Low‐Density Lipoprotein Apheresis Decreases Ferritin, Transferrin and Vitamin B12, Which May Cause Anemia in Serially Treated Patients

Abstract

Clinical observations revealed an increased prevalence of iron deficiency anemia without chronic bleeding in patients treated with serial low-density lipoprotein (LDL) apheresis. Since several different proteins are adsorbed by LDL apheresis beside pro-atherogenic lipoproteins, we examined the modification of the full blood count, plasma iron, vitamin B12, folic acid, and hemolysis by LDL apheresis. Nineteen patients (55 (50-59) years, 4 female, 15 male) undergoing chronic LDL apheresis due to mixed dyslipidemia (N = 17), homozygous familiar hypercholesterolemia (N = 1) or isolated elevated lipoprotein(a) (N = 1) were included in this study. They were treated with direct adsorption of lipoproteins (DALI; N = 6), heparin-induced LDL-precipitation (HELP; N = 7) or double filtration plasmapheresis (DFPP; N = 6). The patients' full blood count, iron metabolism (plasma iron, ferritin, transferrin, transferrin saturation), vitamins involved in erythropoiesis (vitamin B12 and folic acid), and markers of hemolysis (haptoglobin and free hemoglobin) were analyzed directly before and after LDL apheresis. A single LDL apheresis session significantly decreased the levels (reduction in the median [25(th)-75(th) percentiles] of: ferritin 9.8 [1.3-18] %; P = 0.004), transferrin (12.1 [10.0-15.96] %; P = 0.0005), and vitamin B12 (17.8 [16.2-20.8] %; P = 0.0005). Thereby, transferrin and vitamin B12 were decreased in all (N = 19) and ferritin in 74% (N = 14) of the patients. Twelve out of 19 patients (63.2%) had mild anemia despite iron administration in 14 out of 19 patients (73.7%). LDL apheresis had no significant influence on full blood count, plasma iron, transferrin saturation, folic acid, or hemolysis. Similar changes were observed in all LDL apheresis methods used. LDL apheresis significantly decreases ferritin, transferrin, and vitamin B12, suggesting an influence of serial LDL apheresis on erythropoiesis.

Effects of different lipoprotein apheresis methods on serum protein levels

“…In contrast to data published by Bramlage et al [20] we saw a significantly lower decrease of transferrin by DALI when compared with the LF and HELP systems. On the other hand, the reduction pattern of ferritin was similar in both investigations (highest reduction by filtration methods).…”

Hematologic and hemostatic changes induced by different columns during LDL apheresis

“…A German research group has very recently demonstrated that regular LDL apheresis reduces ferritin and iron levels [28] and a community study has indicated that anemia increases the risk for development of cardiovascular disease [29]. Furthermore, anemia increases the mortality in acute coronary syndromes [30].…”

TIDILAP: Treatment of iron deficiency in lipoprotein apheresis patients – A prospective observational multi-center cohort study comparing efficacy, safety and tolerability of ferric gluconate with ferric carboxymaltose

“…(1) Blood loss due to blood remaining in the apheresis lines and repeated blood withdrawals (absolute ID) (2) Ferritin and transferrin loss though binding and removal with apheresis columns during LA (absolute ID) [5,6]. (3) Hemolysis during plasma separation or whole blood adsorption (absolute ID) (4) Anticoagulation in patients with history of cardiovascular events (absolute ID) [5].…”

“…(functional ID) [5]. (6) States of chronic inflammation (functional ID) (7) Insufficient dietary intake and/or absorption (absolute ID/functional ID)…”