Correspondence

Thrombolytic Agents

N Engl J Med 1994; 330:291January 27, 1994

Article

To the Editor:

In their review article “Thrombolysis in Acute Myocardial Infarction” (Sept. 2 issue),1 Anderson and Willerson state that “urokinase is a true enzyme . . . [that] exists in both double-chain and single-chain forms.” This statement obscures the fundamental and clinically important differences between these two forms, a subject never made clear in this otherwise informative review.

Urokinase is a true enzyme. The single-chain form is, in fact, a proenzyme that is inert and stable in plasma (where it is naturally present) and does not form complexes with plasma inhibitors2. Moreover, unlike urokinase, the proenzyme is relatively fibrin specific both in vitro and in vivo3. Because of its particular mode of action, which complements that of tissue plasminogen activator, it is synergistic with tissue plasminogen activator4 as well as with urokinase. The proenzyme is rapidly incorporated by platelets,5 a finding that may explain the exceptionally low rate of reocclusion (1.5 percent) after coronary thrombolysis reported with its use6.

These properties distinguish the proenzyme from urokinase, as well as from the other thrombolytic agents tissue plasminogen activator, streptokinase, and anisoylated plasminogen-streptokinase activator complex. It is currently available in Japan, is expected to be approved in Europe within two years, and is in clinical trials in the United States. It is a novel second-generation activator that should not be confused with first-generation urokinase.

Victor Gurewich, M.D.
Deaconess Hospital, Boston, MA 02215

6 References

1. 1

   Anderson HV, Willerson JT. Thrombolysis in acute myocardial infarction. N Engl J Med 1993;329:703-709
   Full Text | Web of Science | Medline

2. 2

   Pannell R, Gurewich V. Pro-urokinase: a study of its stability in plasma and of a mechanism for its selective fibrinolytic effect. Blood 1986;67:1215-1223
   Web of Science | Medline

3. 3

   Gurewich V, Pannell R, Louie S, Kelley P, Suddith RL, Greenlee R. Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase): a study in vitro and in two animal species. J Clin Invest 1984;73:1731-1739
   CrossRef | Web of Science | Medline

4. 4

   Pannell R, Black J, Gurewich V. The complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained. J Clin Invest 1988;81:853-859
   CrossRef | Web of Science | Medline

5. 5

   Gurewich V, Johnstone M, Loza J-P, Pannell R. Pro-urokinase and prekallikrein are both associated with platelets: implications for the intrinsic pathway of fibrinolysis and for therapeutic thrombolysis. FEBS Lett 1993;318:317-321
   CrossRef | Web of Science | Medline

6. 6

   Weaver WD, Hartmann JK, Reddy PS, et al. Prourokinase achieves rapid and sustained patency for treatment of acute myocardial infarction. J Am Coll Cardiol (in press).