Pregnancy in a patient with homozygous familial hypercholesterolemia undergoing low-density lipoprotein apheresis by dextran sulfate adsorption*1

Teruel, J.L.; Lasunción, Miguel A.; Navarro, Juan F.; Carrero, Pilar; Ortuño, J

doi:10.1016/0026-0495(95)90247-3

Cited by 29 publications

(10 citation statements)

References 24 publications

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“…We acknowledge that the negatively charged column employed in the device removes other critical positively charged proteins from maternal circulation, e.g., fibrinogen, but as we demonstrated previously, these alterations are transient, 13 and resolve even more rapidly than the reduction in sFlt-1. Given the extensive safety record of such devices used in pregnancy (e.g., dialysis, plasma exchange [14][15][16] ) amounting to several thousand person-years of experience, we felt that this was a reasonably safe strategy to pursue for a devastating condition in which no alternative effective therapy other than delivery is available.…”

Section: Discussionmentioning

confidence: 99%

“…Excursions of systolic and diastolic BP, hematocrit, and platelet counts measured during the course of their hospitalization and apheresis treatments are also displayed, showing transient fluctuations in BP but no clinically significant changes in hematocrit or platelet counts. Among women treated multiple times, pregnancy continued on average for 15 days (range [11][12][13][14][15][16][17][18][19][20][21]. Narrative summaries of each patient that underwent multiple apheresis treatments are provided in the figure legends.…”

Section: Maternal Effects Of Apheresismentioning

confidence: 99%

“…9 Although we and others have performed experimental studies for each strategy, [10][11][12][13] therapeutic apheresis exploits the fact that sFlt-1 circulates in blood with a strongly positive charge, and complementary negatively charged columns employed in apheresis devices have already been approved worldwide and are safely used for the treatment of familial hypercholesterolemia, including in pregnant women. [14][15][16] Moreover, selective removal of circulating sFlt-1 avoids the removal of placental sFlt-1, which may be necessary for maintaining placental health. 17 We previously demonstrated that whole-blood apheresis using a negatively charged dextran sulfate column reduces circulating sFlt-1 and proteinuria in women with very preterm preeclampsia.…”

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confidence: 99%

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Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia

Thadhani¹,

Hagmann²,

Schaarschmidt³

et al. 2016

Journal of the American Society of Nephrology

227

145

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Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasmaspecific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP $140 mmHg or diastolic BP $90 mmHg, new onset protein/creatinine ratio .0.30 g/g, and sFlt-1/placental growth factor ratio .85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Section: Maternal Effects Of Apheresismentioning

confidence: 99%

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confidence: 99%

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Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia

Thadhani¹,

Hagmann²,

Schaarschmidt³

et al. 2016

Journal of the American Society of Nephrology

227

145

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“…[23][24][25][26] Preeclampsia is characterized by intravascular volume depletion. 27 Therefore, standard flow rates (80 to 150 mL/min) were lowered to 40 to 60 mL/min to avoid hypotension.…”

Section: Development Of Apheresis Protocols For Preeclampsiamentioning

confidence: 99%

“…24,33 In pregnant women with FH, treatments have continued without major complications. 26,34,35 To determine whether negatively charged DSC columns adsorb circulating sFlt-1, we performed ex vivo studies with recombinant sFlt-1 protein spiked into human whole blood. As shown in Table 2, ϳ80% of the circulating sFlt-1 protein was removed after 2 runs through a DSC column.…”

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confidence: 99%

Pilot Study of Extracorporeal Removal of Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia

et al. 2011

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Background-Targeted therapies to stabilize the clinical manifestations and prolong pregnancy in preeclampsia do not exist. Soluble fms-like tyrosine kinase 1 (sFlt-1), an alternatively spliced variant of the vascular endothelial growth factor receptor 1, induces a preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia. Removing sFlt-1 may benefit women with very preterm (Ͻ32 weeks) preeclampsia. Methods and Results-We first show that negatively charged dextran sulfate cellulose columns adsorb sFlt-1 in vitro. In 5 women with very preterm preeclampsia and elevated circulating sFlt-1 levels, we next demonstrate that a single dextran sulfate cellulose apheresis treatment reduces circulating sFlt-1 levels in a dose-dependent fashion. Finally, we performed multiple apheresis treatments in 3 additional women with very preterm (gestational age at admission 28, 30, and 27ϩ4 weeks) preeclampsia and elevated circulating sFlt-1 levels. Dextran sulfate apheresis lowered circulating sFlt-1, reduced proteinuria, and stabilized blood pressure without apparent adverse events to mother and fetus. Pregnancy lasted for 15 and 19 days in women treated twice and 23 days in a woman treated 4 times. In each, there was evidence of fetal growth. Conclusions-This pilot study supports the hypothesis that extracorporeal apheresis can lower circulating sFlt-1 in very preterm preeclampsia. Further studies are warranted to determine whether this intervention safely and effectively prolongs pregnancy and improves maternal and fetal outcomes in this setting. (Circulation. 2011;124:940-950.)Key Words: angiogenic factor Ⅲ apheresis Ⅲ preeclampsia P reeclampsia is a devastating medical complication of pregnancy associated with significant maternal and fetal morbidity and mortality. 1 The risk is highest in very preterm (Ͻ32 weeks) preeclampsia when the infant mortality rate is 70 times higher than at term. 2,3 Delivery of the placenta remains the only effective means to treat preeclampsia. Randomized trials have tested nonspecific interventions including antihypertensive agents; however, the ability of these and other interventions to prevent or stabilize the clinical manifestations and prolong pregnancy in preterm preeclampsia is limited. 4 -6 The underlying pathogenesis of preeclampsia has remained elusive, hampering successful development of targeted interventions for the condition. Clinical Perspective on p 950The prevailing hypothesis suggests that preeclampsia involves a placental factor that circulates to distal organs and causes damage to the vasculature. 7 We and others have suggested that excess placental derived soluble fms-like tyrosine kinase 1 (sFlt-1) or the soluble vascular endothelial growth factor (VEGF) receptor 1, an alternatively spliced variant of VEGF receptor 1, mediates the signs and symptoms of preeclampsia, and elevated circulating levels are associated with clinical preeclampsia. 8 -11 Circulating sFlt-1 levels in very preterm preeclampsia are among the highest obs...

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Prenatal Diagnosis of Disorders of Lipid Metabolism

Humphries

Mole

Winchester

2015

Genetic Disorders and the Fetus

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Pregnancy in a patient with homozygous familial hypercholesterolemia undergoing low-density lipoprotein apheresis by dextran sulfate adsorption*1

Cited by 29 publications

References 24 publications

Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia

Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia

Pilot Study of Extracorporeal Removal of Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia

Prenatal Diagnosis of Disorders of Lipid Metabolism

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