title: Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal and heparin-treated antiphospholipid syndrome pregnancies.
abstract: Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombosis and recurrent miscarriage. We assessed levels of coagulation activation markers and aPL during normal pregnancy and in women with the antiphospholipid syndrome (aPS). Fluctuations in aPL levels were observed in all patients with aPS. No particular pattern of antibody positivity, or fluctuation in aPL level, was associated with poor pregnancy outcome. A significant increase was observed in levels of factor Xlla (FXIIa; P < 0.001), factor VIIa (FVIIa, P < 0.001), thrombin antithrombin complexes (TAT; P < 0.001), prothrombin fragment F1.2 (F1.2; P < 0.001) and D-dimer (DD; P < 0.05) during normal pregnancy. Factor VIIa, TAT, F1.2 and DD increased significantly before 20 weeks gestation, while a statistically significant increase in FXIIa levels was first detected between weeks 20 and 30 of gestation. In pregnant women with aPS, increases in FXIIa were similar to those in normal pregnancy, but increased FVIIa levels were not observed until after 30 weeks gestation. Similar to normal pregnancy, increased levels of TAT and F1.2 were detected in aPS pregnancies before 20 weeks gestation, but increased DD were not observed until after week 20. Surprisingly, women with aPS receiving low molecular weight heparin prophylaxis had significantly higher (P = 0.02) levels of TAT (median 8.6; interquartile range (IQR) 6.5-20.8) between weeks 20 and 30 of gestation compared to the normal pregnant population (median 5.9; IQR 4.7-7.9), thus indicating increased thrombin generation in women with aPS in mid-pregnancy.
authors.affiliation: Department of Haematology, University College London Medical School, UK.
authors.forename: S
authors.initials: S
authors.lastname: Donohoe
authors.forename: S
authors.initials: S
authors.lastname: Quenby
authors.forename: I
authors.initials: I
authors.lastname: Mackie
authors.forename: G
authors.initials: G
authors.lastname: Panal
authors.forename: R
authors.initials: R
authors.lastname: Farquharson
authors.forename: R
authors.initials: R
authors.lastname: Malia
authors.forename: J
authors.initials: J
authors.lastname: Kingdom
authors.forename: S
authors.initials: S
authors.lastname: Machin
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000097:blood*; D000925:Anticoagulants / Q000008:administration & dosage*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D000990:Antithrombin III / Q000378:metabolism; D015415:Biomarkers; D001777:Blood Coagulation / Q000276:immunology; D015331:Cohort Studies; D015942:Factor VIIa / Q000378:metabolism; D015956:Factor XIIa / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008055:Lipids / Q000097:blood; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D011256:Pregnancy Outcome; D011516:Prothrombin / Q000378:metabolism
chemical_list: D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D008055:Lipids; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D006493:Heparin; D010447:Peptide Hydrolases; D015942:Factor VIIa; D015956:Factor XIIa