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Immunohematological and Clinical Characterization of Complement and Non-Complement Associated Warm Autoimmune Haemolytic Anemia and Risk Factors Predicting their Occurrences

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Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Antigen – antibody complexes on heavily coated red cells in Warm autoimmune haemolytic anemia (WAIHA) often activates the complement pathway and red cells bound C3 complement component are encountered in complement associated WAIHA (CWAIHA). Patients belonging to CWAIHA and non-complement associated WAIHA (NCWAIHA) may demographically, clinically and immunohematologically behave differently therefore we planned to study the clinical and immunohematological characteristics of CWAIHA and NCWAIHA with emphasis to various potential factors associated with CWAIHA. The prospective study included 229 patients of WAIHA. Complete DAT evaluation was performed in all these patients. Details of patients and their hematological and biochemical parameters were obtained from patient file and Hospital Information System. In vivo hemolysis was documented as per the criteria established by previous workers. Statistical analysis was done using SPSS statistical package. Of the total 229 patients of WAIHA, 83 (36.2%) belonged to the complement associated WAIHA group. A total of 146 (63.8%) patients were females of which 43 (29.4%) had CWAIHA. The median age of WAIHA patients was 37 years. A total of 46 (56.1%) patients above age 40 years suffered from CWAIHA. Where secondary WAIHA was found in 121 (52.8%) patients; more than half (61.4%) with CWAIHA had underlying aetiology. Over 95% of patients in both categories presented with weakness and pallor. Strong DAT (> 2 +) was observed in 86.7% of CWAIHA patients. Factors like gender, age, aetiology and DAT IgG dilution were independent risk factors for CWAIHA. DAT remained positive even at the end of 10 months of successful treatment. We conclude that detailed characterization of WAIHA with particular emphasis to complement and non—complement associated WAIHA is essential to evaluate the disease characters, immunological behaviours, prognosis and therapeutic management. Moreover an understanding of the risk factors of CWAIHA will help physicians / hematologists and immunohematologists to manage WAIHA more prudently and solicitously.

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References

  1. Gehrs BC, Friedberg RC (2002) Autoimmune hemolytic anemia. Am J Hematol 69:258–271

    Article  PubMed  Google Scholar 

  2. Duffy TP (2002) Autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria Rossi’s principles of transfusion medicine. In: Simon TL, Dzik WH, Synder EL, Stowell Cpand Strauss RG 3rd (ed) Lippincott Williams and Wilkins publication, Philadelphia

  3. Sokol RJ, Hewitts S, Stamps BK (1981) Autoimmune hemolysis: an 18 years study of 865 cases referred to a regional transfusion center. Br Med J 282:2023–2027

    Article  CAS  Google Scholar 

  4. Petz LD, Garratty G (2003) Immune hemolytic anemias, 2nd edn. Curchill Livingstone, Newyork

    Google Scholar 

  5. Chaplin H Jr (1973) Clinical usefulness of specific antiglobulin reagents in autoimmune hemolytic anemias. Prog Hematol 7:25–49

    Google Scholar 

  6. Abramson N, Gelfand EW, Jandl JH, Rosen FS (1970) The interaction between human monocytes and red cells: specificity for IgG subclasses and IgG fragments. J Exp Med 132:1207–1215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gallagher MT, Branch DR, Mison A, Petz LD (1983) Evaluation of reticuloendothelial function in autoimmune hemolytic anemia using an in vitro assay of monocyte-macrophage interaction of erythrocytes. Exp Hematol 11:82–89

    CAS  PubMed  Google Scholar 

  8. Sokol RJ, Hewitt S, Booker DJ, Bailey A (1990) Red cell autoantibodies, multiple immunoglobulin classes, and autoimmune hemolysis. Transfusion 30:714–717

    Article  CAS  PubMed  Google Scholar 

  9. Jandl JH, Jones AR, Castle WB (1957) The destruction of red cells by antibodies in man. I. observations of the sequestration and lysis of red cells altered by immune mechanisms. J Clin Invest 36:1428–1459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jandl JH, Kaplan ME (1960) The destruction of red cells by antibodies in man. III. quantitative factors influencing the patterns of hemolysis in vivo. J Clin Invest 39:1145–1156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kurlander RJ, Rosse WF (1979) Monocyte-mediated destruction in the presence of serum of red cells coated with antibody. Blood 54:1131–1139

    Article  CAS  PubMed  Google Scholar 

  12. Schreiber AD, Frank MM (1972) Role of antibody and complement in the immune clearance and destruction of erythrocytes I. in vivo effects of IgG and IgM complement-fixing sites. J Clin Invest 51:575–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Meulenbroek EM, Wouters D, Zeerleder S (2014) Methods for quantitative detection of antibody-induced complement activation on red blood cells. J Vis Exp 83:e51161

    Google Scholar 

  14. Packman CH (2008) Hemolytic anemia due to warm autoantibodies. Blood Rev 22:17–31

    Article  CAS  PubMed  Google Scholar 

  15. Dacie J (1992) Auto-immune haemolytic anaemia (AIHA): pathogenesis. In: Dacie J (ed) The haemolytic anaemias. Churchill Livingstone

    Google Scholar 

  16. Abramson N, Gelfand EW, Jandl JH, Rosen FS (1970) The interaction between human monocytes and red cells. specificity for IgG subclasses and IgG fragments. J Exp Med 132:1207–1215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Product inserts; Cat-004041, Cat-004851, Cat-004043V, Cat-004033V, BIO-RAD /DiaMed GmbH, 1785 Cressier s/Morat, Switzerland

  18. Bercher ME (2005) The positive direct antiglobulin test and immune mediated red cell destruction. In: American Association of Blood Banks edition, Technical manual 15th ed. AABB, Bethesda, Maryland 453–482

  19. Das SS, Chaudhary R (2009) Utility of adsorption techniques in serological evaluation of AIHA in a hospital based transfusion service. Blood Transfusion 7:300–304

    PubMed  PubMed Central  Google Scholar 

  20. Wheeler CA, Calhoun L, Blackall DP (2004) Warm reactive autoantibodies: clinical and serological correlations. Am J Clin Pathol 122:680–685

    Article  PubMed  Google Scholar 

  21. Das SS, Zaman RU, Safi M (2014) Incompatible blood transfusion: Challenging yet lifesaving in the management of acute severe autoimmune hemolytic anemia. Asian J Transfus Sci 8:105–108

    Article  PubMed  PubMed Central  Google Scholar 

  22. Roved J, Westerdahl H, Hasselquist D (2017) Sex differences in immune responses: hormonal effects, antagonistic selection, and evolutionary consequences. Horm Behav 88:95–105

    Article  CAS  PubMed  Google Scholar 

  23. Giefing-Kröll C, Berger P, Lepperdinger G, Grubeck-Loebenstein B (2015) How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell 14:309–321

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Das SS, Nityanand S, Chaudhary R (2009) Clinical and serological characterization of autoimmune hemolytic anemia in a tertiary care hospital in North India. Ann Hematol 88:727–732

    Article  PubMed  Google Scholar 

  25. da Costa MG, Poppelaars F, Kooten CV, Mollnes TE, Tedesco F, Wurzner R, Trouw LA, Truedsson L, Daha MR, Roos A, Seelen M (2018) Age and sex-associated changes of complement activity and complement levels in a healthy caucasian population. Front Immunol 9:2664

    Article  CAS  Google Scholar 

  26. Bell CA, Zwicker H, Sacks HJ (1973) Autoimmune hemolytic anemia; routine serologic evaluation in a general hospital population. Am J Clin Pathol 60:903–911

    Article  CAS  PubMed  Google Scholar 

  27. Pirofsky B (1976) Clinical aspects of autoimmune hemolytic anemia. Semin hematol 13:251–265

    CAS  PubMed  Google Scholar 

  28. Naithani R, Agrawal N, Mahapatra M, Kumar R, Pati H, Choudhry VP (2007) Autoimmune hemolytic anemia in children. Pediatr Hematol Oncol 24:309–315

    Article  PubMed  Google Scholar 

  29. Van De Loosdrecht AA, Hendriks DW, Blom NR, Smit JW, De Wolf JT, Vellenga E (2000) Excessive apoptosis of bone marrow erythroblasts in a patient with autoimmune haemolytic anaemia with reticulocytopenia. Br J Haematol 108:313–315

    Article  Google Scholar 

  30. Ravetch J, Kinet JP (1991) Fc receptors. Annu Rev Immunol 9:457–492

    Article  CAS  PubMed  Google Scholar 

  31. Engelfriet CP, Overbreeke MAM, Vondem Borne AEG (1992) Autoimmune hemolytic anemia. Semin Hematol 22:3–12

    Google Scholar 

  32. Sokol RJ, Booker DJ, Stamps R (1992) The pathology of autoimmune hemolytic anemia. J Clin Pathol 45:1047–1052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Anderson CL, Looney RJ (1986) Human leukocyte IgG Fc receptors. Immunol Today 7:264

    Article  CAS  PubMed  Google Scholar 

  34. Das SS, Chaudhary RK (2007) Application of gel technology in the serologic characterization of autoantibody in DAT-positive autoimmune diseases. Immunohematology 23:59–62

    Article  CAS  PubMed  Google Scholar 

  35. Fabijańska-Mitek J, Lopieńska H, Zupańska B (1997) Gel test application for IgG subclass detection in auto-immune haemolytic anaemia. Vox Sang 72:233–237

    Article  PubMed  Google Scholar 

  36. Lai M, Leone G, Landolfi R (2013) Autoimmune hemolytic anemia with gel-based immunohematology tests. Am J Clin Pathol 139:457–463

    Article  CAS  PubMed  Google Scholar 

  37. Young PP, Uzieblo A, Trulock E, Lublin DM, Goodnough LT (2004) Autoantibody formation after alloimmunization: are blood transfusions a risk factor for autoimmune hemolytic anemia? Transfusion 44:67–72

    Article  PubMed  Google Scholar 

  38. Zhu JY, Lan JC, Hu LY, Meng QB, Luo HQ (2004) Study on blood ABO typing in patients with autoimmune hemolytic anemia. Zhongguo shi Yan Xue Ye Xue Za Zhi 12:525–527

    PubMed  Google Scholar 

  39. Petz LD (2004) A physician’s guide to transfusion in autoimmune hemolytic anemia. Br J Hematol 124:712–716

    Article  Google Scholar 

  40. Zeiler T, Müller JT, Hasse C, Kullmer J, Kretschmer V (2001) Flow cytometric determination of RBC survival in autoimmune hemolytic anemia. Transfusion 41:493–498

    Article  CAS  PubMed  Google Scholar 

  41. Shirey RS, Boyd JS, Parwani AV, Tanz WS, Ness PM, King KE (2002) Prophylactic antigen-matched donor blood for patients with warm autoantibodies: an algorithm for transfusion management. Transfusion 42:1435–1441

    Article  CAS  PubMed  Google Scholar 

  42. Rey Calero JD, de Lomas JG, Rodriguez JJV, Morillo OG, de Lomas EG, Rio DELA (1975) The activation of the complement system in various connective tissue diseases. Allergol Immunopathol (Madr) 3:431–444

    Google Scholar 

  43. Pickering M, Cook HT (2011) Complement and glomerular disease: new insights. Curr Opin Nephrol Hypertens 20:271–277

    Article  CAS  PubMed  Google Scholar 

  44. Karsten CM, Kohl J (2012) The immunoglobulin, IgG Fc receptor and complement triangle in autoimmune diseases. Immunobiology 217:1067–1079

    Article  CAS  PubMed  Google Scholar 

  45. Ricklin D, Lambris JD (2013) Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol 190:3831–3838

    Article  CAS  PubMed  Google Scholar 

  46. West EE, Afzali B, Kemper C (2018) Unexpected roles for intracellular complement in the regulation of Th1 responses. Adv Immunol 138:35–70

    Article  CAS  PubMed  Google Scholar 

  47. Liszewski MK, Elvington M, Kulkarni HS, Atkinson JP (2017) Complement’s hidden arsenal: new insights and novel functions inside the cell. Mol Immunol 84:2–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lenkiewicz A, Bujko K, Brzezniakiewicz-Janus K, Xu B, Ratajczak MZ (2019) The complement cascade as a mediator of human malignant hematopoietic cell trafficking. Front Immunol 10:1292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Fries LF, Brickman CM, Frank MM (1983) Monocyte receptors for the Fc portion of IgG increased in number in autoimmune hemolytic anemia and other hemolytic states and are decreased by glucocorticoid therapy. J immunol 131:1240–1245

    CAS  PubMed  Google Scholar 

  50. Gibson J (1988) Autoimmune hemolytic anemia: current concepts. Aust NZ J Med 18:625–637

    Article  CAS  Google Scholar 

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Correspondence to Sudipta Sekhar Das.

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Das, S.S., Chakrapani, A., Bhattacharya, S. et al. Immunohematological and Clinical Characterization of Complement and Non-Complement Associated Warm Autoimmune Haemolytic Anemia and Risk Factors Predicting their Occurrences. Indian J Hematol Blood Transfus 37, 623–631 (2021). https://doi.org/10.1007/s12288-021-01402-3

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