Causes of a Negative Ethanol Gelation Test in Diffuse Intravascular Coagulation

Summary

The clinical value of the ethanol gelation test (EGT) in diagnosing diffuse intravascular coagulation (DIC) has been questioned because of the occasional finding of a negative test, while other laboratory data pointed to DIC. Therefore, the behaviour of the EGT during thrombin infusions in rabbits was studied, with special reference to the fibrinogen level and activation of fibrinolysis. Fibrinolytic activity was inhibited or induced by synchronous infusion of epsilon-aminocaproic acid or plasmin respectively. The results obtained show that apart from severe depletion of fibrinogen strong activation of fibrinolysis can cause a negative EGT during thrombin infusions in rabbits. This phenomenon could not be ascribed to high levels of fibrin degradation products (fdp); it might be due to plasmin digestion of fibrin monomers. In vitro studies with human plasma confirmed that the EGT becomes negative at a fibrinogen level of less than 20 mg per 100 ml or by plasmin activity in the presence of a normal fibrinogen level.

Whereas a positive EGT is highly specific for DIC, these studies show that a negative EGT does not exclude the presence of DIC.

• References

• 1 Blombäck B, Blombäck M. Purification of human and bovine fibrinogen. Arkiv för Kemi 1956; 10: 415
• 2 Bouma B. N. A modification of the immunochemical determination of split products described by Niléhn. Scandinavian Journal of Haematology 1971; Suppl 13: 391
• 3 Breen Jr. F. A, Tullís J. L. Ethanol gelation: a rapid screening test for intravascular coagulation. Annals of Internal Medicine 1968; 69: 1197
• 4 Colman R. W, Robboy S. J, Minna J. D. Disseminated Intravascular Coagulation: an approach. American Journal of Medicine 1972; 52: 679
• 5 Fedder G, Pbakke E. M, Vreeken J. On the early detection of intravascular coagulation. An experimental study. Thrombosis et Diathesis Haemorrhagica 1972; 27: 365
• 6 Godal H. C, Abildgaard U. Gelation of soluble fibrin in plasma by ethanol. Scandinavian Journal of Haematology 1966; 3: 342
• 7 Godal H. C, Abildgaard U, Kierulf P. Ethanol gelation and fibrin monomers in plasma. Scandinavian Journal of Haematology 1971; Suppl 13: 189
• 8 Gurewich V, Lipinski B, Lipinska A. A comparative study of precipitation and paracoagulation by protamine sulphate and ethanol gelation tests. Thrombosis Research 1973; 2: 539
• 9 Kierulf P, Godal H. C. Fibrinaemia in medical patients screened by the ethanol test. Acta Medica Scandinavica 1971; 190: 185
• 10 Kontinnen Y. P, Kempainen L, Turunen O. Comparison of ethanol and protamine tests in demonstration of soluble fibrin and early products of fibrin degradation. Thrombosis et Diathesis Haemorrhagica 1972; 28: 342
• 11 Kopec M, Kowalski E, Stachurski J. Studies on paracoagulation. Role of antithrombin VI. Thrombosis et Diathesis Haemorrhagica 1960; 5: 285
• 12 Latallo Z. S, Wegrzynowicz Z, Teisseyre E, Kopec M. Simple and rapid evaluation of the intravascular coagulation and fibrinolytic states by application of protamine sulphate and Reptilase R. Scandinavian Journal of Haematology 1971; Suppl 13: 387
• 13 Lipinski B, Worowski K. Detection of soluble fibrin monomer complexes in blood by means of protamine sulphate test. Thrombosis et Diathesis Haemorrhagica 1968; 20: 45
• 14 Margolis C. Z. Ethanol gelation test. New England Journal of Medicine 1971; 284: 53
• 15 Merskey C, Johnson A. J, Kleiner G. J, Wohl H. The defibrination syndrome: clinical features and laboratory diagnosis. British Journal of Haematology 1967; 13: 528
• 16 Nalbandian R. M, Kessler D. L, Henry R, Camp Jr. F. R. Ethanol gelation test. New England Journal of Medicine 1971; 284: 502
• 17 Niewiarowski S, GUrewich V. Laboratory identification of intravascular coagulation. The serial dilution protamine sulphate test for the detection of fibrin monomer and fibrin degradation products. Journal of Laboratory and Clinical Medicine 1971; 77: 665
• 18 alos L. A, Sas G. Value of ethanol gelation test. New England Journal of Medicine 1971; 285: 1436
• 19 Sanfelippo M. J, Steven D. J, Koenig R. R. Protamine sulphate test for fibrin monomers. American Journal of Clinical Pathology 1971; 56: 166
• 20 Seaman A. J. The recognition of intravascular clotting: the plasma protamine paracoagulation test. Archives of Internal Medicine 1970; 125: 1016
• 21 Strengers Th, Asberg E. G. M. Een Screeningtest gevolgd door een snelle kwantitatieve microbepaling van fibrinogeen in plasma. Nederlands Tijdschrift voor Geneeskunde 1963; 107: 2044
• 22 Vreeken J, Fedder G, van der Meer J, van Aken W. G, Prakke E. M, Goote Th. M. Some initial aspects of diffuse intravascular coagulation and its relation to the “pre-thrombotic state”(abstract). Third Congress of the International Society on Thrombosis and Haemostasis, Washington, 22-26 August 1972,. 1972: 348
• 23 Yip M. L, Lee S, Sacks H. J. Nonspecificity of the protamine test for disseminated intravascular coagulation. American Journal of Clinical Pathology 1972; 57: 487