Thromb Haemost 1998; 80(01): 167-170
DOI: 10.1055/s-0037-1615157
Rapid Communication
Schattauer GmbH

Is Plasminogen Deficiency a Thrombotic Risk Factor ? – A Study on 23 Thrombophilic Patients and their Family Members

F. Demarmels Biasiutti
From the Central Hematology Laboratory, University Hospital, Inselspital Bern, Switzerland
,
I. Sulzer
From the Central Hematology Laboratory, University Hospital, Inselspital Bern, Switzerland
,
B. Stucki
From the Central Hematology Laboratory, University Hospital, Inselspital Bern, Switzerland
,
W. A. Wuillemin
From the Central Hematology Laboratory, University Hospital, Inselspital Bern, Switzerland
,
M. Furlan
From the Central Hematology Laboratory, University Hospital, Inselspital Bern, Switzerland
,
B. Lämmle
From the Central Hematology Laboratory, University Hospital, Inselspital Bern, Switzerland
› Author Affiliations
Further Information

Publication History

Received 23 December 1997

Accepted 05 March 1998

Publication Date:
08 December 2017 (online)

Summary

The role of plasminogen (plg) deficiency in the pathogenesis of venous thromboembolism is debated in the literature. In the present study we evaluated the prevalence of plg deficiency in our thrombophilia patients and aimed to elucidate the thrombosis risk of plg deficiency as a single defect or in combination with other defects, with special focus on APC resistance.

The study cohort included 1192 consecutive patients with a history of clinically or objectively diagnosed venous and/or arterial thromboembolism and/or positive family history who were referred to our department for thrombophilia investigation from 02/1988 to 03/1997. All available family members of patients with plg deficiency were tested for plg, APC resistance and other thrombophilic defects that were established in the propositus.

23/1192 propositi were plg-deficient corresponding to an overall prevalence of 1.9%, i.e. 2.2% in patients with venous thrombosis and 1.4% in those with arterial events. Out of the 23 plg-deficient propositi, 8 showed one or multiple additional thrombophilic defects, and in 4 patients relevant circumstantial risk factors were present. Of the 53 available family members, 28 were plg-deficient including 5 with additional APC resistance, and 4 subjects had isolated APC resistance. Ten of the 53 family members had already suffered thromboembolic events, i.e. 5 (18%) in the plg-deficient group and 5 (20%) in the non-deficient group, both groups showing an almost identical median age at the time of investigation (28.9 years and 27.1 years, respectively).

Based on our data, plg deficiency is a rare defect in thrombophilic patients and as a single defect it does not seem to be a strong thrombotic risk factor, as 11 of 23 propositi had additional thrombophilic defects or circumstantial risk factors, and in the family members thrombotic events were equally frequent in the plg-deficient and non-deficient subjects.

 
  • References

  • 1 Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V, Chandy M, Dahlbäck B, Ginter EK, Miletich JP, Rosendaal FR, Seligsohn U. Inherited thrombophilia: part 1. Thromb Haemost 1996; 76: 651-62.
  • 2 Francis Jr. RB. Clinical disorders of fibrinolysis: a critical review. Blut 1989; 9: 1-14.
  • 3 Nilsson IM, Ljungner H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: Low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-5.
  • 4 Tait RC, Walker ID, Islam SIA, Mitchell R, Davidson JF. Plasminogen levels and putative prevalence of deficiency in 400 blood donors. Br J Haematol 1991; 77 (01) 10 (Abstr).
  • 5 Beck KH, Walter-Fincke R, Hach V, Scharrer I. Incidence of protein C deficiency in 132 juvenile thrombosis patients in comparison with other inherited fibrinolysis disorders. Thromb Haemost 1985; 54: 142 (Abstr).
  • 6 Heijboer H, Brandjes DPM, Büller HR, Sturk A, ten Cate JW. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep vein thrombosis. N Engl J Med 1990; 323: 1512-6.
  • 7 Hasegawa DK, Tyler BJ, Edson JR. Thrombotic disease in three families with inherited plasminogen deficiency. Blood (S 1) 1982; 60: 213a (Abstr).
  • 8 Aoki N, Moroi M, Sakata Y, Yoshida N, Matsuda M. Abnormal plasminogen. J Clin Invest 1978; 61: 1186-95.
  • 9 Leebeek FWG, Knot EAR, ten Cate JW, Traas DW. Severe thrombotic tendency with a type I plasminogen deficiency. Am J Hematol 1989; 30: 32-5.
  • 10 Girolami A, Marafioti F, Rubertelli M, Cappellato MG. Congenital heterozygous plasminogen deficiency associated with a severe thrombotic tendency. Acta haemat 1986; 75: 54-7.
  • 11 Sartori MT, Patrassi GM, Theodoridis P, Perin A, Pietrogrande F, Girolami A. Heterozygous type I plasminogen deficiency is associated with an increased risk for thrombosis: a statistical analysis in 20 kindreds. Blood Coag Fibrinol 1994; 5: 889-93.
  • 12 Kazama M, Tahara C, Suzuki Z, Gohchi K, Abe T. Abnormal plasminogen, a case of recurrent thrombosis. Thromb Res 1981; 21: 517-22.
  • 13 Dolan G, Greaves M, Cooper P, Preston FE. Thrombovascular disease and familial plasminogen deficiency: a report of three kindreds. Br J Haematol 1988; 70: 417-421.
  • 14 Hach-Wunderle V, Scharrer I, Lottenberg R. Congenital deficiency of plasminogen and its relationship to venous thrombosis. Thromb Haemost 1988; 59: 277-80.
  • 15 Shigekiyo T, Uno Y, Tomonari A, Satoh K, Hondo H, Ueda S, Saito S. Type I congenital plasminogen deficiency is not a risk factor for thrombosis. Thromb Haemost 1992; 67: 189-92.
  • 16 Tait RC, Walker ID, Conkie JA, Islam IAM, McCall F. Isolated familial plasminogen deficiency may not be a risk factor for thrombosis. Thromb Haemost 1996; 76: 1004-8.
  • 17 Schuster V, Mingers A-M, Seidenspinner S, Nüssgens Z, Pukrop T, Kreth HW. Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis. Blood 1997; 90: 958-66.
  • 18 Ploplis VA, Carmeliet P, Vazirzadeh S, Vanvlaenderen I, Moons L, Plow EF, Collen D. Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Circulation 1995; 92: 2585-93.
  • 19 Tait RC, Walker ID, Conkie JA, Islam SIAM, Mc Call F, Mitchell R, Davidson JF. Plasminogen levels in healthy volunteers – influence of age, sex, smoking and oral contraceptives. Thromb Haemost 1992; 68: 506-10.
  • 20 Rodeghiero F, Tosetto A. The VITA Project: Population based distributions of protein C, antithrombin III, heparin-cofactor II and plasminogen – relationship with physiological variables and establishment of reference ranges. Thromb Haemost 1996; 76: 226-33.
  • 21 Demarmels Biasiutti F, Lämmle B. Thrombophilieabklärung: Indikation und Durchführung. Ther Umschau 1992; 49: 850-8.
  • 22 Dolan G, Preston FE. Familial plasminogen deficiency and thromboembolism. Fibrinolysis 1988; 2 (Suppl. 02) 26-34.
  • 23 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
  • 24 Zöller B, Svensson PJ, He X, Dahlbäck B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94: 2521-4.
  • 25 Dahlbäck B, Hillarp A, Rosen S, Zöller B. Resistance to activated protein C, the FV: Q506 allele, and venous thrombosis. Ann Hematol 1996; 72: 166-76.
  • 26 Züger M, Demarmels Biasiutti F, Furlan M, Mannhalter Ch, Lämmle B. Plasminogen deficiency: An additional risk factor for thrombosis in a family with factor VR506Q mutation?. Thromb Haemost 1996; 76: 475-6.