Circulating Immune Complexes Pre and Post Clotting Factor Infusion in Hemophilia

Summary

Circulating immune complexes (CICs) were studied by the Raji cell radioimmune-assay (Raji-RIA) and C_lq-solid phase assay (C_lq-SPA) in sera samples obtained pre and post replacement infusion from 21 young hemophiliac patients (Mean age 9.5 years). Seven patients had repeat studies. Sixteen patients were selected randomly; the other five were selected as having potential infusion related disease processes. All patients had received multiple infusions prior to entering the study. Five patients were infused with FIX concentrates (2 Hemophilia B, one FVII deficiency, 2 with inhibitors to FVIII). Of the hemophilia A patients (13 severe; 3 mild/moderate), six were infused with ABO-Rh type specific cryoprecipitate and 10 were infused with factor concentrate. Preinfusion sera samples evaluated by the Raji-RIA showed 14 of 28 (50%) sera positive. Eleven of 28 (39.3 %) were positive post infusion in the Raji-RIA. Pre and post infusion studies of the same sera samples using the C_lq-SPA showed 5 of 28 (17.9%) positive pre-infusion and 4 of 28(14.3%) positive post infusion. No statistically significant relationship between pre and post infusion studies could be demonstrated.

There was no obvious correlation between CIC levels and patient age, race, Epe of infusate, ABO-Rh blood type, hepatosplenomegaly, the presence or absence of HBsAG, antibody, or chronic joint changes. CICs were detected in the three patients with SGOT/SGPT levels greater than 5 times normal, in both patients with chronic renal disease (chronic glomerulonephritis), and two children who had previously demonstrated a Coombs’-positive hemolytic anemia after factor concentrate infusion. Six of eight patients with extremely high levels of CICs had associated clinical or laboratory abnormalities.

This data indicated that CICs (as detected by the Raji-RIA) are present in increased frequency in hemophiliac patients. Although individual patients developed CICs post infusion, there is no clinical or statistical data supporting a common infusate immunogen. CICs were present in patients with serum hepatitis and other immune related disorders, probably secondary to factor infusion. The immunopathogenicity and origin of CICs in hemophiliacs is uncertain.

Keywords

Circulating immune complexes hemophilia

• References

• 1 Levine PH, McVerry BA, Hock A, Dormandy KM. Health of the intensively treated hemophilic with special reference to abnormal liver chemistries and splenomegaly. Blood 1977; 50: 1-9
• 2 Craske J, Spooner RJ D, Vandervelde EM. Evidence for existence of at least two types of factor-VUI-associated non-B transfusion hepatitis. Lancet 1978; 2: 1051-1052
• 3 Spero A, Lewis JH, Fisher SE, Hasiba U, Van Thiel DH. The high risk of chronic liver disease in multitransfused juvenile hemophiliac patients. J Pediatr 1979; 94: 875-878
• 4 Aronson DL. Therapeutic use of plasma proteins: Factor VIII (antihemophiliac globulin). Semin Thromb Hemostas 1979; 6: 12-27
• 5 Prager D, Djerassi J, Eyster ME, Gill FM, Kajani NK, Lewis JH, Lusch C, Rics S, Shapiro SS. Pennsylvania State-Wide Hemophilia Program: Summary of immediate reactions with the use of Factor VIII and Factor IX concentrate. Blood 1979; 56: 1012-1013
• 6 Verroust P, Verroust F, Adam C. Immunobiological studies in hemophilia: Complement levels and circulating immune complexes. XVIII Congress Int Soc Hematol. 1978
• 7 Hilgartner MW, Kelley B. Immune complex disease in hemophilia. Ped Res 1979; 13: V32
• 8 McVerry BA, Voke J, Mohammed I, Dormandy KM, Holborow EJ. Immune complexes and abnormal liver function in hemophilia. J Clin Pathol 1979; 30: 1142-1146
• 9 Theofilopoulos AN, Wilson CB, Dixon FJ. The Raji Cell assay for detecting immune complexes in human sera. J Clin Invest 1977; 57: 169-182
• 10 Hay FC, Nineham LJ, Roit IM. Routine assay for the detection of immune complexes of known immunoglobulin class using solid phase C_lq . Clin Exp Immunol 1976; 24: 296-400
• 11 Yonemasu K, Stroud RM C. rapid purification method for preparation of monospecific antisera and for biochemical studies. J Immunol 1971; 196: 304-313
• 12 Sokai RR, Rohif RJ. The principle and practice of statistics in biological research. San Francisco: W H Freeman & Co; 1969
• 13 Lambert PH, Dixon FJ, Zuble RH et al. A WHO collaborative study for the evaluation of eighteen methods of detecting immune complexes in serum. J Clin Lab Immunol 1978; 11: 1-15
• 14 Barnett EV, Knutson DW, Abrass CK, Chia DS, Young LS, Lieblin MR. Circulating immune complexes: Their immunochemistry detec-tion and importance. Ann Intern Med 1979; 91: 430-440
• 15 Prentice CR M, Izatt MM, Adams JF, McNicol GP, Douglas AS. Amyloidosis associated with the nephrotic syndrome and transfusion reactions in a hemophiliac. Br J Haematol 1971; 21: 305-308
• 16 Goudemand M, Delmar-Marsalet Y, Parquet-Gmz A, Habart-Lerach B. Limitation des fractions anti-hémophiliques d’origine animale dans l’hémophilie. Presse Med 1968; 5: 197-199
• 17 Rosati LA, Barnes B, Oberman HA, Penne J. Hemolytic anemia due to anti-A in concentrated antihemophiliac factor concentrates. Trans-fusion 1980; 10: 139-141
• 18 Seeler RA. Hemolysis due to anti-A and anti-B in Factor VIII preparation. Arch Intern Med 1972; 130: 101-103