Thromb Haemost 1992; 67(02): 200-202
DOI: 10.1055/s-0038-1648412
Original Articles
Schattauer GmbH Stuttgart

Markers of Procoagulant Imbalance in Patients with Inherited Thrombophilic Syndromes

P M Mannucci
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
A Tripodi
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
B Bottasso
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
F Baudo
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
G Finazzi
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
V De Stefano
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
G Palareti
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
C Manotti
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
M G Mazzucconi
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
,
G Castaman
A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano; Hematology Departments, Niguarda Cà Granda Hospital of Milano, Maggiore Hospital of Bergamo; Catholic University and State University of Rome; Angiology and Blood Coagulation Department, University of Bologna; 6th Division of Internal Medicine, Hospitals of Parma; Hemophilia and Thrombosis Center and Hematology Department, Vicenza, Italy
› Author Affiliations
Further Information

Publication History

Received 01 May 1991

Accepted after revision 05 September 1991

Publication Date:
02 July 2018 (online)

Summary

In 107 asymptomatic and untreated patients with inherited syndromes associated with thrombophilia (antithrombin III, protein C and protein S deficiencies), we compared in parallel two plasma peptides which reflect activation of the common coagulation pathway: the prothrombin fragment 1 + 2 (F1+2) and fibrinopeptide A (FPA). Both F1+2 and FPA were measured with simple, commercially available ELISA methods. High levels of F1+2 or FPA were found in about one fourth of the patients as a whole. When patients were divided according to the type of inherited thrombophilie syndrome, it appeared that F1+2 was more frequently elevated in protein C and protein S deficiencies than in antithrombin deficiency; and that, in general, it was no more frequently elevated than FPA. Although our data confirm the existence of a procoagulant imbalance in inherited thrombophilie syndromes due to defects of natural anticoagulant proteins, they do not confirm that such imbalance can be more frequently diagnosed by measuring F1+2 levels, particularly in patients with antithrombin deficiency.

 
  • References

  • 1 Aronson DL, Stevan L, Bail AP, Franza Jr BR, Finlayson JS. Generation of the combined prothrombin activation peptide (FI.2) during the clotting of blood and plasma. J Clin Invest 1977; 60: 1410-1418
  • 2 Nossel HL, Yudelman I, Canfield RE. et al Measurement of fibrinopeptide A in human blood. J Clin Invest 1974; 54: 43-53
  • 3 Bauer KA, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: insights gained from studies using marker of the hemostatic system activation. Blood 1987; 70: 343-350
  • 4 Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD. Aging-associated changes in indices of thrombin generation and protein C activation in humans. Normative aging study. J Clin Invest 1987; 80: 1527-1534
  • 5 Bauer KA, Goodman TL, Kass BL, Rosenberg RD. Elevated factor Xa activity in the blood of asymptomatic patients with congenital antithrombin deficiency. J Clin Invest 1985; 76: 826-836
  • 6 Bauer KA, Broekmans AW, Bertina RM. et al Hemostatic enzyme generation in the blood of patients with hereditary protein C deficiency. Blood 1988; 71: 1418-1426
  • 7 Mannucci PM, Bauer KA, Gringeri A. et al Thrombin generation is not increased in the blood of hemophilia B patients after the infusion of a purified factor IX concentrate. Blood 1990; 76: 2540-2545
  • 8 Teitel JM, Bauer KA, Lau HK, Rosenberg RD. Studies of the prothrombin activation pathway utilizing radioimmunoassays for the F2/Fi+2 fragment and thrombin-antithrombin complex. Blood 1982; 59: 1086-1097
  • 9 Pelzer H, Schwarz A, Sttiber W. Determination of human prothrombin activation fragment F1+2 in plasma with an antibody against a synthetic peptide. Thromb Haemostas 1991; 65: 153-159
  • 10 Shi D, Ruiz JA, Perez LM. et al Detection of prothrombin activation with a two-site enzyme immunoassay for the fragment F1+2 . Thromb Haemostas 1989; 62: 165 (Abstr)
  • 11 Hursting M, Butman B, Steiner J. et al A quantitative ELISA for plasma prothrombin fragment 1.2 (FI.2). Blood 1989; 74 (suppl): 257a (Abstr)
  • 12 Tripodi A, Mannucci PM. A survey of inherited thrombotic syndromes in Italy. Res Clin Lab 1989; 19: 67-74
  • 13 Mannucci PM, Tripodi A. Laboratory screening of inherited thrombotic syndromes. Thromb Haemostas 1987; 57: 247-251
  • 14 Bauer KA, Barzegar S, Rosenberg RD. Influence of anticoagulants used for blood collection on plasma prothrombin fragment F1+2 measurements. Thromb Res 1991; 63: 617-628