Article

Effects of unfractionated and low molecular weight heparin on antiphospholipid antibody binding in vitro

Division of Reproductive Endocrinology and Immunology, Department of Obstetrics & Gynecology, University of Tennessee, 956 Court Avenue, Memphis, TN 38163, USA.
Obstetrics and Gynecology (Impact Factor: 4.37). 03/2003; 101(3). DOI: 10.1016/S0029-7844(02)02520-6

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.

0 Bookmarks
 · 
12 Views
  • [Show abstract] [Hide abstract]
    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. · 3.34 Impact Factor
  • Source
    [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 03/2014; 41:113-132. · 1.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear. To assess whether subcutaneous LMWH treatment improves the salvage rate of the digits in patients with digital replantation after traumatic amputation. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (October 2012), CENTRAL (2012, Issue 10) and trials databases. In addition, the authors searched PubMed, CNKI (China National Knowledge Infrastructure) and CEPS (Chinese Electronic Periodical Services), and sought additional trials from reference lists of relevant publications. We selected randomised or quasi-randomised controlled trials of LMWH in patients who received digital replantation. Two review authors independently extracted data and assessed the risk of bias of the included trials. Disagreements were resolved by discussion. Two randomised trials involving 114 patients with at least 122 replanted digits met the inclusion criteria and were included. Both trials compared the efficacy and safety of LMWH with UFH. We found no trials comparing LMWH with placebo or other anticoagulants. The data from the two included studies were insufficient for meta-analysis. The overall success rate of replantation did not differ between the LMWH and UFH groups, 92.3% versus 89.2% in one trial (risk ratio (RR) 1.03; 95% confidence interval (CI) 0.87 to 1.22) and 94.3% versus 94.15% in the other trial (RR 1.00; 95% CI 0.89 to 1.13). The incidence of both postoperative arterial and venous insufficiency were reported in one trial and did not significantly differ between the LMWH and UFH groups (RR 1.08; 95% CI 0.16 to 7.10 and RR 0.81; 95% CI 0.20 to 3.27, respectively). Direct and indirect causes of microvascular insufficiency were not reported in the trials. Different methods were used to monitor the adverse effects related to anticoagulation in the two trials. Bleeding tendency was monitored for the LMWH and UFH groups in one trial and was reported by the incidence of wound haemorrhage (11.5% versus 17.9%; RR 0.65; 95% CI 0.17 to 2.44), ecchymoses (3.8% versus 10.7%; RR 0.36; 95% CI 0.04 to 3.24), haematuria (3.8% versus 7.1%; RR 0.54; 95% CI 0.05 to 5.59), nasal bleeding (0% versus 7.1%; RR 0.21; 95% CI 0.01 to 4.28), gingival bleeding (0% versus 10.7%; RR 0.15, 95% CI 0.01 to 2.83) and faecal occult blood (0% versus 3.6%; RR 0.36; 95% CI 0.02 to 8.42). The bleeding tendency was increased in the UFH group but this was not statistically significant. This trial also monitored coagulability changes using parameters such as antithrombin activity, factor Xa activity, bleeding time, clotting time and activated partial thromboplastin time (aPTT). No comparison was made between the LMWH and UFH groups but all data consistently showed that coagulability was reduced more in the UFH group than in the LMWH group. The other trial reported a postoperative decrease in platelet count in the UFH group (preoperative 278.4 ± 18.7 x 10(9)/L, postoperative 194.3 ± 26.5 x 10(9)/L; P < 0.05) but not in the LMWH group (preoperative 260.8 ± 32.5 x 10(9)/L, postoperative 252.4 ± 29.1 x 10(9)/L; P > 0.05). Current limited evidence based on two small-scaled low-to-medium quality randomised trials found no differences in the success rate of replantation between LMWH and UFH, but a lower risk of postoperative bleeding and hypocoagulability after the use of LMWH. Further well-designed and adequately powered clinical trials are warranted.
    Cochrane database of systematic reviews (Online) 07/2013; 7:CD009894. · 5.94 Impact Factor

Full-text (2 Sources)

Download
12 Downloads
Available from
Jul 17, 2014