Differential Indication of Lipoprotein Apheresis During Pregnancy

Abstract

Lipoprotein apheresis is an effective treatment for severe disorders of lipid metabolism. It is the only life prolonging therapy for patients with homozygous familial hypercholesterolemia. Changes of lipid metabolism during pregnancy related to changes of hormone concentrations do not cause clinical complications in the majority of cases. However, in particular clinical situations there is the need to offer a therapeutic option. Increasing morbidity and mortality of mother and child due to severe disorders of lipid metabolism have to be prevented. In general, lipid lowering drugs are contraindicated during pregnancy. Therefore, lipoprotein apheresis offers an alternative, which could be used in select cases to treat acute or chronic hyperlipoproteinemia associated with pregnancy. This article summarizes experiences with patients, who became pregnant during chronic lipoprotein apheresis, or who were treated by lipoprotein apheresis because of acute disorders of lipid metabolism during pregnancy. In conclusion, after individual risk benefit analysis for mother and child lipoprotein apheresis can be safely performed during pregnancy.

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

“…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.…”

“…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.…”

“…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.…”

“…13 To improve the efficiency of sFlt-1 removal, minimize the need for therapeutic anticoagulation, reduce potential activation of immune cells, and obtain detailed outcome information regarding fetuses and neonates, we conducted this single-arm pilot study using an apheresis device that first separates plasma from whole blood before passing through a plasma-specific dextran sulfate (PSDS) column. These columns are widely available 16 and we suspected that their side-effect profiles might be superior to whole-blood column apheresis when used in women with preterm preeclampsia. We aimed to treat 10-12 patients to provide evidence of safety sufficient to inform design of a subsequent randomized trial; the first several patients were to be treated once, and the rest more than once.…”

I Diretriz Brasileira de Hipercolesterolemia Familiar (HF)

“…As resinas, como o colesevelam e a colestiramina, são agentes da categoria B na gravidez e lactação, e portanto podem ser consideradas para tratamento da HF nessas condições, desde que sob supervisão médica 15 . A LDL-aférese é uma modalidade de tratamento que também pode ser utilizada em casos especiais, em que o risco cardiovascular da paciente, na ausência de tratamento, é muito alto, como em pacientes com HF homozigótica ou com HF heterozigótica e doença aterosclerótica grave 195 .…”