Plasmodium falciparum-infected erythrocytes induce tissue factor expression in endothelial cells and support the assembly of multimolecular coagulation complexes.

BACKGROUND: Plasmodium falciparum malaria infects 300-500 million people every year, causing 1-2 million deaths annually. Evidence of a coagulation disorder, activation of endothelial cells (EC) and increase in inflammatory cytokines are often present in malaria. OBJECTIVES: We have asked whether interaction of parasitized red blood cells (pRBC) with EC induces tissue factor (TF) expression in vitro and in vivo. The role of phosphatidylserine-containing pRBC to support the assembly of blood coagulation complexes was also investigated. RESULTS: We demonstrate that mature forms of pRBC induce functional expression of TF by EC in vitro with productive assembly of the extrinsic Xnase complex and initiation of the coagulation cascade. Late-stage pRBC also support the prothrombinase and intrinsic Xnase complex formation in vitro, and may function as activated platelets in the amplification phase of the blood coagulation. Notably, post-mortem brain sections obtained from P. falciparum-infected children who died from cerebral malaria and other causes display a consistent staining for TF in the EC. CONCLUSIONS: These findings place TF expression by endothelium and the amplification of the coagulation cascade by pRBC and/or activated platelets as potentially critical steps in the pathogenesis of malaria. Furthermore, it may allow investigators to test other therapeutic alternatives targeting TF or modulators of EC function in the treatment of malaria and/or its complications.

Delaying transfer to the third day post-insemination, to select non-arrested embryos, increases development to the fetal heart stage.

The purpose of this study was to determine whether delaying embryo transfer by 24 h, until day 3 post-insemination, allowed improved selection of non-arrested embryos for transfer. We have retrospectively analysed pregnancy rates in a large series of patients who had embryo transfer either on day 2 or on day 3 post-insemination over a 27 month period. From January 1990 to March 1992, 567 patients received embryo transfer on day 2, and 661 patients had transfer on day 3 post-insemination, but these transfers were not contemporary. Pregnancy rates were slightly higher in patients who had embryo transfer on day 3 (37%) than in those patients who had their embryos transferred on day 2 (35%), but this difference was not significant. The implantation rate, as measured by the proportion of embryos developing to the fetal heart stage, was significantly higher following transfer on day 3 (23%) than after transfer on day 2 (19%) (P < 0.05), suggesting that selection of viable embryos is improved on day 3. Furthermore, of the embryos which gave rise to a fetal sac, significantly fewer miscarried before the fetal heart stage (P < 0.05) following transfer on day 3 (6%) than after transfer on day 2 (12%). Delaying transfer until day 3 provides a further 24 h to observe embryo development. During this period 16% of embryos arrested or became developmentally retarded; thus waiting until day 3 allowed these embryos to be identified and avoided for consideration for transfer. Embryo transfer may be safely delayed until day 3, and this may help in selecting embryos most likely to implant and develop after transfer.