Franklin, R.D. & Kutteh, W.H. Effects of unfractionated and low molecular weight heparin on antiphospholipid antibody binding in vitro. Obstet. Gynecol. 101, 455−462

Department of Obstetrics and Gynecology, University of Tennessee, Knoxville, Tennessee, United States
Obstetrics and Gynecology (Impact Factor: 5.18). 03/2003; 101(3). DOI: 10.1016/S0029-7844(02)02520-6


To compare the efficacy of unfractionated heparin and low molecular weight heparin in the in vitro binding of antiphospholipid antibodies obtained from the sera of patients with recurrent pregnancy loss.
Women with immunoglobulin (Ig) G antibodies to the phospholipids cardiolipin and phosphatidylserine were selected based on a positive test by a standard enzyme-linked immunosorbent assay (ELISA). The sera were reassayed for antiphospholipid antibodies in a modified ELISA using increasing doses of unfractionated heparin or low molecular weight heparin (0, 16, 32, 64, 128, and 256 IU). Sera were fractionated by unfractionated and low molecular weight heparin affinity chromatography to compare the binding avidity and antiphospholipid antibody activity.
All sera demonstrated a dose-dependent inhibition in measured antiphospholipid antibody activity with the addition of unfractionated or low molecular weight heparin. Levels of IgG cardiolipin and IgG phosphatidylserine were significantly inhibited in the presence of 32 IU of low molecular weight heparin (P <.001 and P <.05, respectively) and in the presence of 64 IU of unfractionated heparin (P <.001 and P <.05, respectively). Antiphospholipid antibody binding activity in serum as measured in the ELISA was maximally reduced 76-89% with 256 IU of either heparin derivative. Affinity chromatography with unfractionated or low molecular weight heparin columns absorbed 72% and 66% of IgG cardiolipin activity, respectively, and 46% and 54% of IgG phosphatidylserine activity, respectively.
These data suggest that low molecular weight heparin and unfractionated heparin reduce the in vitro binding of antiphospholipid antibodies on a per unit basis. Both heparins demonstrate binding activity similar to that of antiphospholipid antibodies in vitro.

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Available from: William H Kutteh, Jul 17, 2014
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    • "Pregnancies in women with certain thrombophilic conditions, such as antiphospholipid syndrome (aPLs), activated protein C resistance, protein S deficiency and factor V Leiden mutation, are known to be at a higher risk for the latter complications (Kupferminc et al., 1999; Greer, 2003). Since the use of heparin can result in a significant reduction in pregnancy complications in women with aPLs, it has been suggested that the beneficial effects in pregnancy relate to anticoagulant actions (Woodhams et al., 1989; Chamley, 1998; Franklin and Kutteh 2003). More recent reports suggest that heparin may act by many different mechanisms, such as reducing aPL antibody binding, inhibiting complement binding, inhibiting placental apoptosis and stimulating placental proliferation (Bose et al., 2004; Hills et al., 2006). "
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    • "The cellular mechanisms by which heparin exerts its beneficial effects still have to be ascertained. Several authors (McIntyre et al., 1993; Ermel et al., 1995; Franklin and Kutteh, 2003) suggested direct binding of heparin to aPL antibodies showing a decrease in aPL antibody binding with increasing dose of heparin. This was not thought to be due to an electrostatic interaction, as chondroitin sulphate which has a negative charge similar to that of heparin had no effect on aPL concentrations in the enzyme-linked immunosorbent assay. "
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