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Available online 6 December 2024
Therapeutic apheresis in a pregnant woman with heterozygous familial hypercholesterolemia
Aféresis terapéutica en gestante con hipercolesterolemia familiar heterocigota
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Zoila Stany Albines Fiestasa,
Corresponding author
zoilastany@gmail.com

Corresponding author.
, María Victoria Rubio Rubioa, José Antonio Gimeno Ornab, Ana Belén Mañas Martínezb, Virginia Arroyo Espallargasa, Jordi Bosch Melguizoc, Beatriz María Rojas Pérez-Ezquerrad, Carmen Criado Mainara, Fernando Anaya-Fernández Lomanae,1, Pablo Iñigo Gila
a Servicio de Nefrología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
b Servicio de Endocrinología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
c Servicio de Radiología Intervencionista, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
d Servicio de Ginecología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
e Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Table 1. Pre- and post-session analytical parameters of LDL apheresis.
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Dear Editor,

Pregnancy involves an atherogenic lipid profile driven by increased resistance to insulin, oestrogen, progesterone and placental lactogen.1,2 This increase may worsen the underlying hypercholesterolaemia in pregnant patients with heterozygous familial hypercholesterolaemia (HFH).3 Total cholesterol increases by 25–50% and LDL cholesterol (LDL-C) by 50%4 with a predisposition to endothelial damage in the foetus, which begins during intrauterine life, and postnatal susceptibility to arteriosclerosis.5

Therapeutic management and target achievement are complex, since lipid drug therapy is limited by the teratogenic risk and experience with therapeutic apheresis is limited.

We present the case of a 33-year-old woman with HFH diagnosed in 2019 (LDLR gene mutation), with corneal arcus and left Achilles xanthoma. Family history includes a father who died at age 50 from a myocardial infarction and a sister who had a cerebrovascular accident at age 29.

The patient continued with routine follow-up in Endocrinology, with ezetimibe and atorvastatin providing good lipid control. Due to her desire to have children, treatment was changed to colestyramine, with total cholesterol levels of 516 mg/dl and LDL-C of 402 mg/dl during the second trimester of pregnancy then, after a multidisciplinary we were consulted to start LDL apheresis, assessment. The patient had concomitant gestational diabetes.

After obtaining informed consent, under ultrasound and fluoroscopic control (with 1 second of time of fluoroscopy), a right jugular tunnelled catheter was inserted in the 26th week of gestation and LDL apheresis was started, using the double filtration technique.

We used the Plasauto Σ™ monitor indicating 1L as the target volume of plasma to be treated, 30% plasma/blood ratio, 10% drainage/plasma and 10% replacement/plasma, in order to avoid haemodynamic abnormalities and prioritise foetal well-being. After each session, a gestational ultrasound was performed, with no abnormalities observed in the foetus and the in the amount of amniotic fluid preserved.

The frequency of the sessions was based on the calculation of mean LDL-C or Cave (known as time-averaged LDL-C), with the target Cave being <250, with maximum LDL-C of 300 mg/dl. The blood flow used was 100 ml/min and an initial bolus of heparin sodium was administered as the anticoagulant treatment necessary for the technique. The catheter was sealed with 1% heparin.

A total of six sessions were carried out during pregnancy and six sessions during the lactation period; after all sessions a decrease in total cholesterol and LDL-C to target values was observed as agreed with the Endocrinology department (Table 1). The sessions were well tolerated clinically and haemodynamically.

Table 1.

Pre- and post-session analytical parameters of LDL apheresis.

Session No.  TC  LDL-C  Cave  TG  IgG  Fibrinogen 
1. Pre  516  402    407  894  572 
1. Post  350  274.2  367.49  199  766  442 
2. Pre  411  304.2    344  820  527 
2. Post  331  252.8  290.32  221  727  416 
3. Pre  424  323.6    282  864  567 
3. Post  318  238.6  300.65  212  750  431 
4. Pre  410  308    445  836  552 
4. Post  305  222.4  286.48  228  732  412 
5. Pre  417  298    421  892  508 
5. Post  304  217.4  276.24  218  478  308 
6. Pre  419  299.8    336  826  536 
6. Post  263  193.4  271.07  158  590  362 
7. Pre  492  401.06    219  996  677 
7. Post  283  221.8  352.65  116  779  428 
8. Pre  432  354.6    204  1,100  529 
8. Post  229  176.9  306.62  114  832  296 
9. Pre  375  315.2    116  1,040  446 
9. Post  148  105.3  258.52  71  836  218 
10. Pre  415  348    130  1,080  418 
10. Post  151  110  283.74  63  783  212 
11. Pre  408  348    107  1,160  396 
11. Post  153  111.8  284.37  60  842  191 
12. Pre  388  333.6    76  1,120  413 
12. Post  118.7  84.1  266.23  42  837  191 

IgG: immunoglobulin G (mg/dl); LDL-C: LDL cholesterol (mg/dl); TC: total cholesterol (mg/dl); TG: triglycerides (mg/dl).

Average LDL cholesterol calculation (Cave): Cave = Cmin + K (Cmax–Cmin).

Cmin = LDL-C immediately after apheresis. Cmax = LDL-C immediately prior to apheresis. K or rebound coefficient = 0.73 (heterozygotes).

In week 35 + 3 of pregnancy, the patient presented with premature rupture of membranes, with eutocic delivery of a male newborn, weighing 2,565 g, measuring 47 cm and Apgar scores of 9 and 10 at minutes 1 and 5, respectively.

In the sessions carried out during the lactation period, the volume of plasma treated was greater (2,500–2,800 cc per session), with all other parameters similar to the procedures described.

After completing the sessions, the tunnelled catheter was removed without incident.

During pregnancy, a detailed assessment of lipid metabolism should be performed in patients with a previous diagnosis of HFH, not only due to the acute complications that may arise, but also because of future cardiovascular morbidity and mortality in the newborn.

Despite the new lipid-lowering drugs that achieve optimal lipid control, their safety profile during pregnancy is inadequate owing to the risk of teratogenesis.6,7 Currently, in the different consensuses, LDL apheresis is considered to be part of the therapeutic arsenal of patients with HFH during pregnancy. The exact reference values for cholesterol during pregnancy are unknown, but the indications for starting therapeutic apheresis in the general population are: LDL-C >300 mg/dl without cardiovascular disease, and LDL-C >200 mg/dl with cardiovascular disease.8,9

Double filtration is an extracorporeal procedure which, subsequent to plasma separation, processes the plasma through a second filter in order to eliminate components according to their molecular weight, such as circulating lipoproteins containing ApoB, mainly LDL-C and Lp(a). The American Society for Apheresis (ASFA) guidelines10 do not describe what the ideal regimen to use during pregnancy should be, and it is important to individualized for each patient and adapt the technique used.

Side effects are rare and mild, and include hypotension, headache, nausea and problems with vascular access, which the patient did not experience, perhaps due to the volumes used during pregnancy.

In conclusion, we report a case of a pregnant woman with HFH controlled with LDL apheresis, which involved a multidisciplinary approach and posed a therapeutic challenge given the lack of consensus documents on the use of this technique in pregnancy. The treatment regimen used is described, which was successful in our experience, with an adequate safety profile.

Key points

  • -

    Familial hypercholesterolaemia can pose a challenge in the therapeutic management of pregnant women.

  • -

    Double filtration is an extracorporeal procedure that selectively removes atherogenic components from plasma with an adequate safety profile.

  • -

    Therapeutic lipid apheresis can be considered part of the therapeutic arsenal in the management of familial hypercholesterolaemia in pregnant women.

References
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Pregnancy in women suffering from familial hypercholesterolemia: a harmful period for both mother and newborn?.
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Maternal cardiac metabolism in pregnancy.
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Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society.
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L Connelly-Smith, C Alquist, N Aqui, JC Hofmann, R Klingel, OA Onwuemen, et al.
Guidelines on the use of therapeutic apheresis in clinical practice - evidence-based approach from the writing committee of the American Society for Apheresis: the ninth special issue.
J Clin Apher, 38 (2023), pp. 77-278

Nephrologist specialising in “therapeutic apheresis” who advised us with regard to the apheresis guidelines.

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