Patients with homozygous familial hypercholesterolaemia are optimally treated with low-density lipoprotein apheresis. Young patients who do not meet a weight threshold (25 kg) receive regular plasmapheresis. This approach may remove excessive immunoglobulins and vascular access set-up can be challenging. We report the case of a 4 year-old child who exhibited repeated septic infections (5 in 6 months) and had recurrent access issues before two interventions were implemented: (1) the percutaneous central venous line was modified to two implanted paediatric ports, and (2) the patient started receiving two bags of Octaplasma at the end of each plasmapheresis treatment to account for the excessive loss of immunoglobulins. For the paediatric plasmapheresis access port, a 19-gauge Huber needle had to be used for the arterial port to prevent the collapse of the extension. These two simple changes have left the patient infection-free for 9 months.