Thromb Haemost 1995; 74(02): 718-721
DOI: 10.1055/s-0038-1649803
Original Article
Fibrinolysis
Schattauer GmbH Stuttgart

Does Low Protein Concentration of Tissue-type Plasminogen Activator Predict a Low Risk of Spontaneous Deep Vein Thrombosis?

Jørgen Gram
The Department of Clinical Biochemistry, Ribe County Hospital in Esbjerg and Institute for Thrombosis Research, South Jutland University Centre, Esbjerg, Denmark
,
Johannes Sidelmann
The Department of Clinical Biochemistry, Ribe County Hospital in Esbjerg and Institute for Thrombosis Research, South Jutland University Centre, Esbjerg, Denmark
,
Jørgen Jespersen
The Department of Clinical Biochemistry, Ribe County Hospital in Esbjerg and Institute for Thrombosis Research, South Jutland University Centre, Esbjerg, Denmark
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 08. Februar 1995

Accepted after resubmission 04. April 1995

Publikationsdatum:
06. Juli 2018 (online)

Summary

Many reports have demonstrated an abnormal fibrinolysis in a subset of patients with deep vein thrombosis. We have studied systemic global fibrinolytic activity and protein concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in plasma of 25 young patients with a previous instance of spontaneous deep vein thrombosis documented by phlebography and in 50 healthy controls. The two populations were comparable with respect to a number of base-line variables (age, height, weight, etc.), while the patients had significantly lower fibrinolytic activity (p <0.02), and significantly higher protein concentrations of t-PA (p <0.0001) and PAI-1 (p <0.0006).

We used probit scale plots to identify the consequence of different cut-off points to separate patients from controls. Reasonable separation could be obtained for t-PA with a cut-off point of 5.2 ng/ml and for PAI-1 18 ng/ml. The sensitivity and specificity for these cut-off points were for t-PA 73% (95% confidence interval 63%-84%) and for PAI-1 67% (confidence interval 55%-77%). The negative predictive value with a cut-off point t-PA concentration of 5.2 ng/ml was 85% (95% confidence interval 70%-94%). We observed a significantly negative association between concentration of t-PA and fibrinolytic activity (rs = -0.47; p <0.005) and also between PAI-1 and fibrinolytic activity (rs = -0.78; p <0.005).

We conclude that a young healthy population is characterized by low protein concentration of t-PA (and PAI-1) compared with young patients with a previous instance of spontaneous vein thrombosis, and we tentatively state that a low protein concentration of t-PA predicts a low risk of spontaneous deep vein thrombosis.

 
  • References

  • 1 Isacson S, Nilsson IM. Defective fibrinolysis in blood and vein walls in recurrent “idiopathic” venous thrombosis. Acta Chir Scand 1972; 138: 313-319
  • 2 Korninger C, Lechner K, Niessner H, Gössinger H, Kundi M. Impaired fibrinolytic capacity for recurrence of venous thrombosis. Thromb Haemost 1984; 52: 127-130
  • 3 Wiman B, Ljungberg B, Chmielewska J, Urdén G, Blombäck M, Johnsson H. The role of the fibrinolytic system in deep vein thrombosis. J Lab Clin Med 1985; 105: 265-270
  • 4 Paramo JA, Alfaro MJ U, Rocha E. Postoperative changes in the plasmatic levels of tissue-type plasminogen activator and its fast acting inhibitor: relationship to deep vein thrombosis and influence of prophylaxis. Thromb Haemost 1985; 54: 713-716
  • 5 Pizzo SV, Fuchs HE, Doman KA, Petruska DB, Berger jr H. Release of tissue plasminogen activator and its fast-acting inhibitor in defective fibrinolysis. Arch Intern Med 1986; 146: 188-191
  • 6 Jørgensen M, Bonnevie-Nielsen V. Increased concentration of the fastacting plasminogen activator inhibitor in plasma associated with familial venous thrombosis. Br J Haematol 1987; 65: 175-180
  • 7 Juhan-Vague I, Valadier J, Alessi MC, Aillaud MF, Ansaldi J, Philip-Joet C, Holvoet P, Serradimigni A, Collen D. Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis. Thromb Haemost 1987; 57: 67-72
  • 8 Nguyen G, Horellou MH, Kruithof EKO, Conard J, Samama MM. Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep venous thrombosis. Blood 1988; 72: 601-605
  • 9 Tabernero M, Estellés A, Vincente V, Alberca I, Aznar J. Incidence of increased plasminogen activator inhibitor in patients with deep venous thrombosis and/or pulmonary embolism. Thromb Res 1989; 56: 565-570
  • 10 Engesser L, Brommer EJ P, Kluft C, Brië E. Elevated plasminogen activator inhibitor (PAI), a cause of thrombophilia. A study in 203 patients with familial or sporadic venous thrombophilia Thromb Haemost 1989; 62: 673-680
  • 11 Hejboer H, Brandjes DPM, Buller 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: 1512-1516
  • 12 Nilsson IM, Ljungnér If, 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: 1453-1456
  • 13 Grimaudo V, Bachmann F, Fauert J, Christe M-A, Kruithof EKO. Hypo-fibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism. Thromb Haemost 1992; 67: 397-401
  • 14 Malm J, Laurell M, Nilsson IM, Dahlbäck B. Thromboembolic disease critical evaluation of laboratory investigation. Thromb Haemost 1992; 68: 7-13
  • 15 Ridker FM, Vaughan DE, Stampfer MJ, Manson JE, Shen C, Newcomer EM, Goldhaber SZ, Hennekes CH. Baseline fibrinolytic state and the risk of future venous thrombosis. A prospective study of endogenous tissue-type plasminogen activator and plasminogen activator inhibitor Circulation 1992; 85: 1822-1827
  • 16 Sidelmann J, Jespersen J, Gram J. A spectroscopic microtiter fibrin plate assay. Fibrinolysis 1994; 8 Suppl (Suppl. 01) 354
  • 17 Jespersen J, Sidelmann J. A study of the conditions and accuracy of the thrombin time assay of plasma fibrinogen. Acta Haematol 1982; 67: 2-7
  • 18 Harris EK, Yasaka T. On the calculation of a “reference change” for comparing two consecutive measurements. Clin Chem 1983; 29: 25-30
  • 19 Petersen PH, Hørder M. Ways of assessing quality goals for diagnostic tests in clinical situations. Arch Pathol Lab Med 1988; 112: 435-443
  • 20 Gowans EM S, Eraser CG, Petersen PH. A guide to the use of probit transformation of gaussian distributions. Biochim Clin 1989; 13: 327-336
  • 21 Petersen PH, Hørder M. Influence of analytical quality on test results. Scand J Clin Lab Invest 1992; 52 Suppl 208: 65-88
  • 22 Sidelmann J, Gram J. The influence of venepuncture, mixing and separation of blood on the measurement of thrombin-antithrombin-III-complex and plasminogen activator inhibitor. Fibrinolysis 1990; 4 Suppl 2: 124-126
  • 23 Sidelmann J. The influence of centrifugation load on platelet number and PAI-1 antigen concentration in human plasma. Fibrinolysis 1994; 8 Suppl 23: 148-149
  • 24 Allen RA, Kluft C, Brommer EJ P. The acute effect of smoking on fibrinolysis: increase in the activity level of circulating extrinsic (tissue-type) plasminogen activator. Eur J Clin Invest 1984; 14: 354-361
  • 25 Jespersen J. The diurnal increase in euglobulin fibrinolytic activity in women using oral contraceptives and in normal women, and the generation of intrinsic fibrinolytic activity. Thromb Haemost 1986; 56: 183-188
  • 26 Grimaudo V, Hauert J, Bachmann F, Kruithof EK O. Diurnal variation of the fibrinolytic system. Thromb Haemost 1986; 56: 183-188
  • 27 Marckmann P, Jespersen J, Leth T, Sandström B. Effect of fish diet versus meat diet on blood lipids, coagulation and fibrinolysis. J Intern Med 1991; 229: 317-323
  • 28 Hendriks HF J, Veenstra J, Wierik EJ M V, Schaafsma G, Kluft C. Effect of moderate dose of alcohol with evening meal on fibrinolytic factors. Br Med J 1994; 308: 1003-1006
  • 29 Jespersen J. Pathophysiology and clinical aspects of fibrinolysis and inhibition of coagulation. Experimental and clinical studies with special reference to women on oral contraceptives and selected groups of thrombosis prone patients Dan Med Bull 1988; 35: 1-33
  • 30 Prandoni P, Lensing AW A, Büller HR, Cogo A, Prins MH, Cattelan AM, Cuppini S, Noventa F, Ten Cate JW. Deep vein thrombosis and incidence of subsequent symptomatic cancer. N Engl J Med 1992; 327: 1128-1133
  • 31 Kluft C, Verheijen JH. Leiden fibrinolysis working party: blood collection and handling procedures for assessment of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). Fibrinolysis 1990; 4 Suppl 2: 155-161
  • 32 Kluft C, Verheijen J, Jie AF H, Rijken DC, Preston FE, Sue-Ling HM, Jespersen J, Aasen AO. The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-type plasminogen activator after trauma. Scand J Clin Lab Invest 1985; 45: 605-610
  • 33 Marckmann P, Sandström B, Jespersen J. The variability of and associations between measures of blood coagulation fibrinolysis and blood lipids. Atherosclerosis 1992; 96: 235-244