heparitin-sulfate and Abortion--Spontaneous

Danaparoid case reports of 91 pregnancies in 83 patients with a history of thrombophilia and/or intra-uterine growth retardation have been analysed. All had intolerance to the heparins including HIT and acute or past thromboses or a history of repeated pregnancy loss (RPL). Danaparoid was started in the first, second and third trimesters in 60.2%, 19.3% and 20.5% pregnancies respectively at a dosing intensity of 1000 to 7500 U/day. Subcutaneous and/or intravenous administration was continued for a median 105 days (range 1-252) during pregnancy and 7 days (range 2 to 56) post-partum. The live birth rate was 90.4% (75/81) and danaparoid was restarted after 37 deliveries. Maternal adverse events in 46.2% of the pregnancies included 2 post cesarean deaths (a failed post-operative resuscitation and a major bleed in a patient refusing transfusion), 3 non-fatal major bleeds (associated with cesarean section and faulty placental implantation), 3 thrombo-embolic events unresponsive to danaparoid dose increase and 10 recurrent rashes. Seven early miscarriages, 1 therapeutic termination and 1 neonatal death occurred. In 13 reports a maternal, but no fetal, adverse event was attributed to danaparoid. Anti-Xa activity levels in maternal plasma were between 0.1 and 1.2 U/mL, absent from 6 fetal cord blood samples and 0 - 0.07 U/mL in the 5 maternal breast milk samples tested.. The successful birth rate and adverse event profile indicates that danaparoid can be an effective and safe alternative anti-thrombotic in pregnancies complicated by HIT or intolerance or resistance to (LMW)heparins.

Topics: Abortion, Spontaneous; Chondroitin Sulfates; Dermatan Sulfate; Exanthema; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Infant, Newborn; Infusions, Intravenous; Injections, Subcutaneous; Pregnancy; Research; Thrombosis; Treatment Outcome

Heparan sulfate, a glycosaminoglycan component of vascular endothelial proteoglycans, provides the anticoagulant functions associated with heparin on the endothelial cell surface. We have demonstrated the presence of spontaneous occurring antibodies to heparin polysaccharides (HPS) in humans. Elevation of serum anti-HPS antibodies were closely associated with the prevalence of thrombosis or fetal loss in patients with autoimmune disease. Affinity purified anti-HPS antibodies inhibited heparin dependent formation of thrombin-antithrombin III complexes. In order to further analyze these autoantibodies, a murine IgG monoclonal anti-HPS antibody, designated H16, was generated. H16 mAb specifically bound to heparin, heparan sulfate and human umbilical vascular endothelial cells (HUVEC). The binding of H16 mAb to HUVEC was specifically inhibited by heparin. Further, H16 mAb inhibited the binding of antithrombin III to heparin in a dose dependent manner. These results indicate that this mAb could recognize antithrombin III-binding sites on vascular endothelial heparan sulfate, leading to procoagulant states through the inhibition of heparin/heparan sulfate dependent anticoagulant process.

Topics: Abortion, Spontaneous; Animals; Antibodies, Monoclonal; Antithrombin III; Autoantibodies; Autoimmune Diseases; Binding Sites; Endothelium, Vascular; Female; Heparitin Sulfate; Humans; Mice; Peptide Hydrolases; Pregnancy; Thrombosis