Lipoprotein apheresis is essential for managing pregnancies in patients with homozygous familial hypercholesterolemia: Seven case series and discussion Masatsune Ogura a, * , Hisashi Makino b , Chizuko Kamiya c , Jun Yoshimatsu c , Handrean Soran d , Ruth Eatough d , Giuseppina Perrone e , Mariko Harada-Shiba a , Claudia Stefanutti f a Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan b Division of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center Hospital, Osaka, Japan c Department of Perinatology, National Cerebral and Cardiovascular Center Hospital, Osaka, Japan d Department of Medicine, Central Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom e Department of Obstetrics and Gynecology, “Sapienza” University of Rome, Roma, Italy f Departments of Immunohematology and Transfusion Medicine and Department of Molecular Medicine e Lipid Clinic and Atherosclerosis Prevention Centre, “Sapienza” University of Rome, Roma, Italy article info Article history: Received 20 July 2016 Received in revised form 6 October 2016 Accepted 7 October 2016 Available online 8 October 2016 Keywords: Lipoprotein apheresis Homozygous familial hypercholesterolemia Pregnancy Coronary artery disease Aortic valvular disease abstract Background and aims: For patients with homozygous familial hypercholesterolemia (HoFH), atherogenic lipoprotein changes and increased stress on cardiovascular system during pregnancy may pose sub- stantial risk for both the mother and her fetus. Although lipoprotein apheresis (LA) is reported as the most effective therapy to control LDL-C levels during pregnancy in HoFH patients, only case reports have been published, and there is no guidance for management. Methods: We report twelve pregnancies and ten deliveries in seven patients with HoFH, and compare the clinical outcomes between patients who received LA during pregnancy and those who did not. Results: One patient who refused LA during pregnancy died from acute myocardial infarction after de- livery. Another patient whose adherence to LA was poor also died of myocardial infarction during pregnancy. One patient who initiated LA at the age of 18 had to discontinue LA due to severe symptoms of angina pectoris during pregnancy. Another had symptoms of nausea, hypotension, and bradycardia with increased levels of serum bradykinin during a dextran sulfate cellulose absorption-based LA pro- cedure. Although two of the other three patients had already had coronary artery disease by the time of pregnancy, early initiation of LA from childhood and good adherence to it during pregnancy resulted in the delivery of healthy infants without adverse effects. Conclusions: LA is essential for managing pregnancy safely in patients with HoFH. Increasing numbers of documented cases, including ours, will be helpful to guide future therapeutic decisions. © 2016 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder of lipid metabolism with a prevalence of 1:160,000e1,000,000. It is characterized by extremely high levels of low-density lipoprotein cholesterol (LDL-C) since birth. Multiple cutaneous and tendon xanthoma and coronary artery disease (CAD) are evident even in childhood [1]. HoFH patients are usually identified in early childhood because of the appearance of xanthoma associated with an extraordinarily high plasma LDL-C levels. Early initiation of sustained cholesterol- lowering treatment including lipoprotein apheresis (LA), high dose statins, and ezetimibe have reportedly improved longevity in HoFH [2] [3]. Managing these patents during child-bearing age presents many challenges for clinicians because LDL-C increases during gestation, * Corresponding author. Department of Molecular Innovation in Lipidology, Na- tional Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail address: enustasam@ncvc.go.jp (M. Ogura). Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis http://dx.doi.org/10.1016/j.atherosclerosis.2016.10.018 0021-9150/© 2016 Elsevier Ireland Ltd. All rights reserved. Atherosclerosis 254 (2016) 179e183