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Clinical Relevance of Clot Selectivity

Clinical Relevance of Clot Selectivity. Action of Clot-Selective Agents. Action of Non-Clot-Selective Agents. (TNK-tPA, staphylokinase, t-PA). (r-PA, SK, n-PA, UK). Clot-selective Clot Blood vessel plasminogen activators. Non-clot-selective Clot Blood vessel plasminogen activators.

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Clinical Relevance of Clot Selectivity

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  1. Clinical Relevance of Clot Selectivity Action of Clot-Selective Agents Action of Non-Clot-Selective Agents (TNK-tPA, staphylokinase, t-PA) (r-PA, SK, n-PA, UK) Clot-selective Clot Blood vessel plasminogen activators Non-clot-selective Clot Blood vessel plasminogen activators

  2. TIMI-10B: Clinical Evidence of Increased Fibrin Specificity with TNK-tPA Fibrinogen Plasminogen 30 40 40 40 30 30 30 30 30 50 40 50 40 40 TNK-tPA 50 50 50 50 Percent Changes in Parameters (median) TNK-tPA A A A A A alteplase (t-PA) A alteplase (t-PA) 1 1 Hours Post-Dose Hours Post-Dose Cannon CP, Gibson CM, McCabe CH et al. Circulation. 1998;98:2805-2814.

  3. Lower Fibrinogen Levels Are Associated with Bleeding Wintrobs Clinical Hematology 9th Edition 100 mg / dl is needed for normal hemostasis Fibrinogen mg/dl Bleed Don’t Bleed Melerhenrich et al, Int J Cardiol 1998

  4. Fibrinogen Depletion and Bleeding Adapted from Smalling et al, Circ 1995;2725-2732 TNK: Fibrinogen remains within 10-15% of baseline TNK Wintrobs Clinical Hematology 9th Edition 100 mg / dl is needed for normal hemostasis

  5. ASSENT-2: Significantly Fewer Noncerebral Bleeding Events With TNK-tPA TNK-tPA t-PA P Value (n=8,461) (n=8,488) 26.4 29.0 0.0003 Total bleeds (%) 4.7 5.9 0.0002 Major bleeds (%) 21.8 23.0 0.0553 Minor bleeds (%) Units transfused 4.3 5.5 0.0002 Any - 1-2 units 2.6 3.2 - >2 units 1.7 2.2 ASSENT-2 Investigators. Lancet. 1999;354:716-722.

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