Download PDF
Thromb Haemost 1982; 48(01): 027-032
DOI: 10.1055/s-0038-1657209
Original Article
Schattauer GmbH Stuttgart

Factor XII and Other Hemostatic Protein Abnormalities in Nephrotic Syndrome Patients

Arthur R Thompson
The Department of Medicine, University of Washington, the Seattle Public Health Hospital and the Puget Sound Blood Center, Seattle, Washington, U.S.A.
› Author Affiliations
Further Information

Publication History

Received 10 February 1982

Accepted 11 May 1982

Publication Date:
13 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Factor XII clotting activities and antigen levels were assayed in 14 plasma samples from 10 patients with nephrotic syndrome; the group was heterogeneous clinically and histologically. Factor XII was low at initial sampling in 7 of the 10 patients; in 7 of the 14 samples, factor XII antigen was in excess over clotting activity. Inhibition of factor XII could not be demonstrated; excess plasma antigen and urinary antigen (when present) had normal patterns on crossed-immunoelectrophoresis, indicating no major changes in charge or size. In 3 patients tested more than once, plasma levels of factor XII were increased up to 6fold in steroid-induced remission.

Of other hemostatic factors assessed for comparison, factor VIII was elevated in 11 of the 14 samples; eight of these had elevated factor VII levels as well. Eight samples from six patients showed low antithrombin III levels; one of these patients had recurrent thromboses. Antithrombin III levels correlated with the serum albumin concentration.

Only two of the eight urines tested had detectable factor XII antigen; a third had factor IX and prothrombin and no factor XII. Plasminogen and antithrombin III were readily demonstrated in all urine samples with higher concentrations in those patients with less selective proteinuria. Urinary and plasma levels were not correlated, suggesting that increased consumption or turnover was not simply related to increased filtration.

Keywords

Nephrotic syndrome - Hemostasis - Factor XII
 

  • References

  • 1 Handley DA, Lawrence JR. Factor IX deficiency in the nephrotic syndrome. Lancet 1967; 1: 1079-1081
    PubMedGoogle Scholar
  • 2 Natelson EA, Lynch EC, Hettig RA, Alfrey CP. Acquired factor IX deficiency in the nephrotic syndrome. Ann Intern Med 1970; 73: 373-378
    CrossrefPubMedGoogle Scholar
  • 3 Honig GR, Lindley A. Deficiency of Hageman factor (factor XII) in patients with the nephrotic syndrome. J Pediatr 1971; 78: 633-637
    CrossrefPubMedGoogle Scholar
  • 4 Hruby MA, Honig GR, Shapira E. Immunoquantitation of Hageman factor in urine and plasma of children with nephrotic syndrome. J Lab Clin Med 1980; 96: 501-510
    PubMedGoogle Scholar
  • 5 Saito H, Goodnough LT, Makker SP, Kallen RJ. Urinary excretion of Hageman factor (factor XII) and the presence of nonfunctional Hageman factor in the nephrotic syndrome. Am J Med 1981; 70: 531-534
    CrossrefPubMedGoogle Scholar
  • 6 Lange LG, Carvalho A, Bagdasarian A, Lahiri B, Colman RW. Activation of Hageman factor in the nephrotic syndrome. Am J Med 1974; 56: 565-569
    CrossrefPubMedGoogle Scholar
  • 7 Green D, Amida J, Honig G, Muehrcke RC. Urinary loss of clotting factors due to hereditary membranous glomerulopathy. Am J Clin Pathol 1976; 65: 376-383
    CrossrefPubMedGoogle Scholar
  • 8 van Royen EA, de Boer JEG, Wilmink JM, Jenkins CSP, ten Cate JW. Acquired factor XII deficiency in a patient with nephrotic syndrome. Acta Med Scand 1979; 205: 535-539
    PubMedGoogle Scholar
  • 9 Kanfer A, Kleinknecht D, Broyer M, Josso F. Coagulation studies in 45 cases of nephrotic syndrome without uremia. Thromb Haemostas 1970; 24: 562-571
    PubMedGoogle Scholar
  • 10 Thomson C, Forbes CD, Prentice CRM, Kennedy AC. Changes in blood coagulation and fibrinolysis in the nephrotic syndrome. Q J Med 1974; 43: 399-407
    PubMedGoogle Scholar
  • 11 Vaziri ND, Branson HE, Ness R. Changes of coagulation factors IX, VIII, VII, X and V in nephrotic syndrome. Am J Med Sci 1980; 280: 167-171
    CrossrefPubMedGoogle Scholar
  • 12 Thaler E, Balzar E, Kopsa H, Pinggera WF. Acquired antithrombin III deficiency in patients with glomerular proteinuria. Haemostasis 1978; 7: 257-272
    PubMedGoogle Scholar
  • 13 Kauffmann RH, Veltkamp JJ, van Tilburg NH, van Es LA. Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome. Am J Med 1978; 65: 607-613
    CrossrefPubMedGoogle Scholar
  • 14 Lau SO, Tkachuck JY, Hasegawa DK, Edson JR. Plasminogen and antithrombin III deficiencies in the childhood nephrotic syndrome associated with plasminogenuria and antithrombinuria. J Pediatr 1980; 96: 390-392
    CrossrefPubMedGoogle Scholar
  • 15 Thompson AR. Hemostatic proteins in nephrotic syndrome. Clin Res 1981; 29: 523A
    PubMedGoogle Scholar
  • 16 Thompson AR, Counts RB. Removal of heparin and protamine from plasma. J Lab Clin Med 1976; 88: 922-929
    PubMedGoogle Scholar
  • 17 Thompson AR. Factor IX antigen by radioimmunoassay: abnormal factor IX protein in patients on warfarin therapy and with hemophilia B. J Clin Invest 1977; 59: 900-910
    CrossrefPubMedGoogle Scholar
  • 18 Thompson AR. High affinity binding of human and bovine thrombins to p-chlorobenzylamido-ε-aminocaproyl agarose. Biochim Biophys Acta 1976; 422: 200-209
    CrossrefPubMedGoogle Scholar
  • 19 Bouma BN, Griffin JH. Human blood coagulation factor XI; purification, properties, and mechanism of activation by activated factor XII. J Biol Chem 1977; 252: 6432-6437
    PubMedGoogle Scholar
  • 20 Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Int J Immunochem 1965; 2: 235-254
    CrossrefPubMedGoogle Scholar
  • 21 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
    CrossrefPubMedGoogle Scholar
  • 22 Thompson AR, Enfield DL. Human plasma P component: isolation and characterization. Biochemistry 1978; 17: 4304-4311
    CrossrefPubMedGoogle Scholar
  • 23 Counts RB. Solid-phase immunoradiometric assay of factor VIII protein. Br J Haematol 1975; 31: 429-436
    CrossrefPubMedGoogle Scholar
  • 24 Bateman D, Gokal R, Prescott R, Hamilton PJ, Kerr DNS. Minimalchange glomerulonephritis associated with circulating anticoagulant to factor XII. Br Med J 1980; 281: 358
    PubMedGoogle Scholar
  • 25 Kallen RJ, Lee SK. A study of the plasma kinin-generating system in children with the minimal lesion, idiopathic nephrotic syndrome. Pediatr Res 1975; 9: 705-709
    CrossrefPubMedGoogle Scholar
  • 26 Bouissou F, Barthe P, Boneu B. Deficits acquis en facteur XII et antithrombine III (ATIII) dans les néphroses de l’enfant. Nouv Presse Méd 1980; 9: 25
    PubMedGoogle Scholar
  • 27 Sabatier JC, Croze M, Genin C, Gonthier R, Berthoux FC. Acquired factor XII (Hageman) deficiency associated with renal amyloidosis. Kidney Int 1980; 17: 705
    PubMedGoogle Scholar
  • 28 Glassock RJ. Management of the idiopathic nephrotic syndrome. Contrib Nephrol 1980; 23: 158-180
    PubMedGoogle Scholar
  • 29 Gordon EM, Donaldson VH, Saito H, Su E, Ratnoff OD. Reduced titers of Hageman factor (factor XII) in orientals. Ann Intern Med 1981; 95: 697-700
    CrossrefPubMedGoogle Scholar
  • 30 Saito H, Ratnoff OD, Pensky J. Radioimmunoassay of human Hageman factor (factor XII). J Lab Clin Med 1976; 88: 506-514
    PubMedGoogle Scholar
  • 31 Kendall AG, Lohmann RC, Dossetor JB. Nephrotic syndrome: A hypercoagulable state. Arch Intern Med 1971; 127: 1021-1027
    CrossrefPubMedGoogle Scholar
  • 32 Andrassy K, Ritz E, Bommer J. Hypercoagulability in the nephrotic syndrome. Klin Wochenschr 1980; 58: 1029-1036
    CrossrefPubMedGoogle Scholar
  • 33 Trew PA, Biava CG, Jacobs RP, Hopper J. Renal vein thrombosis in membranous glomerulonephropathy: incidence and association. Medicine (Baltimore) 1978; 57: 69-82
    CrossrefPubMedGoogle Scholar
  • 34 Llach F, Papper S, Massry SG. The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 1980; 69: 819-827
    CrossrefPubMedGoogle Scholar
  • 35 Adikari W, Coovadia HM, Greig HBW, Christensen S. Factor VIII procoagulant activity in children with nephrotic syndrome and poststreptococcal glomerulonephritis. Nephron 1978; 22: 301-305
    CrossrefPubMedGoogle Scholar
  • 36 Bernard D, Gouault-Heilmann M, Ansquer J-C, Levent M, Ladieu D, Lagrue G. Etude des facteurs de l’hémostase au cours des syndromes néphrotiques. Ann Méd Interne 1977; 128: 325-333
    PubMedGoogle Scholar
  • 37 Salem HH, Whitworth JA, Koutts J, Kincaid-Smith PS, Firkin BG. Hypercoagulation in glomerulonephritis. Br Med J 1981; 282: 2083-2085
    CrossrefPubMedGoogle Scholar
  • 38 Epstein O, Bevan G, Siddiqui N, Ardeman S. Factor VII deficiency associated with nephrotic syndrome. Br Med J 1976; 2: 1361
    CrossrefPubMedGoogle Scholar
  • 39 Jørgensen KA, Stoffersen E. Antithrombin III and the nephrotic syndrome. Scand J Haematol 1979; 22: 442-448
    PubMedGoogle Scholar
  • 40 Loirat C, Pillion G, Schlegel N, Douenias R, Mathieu H. Etude des proteines de la coagulation et de la fibrinolyse au cours des syndromes néphrotiques de l’enfant. Arch Fr Pediatr 1979; 36: 56-63
    PubMedGoogle Scholar
  • 41 Yoshida N, Aoki N. Release of arachidonic acid from human platelets. A key role for the potentiation of platelet aggregability in normal subjects as well as in those with nephrotic syndrome. Blood 1978; 52: 969-977
    PubMedGoogle Scholar
  • 42 Remuzzi G, Mecca G, Marchesi D, Livio M, de Gaetano G, Donati MB, Silver MJ. Platelet hyperaggregability and the nephrotic syndrome. Thromb Res 1979; 16: 345-354
    CrossrefPubMedGoogle Scholar
  • 43 Adler AJ, Lundin AP, Feinroth MV, Friedman EA, Berlyne GM. β-thromboglobulin levels in the nephrotic syndrome. Am J Med 1980; 69: 551-554
    CrossrefPubMedGoogle Scholar
  • 44 Shimojo N, Funae Y, Fujii S, Wada M. Gel filtration profile of plasma active and inactive renin in normals and patients with nephrotic syndrome. Clin Chim Acta 1981; 109: 345-349
    CrossrefPubMedGoogle Scholar
  • 45 Blumberg AL, Sealey JE, Atlas SA, Laragh JH, Dharmgrongartama B, Kaplan AP. Contact activation of human plasma prorenin in vitro. J Lab Clin Med 1981; 97: 771-778
    PubMedGoogle Scholar
  • 46 Colman RW, Wong PY. Participation of Hageman factor dependent pathways in human disease states. Thromb Haemostas 1977; 38: 751-775
    PubMedGoogle Scholar
  • 47 Saito H. Hageman factor (factor XII) in health and diseases. Acta Haematol Jpn 1981; 44: 1460-1465
    PubMedGoogle Scholar