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To cite this article: Brenner B, Hoffman R, Carp H, Dulitsky M, Younis J for the LIVE-ENOX Investigators. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE-ENOX study. J Thromb Haemost 2005; 3: 227-9.See also Lindqvist PG, Merlo J. Low molecular weight heparin for repeated pregnancy loss: is it based on solid evidence? This issue, pp 221-3; Gris JC, Maré s P. The long and winding road... towards LMWH for pregnancy loss. This issue, pp 224-6. Clinical studies suggest that the use of low-molecular-weight heparins (LMWHs) during pregnancy may result in an improved outcome in women with thrombophilia and recurrent pregnancy loss (RPL) [1][2][3]. LMWHs also appear to be safe when administered to women during pregnancy [4]. In a study population of 50 women with RPL, our group has previously demonstrated that treatment with enoxaparin 40 mg day )1 or 80 mg day )1 resulted in favorable pregnancy outcomes with live birth rates of 69% and 83%, respectively [1]. The data suggested that the higher dosage of 80 mg dayenoxaparin was potentially beneficial for women at a greater risk of thrombosis due to more than one thrombophilic defect [1]. We therefore compared the efficacy and safety of enoxaparin 40 mg day )1 and 80 mg dayin improving pregnancy outcomes of women with thrombophilia and a history of RPL. In total, 180 women were enrolled in the LIVE-ENOX study, a multicenter, prospective, randomized, open-label trial, at 12 centers in Israel. Women were enrolled at 5-10 weeks of pregnancy, if aged ‡ 18 years, with thrombophilia and a history of RPL which was defined as three or more losses before the end of the first trimester, two or more in the second trimester or one intrauterine fetal death in the third trimester. Exclusion criteria were: pregnancy loss within 3 months prior to enrollment, prior thromboembolic disease, history of epilepsy, thrombocytopenia, renal or hepatic insufficiency, or contraindication to LMWHs.Patients received either enoxaparin 40 mg day(once daily)] or enoxaparin 80 mg day )1 (40 mg b.i.d), which was self-administered by subcutaneous injection using prefilled syringes. Study treatment commenced at 5-10 weeks of pregnancy, and continued throughout pregnancy and up to 6 weeks postpartum. The primary efficacy endpoint was the delivery of a live, healthy infant. The safety endpoints included maternal thrombocytopenia, and any drug-related adverse events throughout the study. Over 90% of women in each group completed the study. The baseline characteristics of the patients receiving each dosage of enoxaparin are shown in Table 1. Thrombophilic defects were not significantly different between the two treatment groups (Table 1). In both groups, only about 28% of previous pregnancies had resulted in live births.Of the 166 women completing the study, 135 gestations resulted in live births: 70 (84.3%) in the 40 mg day )1 group and 65 (78.3%) in the 80 mg day )1 group. There was no significant difference in pregnancy outcome between the 4...

The hematopoietic system is derived from ventral mesoderm. A number of genes that are important in mesoderm development have been identified including members of the transforming growth factor-β (TGF-β) superfamily, the fibroblast growth factor (FGF) family, and the Wnt gene family. Because TGF-β plays a pleiotropic role in hematopoiesis, we wished to determine if other genes that are important in mesoderm development, specifically members of theWnt gene family, may play a role in hematopoiesis. Three members of the Wnt gene family (Wnt-5A, Wnt-2B, and Wnt-10B) were identified and cloned from human fetal bone stromal cells. These genes are expressed to varying levels in hematopoietic cell lines derived from T cells, B cells, myeloid cells, and erythroid cells; however, only Wnt-5A was expressed in CD34+Lin− primitive progenitor cells. The in vitro biological activity of these Wnt genes on CD34+Lin− hematopoietic progenitors was determined in a feeder cell coculture system and assayed by quantitating progenitor cell numbers, CD34+ cell numbers, and numbers of differentiated cell types. The number of hematopoietic progenitor cells was markedly affected by exposure to stromal cell layers expressing Wnt genes with 10- to 20-fold higher numbers of mixed colony-forming units (CFU-MIX), 1.5- to 2.6-fold higher numbers of CFU-granulocyte macrophage (CFU-GM), and greater than 10-fold higher numbers of burst-forming units-erythroid (BFU-E) in the Wnt-expressing cocultures compared with the controls. Colony formation by cells expanded on theWnt-expressing cocultures was similar for each of the three genes, indicating similar action on primitive progenitor cells; however, Wnt-10B showed differential activity on erythroid progenitors (BFU-E) compared with Wnt-5A and Wnt-2B. Cocultures containing Wnt-10B alone or in combination with all three Wnt genes had threefold to fourfold lower BFU-E colony numbers than the Wnt-5A– or Wnt-2B–expressing cocultures. The frequency of CD34+ cells was higher inWnt-expressing cocultures and cellular morphology indicated that coculture in the presence of Wnt genes resulted in higher numbers of less differentiated hematopoietic cells and fewer mature cells than controls. These data indicate that the gene products of theWnt family function as hematopoietic growth factors, and that they may exhibit higher specificity for earlier progenitor cells. © 1998 by The American Society of Hematology.

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