urokinase in the treatment of pulmonary embolism

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Urokinase in the Treatment of Pulmonary Embolism 2000 IU/kg/hour + heparin for 24 hours is equivalent to 4000 IU/kg/hour for 12 hours ... 129 evaluable patients suffering from massive pulmonary embolism (pulmonary angiogram showing vascular obstruction > 30%) received urokinase 2000 IU/kgjhour for 24 hours in combination with heparin or urok1nase 4400 IU/kg/hour for 12 hours, with heparin instituted after this time. Both treatments resulted in a significant resolution of pulmonary emboli, with 26 and 20% improvements in the low dose and high dose groups, respectively. The between-group difference was not significant. Both groups had a similar frequency of bleeding complications during the first 48 hours of treatment, most of which was mild to moderate, with severe bleeding occurring in only 5 patients. This trial shows that ' ... effective thrombolysis can be achieved without a loading dose and with one half (20001U kg- 1 h- 1 ) of the previously recommended hourly dose (44001U kg- 1 h- 1 ) during 24h, when combined with heparin'. Additionally heparin therapy may be used with this urokinase regimen. 'Our data suggest a trend, although not statistically significant, that increased emboli resolution can be obtained with moderate doses of UK [urokinase] combined with heparin for at least 24h.' UKEP Study Research Group European Heart Journal 8 2-10, Jan 1987 ... and either streptokinase or urokinase appears useful in massive embolic disease 38 patients with symptoms of massive pulmonary embolism received urokinase (n = 6 patients previously treated w1th streptokinase or with a high bleeding risk) 2000 CT A U/kg/hour (Committee on Thrombolytic Agents) or streptokinase 100,000 U/hour (n = 33) for 12-72 hours via an angiographic catheter. Follow-up treatment consisted of a maintenance dose of IV heparin 500-600 U/kg/day for 15 days and then oral acenocoumarol [nicoumalone]. S1gnif1cant improvements in angiographic scores and haemodynamic measurements were found in 33 patients and 1 other patient showed clinical improvement with no change in angiographic score. A temperature rise > 1 °C occurred in 11 patients and despite IV methylprednisolone prophylaxis, 3 streptokinase-treated patients had anaphylactic reactions. Other side effects included bleeding related to puncture or cut-down sites (n = 14), haematuria (n = 3), haemoptysis (n = 2) and epistaxis (n = 1). Colonic cancer was diagnosed in 1 patient with rectal bleeding, and 1 patient with a history of deep vein thrombosis and repeated pulmonary embolism that had been treated with heparin died after a cerebral haemorrhage 6 hours after receiving a single bolus of urokinase. Three other patients, all of whom had fibrinogen levels > 1 g/L, died 12-24 hours after treatment was begun. The authors concluded that ' ... SK [streptokinase] or UK [uroklnase]ls the suitable treatment for most patients with MPE [massive pulmonary embolism]; however, If by twelve hours after the start of treatment, a fibrinolytic state has not been obtained, then heparin treatment must be begun because of the high risk of rethrombosis or extension of the thrombus'. Grau E. Fontcuberta J. Pages MA. Mart1nez R, Felez J, et al Ang1ology 37 832-839, Nov 1986 12 INPHARMA" 11 Apri/1987 0156-2703/87 /0411-0012!0$01.00/0 © ADI_$7

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Page 1: Urokinase in the Treatment of Pulmonary Embolism

Urokinase in the Treatment of Pulmonary Embolism 2000 IU/kg/hour + heparin for 24 hours is equivalent to 4000 IU/kg/hour for 12 hours ...

129 evaluable patients suffering from massive pulmonary embolism (pulmonary angiogram showing vascular obstruction > 30%) received urokinase 2000 IU/kgjhour for 24 hours in combination with heparin or urok1nase 4400 IU/kg/hour for 12 hours, with heparin instituted after this time.

Both treatments resulted in a significant resolution of pulmonary emboli, with 26 and 20% improvements in the low dose and high dose groups, respectively. The between-group difference was not significant.

Both groups had a similar frequency of bleeding complications during the first 48 hours of treatment, most of which was mild to moderate, with severe bleeding occurring in only 5 patients.

This trial shows that ' ... effective thrombolysis can be achieved without a loading dose and with one half (20001U kg- 1h-1) of the previously recommended hourly dose (44001U kg- 1h- 1) during 24h, when combined with heparin'. Additionally heparin therapy may be used with this urokinase regimen. 'Our data suggest a trend, although not statistically significant, that increased emboli resolution can be obtained with moderate doses of UK [urokinase] combined with heparin for at least 24h.'

UKEP Study Research Group European Heart Journal 8 2-10, Jan 1987

... and either streptokinase or urokinase appears useful in massive embolic disease 38 patients with symptoms of massive pulmonary embolism received urokinase (n = 6 patients

previously treated w1th streptokinase or with a high bleeding risk) 2000 CT A U/kg/hour (Committee on Thrombolytic Agents) or streptokinase 100,000 U/hour (n = 33) for 12-72 hours via an angiographic catheter. Follow-up treatment consisted of a maintenance dose of IV heparin 500-600 U/kg/day for 15 days and then oral acenocoumarol [nicoumalone].

S1gnif1cant improvements in angiographic scores and haemodynamic measurements were found in 33 patients and 1 other patient showed clinical improvement with no change in angiographic score. A temperature rise > 1 °C occurred in 11 patients and despite IV methylprednisolone prophylaxis, 3 streptokinase-treated patients had anaphylactic reactions. Other side effects included bleeding related to puncture or cut-down sites (n = 14), haematuria (n = 3), haemoptysis (n = 2) and epistaxis (n = 1). Colonic cancer was diagnosed in 1 patient with rectal bleeding, and 1 patient with a history of deep vein thrombosis and repeated pulmonary embolism that had been treated with heparin died after a cerebral haemorrhage 6 hours after receiving a single bolus of urokinase. Three other patients, all of whom had fibrinogen levels > 1 g/L, died 12-24 hours after treatment was begun.

The authors concluded that ' ... SK [streptokinase] or UK [uroklnase]ls the suitable treatment for most patients with MPE [massive pulmonary embolism]; however, If by twelve hours after the start of treatment, a fibrinolytic state has not been obtained, then heparin treatment must be begun because of the high risk of rethrombosis or extension of the thrombus'.

Grau E. Fontcuberta J. Pages MA. Mart1nez R, Felez J, et al Ang1ology 37 832-839, Nov 1986

12 INPHARMA" 11 Apri/1987 0156-2703/87 /0411-0012!0$01.00/0 © ADI_$7