Nephrology

5412 STREPTOKINASE UROKINASE

  • Thrombolytic drugs activate plasminogen to plasmin.   Uninjured vessels do not bleed during normal thrombolytic therapy.  A systemic lytic state can be reversed by stopping the infusion and administering plasma or cryoprecipitate.  Epsilon aminocaproic acid is a plasmin inhibitor but is potentially dangerous and rarely used.

    Streptokinase

    • Depletes Plasminogen, Fibrinogen, & Factors V and VIII
    • Neutralizing antibodies often cause irregular dose-response
    • 1/2 life 23 minutes
    • More predictable dose-response than streptokinase
    • Depletes same factors as streptokinase but more clot-specific
    • Less likely to produce a systemic lytic state than streptokinase
    • Costs 6 times as much as streptokinase
    • Elicits no immune response
    • 1/2 life 16 minutes

    Modes of Infusion and Doses

    These drugs are most effective when infused directly onto or into the thrombus.   They are rarely used systemically these days.  Various dosage protocols have been tried:-

    Original Low Dose Local Infusion protocols

    Streptokinase 5000 u/hour in a concentration of 100 u/ml

    Urokinase 20,000 u/hour  in 50 ml/hour

    These doses are usually given for 4 -5 days according to angiographic findings (assessed every 12 - 24 hours)

    Bleeding problems are more likely with these long infusions than with higher dose shorter infusions

    Higher Dose Local Streptokinase Therapy

    Three separate doses of streptokinase (1000 Units in 2 ml of saline) are given at 3 minute intervals directly onto the clot.   The catheter is then advanced and the 3 infusions are repeated, continuing like this until the vessel is clear. 20,000 -30,000 units over about 90 minutes are usually required

    Higher Dose Local Urokinase Therapy

    1000 -4000 Units/minute (often 100,000 Units/hour) is infused directly onto/into the clot.   Check angiography every 1 - 2 hours

    Up to 18 hours infusion may be required

    "Failure to see at least 10% lysis of the occluded segment  after 500,000 units is an indication to discontinue lytic therapy."

    Heparinization

    Heparinization for several days, beginning 12 hours after cessation of lytic therapy, is recommended to prevent re-thrombosis.

    Results

    • Low dose streptokinase is reported to achieve partial or complete lysis in 50 to 56% of cases
    • Higher dose urokinase produces lysis in 80 to  90% of cases and the lysis is more often complete than with streptokinase
    • Thrombosed bypass grafts of synthetic material have poorer results
    • Bleeding requiring plasma or cryoprecipitate occurs in 12-17% patients on low dose streptokinase, 2 to 4% on high dose streptokinase, and 3 to 6% on high dose urokinase
    • Renal artery occlusions have been lysed up to 10 days after thrombosis