235:genetics*; D001327:Autoimmune Diseases / Q000097:blood* / Q000235:genetics*; D001483:Base Sequence; D004198:Disease Susceptibility / Q000276:immunology; D004789:Enzyme Activation; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000097:blood / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D016682:Lupus Coagulation Inhibitor / Q000032:analysis; D008875:Middle Aged; D008969:Molecular Sequence Data; D010314:Partial Thromboplastin Time; D010718:Phosphatidylserines / Q000276:immunology; D010743:Phospholipids / Q000276:immunology*; D017354:Point Mutation; D011247:Pregnancy; D011486:Protein C / Q000378:metabolism*; D013923:Thromboembolism / Q000209:etiology*
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016682:Lupus Coagulation Inhibitor; D010718:Phosphatidylserines; D010743:Phospholipids; D011486:Protein C; D005165:Factor V