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Thromboembolic disease
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
Some women (1%–2%) develop a local allergic reaction to LMWH. If this occurs, women usually develop a similar localized pruritic urticarial skin eruption to all forms of UFH and LMWH. In these unusual cases, heparinoids such as danaparoid or fondaparinux (see next) have been used successfully and seem safe during pregnancy and breastfeeding.
Haemostasis: Normal Physiology, Disorders of Haemostasis and Thrombosis
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Elizabeth Jones, Russell David Keenan
These are rarely used. Danaparoid is a heparinoid with mostly anti-Xa action and a little anti-IIa activity. It is renally excreted with no specific antidote. Fondaparinux is a pentasaccharide (synthetic) that acts indirectly through its anti-Xa activity. Again, it is renally excreted with no specific antidote. Bivalirudin is a direct thrombin inhibitor and has a short half-life but IV infusion is required for ongoing anticoagulation, so stopping it and general haemostatic measures are usually adequate.
Thromboembolism
Published in Daryl Dob, Griselda Cooper, Anita Holdcroft, Philip Steer, Gwyneth Lewis, Crises in Childbirth Why Mothers Survive, 2018
Although systematic reviews suggest that some heparins are safe for the fetus,37 several maternal complications have been described. Heparin-induced osteoporosis is an important problem associated with long-term UFH use. The reported incidence of symptomatic vertebral fractures is about 2–3%, and reversible reductions in bone density have been documented in up to 30% of patients.45 LMWH is probably associated with a lower risk of osteoporosis.9Heparin-induced thrombocytopenia is an immune IgG-mediated reaction characterised by the development of serious, sometimes life-threatening arterial or venous thrombosis, which usually occurs between 5 and 15 days after the initial administration of heparin. It has been estimated that the risk in non-pregnant patients treated with UFH is 1–3%, but is considerably lower with LMWH.46 In pregnant women who develop or have a history of heparin-induced thrombocytopenia, danaparoid sodium is recommended as a safe option because of the low cross-reactivity with both heparins.
Heparin-induced thrombocytopenia: pathophysiology, diagnosis and treatment
Published in Expert Review of Hematology, 2021
Anne-Mette Hvas, Emmanuel J Favaloro, Maja Hellfritzsch
Magnani et al. extensively described real-world use in 1,418 patients treated with danaparoid due to suspected or confirmed HIT in the period from 1982 to mid-2004 [56]. In 1,291 HIT treatment episodes with serologically confirmed HIT, thrombosis was apparent in 39.4% [56]. The evaluation of efficacy demonstrated that in 11% of the danaparoid treatment episodes, a new thromboembolic event occurred despite anticoagulant treatment. As regards to safety, 20% suffered serious, but non-fatal adverse events (e.g. new or extended thrombosis), and 8% experienced major bleeding. Thus, these observations on real-world experience with danaparoid demonstrates that changing to non-heparin anticoagulant therapy does not totally protect against recurrent thrombosis, and the treatment comes at a cost of adverse events.
High-dose intravenous immunoglobulin for the treatment and prevention of heparin-induced thrombocytopenia: a review
Published in Expert Review of Hematology, 2019
My recommendation for intra- and postoperative anticoagulation was to give therapeutic-dose danaparoid. This is because a single preoperative dose (1500 anti-factor Xa units for a patient weighing about 50 kg) would provide immediate and predictable therapeutic-dose anticoagulation. Further, because of the life- and limb-threatening nature of the HIT, I also ordered high-dose IVIG immediately postoperatively, 1g/kg for two consecutive days. The product provided was Gammagard Liquid (Immune Globulin Infusion [Human] 10%, Shire Pharma Canada manufacturer), which is manufactured by Cohn fractionation and cation exchange chromatography, followed by three virus reduction steps (solvent/detergent treatment, nanofiltration, low pH/elevated temperature incubation); this process ensures that native IgG structure is maintained through to the final product.
Danaparoid is effective and safe for patients with obstetric antiphospholipid syndrome
Published in Modern Rheumatology, 2020
Hiroyuki Yoshihara, Mayumi Sugiura-Ogasawara, Tamao Kitaori, Kinue Katano, Yasuhiko Ozaki
Although UFH was replaced by LMWH to prevent maternal bleeding, both of these compounds have such side effects as heparin-induced thrombocytopenia (HIT) and osteoporosis. With danaparoid sodium (Orgaran®), however, the possibility of a serious complication such as hemorrhage, HIT, or osteoporosis is diminished [15]. HIT is caused by immunoglobulin G directed against platelet factor 4 (PF4)-heparin complex. Since PF4 forms a tetramer and has a strong positive charge on its surface, it binds to glycosaminoglycan causing a morphological change, and the new structure is thought to act as an antigen to stimulate production of HIT antibody. The degree of the morphological change of PF4 is related to the degree of negatively charged sulfation of glycosaminoglycan and the length of the chain. This is why the variation in the frequency of HIT antibody production is dependent on the type of heparin used [16,17]. Danaparoids are composed of heparan sulfate, dermatan sulfate and chondroitin sulfate, and since the degree of sulfation is low and the sugar chains are short, cross reactions are rare, and these compounds have little ability to worsen HIT [18]. Indeed, alternative anticoagulation with danaparoid was reported in two pregnancies in a patient with previous HIT, a homozygous factor V Leiden mutation, and a history of venous thrombosis and RPL [19]. Danaparoid was found to be safe and effective for improving the live birth rate and preventing thromboembolism in patients with thrombophilia [20]. However, there has been no study examining the efficacy of this therapy in patients with obstetric APS (oAPS). Furthermore, none of the studies considered patients whose miscarriages were caused by an abnormal embryonic karyotype.