ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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УЖМБС 2018, 3(4): 212–219
https://doi.org/10.26693/jmbs03.04.212
Biology

Autoimmune Hemolisis in the Patients with B-Cell Non-Hodgkin Lymphomas

Tymoshenko U. V., Myronenko G. A., Sivkovych S. O., Pavlyuk R. P.
Abstract

Autoimmune hemolytic anemia (AIHA) can complicate B-cell non-Hodgkin's lymphomas. It can develop as a consequence of the oncological process and may be a complication of drug therapy. Hemolysis is able to inhibit the C1q component of complement and affect the effectiveness of rituxim therapy. The purpose of the study was to determine the frequency of autoimmune anti-erythrocyte antibodies and laboratory signs of hemolysis (levels of free hemoglobin, haptoglobin and indirect bilirubin) in patients with B-NHL, depending on the stage of the disease and the regimen of therapy. Materials and methods. 57 patients with B-NHL were divided into 3 groups. The group I included those who did not receive specific therapy, group II – who received CHOP, CHOEP, COP or FC, group III – R-CHOP, R-CHOEP, R-COP, R-FC. Anti-erythrocyte autoimmune antibodies, levels of free hemoglobin (fHb), haptoglobin (Hp), indirect bilirubin were tested in patients’ venous blood. Elevated level of fHb and reduced of Hp are markers of intravascular hemolysis, and elevated levels of indirect bilirubin is marker of extravascular one. Results and discussion. Antibodies were detected in 42.9% of patients of group II. IgG / C3 were detected in 28,6% of ones, cold agglutinin – 7,1%, acidic haemolysins – 21.4%, C3d and / or C3c – 14.3%. Antibodies were found in 12.9% of the patients of group III: IgG – 3,2%, acid haemolysins – 6,4%, C3d and / or C3c – 3,2% (many patients showed several serological types). In I group antibodies were detected in 16,7% (IgG – 8,3%, acid haemolysins also in 8,3%). Laboratory signs of intra- and extravascular hemolysis and decreased hemoglobin levels were found in the vast majority of patients of group II. Patients of group I and group III had signs of extravascular hemolysis. The majority of patients with autoimmune anti-erythrocyte antibodies and with stage III of the disease were in the group II. The majority of patients with stage I were in groups I and III. Conclusions. Rituxim therapy reduced the frequency of autoimmune hemolytic complications. No signs of extrasvascular hemolysis were found in patients taking rituxim. Rituxim prevented the progression of the disease.

Keywords: anti-erythrocyte autoimmune antibodies, haptoglobin, free hemoglobin, indirect bilirubin

Full text: PDF (Rus) 235K

References
  1. Anoshina MY, Goryaіnova NV, Tretyak NM, Basova OV. Funktsіonal'nii stan gemoglobіnu u hvorih na gostru mіyeloidnu leikemіyu. In: Tretyak NM editor. Proceedings of the Malignant diseases of the blood and lymphoid tissue system: achievements and prospects. 2013 Oct 10-11; Kyiv. Kyiv UA: TOV "Zіrka"; 2013. p. 22-3. [Ukrainian]
  2. Patent 99298 Ukraine. Sposіb viznachennya monofaznih avtoіmunnih kislotnih teplovih ta holodovih gemolіzinіv mіkrometodom / Pavliuk RP, Timoshenko UV, Mironenko GA, Lavrovs'ka LN. (UA); zayavnik i vlasnik patentu State institution “Institute of haematology and transfusiology NAMS Ukraine”, patentovlasnyk. opubl 25.05.2015. Byul № 7. [Ukrainian]
  3. Anderson LA, Gadalla S, Morton LM, Landgren O, Pfeiffer R, Warren JL, et al. Population-based study of autoimmune conditions and the risk or specific lymphoid malignancies. Int J Cancer [Internet]. 2009 Jan [cited 2017 Jul 07]; 125: 398-405. https://www.ncbi.nlm.nih.gov/pmc/articles/2692814. https://doi.org/10.1002/ijc.24287
  4. Balla G, Lakatos L, Balla J. Effects of free hemoglobin in human pathologies. ECNE. 2017 Apr 06; 5 (5): 181-3.
  5. Barcellini W, Fattizzo B. Clinical applications of hemolytic markers in the differential diagnosis and management of hemolytic anemia. Disease Markers [Internet]. 2015 Dec [cited 2017 Jul 06]; 2015: 1-7. https://doi.org/10.1155/2015/635670
  6. Borthacur G, O`Brien S, Wierda WG, Thomas DA, Cortes JE, Giles FG, et al. Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab – incidence and predictors. Br J Haematol. 2007 Mar 2; 136: 800-5. https://doi.org/10.1111/j.1365-2141.2007.06513.x
  7. Brig RS Sarkar, Col J Philip, Surg Cdr RS Mallhi, Neelesh J. Drug-induced immune hemolytic anemia (Direct Antiglobulin Test positive). MJAFI. 2012 Aug 4; 69: 190-2. https://doi.org/10.1016/j.mjafi.2012.04.017
  8. Dati F, Lammers M, Adam A, Sondag D, Stienen L. Referenzwerte für 18 Plasmaproteine am Behring-Nephelometer-System. Lab Med. 1989; 13: 87-90. https://doi.org/10.1515/labm.1989.13.3.87
  9. Garraty G. Drug-indused immune hemolytic anemia. Hematology. 2009 Jan 1; 2009 (1): 73-9. https://doi.org/10.1182/asheducation-2009.1.73
  10. Haddad H, Mohammad F, Dai Q. Bendamustine-indused immune hemolytic anemia in a chronic lymphocytic leukemia patient: A case report and review of the literature. Hematol Oncol Stem Cell Ther. 2014 Jan 11; 7 (4): 162-4. https://doi.org/10.1016/j.hemonc.2014.04.001
  11. Johnson ST, Fueger JT, Gottschall JL. One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia – a new paradigm. Transfusion. 2007 Mar 2; 47 (4): 697-702. https://doi.org/10.1111/j.1537-2995.2007.01173.x
  12. Khosroshahi BN, Jafari M, Vazini H, Ahmadi A, Shams K, Kholoujini M. Cold autoimmune hemolytic anemia due to high-grade non Hodgkin’s B-cell lymphoma with weak response to rituximab and chemotherapy regimens. IJHOSCR. 2015 Jul 1; 9 (3): 157-60. https://www.ncbi.nlm.nih.gov/pubmed/26261701
  13. Longinotti M, Fozza C. Use of Rituximab in autoimmune hemolytic anemia associated with non-Hodgkin lymphomas. Advances in Hematology [Internet]. 2011 Feb [cited 2017 Jul 07]; 2011: 1-4. https://doi.org/10.1155/2011/960137
  14. Rifkind JM, Mohanty JG, Nagabadu E. The pathophysiology of extracellular hemoglobin associated with enhanced oxidative reactions. Front Physiol. 2015 Jan 14; 5 (500): 1-7. https://doi.org/10.3389/fphys.2014.00500
  15. Roumenina L, Radanova M, Atanasov BP, Popov KT, Kaveri SV, Lacroix-Desmazes S, et al. Heme interacts with C1q and inhibits the classical complement pathway. JBC. 2011 Mar 1; 286 (18): 16459-69. https://doi.org/10.1074/jbc.M110.206136.
  16. Sallah S, Sigounas G, Vos P, Wan JY, Nguyen NP. Autoimmune hemolytic anemia in patients with non-Hodgkin’s lymphoma: Characteristics and significance. Annals of Oncology. 2000 Dec; 11: 1571-7. https://www.ncbi.nlm.nih.gov/pubmed/11205465. https://doi.org/10.1023/A:1008319532359
  17. Smedby KE, Vajdic CM, Falster M, Engels EA, Martinez-Maza O, Turner J, et al. Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooler analysis within the InterLymph Consortium. Blood. 2008 Jan 25; 111 (8): 4029-38. https://doi.org/10.14740/jh303w
  18. Song J, Dormosh M, Ayres J, Swami V. A case of diffuse large B cell Lymphoma presenting as cold agglutinin disease. The internet Journal of Hematology [Internet]. 2013 [cited 2017 Jul 07]; 9 (1): 1-5. Available from: http://ispub.com/IJHE/9/1/144
  19. Sudulagunta SR, Kumbhat M, Sodalagunta MB, Nataraju AS, Bangalore Raja SK, Thejaswi KC, et al. Warm autoimmune hemolytic anemia: clinical profile and management. J Hematol. 2017 Nov 04; 6 (1): 12-20. https://doi.org/10.14740/jh303w
  20. Tietz NW, Pruden EL, McPherson RA, Fuhrman SA. Clinical guide to laboratory tests. 3rd ed. Philadelphia: W.B. Saunders Company; 1983. 695 p.
  21. Yamashita T, Ishida M, Moro H, Yumoto H, Uchibayashi S, Yoshii M, et al. Primary bone marrow diffuse large B-cell lymphoma accompanying cold agglutinin disease: A case report with review of the literature. Oncology letters. 2013 Nov 21; 7: 79-81. https://doi.org/10.3892/ol.2013.1695