Bevacizumab-Mediated Interference With VEGF Signaling Is Sufficient to Induce a Preeclampsia-Like Syndrome in Nonpregnant Women

Reviews in Obstetrics and Gynecology

Thomas J Rutherford²  Errol R Norwitz¹  Sarah N Cross²  Elena Ratner²  Peter E Schwartz² 

[1] Department of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA;Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT

关键词: Bevacizumab;    Hypertension;    Preeclampsia;    Eclampsia;    Vascular endothelial growth factor;    Reversible posterior leukoencephalopathy syndrome;   

DOI  :  

学科分类：医学（综合）

来源: MedReviews, LLC

【 摘 要 】

Preeclampsia (gestational proteinuric hypertension) complicates 5% to 8% of all pregnancies, and is a major cause of maternal and perinatal morbidity and mortality. It is a multisystem disorder specific to human pregnancy and the puerperium. Although the etiology is unknown, increasing evidence from both animal and human studies suggests that an imbalance in circulating pro-(vascular endothelial growth factor [VEGF], placental growth factor) and anti-angiogenic factors (soluble fms-like tyrosine kinase 1, soluble endoglin) may be important. Bevacizumab (Avastin®; Genentech, South San Francisco, CA), a humanized recombinant monoclonal IgG antibody that binds VEGF, has been shown to inhibit endothelial cell proliferation, suppress angiogenesis, and shrink a variety of solid tumors. We present two cases of bevacizumab toxicity that mimic preeclampsia with a reversible syndrome characterized by acute-onset severe hypertension, proteinuria, central nervous system irritability (headache, photophobia, blurred vision, seizures), abnormal laboratory tests (elevated liver function tests, thrombocytopenia), and evidence of reversible posterior leukoencephalopathy on neuroimaging. In both cases, the clinical and laboratory manifestations returned to normal with discontinuation of bevacizumab therapy and supportive care. Bevacizumab toxicity can mimic preeclampsia in nonpregnant women. These data suggest that interference with VEGF signaling is sufficient to induce a preeclampsia-like syndrome in nonpregnant patients. VEGF signaling therefore appears to play a central role—perhaps the central role—in the pathogenesis of preeclampsia, and provides a potential biomarker for the prediction, prevention, and treatment of this dangerous disorder.

【 授权许可】

Unknown