Behaviour of the Contact Phase of Blood Coagulation in the Adult Respiratory Distress Syndrome (ARDS)

Summary

In order to assess the role of the kallikrein-kinin (K-K) system in the pathogenesis of the adult respiratory distress syndrome (ARDS) we have prospectively determined coagulation contact phase, blood gas and hemodynamic parameters in patients with ARDS at 0, 36 and 72 h from diagnosis.

Compared to normal values, significantly lower mean levels of factor XII (71.4 ± 9.8%, p <0.0005), prekallikrein (PPK) (52 ± 5.7%, p <0.0005), high molecular weight kininogen (HMWK) (73 ± 2%, p <0.0005) and α₂-macroglobulin (α₂-M) (51 ± 7.1%, p <0.0005) were found in ARDS patients.

The functional kallikrein inhibitory activity (KKI) and Cr esterase inhibitor antigenic (CIINH) were significantly higher in these patients (113.2 ± 5, p <0.005 and 124.7 ± 7.6, p <0.0005 respectively) compared with normal values during the entire study period.

The KKI/CIINH ratio decreased significantly in our ARDS patients at 0, 36 and 72 h (p <0.025; p <0.05 and p <0.005 respectively).

We found a significant correlation between PPK levels and oxigenation index (r = 0.69, p <0.001), PPK and the static thoracic compliance values (r = 0.64, p <0.001). There was also a significant correlation between PPK levels and Qs/Qt (r = -0.89, p <0.001). ARDS patients that survived presented a stability in the PPK values in successive tests. Nevertheless non-survivors showed a progressive decrease in PPK levels during the follow-up period.

Our results suggest that the plasma kallikrein system becomes activated during ARDS and that this activation might increase the lung vessels’ permeability. In addition, PPK levels are in our opinion a useful prognostic parameter in predicting the outcome of ARDS patients.

Keywords

ARDS - Contact system

• References

• 1 Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 1967; 2: 319-323
• 2 Petty TL, Ashbaugh DG. The adult respiratory distress syndrome: Clinical features, factors influencing prognosis and principles of management. Chest 1971; 60: 133-239
• 3 Hyers TM. Pathogenesis of adult respiratory distress syndrome; current concepts. Semin Respir Med 1981; 2: 104-108
• 4 Saldeen T. The microembolism syndrome. Microvasc Res 1976; 11: 227-259
• 5 Scheider RC, Zapol WM. Carvalho A C Platelet consumption and sequestration in severe acute respiratory failure. Am Rev Respir Dis 1980; 122: 445-451
• 6 Lonky SA, Wolh H. Stimulation of human leukocyte elastase by platelet factor 4: physiologic morphologic and biochemical effect on hamster lung in vitro. J Clin Invest 1981; 67: 817-826
• 7 Bone RC, Francis PB, Pierce AK. Intravascular coagulation associated with the adult respiratory distress syndrome. Am J Med 1976; 61: 585-589
• 8 Gerdin B, Saldeen T. Effect of fibrin degradation products on microvascular permeability. Thromb Res 1978; 13: 995-1006
• 9 Carlson RW, Schaeffer RC, Carpio M, Weil MH. Edema fluid and coagulation changes during fulminant pulmonary edema. Chest 1981; 79: 43-49
• 10 Petty TL, Fowler A. Another look at ARDS. Chest 1982; 82: 989-1004
• 11 Caen J, Larrieu MJ, Samama M. La Hemostasia. Toray-Masson; Barcelona: 1977
• 12 Gallimore MJ, Ammundsen E, Larsbraaten M, Lyngaas K, Fareid E. Studies on plasma inhibitors of plasma kallikrein using chromogenic peptide substrate assay. Thromb Res 1979; 16: 695-703
• 13 Laurell CN. Quantitative estimation of protein by electrophoresis in agarose gel containing antibodies. Ann Biochem 1966; 15: 45-52
• 14 Cherniack K. Pulmonary function testing. Philadelphia: W B Saunder Company; 1977
• 15 Mcguire WW, Spragg RG, Cohen AB, Cochrane CG. Studies on the pathogenesis of the adult respiratory distress syndrome. J Clin Invest 1982; 69: 543-553
• 16 Colman RW. Surface-mediated defense reactions. The plasma contact activation system J Clin Invest 1984; 73: 1249-1253
• 17 Kaplan AP. Initiation of Jhe intrinsic coagulation and fibrinolytic pathways of man: the role of surfaces, Hageman factor prekallikrein, high molecular weight kininogen and factor XI. Prog Hemostas Thromb 1978; 4: 127-175
• 18 Saugstad OD, Aasen AO, Guldvog I, Lium B, Lyngaask K, Ammundsen E. Changes of components of the plasma kallikrein-kinin system during experimental lung insufficiency in dogs. Acta Chir Scand 1982; Suppl (Suppl. 509) 61-67
• 19 Saugstad OD, Harvie A, Langslet A. Activation of the kallikrein-kinin system in premature infants with respiratory distress syndrome. Acta Chir Scand 1982; Suppl (Suppl. 509) 79
• 20 Aasen AO, Smith-Erichsen N, Gallimore MJ, Ammundsen E. Studies on the components of the plasma kallikrein-kinin system in plasma samples from normal individuals and patients with septic shock. In Advances in shock research Schumer W, Spitzer JJ, Marshall BE. eds Vol 4 1-10 Liss, Alan R, Inch.; New York: 1980
• 21 Schapira M, Despland E, Scott F, Boxer LA, Colman RW. Purified human plasma kallikrein aggregates human blood neutrophils. J Clin Invest 1982; 69: 1199-1202
• 22 Wachtfogel YT, Kucich H, James HL. et al Human plasma kallikrein releases neutrophil elastase during blood coagulation. J Clin Invest 1983; 72: 1672-1677
• 23 Landerman NS, Webster ME, Becker EL, Ratcliffe HE. Hereditary angineurotic edema. Deficiency of inhibitor for serum globulin permeability factor and/or plasma kallikrein J Allergy 1962; 33: 330-334
• 24 Saito H, Goldsmith GH, Moroi M, Aoki N. Inhibitory spectrum of 2-plasmin inhibitors. Proc Natl Acad Sci USA 1979; 76: 2013-2017
• 25 Schapira M, Scott CF, Colman RW. Contribution of plasma protease inhibitors to the inactivation of kallikrein in plasma. J Clin Invest 1982; 69: 462-468
• 26 Harpel PC. Human plasma 2-macroglobulin. An inhibitor of plasma kallikrein. J Exp Md 1970; 132: 329-352
• 27 Van der Graaf F, Koedam JA, Bouma BN. Inactivation of kallikrein in human plasma. J Clin Invest 1983; 71: 149-158
• 28 Harpel PC. Human a-2-Macroglobulin. In: Methods in Enzymology Lorand L. ed vol 45 639-652 Academic Press; New York: 1976