Difficulty of diagnostics and efficiency of pathogenetic therapy of paroxysmal nocturnal hemoglobinuria (clinical case)

Abstract

To show the features of the clinical picture of this orphan disease and demonstrate the effectiveness of a long-term pathogenetic treatment of this disease using the case history of a patient with paroxysmal nocturnal hemoglobinuria (PNH) as an example. Complaints, anamnesis, physical status, as well as laboratory and instrumental studies used for a patient with PNH were presented. Modern literature data on the diagnosis and treatment of PNH have been studied.

Complaints, anamnesis, physical status as well as laboratory and instrumental studies used for PNH patient were analyzed in comparison with the world literature data on this pathology.

A conclusion was made regarding the need for a wide coverage of the clinical picture and diagnosis of PNH. The effectiveness of a long-term (for 13 years) pathogenetic treatment of the classical form of PNH with eculizumab was shown.

Keywords

Complement system / paroxysmal nocturnal hemoglobinuria / complement-mediated hemolysis / anti-complement therapy / eculizumab / bioanalogs / monoclonal antibodies

References

[1] Bessler M., Mason P.J., Hillmen P., Miyata T., Yamada N., Takeda J., Luzzatto L., Kinoshita T. Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. EMBO J. 1994; 13 (1): 110–117.

[2] Takeda J., Kawagoe K., Iida Y., Endo Y., Fujita T., Takahashi M., Kitani T., Kinoshita T. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993; 73 (4): 703–711.

[3] Medof B.Y.M.E., Kinoshita T., Nussenzweig V. Inhibition of complement of cells after activation on the of incorporation (DAF) into their membranes a key step in complement activation on targets is the deposition of C4b and / or C3b fragments. These major cleavage products of C3 and C4 can associa. J. Exp. Med. 1984; 160: 1558–1578.

[4] Lublin D.M., Atkinson J.P. Decay-Accelerating Factor: Biochemistry, Molecular Biology, and Function. Annu. Rev. Immunol. 1989; 7 (1): 35–58.

[5] Rollins S.A., Sims P.J. The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b-9. J. Immunol. 1990; 144 (9): 3478 LP3483.

[6] Paroxysmal nocturnal hemoglobinuria: Clinical guidelines. Moscow 2021–2022–2023 (in Russian).

[7] Пароксизмальная ночная гемоглобинурия: клинические рекомендации. М. 2021–2022–2023.

[8] Kulagin A.D., Klimova O.U., Dobronravov A.V., Ivanova M.O., Rudakova T.A., Babenko E.V., Dobronravov V.A., Clinical manifestation and diagnostic errors of classical paroxysmal nocturnal hemoglobinuria: an analysis of 150 observations. Clinical Oncohematology 2017; 10 (3): 333–41 (in Russian).

[9] Кулагин А.Д., Климова О.У., Добронравов А.В., Иванова М.О., Рудакова Т.А., Бабенко Е.В., Добронравов В.А. Клиническая манифестация и ошибки диагностики классической пароксизмальной ночной гемоглобинурии: анализ 150 наблюдений. Клиническая онкогематология 2017; 10 (3): 333–41.

[10] Brodsky R.A. Stem cell transplantation for paroxysmal nocturnal hemoglobinuria. Br J Haematol. 2010; 95 (6): 855–856.

[11] de Latour R.P., Schrezenmeie H., Bacigalupo A., Blaise D., de Souza C.A., Vigouroux S., Willemze R., Terriou L., Tichell A., Mohty M., de Guibert S., Marsh J. C, Passweg J., Mary J.Y., Socié G. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica 2012; 97 (11): 1666–1673.

[12] de Latour R.P., Schrezenmeie H., Bacigalupo A., Blaise D., de Souza C. A, Vigouroux S., Willemze R., Terriou L., Tichell A., Mohty M., de Guibert S., Marsh J. C, Passweg J., Mary J.Y., Socié G. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica. 2012; 97 (11): 1666–1673.

[13] Peter Hillmen P., Elebute M., Kelly R., Urbano-Ispizua A., Hill A., Rothe R.P., Khursigara G., Fu C.L., Omin M. e, Browne P., l Rosse W. Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am. J. Hematol. 2010; 85 (8): 553–559.

RIGHTS & PERMISSIONS

Barlamov P.N., Vasilyeva E.R., Zholobov V.G.