Thromb Haemost 1995; 74(06): 1442-1446
DOI: 10.1055/s-0038-1649962
Original Articles
Clinical Studies
Schattauer GmbH Stuttgart

Blood Coagulation and Fibrinolysis Activation during Sudden Arterial Occlusion of Lower Extremities – an Association with Ischemia and Patient Outcome

Seija Peltonen
1   The Wihuri Research Institute, Helsinki, Finland
,
Riitta Lassila
1   The Wihuri Research Institute, Helsinki, Finland
,
Perttu Rossi
2   The Department of Surgery, Tampere University Hospital, Tampere, Helsinki, Finland
,
Juha-Pekka Salenius
2   The Department of Surgery, Tampere University Hospital, Tampere, Helsinki, Finland
,
Mauri Lepäntalo
3   The Department of Surgery, Division of Vascular Surgery, Helsinki University Central Hospital, Helsinki, Finland
› Author Affiliations
Further Information

Publication History

Received: 05 July 1995

Accepted after revision 28 August 1995

Publication Date:
10 July 2018 (online)

Summary

We compared hemostatic and fibrinolytic plasma markers in 41 patients having acute or subacute occlusion of lower limb arteries with 20 patients suffering stable peripheral arterial occlusive disease (PAOD). During occlusion, the amount of thrombin-antithrombin III (TAT) complex was five-fold higher compared with stable PAOD, being 16 μg/l [95% confidence interval (CI) 11-21 μg/1] vs 3 μg/l (95% CI 2-4 μg/l), p <0.003. Similarly, D-dimer was over four-fold (p = 0.0001), while tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) antigens were about two-fold (p = 0.02 and p <0.003, respectively) higher than in PAOD. Coagulation and fibrinolysis markers were increased most in patients with recent symptom onset, which mainly represented embolus rather than thrombosis. The marker levels assessing coagulation and fibrinolysis were related with myoglobin and CK, indicators of skeletal muscle damage. Finally, increased TAT, PAI-1 antigen, and myoglobin concentrations associated with poor outcome.

 
  • References

  • 1 Teitel JM, Bauer KA, Lau HK, Rosenberg RD. Studies of the prothrombin activation pathway utilizing radioimmunoassay for the F2/F1+2 fragment and the thrombin-antithrombin complex. Blood 1982; 59: 1086-1097
  • 2 Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemost 1988; 59: 101-106
  • 3 Pelzer H, Schwart A, Stuber W. Determination of human prothrombin activation fragment 1+2 in plasma with an antibody against the synthetic peptide. Thromb Haemost 1991; 65: 153-159
  • 4 Nieuwenhuizen W. Plasma assays for derivatives of fibrin and fibrinogen, based on monoclonal antibodies. Fibrinolysis 1988; 2: 1-5
  • 5 Bounameaux H, Cirafici P, de Moerloose P, Schneided PA, Slossman D, Reber G, Unger PF. Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism. Lancet 1990; 337: 196-200
  • 6 Boneu B, Bes G, Pelzer H, Sie P, Boccalon H. D-dimers, thrombin-antithrombin III complexes and prothrombin fragments 1+2 diagnostic value in clinically suspected deep vein thrombosis. Thromb Haemost 1991; 65: 28-32
  • 7 Szczeklik A, Dropinski J, Radwan J, Krzanowski M. Persistent generation of thrombin after acute myocardial infarction. Arteriosclerosis Thrombosis 1992; 12: 548-553
  • 8 Merlini PA, Bauer KA, Oltrona L, Adrissino D, Cattaneo M, Belli C, Mannucci M. Persistent activation of the coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994; 90: 61-68
  • 9 Lassila R, Peltonen S, Lepäntalo M, Saarinen O, Kauhanen P, Manninen V. Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin. Arterioscler Thromb 1993; 13: 1738-1742
  • 10 Herren T, Strecker H, Haeberli A, Do D-D, Straub PW. Fibrin formation and degradation in patients with arteriosclerotic disease. Circulation 1994; 90: 2679-2686
  • 11 Heinrich J, Schulte H, Schönfeld R, Köhler E, Assman G. Association of variables of coagulation, fibrinolysis and acute-phase with atherosclerosis in coronary and peripheral arteries and those arteries supplying the brain. Thromb Haemost 1995; 73: 374-379
  • 12 Fowkes FG R, Lowe GD O, Housley E, Rattray A, Rumley A, Elton RA, MacGregor IR, Dawes J. Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart disease. Lancet 1993; 342: 84-86
  • 13 Cortellaro M, Cofrancesco E, Boschetti C, Mussoni L, Donati MB, Cardillo M, Catalano M, Garbrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, Pozzoli E, Turri M. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case- control study Arterioscler Thromb 1993; 13: 1412-1417
  • 14 Rutherford RB, Flanigan DP, Gupta SK, Johnston KW, Karmody A, Whittemore AD, Baker JD, Ernst CB. Suggested standards for reports dealing with lower extremity ischemia. J Vase Surg 1986; 4: 80-94
  • 15 Takolander R. Differentation between acute and acute on chronic limb ischaemia. Ann Chir Gynaecol 1992; 81 (02) 143-145
  • 16 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 (Suppl. 02) 155-161
  • 17 European Committee for Clinical Laboratory Standards. Standards for Enzyme Determination. Determination of the catalytic activity concentration in serum of creatine kinase (EC2.7.3.2., CK) Klin Lab 1990; 6: 120-126
  • 18 Rosano TG, Kenny MA. A radioimmunoassay for human serum myoglobin: method, development and normal values. Clin Chem 1977; 23: 69-75
  • 19 Campbell MJ, Machin D. Medical statistics. John Wiley & Sons Ltd; Chichester, England: 1992. pp 80-81
  • 20 Kumagai K, Fukunami M, Ohmori M, Kitabatake A, Takenobu K, Hoki N. Increased intracardiovascular clotting in patients with chronic atrial fibrillation. J Amer Coll Cardiol 1990; 16: 377-380
  • 21 Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326: 242-250
  • 22 Ljungman C, Eriksson I, Ronquist G, Roxin LE, Venge P, Wistrand P. Muscle ATP and lactate and the release of myoglobin and carbanhydrase III in acute lower-limb ischaemia. Eur J Vase Surg 1991; 5: 407-414
  • 23 Bauer KA. New markers for in vivo coagulation. Curr Opin Hematol 1994; 1: 341-346
  • 24 Diquelou A, Lemozy S, Dupouy B, Boneu B, Sakariassen KS, Cadroy Y. Effect of blood flow on thrombin generation is dependent on the nature of the thrombogenic surface. Blood 1994; 84: 2206-2213
  • 25 Jackson GM. Mechanisms of prothrombin activation. In: Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. eds. J.B. Lippincott Company; Philadelphia, PA: 1987. pp 135-147
  • 26 Fenton II JW, Ofosu FA, Brezniak DV, Hassouna HI. Understanding thrombin and hemostasis. Hematol/Oncol Clin N Am 1994; 7: 1107-1119
  • 27 Smith FB, Lee AJ, Rumley A, Fowkes GR, Lowe GD O. Tissue-plasminogen activator, plasminogen activator inhibitor and risk of peripheral arterial disease. Atherosclerosis 1995; 115: 35-43
  • 28 Stringer HA R, van Swieten P, Heijnen HF G, Sixma JJ, Pannekoek H. Plasminogen activator inhibitor-1 released from activated platelets plays a key role in thrombolysis resistance: studies with thrombi generated in the Chandler loop. Arterioscler Thromb 1994; 14: 1452-1458