Hidden relationship between fingolimod and bleeding: Possible novel management of fingolimod-associated lymphopenia

Akira Hanazono; Yui Sanpei; Sachiko Kamada; Masashiro Sugawara; Katsunori Iijima

doi:10.1016/j.mehy.2020.109635

Hidden relationship between fingolimod and bleeding: Possible novel management of fingolimod-associated lymphopenia

Med Hypotheses. 2020 Feb 17:140:109635. doi: 10.1016/j.mehy.2020.109635. Online ahead of print.

Authors

Akira Hanazono¹, Yui Sanpei², Sachiko Kamada², Masashiro Sugawara², Katsunori Iijima²

Affiliations

¹ Akita University Graduate School of Medicine, Department of Neurology, 1-1-1 Hondo, Akita 010-8543, Japan. Electronic address: hanazono@doc.med.akita-u.ac.jp.
² Akita University Graduate School of Medicine, Department of Neurology, 1-1-1 Hondo, Akita 010-8543, Japan.

PMID: 32092561
DOI: 10.1016/j.mehy.2020.109635

Abstract

Fingolimod, a functional antagonist of sphingosine-1 phosphate receptor, is a disease modifying drug of multiple sclerosis and its remarkable adverse effect is peripheral lymphopenia because the drug retains lymphocyte in the secondary lymphoid tissues. Therefore, in theory, when severe bleedings occurred, the fingolimod-treated patients could not compensate for the loss of lymphocytes induced by bleedings because of the retention in the secondary lymphoid tissues. In addition, because most of the fingolimod is reported to be distributed in the erythrocytes, and the erythrocytes are the main regulator of serum sphingosine-1 phosphate concentration, bleeding may also affect metabolism of fingolimod and prognosis of multiple sclerosis. However, no study had focused the relationship between fingolimod and bleedings in multiple sclerosis. We encountered the first case in which fingolimod-associated lymphopenia worsened synchronously with gynecological bleeding, and was improved by the bleeding prophylaxis, uterine myomectomy. This case had statistically significant positive correlation between the serum hemoglobin level and peripheral lymphocyte count (P = 0.0000000507). We then had three similar cases. In these 4 correlative patients out of the 14 fingolimod-treated patients in our institution, the importance of the bleeding in fingolimod-treated patients was indicated by line graphs, point diagrams, and statistically significant correlation coefficients. Bleeding should be focused on by all of physicians treating multiple sclerosis with fingolimod.