Elevated sFlt1 Level and Preeclampsia with Parvovirus-Induced Hydrops
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《新英格兰医药杂志》
To the Editor: Previous reports have described an association between hydropic placentas and the occurrence of preeclampsia.1,2 One proposed explanation is that an enlarged placenta may cause a systemic inflammatory response by shedding an increased amount of trophoblast debris into the maternal blood, although the mediators of such a response have been unclear. One potential mediator is soluble fms-like tyrosine kinase 1 (sFlt1). In animal models, infusion of sFlt1 induces manifesations of preeclampsia, including hypertension and proteinuria.3 In humans, sFlt1 is dramatically up-regulated in the preeclamptic placenta, and a marked increase in the levels of circulating sFlt1 has been noted weeks before the development of clinical manifestations of preeclampsia.4,5
We report the case of a 26-year-old woman (gravida 1, para 0) who was referred at 24 weeks' gestation because of fetal ascites. Ultrasonography showed a hydropic placenta (diameter, 69 mm; normal, 50 mm) and generalized fetal hydrops. The systolic velocity in the middle cerebral artery was increased (48.7 cm per second), an indication of fetal anemia. Cordocentesis confirmed severe fetal anemia and parvovirus B19 infection. The patient's blood pressure was 170/110 mm Hg; the rate of urinary protein excretion was 2 g per 24 hours. The plasma level of sFlt1 was 14,117 pg per milliliter; this value exceeded that reported in both normal and preeclamptic pregnancies. (The mean sFlt1 level in patients with preeclampsia was 4382 pg per milliliter in the study by Levine et al.4 and 7247 pg per milliliter in our study,5 with both values measured with the use of the same commercial kit.)
The patient was treated twice with intravascular transfusion. Serial ultrasonography showed that hydrops of placenta and fetus started to improve after 1 week; fetal hydrops had completely resolved at 27 weeks 6 days of gestation. A follow-up examination (at 36 weeks 4 days) revealed normal blood pressure (100/60 mm Hg) and resolution of proteinuria. On repeated measurement, the plasma sFlt1 level was 7489 pg per milliliter, a value still in the range reported for patients with preeclampsia4,5 but markedly lower than the earlier measurement in the setting of hypertension and proteinuria.
This report demonstrates an association between enlargement of the placenta in the setting of parvovirus infection, extremely high maternal plasma levels of sFlt1, and signs of preeclampsia. With resolution of hydrops after transfusion, the sFlt1 level fell, and signs of preeclampsia resolved. These findings suggest that elevated levels of sFlt1 may be triggered by various forms of placental pathology. Although we do not have data to indicate whether the increase in sFlt1 levels preceded the resolution of the manifestations of preeclampsia, this case supports the need for further study of the potential role of interventions to reduce sFlt1 levels in the treatment of preeclampsia.
Holger Stepan, M.D.
Renaldo Faber, M.D.
University of Leipzig
04103 Leipzig, Germany
holger.stepan@medizin.uni-leipzig.de
References
Anand A, Gray ES, Brown T, Clewley JP, Cohen BJ. Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med 1987;316:183-186.
Zaki M, Greenwood C, Redman CW. The spontaneous reversal of pre-eclampsia associated with parvovirus-induced hydrops and the placental theory of pre-eclampsia: a case report. BJOG 2003;110:1125-1126.
Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003;111:649-658.
Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672-683.
Stepan H, Geide A, Faber R. Soluble fms-like tyrosine kinase 1. N Engl J Med 2004;351:2241-2242.
We report the case of a 26-year-old woman (gravida 1, para 0) who was referred at 24 weeks' gestation because of fetal ascites. Ultrasonography showed a hydropic placenta (diameter, 69 mm; normal, 50 mm) and generalized fetal hydrops. The systolic velocity in the middle cerebral artery was increased (48.7 cm per second), an indication of fetal anemia. Cordocentesis confirmed severe fetal anemia and parvovirus B19 infection. The patient's blood pressure was 170/110 mm Hg; the rate of urinary protein excretion was 2 g per 24 hours. The plasma level of sFlt1 was 14,117 pg per milliliter; this value exceeded that reported in both normal and preeclamptic pregnancies. (The mean sFlt1 level in patients with preeclampsia was 4382 pg per milliliter in the study by Levine et al.4 and 7247 pg per milliliter in our study,5 with both values measured with the use of the same commercial kit.)
The patient was treated twice with intravascular transfusion. Serial ultrasonography showed that hydrops of placenta and fetus started to improve after 1 week; fetal hydrops had completely resolved at 27 weeks 6 days of gestation. A follow-up examination (at 36 weeks 4 days) revealed normal blood pressure (100/60 mm Hg) and resolution of proteinuria. On repeated measurement, the plasma sFlt1 level was 7489 pg per milliliter, a value still in the range reported for patients with preeclampsia4,5 but markedly lower than the earlier measurement in the setting of hypertension and proteinuria.
This report demonstrates an association between enlargement of the placenta in the setting of parvovirus infection, extremely high maternal plasma levels of sFlt1, and signs of preeclampsia. With resolution of hydrops after transfusion, the sFlt1 level fell, and signs of preeclampsia resolved. These findings suggest that elevated levels of sFlt1 may be triggered by various forms of placental pathology. Although we do not have data to indicate whether the increase in sFlt1 levels preceded the resolution of the manifestations of preeclampsia, this case supports the need for further study of the potential role of interventions to reduce sFlt1 levels in the treatment of preeclampsia.
Holger Stepan, M.D.
Renaldo Faber, M.D.
University of Leipzig
04103 Leipzig, Germany
holger.stepan@medizin.uni-leipzig.de
References
Anand A, Gray ES, Brown T, Clewley JP, Cohen BJ. Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med 1987;316:183-186.
Zaki M, Greenwood C, Redman CW. The spontaneous reversal of pre-eclampsia associated with parvovirus-induced hydrops and the placental theory of pre-eclampsia: a case report. BJOG 2003;110:1125-1126.
Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003;111:649-658.
Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672-683.
Stepan H, Geide A, Faber R. Soluble fms-like tyrosine kinase 1. N Engl J Med 2004;351:2241-2242.