Factor XII, Plasma Prekallikrein, α₂-Macroglobulin and C1-Inhibitor Levels in Renal Allograft Recipients During Immunosuppression with Cyclosporin A – Sequential Measurements over Four Months in 17 Patients

Summary

Factor XII clotting activity (F XII), plasma prekallikrein amidolytic activity (PK), α₂-Macroglobulin (α₂-M) and C1-Inhibitor (C1-Inh) antigens have been measured in 17 patients immediately before and sequentially for up to four months after kidney transplantation. Before transplantation mean F XII and PK levels were normal (99 ± 27% and 102 ± 21%, respectively, mean ± S. D.) and α₂-M and C1-Inh levels were slightly elevated (115 ± 55% and 129 ± 32%, respectively, mean ± S. D.). In the first two weeks after transplantation a significant decrease of F XII to 65 ± 27%, of PK to 67 ± 20% and of α₂-M to 88 ± 42%, and a rise of C1-Inh to 201 ± 44% (mean ± S. D.) were observed (2 p <0.005). F XII levels four month after operation remained significantly (2 p <0.05) lower than preoperatively. PK and α₂-M values, however, were significantly higher (2 p <0.05) at four months as compared to the pretransplant period. Mean F XII levels in the 17 patients at various time points after transplantation correlated positively with PK, α₂-M and serum albumin and negatively with CyA level and dose and serum bilirubin. PK and α₂-M correlated positively with each other and albumin and negatively with creatinine, bilirubin and CyA (2 p <0.01). Whether CyA has a direct influence on production or consumption of F XII, PK, α₂-M and C1-Inh, or whether the changes merely reflect altered protein metabolism awaits further study.

Keywords

Factor XII - Plasma prekallikrein - α₂-Macroglobulin - C1-Inhibitor - Kidney transplantation - Cyclosporin A

• References

• 1 Caine RY, White D JG, Thiru S, Evans DB, McMaster P, Dunn DC, Craddock GN, Pentlow BD, Rolles K. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet 1978; II: 1323-1327
• 2 Bonser RS, Adu D, Franklin I, McMaster P. Cyclosporin-induced haemolytic uraemic syndrome in liver allograft recipient. Lancet (letter) 1984; II: 1337
• 3 Mihatsch MJ, Thiel G, Spichtin HP, Oberholzer M, Brunner FP, Harder E, Olivieri V, Bremer R, Ryffel B, Stoecklin E, Torhorst J, Gudat F, Zollinger HU, Loertscher R. Morphological findings in kidney transplants after treatment with cyclosporine. Transplant Proc 1983; 15 Suppl. [phone]
• 4 Kaplan BS, Drummond KN. The hemolytic-uremic syndrome is a syndrome. N Engl J Med 1978; 298: 964-966
• 5 Goldstein MH, Churg J, Strauss L, Gribetz D. Hemolytic-uremic syndrome. Nephron 1979; 23: 263-272
• 6 Neild GH, Rocchi G, Imberti L, Fumagalli F, Brown Z, Remuzzi G, Williams DG. Effect of Cyclosporin A on prostacyclin synthesis by vascular tissue. Thromb Res 1983; 32: 373-379
• 7 Huser B, Lämmle B, Tran TH, Oberholzer M, Thiel G, Duckert F. Hämostase-Kriterien bei Nierentransplantatträgern. Vergleich zwischen Patienten unter Immunsuppression mit Ciclosporin bzw. Azathioprin/Steroiden. Schweiz Med Wschr 1984; 114: 1149-1154
• 8 Cochrane CG, Griffin JH. The biochemistry and pathophysiology of the contact system of plasma. Advances in Immunology 1982; 33: 241-306
• 9 Colman RW. Surface-mediated defense reactions. The plasma contact activation system. J Clin Invest 1984; 73: 1249-1253
• 10 Schapira M, Agostini Arianede, Schifferli JA, Colman RW. Biochemistry and pathophysiology of human Cl-Inhibitor. Complement 1985; 2: 111-126
• 11 Van der Graaf F, Koedam JA, Bouma BN. Inactivation of kallikrein in human plasma. J Clin Invest 1983; 71: 149-158
• 12 Agostini Ade, Lijnen HR, Pixley RA, Colman RW, Schapira M. Inactivation of Factor XII active fragments in normal plasma. Predominant role of Cl-Inhibitor. J Clin Invest 1984; 73: 1542-1549
• 13 Pixley RA, Schapira M, Colman RW. The regulation of human Factor XIIa by plasma proteinase inhibitors. J Biol Chem 1985; 260: 1723-1729
• 14 Donatsch P, Abisch E, Homberger M, Traber R, Trapp M, Voges R. A radioimmunoassay to measure Cyclosporin A in plasma and serum samples. Immunoassay 1981; 2: 19-32
• 15 Proctor RR, Rapaport SI. The partial thromboplastin time with kaolin. A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Path 1961; 36: 212-219
• 16 Lammle B, Tran TH, Duckert F. Assay of Factor XII clotting activity in heparinized plasma. Am J Clin Path 1983; 80: 474-477
• 17 Gallimore MJ, Friberger P. Simple chromogenic peptide substrate assays for determining prekallikrein, kallikrein inhibition and kallikrein “like” activity in human plasma. Thromb Res 1982; 25: 293-298
• 18 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
• 19 Lammle B, Tran TH, Ritz R, Duckert F. Plasma prekallikrein. Factor XII, Antithrombin III, Cl-Inhibitor and a-2-Macroglobulin in critically ill patients with suspected disseminated intravascular coagulation (DIC). Am J Clin Pathol 1984; 82: 396-404
• 20 Dixon W, Brown MB. (Eds.) Biomedical computer programs (BMDP). University of California press; Los Angeles: 1981
• 21 Glassner GJ, Winter RF. Critical values of rank correlation for testing the hypothesis of independence. Biometrika 1961; 48: 444-448
• 22 Vaziri ND, Toohey J, Paule P, Alikhani S, Hung E. Effect of hemodialysis on contact group of coagulation factors, platelets, and leukocytes. Am J Med 1984; 77: 437-441
• 23 Deutsch E, Dragosics B, Kopsa H, Mannhalter Ch, Rainer H. Prekallikrein, HMW-Kininogen and Factor XII in various disease states. Thromb Res 1983; 31: 351-364
• 24 Mannhalter Ch, Deutsch E, Kopsa H. Clotting activities and antigen concentrations of contact factors in kidney disease. Thromb Res 1985; 39: 475-484
• 25 Ragni MV, Lewis JH, Hasiba U, Spero JA. Prekallikrein (Fletcher factor) deficiency in clinical disease states. Thromb Res 1980; 18: 45-54
• 26 Christe M, Fritschi J, Lammle B, Tran TH, Marbet GA, Berger W, Duckert F. Fifteen coagulation and fibrinolysis parameters in diabetes mellitus and in patients with vasculopathy. Thromb Haemostas 1984; 52: 138-143
• 27 Christe M, Gattlen P, Fritschi J, Lammle B, Berger W, Marbet GA, Duckert F. The contact phase of blood coagulation in diabetes mellitus and in patients with vasculopathy. Thromb Haemostas 1984; 52: 221-223
• 28 Hedner U, Martinsson G, Bergqvist D. Influence of operative trauma on Factor XII and inhibitor of plasminogen activator. Haemostasis 1983; 13: 219-226
• 29 Lortscher R, Wenk M, Harder F, Brunner F, Follath F, Thiel G. Hyperbilirubinaemia and Cyclosporin A levels in renal transplant patients. Lancet (letter) 1981; II: 635-636
• 30 Graffenried von B, Krupp P. Nebenwirkungen von Ciclosporin nach Nierentransplantation und bei Patienten mit Autoimmunerkrankungen. Internist 1985; 26: 542-548
• 31 Klintmalm G BG, Iwatsuki S, Starzl TE. Cyclosporin A hepatotoxic-ity in 66 renal allograft recipients. Transplantation 1981; 32: 488-489
• 32 Saito H, Poon MC, Vicic W, Goldsmith GH, Menitove JE. Human plasma prekallikrein (Fletcher factor) clotting activity and antigen in health and disease. J Lab Clin Med 1978; 92: 84-95
• 33 Bruhn HD, Briick M, Albert JP. Plasma prekallikrein in hypertension. Acta Chir Scand (Suppl.) 1982; 509: 133-135
• 34 Walker IR, Milner RA, Johnston MA, Rand CA, Neame PB, Hirsh J. Factors XI and XII are low in subjects with liver disease. Dig Dis Sc 1983; 28: 967-970
• 35 Cordova C, Musca A, Violi F, Alessandri C, Ferro D, Piromalli A, Balsano F. Prekallikrein behaviour in chronic active hepatitis and in cirrhotic patients. Haemostasis 1984; 14: 218-222
• 36 Bodmer JL, Schnehli HP. Plasma proteinase inhibitors. Schweiz Med Wschr 1984; 114: 1359-1363
• 37 Crockson RA, Payne CJ, Ratcliff AP, Soothill JF. Time sequence of acute phase reactive proteins following surgical trauma. Clin Chim Acta 1966; 14: 435-441