Urinary type plasminogen activator (u-PA) is present either as a single chain proenzyme form (scu-PA) with a very low plasminogen activating activity or as an activated two-chain form (tcu-PA). tcu-PA occurs as both high molecular weight (HMW tcu-PA) or low molecular weight (LMW tcu-PA) enzyme species. HMW tcu-PA is 2-3 times more potent than LMW tcu-PA in biological assays such as the clot lysis method but their amidolytic activity on the chromogenic substrate S-2444 is equivalent (1). The International Reference Preparation (IRP) of urokinase (66/46) was established by the Expert Committee on Biological Standardization of the WHO in 1968 (2) . Until then urokinase was expressed in casein Ploug (Leo standard) or CTA units (CTA standard). These units were related to the amount of urokinase capable to hydrolyze a certain amount of casein in a defined time. 1 CTA-U was assumed to be identical to 1 International Unit (IU). Although there was no official numerical relationship between Ploug units and IU, 1.5 IU has been accepted to be equivalent to 1 Ploug unit. The IRP 66/46 is a mixture of 66% LMW and 34% HMW forms of tcu-PA (3).

Following the need of a HMW International Standard, a new international standard (87/594) was established in 1989 (4).

Due to the complexity of u-PA it is difficult to determine a direct relationship between IU, CTA-U, Plough-U and nkat chromogenic substrate S-2444.

In 1983 Friberger (5) reported that 0.34 nkat chromogenic substrate S-2444 correspond to 110 Plough-U, 160 CTA-U or about 160 IU.

In an earlier work by Paar D and Marhulm D, on urokinase purified from urine (6) , 100 CTA-U corresponded to 0.27 nkat chromogenic substrate S-2444.

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    Twenty First Meeting. Expert Committee on Biological Standardization. WHO Tech Rep Ser No 413, 1968.
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    Assay methodology for urokinase. Its use in assessing the composition of mixtures of high- and low- molecular weight urokinases. Thromb Res 21, 81-88 (1981).
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    A collaborative study to establish a standard for high molecular weight urinary-type plasminogen activator (HMW/u-PA). Thromb Haemost 64, 398-401 (1990).
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  6. Paar D and Marhulm D. Spectrophotometric determination of urokinase in urine after gel filtration, using the chromogenic substrate S-2444. J Clin Chem Clin Biochem 18, 557-562 (1980).