Rarely, skin necrosis can occur at sites of injec- tion. In these cases, HIT should be suspected. In a single case report, fondaparinux was used success- fully in a patient who developed skin reactions to three different LMWH preparations.209 To date, studies on the effects of fondaparinux on bone metabolism have been limited to in vitro exper- iments using cultured osteoblasts. In one study, fondaparinux was compared with heparin, dalteparin, or enoxaparin. Osteoblasts exposed to fondaparinux showed signi cantly higher mitochondrial activity and protein synthesis than unexposed osteoblasts. In contrast, therapeutically relevant concentrations of heparin, dalteparin, or enoxaparin decreased matrix collagen type 2 content and calcification; fonda- parinux had no effect on these measures of osteo- blastic activity.210 A second study compared the effects of fondaparinux and dalteparin on human osteoblasts in culture. Dalteparin inhibited osteoblast prolifera- tion, protein synthesis, and the decreased levels of osteocalcin and alkaline phosphatase. In contrast, fondaparinux had no effect.211 Because of insuf cient safety data, fondaparinux is not widely used in pregnancy. Although one pharma- cologic study showed that there was no placental transfer of the pentasacccharide,212 low levels of anti-Xa activity were detected in the umbilical cord blood in newborns of mothers treated with 1.4 Danaparoid Sodium Although it is a mixture of glycosaminoglycans (heparan sulfate, dermatan sulfate, and chondroitin sulfate), danaparoid acts as an anticoagulant primarily by catalyzing the inhibition of factor Xa in an AT-dependent fashion. The drug has low speci c anti-Xa activity. Based on anti-Xa levels, danaparoid has a half-life of approximately 25 h. Although danaparoid was shown to be effective for the prevention of venous thrombosis in high-risk patients, it is no longer marketed for this indication. 