Download PDF
Thromb Haemost 1984; 52(02): 196-200
DOI: 10.1055/s-0038-1661171
Original Article
Schattauer GmbH Stuttgart

Inherited Fibrinolytic Disorder Due to an Enhanced Plasminogen Activator Level

J Aznar
1   The Department of Clinical Pathology, “La Fe” Hospital, Valencia, Spain
,
A Estellés
2   The Research Center, “La Fe” Hospital, Valencia, Spain
,
V Vila
2   The Research Center, “La Fe” Hospital, Valencia, Spain
,
E Regañón
2   The Research Center, “La Fe” Hospital, Valencia, Spain
,
F España
2   The Research Center, “La Fe” Hospital, Valencia, Spain
,
P Villa
1   The Department of Clinical Pathology, “La Fe” Hospital, Valencia, Spain
› Author Affiliations
Further Information

Publication History

Received 27 March 1984

Accepted 10 July 1984

Publication Date:
19 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

A family with “in vitro” increased red-cell fall out from the blood clot was studied. One member of the family (JVM) had a clinical history of hemorrhages after minor trauma or dental extractions. Routine coagulation and platelet function were normal except for the fibrinogen level which was slightly low in several members. The antigenic as well as functional evaluation of factor XIII was within normal limits. No factor XIII inhibitors were present. An increase in the clot permeability index was observed in most family members.

The study of the fibrinolytic system showed an enhanced lysis of euglobulins, a normal plasminogen value, normal level of fibrin/ogen degradation products, normal fibrinolytic inhibitors, and an increase in the activity of the plasminogen activator. The activity of this activator was inhibited by an antiserum against tissue-type plasminogen activator. The t-pA inhibitor was in the normal range.

It is concluded that the family studied in this paper shows familial alteration in the fibrinolytic system due to an excess of plasminogen activator immunologically related to that in human tissue.

Keywords

Fibrinolytic hyperactivity - Tissue-type plasminogen activator - Familial hyperfibrinolysis
 

  • References

  • 1 Jacobsen CD. A family with low proteolytic capacity in plasma probably related to a low plasminogen content. Scand J Clin Lab Invest 1966; 18: 359-360
    CrossrefPubMedSearch in Google Scholar
  • 2 Aoki N, Moroi M, Sakata Y, Yoshida N, Matsuda M. Abnormal plasminogen. A hereditary molecular anormality found in a patient with recurrent thrombosis J Clin Invest 1978; 61: 1186-1195
    CrossrefPubMedSearch in Google Scholar
  • 3 Alexandre P, Larcan A, Briquel ME. Recurring thrombo-embolic accidents caused by family-related deficiency of the fibrinolysis system. Blut 1980; 41: 437-444
    CrossrefPubMedSearch in Google Scholar
  • 4 Johansson L, Hedner V, Nilsson IM. A family with thromboembolic disease associated with deficient fibrinolytic activity in vessel wall. Acta Med Scand 1978; 203: 477-480
    PubMedSearch in Google Scholar
  • 5 Jørgensen M, Mortensen JZ, Madsen AG, Thorsen S, Jacobsen B. A family with reduced plasminogen activator activity in blood associated with recurrent venous thrombosis. Scand J Haematol 1982; 29: 217-223
    PubMedSearch in Google Scholar
  • 6 Koie K, Kamiya T, Ogata K, Takamatsu J. α2-plasmin inhibitor deficiency (Miyasato Disease). Lancet 1978; 2: 1334-1336
    PubMedSearch in Google Scholar
  • 7 Aoki N, Saito H, Kamiya T, Koie K, Sakata Y, Kobakira M. Congenital deficiency of α2-plasmin inhibitor associated with severe hemorrhagic tendency. J Clin Invest 1979; 63: 877-884
    CrossrefPubMedSearch in Google Scholar
  • 8 Kluft C, Vellenga E, Brommer EJ P. Homozygous α2-antiplasmin deficiency. Lancet 1979; 2: 206
    PubMedSearch in Google Scholar
  • 9 Hampton JW, Oldham FB, Bannerjee D, Kalmaz E, Delaney R. Plasma activator of plasminogen: Cause of a familial bleeding diathesis. J Clin Invest 1972; 51: 42 (Abstr)
    PubMedSearch in Google Scholar
  • 10 Hampton JW, Weidenbach A, Skye GE, Rubenstein E, Taylor FB. Haemophilia: Modified by a post-exercise plasminogen activator. Thrombos Diathes Haemorrh 1975; 34: 612 (Abstr)
    PubMedSearch in Google Scholar
  • 11 Self J, Matthews C. Inherited fibrinolytic hyperactivity. Arch Intern Med 1968; 122: 857-858
    PubMedSearch in Google Scholar
  • 12 Booth NA, Bennett B, Wijngaards G, Grieve JH K. A new life-long hemorrhagic disorder due to excess plasminogen activator. Blood 1983; 61: 267-275
    PubMedSearch in Google Scholar
  • 13 Comp PC, Jacoeks RM, Rubenstein C, Radcliffe R. A lysine-adsorbable plasminogen activator is elevated in conditions associated with increased fibrinolytic activity. J Lab Clin Med 1981; 97: 645-647
    PubMedSearch in Google Scholar
  • 14 Wiman B, Mellbring G, Ranby M. Plasminogen activator release during venous stasis and exercise as determined by a new specific assay. Clin Chim Acta 1983; 127: 279-288
    CrossrefPubMedSearch in Google Scholar
  • 15 Aznar J, España F. Hageman trait. Thromb Haemostas 1978; 39: 234-235
    PubMedSearch in Google Scholar
  • 16 Aznar JA, España F, Aznar J, Tascón A, Jimenez C. Fletcher factor deficiency: report of a new family. Scand J Haematol 1978; 21: 94-98
    PubMedSearch in Google Scholar
  • 17 Saito H, Goodnough LT, Soria J, Soria C, Aznar J, España F. Heterogeneity of human prekallikrein deficiency (Fletcher trait). Evidence that five of 18 cases are positive for cross-reacting material N Engl J Med 1981; 305: 910-914
    CrossrefPubMedSearch in Google Scholar
  • 18 España F, Ratnoff OD. The role of prekallikrein and high molecular weight kininogen in the contact activation of Hageman factor (factor XII) by sulfatides and other agents. J Lab Clin Med 1983; 102: 487-499
    PubMedSearch in Google Scholar
  • 19 España F, Ratnoff OD. Activation of Hageman factor (factor XII) by sulfatides and other agents in the absence of plasma proteases. J Lab Clin Med 1983; 102: 31-45
    PubMedSearch in Google Scholar
  • 20 Harpel PC, Cooper NR. Studies on human plasma C1-inactivator-enzyme interactions. I. Mechanisms of interaction with C1s, plasmin and trypsin. J Clin Invest 1975; 55: 593-604
    CrossrefPubMedSearch in Google Scholar
  • 21 Hojima J, Pierce JV, Pisano JJ. Hageman factor fragment inhibitor in corn seeds: purification and characterization. Thromb Res 1980; 20: 149-162
    CrossrefPubMedSearch in Google Scholar
  • 22 Deutsch DG, Mertz ET. Plasminogen purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096
    CrossrefPubMedSearch in Google Scholar
  • 23 Born GV R. Aggregation of blood platelets by ADP and its reversal. Nature 1962; 194: 927-929
    PubMedSearch in Google Scholar
  • 24 España F, Aznar J. Factor XII (Hageman factor) purification and anti-Hageman antibodies production. Sangre 1978; 23: 393-401
    PubMedSearch in Google Scholar
  • 25 Stenberg P, Stenflo J. A rapid and specific fluorescent activity staining procedure for transamidating enzymes. Ann Biochem 1979; 93: 445-452
    CrossrefPubMedSearch in Google Scholar
  • 26 Laurell CB. Electroimmunoassay. Scand J Clin Lab Invest 1972; 29 (suppl) (Suppl. 124) 21-37
    CrossrefPubMedSearch in Google Scholar
  • 27 Godal HC, Ly B. An inhibitor of activated factor XIII, inhibiting fibrin cross-linking but not incorporation of amine into casein. Scand J Haematol 1977; 19: 443-448
    PubMedSearch in Google Scholar
  • 28 Low EM, Hill HB, Searcy RL. Simple method for detection of abnormal plasma fibrinogen levels. Am J Clin Pathol 1967; 47: 538-548
    CrossrefPubMedSearch in Google Scholar
  • 29 Aznar J, Tascon A, Aznar JA, Rodriguez A. Técnica rápida para la valoración del fibrinógeno por el método de precipitación al calor. Rev Diag Biol 1973; 22: 373-382
    PubMedSearch in Google Scholar
  • 30 Vila V, Regañón E, Aznar J. A method to determine the fibrinogen level of plasma. Haemostasis 1982; 12: 60 (Abstr)
    PubMedSearch in Google Scholar
  • 31 Regañón E, Vila V, Aznar J. Gelation of fibrinogen in plasma. A kinetic study by turbidity measurement Haemostasis 1984; 14: 170-178
    PubMedSearch in Google Scholar
  • 32 Lundblad RL, Kingdon HS, Maun KG. Blood clotting enzymes. In Methods in Enzymology 1976; 45: 156-176
    PubMedSearch in Google Scholar
  • 33 Hantgan RR, Hermans J. Assembly of fibrin. A light scattering study J Biol Chem 1979; 254: 11272-11281
    PubMedSearch in Google Scholar
  • 34 Vila V, Regañón E, Aznar J. Isolation of human fibrinogen using nitroblue tetrazolium (NBT). Clin Chim Acta 1984; 138: 215-219
    CrossrefPubMedSearch in Google Scholar
  • 35 Davies BJ. Disc electrophoresis. II. Method and application to human serum proteins. Ann N Y Acad Sci 1964; 121: 404-427
    PubMedSearch in Google Scholar
  • 36 Buckell M. The effect of citrate on euglobulin methods of estimating fibrinolytic activity. J Clin Pathol 1958; 11: 403-405
    CrossrefPubMedSearch in Google Scholar
  • 37 Highsmith RF, Burnett CJ, Weirich CJ. The interaction of Cl- Esterase inhibitor and plasmin human euglobulin. J Lab Clin Med 1979; 93: 459-471
    PubMedSearch in Google Scholar
  • 38 Bishop R, Ekert H, Gilchrist G, Shanbron E, Fekete L. The preparation and evaluation of a standardized fibrin plate for the assessment of fibrinolytic activity. Thromb Haemostas 1970; 23: 202-210
    PubMedSearch in Google Scholar
  • 39 Estellés A, Aznar J, Ortega C, Parrilla JJ, Vila V. Técnica para la valoración del plasminógeno humano por un método de inhibición de la hemaglutinación. Sangre 1975; 20: 358-365
    PubMedSearch in Google Scholar
  • 40 Wu JJ, Jacobsen CD, Hoak JC. Highly sensitive method for the assay for plasminogen. J Lab Clin Med 1973; 81: 484-488
    PubMedSearch in Google Scholar
  • 41 Friberger P, Knoss M, Gustavsson S, Aureli L, Claeson G. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis 1978; 7: 138-145
    PubMedSearch in Google Scholar
  • 42 Teger-Nilsson AC, Friberger P, Gyzander E. Determination of a new rapid plasmin inhibitor in human blood by means of a plasmin specific tripeptide substrate. Scand J Clin Lab Invest 1977; 37: 403-409
    CrossrefPubMedSearch in Google Scholar
  • 43 Mancini G, Carbonara AD, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 1965; 2: 235-254
    CrossrefPubMedSearch in Google Scholar
  • 44 Merskey C, Lalezari P, Johnson AJ. A rapid, simple, sensitive method for measuring fibrinolytic split products in human serum. Proc Soc Exp Biol Med 1969; 131: 871-875
    CrossrefPubMedSearch in Google Scholar
  • 45 Saito H. The participation of plasma thromboplastin antecedent (factor XI) in contact-activated fibrinolysis. Proc Soc Exp Biol Med 1980; 164: 153-157
    CrossrefPubMedSearch in Google Scholar
  • 46 Chmielewska J, Rånby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thromb Res 1983; 31: 427-436
    CrossrefPubMedSearch in Google Scholar
  • 47 Lipinska I, Lipinski B, Gurewich V. Fibrinogen heterogeneity in human plasma. Electrophoretic demonstration and characterization of two major fibrinogen components J Lab Clin Med 1974; 84: 509-516
    PubMedSearch in Google Scholar
  • 48 Ratnoff OD, Moneme V. Inhibition of ellagic acid-activated Hageman factor (factor XII) and Hageman factor fragment by popcorn inhibitor. Proc Soc Exp Biol Med 1981; 166: 297-299
    CrossrefPubMedSearch in Google Scholar
  • 49 Cohen D. On the regulation and control of fibrinolysis. Thromb Haemostas 1980; 43: 77-89
    PubMedSearch in Google Scholar
  • 50 Hoylaerts M, Rijken DC, Cohen D. Kinetic of the activation of plasminogen by human tissue plasminogen activator. J Biol Chem 1982; 257: 2912-2919
    PubMedSearch in Google Scholar