Use in Children and Pregnant Women

Danaparoid has been used in a small number of pediatric patients (Saxon et al., 1999; Bidlingmaier et al., 2005; see Chapter 20). For 33 of 34 children aged between 2 wk and 17 yr, danaparoid was used for the treatment of HIT. Sixteen children were treated with danaparoid for various indications, including maintenance of catheter patency, renal failure, cardiac surgery, and thrombosis. In general, it was noted that children, particularly infants, often required higher doses of danaparoid than adults on a weight-adjusted basis. Twenty-six children survived (78.8%), five died, and for two, there is no outcome information. The causes of death were thrombotic (one of three patients with a thrombotic event), bleeding (two of four patients with a major bleeding event), treatment withdrawn (one), and septicemia-induced multiple organ failure (one). Overall, danaparoid appeared safe and effective in children, except in cases requiring CPB, since this was associated with three of the four major bleeds.

Danaparoid is reported to have been used in at least 32 pregnancies complicated by HIT (Lindhoff-Last et al., 2005). All had a history of thrombosis, either acute or during a previous pregnancy. Danaparoid therapy was initiated in the first trimester in 18/32 (56.3%) and continued for up to 34 wk. The doses used were the same as those in non-pregnant women for the same indications. In 24 pregnancies (75%) carried to term, normal babies were delivered either vaginally or by caesarian section, although in some a maternal adverse event (usually associated with a placental abnormality) occurred. In eight pregnancies, danapar-oid was stopped prematurely. In two patients, this was because of successful short-term use (no further follow-up). Early fetal death occurred in three pregnancies, two in association with the maternal antiphospholipid syndrome, the other a therapeutic abortion necessitated by a maternal amputation due to thrombosis extension in the second trimester. In two pregnancies, major bleeds occurred, one due to placental abruption (fatal bleeding followed caesarian section in a Jehovah's Witness) after 24 wk of problem-free danaparoid use, and one due to placenta previa with fatal cardiopulmonary complications after caesarian section. One pregnancy was complicated by the onset of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, which manifested 6 wk into treatment with danaparoid. Danaparoid was replaced by warfarin and aspirin, but 2 wk later an emergency caesarian was needed because of impaired fetal growth and the premature, 24 wk, neonate died 2 days later of pulmonary hemorrhage.

In five infants' cord plasma no anti-Xa activity could be detected and four breast milk samples obtained from mothers continuing danaparoid postpartum had virtually undetectable anti-Xa activity. Thus, at least the main antithrombotic subfraction of danaparoid does not cross the placenta, and the tiny amounts that appear in the breast milk are probably hydrolyzed in the infant's stomach (Lindhoff-Last and Bauersachs, 2002). No increase in postpartum bleeding in 22 danaparoid-treated pregnant mothers was reported. The 19 treatment outcomes in non-HIT pregnancies were similar (Lindhoff-Last et al., 2005).

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