Effects of unfractionated and low molecular weight heparin on antiphospholipid antibody binding in vitro.
ABSTRACT 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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ABSTRACT: APS is an autoimmune disease that leads to arterial and/or venous thrombosis, recurrent pregnancy loss and persistently positive aPLs. Patients with clinical manifestations highly suggestive of APS but persistently negative conventional aPLs are classified as having seronegative APS. Ongoing research has revealed the existence of non-criteria antibodies proposed to be relevant to APS and that can be potentially included in the disease's classification criteria. We present a literature review on the most promising antibodies of this heterogeneous aPL family, which includes antibodies to a zwitterionic phospholipid, namely phosphatidylethanolamine, phospholipid-binding plasma proteins, phospholipid-protein complexes and anionic phospholipids other than cardiolipin. Although these molecules can increase the diagnostic yield of APS, their clinical relevance is still debatable and needs to be confirmed by interlaboratory efforts toward standardizing diagnostic tools, in addition to experimental data and larger longitudinal studies.Rheumatology (Oxford, England) 03/2013; · 4.24 Impact Factor
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ABSTRACT: The antiphospholipid syndrome was first described in the early 1980s. The term was first coined to describe patients presenting with recurrent arterial and venous thrombosis or pregnancy complications. Antiphospholipid syndrome was first reported in systemic lupus erythematosus patients, but later on it became obvious that systemic lupus erythematosus is not a necessary condition for its occurrence. It has been shown that antibodies to phospholipids are the main causative agents of the disease, hence its name. The diagnosis of the disease has witnessed a remarkable evolution over the course of the past 25 years. With the observation that clinical parameters would not be enough to accurately diagnose the disease, antiphospholipid antibodies were recognized to play a central role in this regard. The main hindrance to an accurate diagnosis was the lack of standardization between different laboratory parameters that tested for the antiphospholipid antibodies. Lately, a combination of tests has been acknowledged to play a crucial role in diagnosis.Expert Review of Clinical Immunology 07/2013; 9(7):659-68. · 2.89 Impact Factor
Article: Antiphospholipid Antibody Syndrome[Show abstract] [Hide abstract]
ABSTRACT: KEYWORDS � Antiphospholipid syndrome � Antiphospholipid antibodies � Recurrent pregnancy loss � Fetal demise � Unfractionated heparin � Complications of pregnancy KEY POINTS � Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids, a group of inner and outer cell membrane antigens found in mammals. � Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. � Although obstetric APS was originally reported in association with slow progressive throm- bosis and infarction in the placenta, it is most often associated with a poor obstetric outcome. � Several pathophysiologic mechanisms of action of aPLs have been described. � The most common histopathologic finding in early pregnancy loss has been defective en- dovascular decidual trophoblastic invasion. � Treatment with heparin and aspirin is emerging as the therapy of choice, with approxi- mately 75% of treated women with RPL and aPL having a successful delivery, compared with less than 30% without treatment.Obstetrics and Gynecology Clinics of North America 01/2014; 41:113-132. · 1.45 Impact Factor