Thrombolytics Lepirudin

Concomitant use with thrombolytic therapy Clinical trials in HIT patients have provided only limited information on the combined use of lepirudin and thrombolytic agents. The following dosage regimen of lepirudin was used in 9 HIT patients in the studies who presented with TECs at baseline and were started on both lepirudin and thrombolytic therapy (alteplase, urokinase, or streptokinase). 

Pay special attention to the fact that thrombolytic agents per se may increase the aPTT ratio. Therefore, aPTT ratios with a given plasma level of lepirudin are usually higher in patients who receive concomitant thrombolysis than in those who do not. 

Intracranial bleeding Following concomitant thrombolytic therapy with alteplase (tPA) or streptokinase may be life-threatening. Carefully assess the risk of lepirudin administration vs its anticipated benefit in patients with increased risk of bleeding. In particular, this includes the following conditions ... 

Drugs that may interact with lepirudin and increase the risk of bleeding include thrombolytics (eg, tPA, streptokinase) and coumarin derivatives (vitamin K antagonists). 

HIRUDINS THROMBOLYTICS t risk of bleeding complications when alteplase or streptokinase is co administered with lepirudin Additive effect on clotting cascade Watch for bleeding complications. Risk-benefit analysis is needed before co-administering this will involve availability of alternative therapies such as primary angioplasty... 

From the therapeutic point of view, prophylaxis of thrombosis must be continued after withdrawal of heparin, since even when there is no evidence of thrombosis in association with heparin-induced thrombocytopenia, thrombosis can follow after some days (52). Because of cross-reactivity, low molecular weight heparin should not be used when heparin has been withdrawn because of heparin-induced thrombocytopenia nor should warfarin be used, because of the risk of venous gangrene, at least until the thrombocytopenia has resolved. Patients with life-threatening or limb-threatening thrombosis can be treated with thrombolytic drugs. Current views are that two antithrombotic drugs should be used, for example danaparoid plus lepirudin (58). 

Platelet counts should be carefully monitored for any decline. If thrombocytopenia develops, the time course and severity should help differentiate which type of HIT exists. If HIT I is suspected, heparin may be continued with caution. If HIT II is suspected, heparin therapy should be discontinued and an alternate form of anticoagulation therapy begun. If a low platelet count is encountered with a thrombotic complication, heparin should be discontinued immediately. Thrombolytic therapy or embolectomy may be necessary. Lepirudin (recombinant hirudin) is... 

Heparin and warfarin are anticoagulants that affect activation or formation of proteins in the clotting cascade. Lepirudin is an inhibitor of thrombin, and aminocaproic acid is an inhibitor, not an activator, of fibrinolysis and the conversion of plasminogen to plasmin. Reteplase is the only thrombolytic drug listed. The answer is (D). 

The manufacturers of lepirudin say that no formal interaction studies have been done but they reasonably warn that the concurrent use of lepirudin and other thrombolytics (they name alteplase and streptokinase) may increase the risk of Isleeding complications and considerably enhance the effect of lepirudin on the aPTT. They also warn about the increased risks of bleeding if antiplatelet drugs such as ciopidogrei, ticlopidine, abciximab, eptifibatide or tirofiban are used concurrently... 

Low-dose aspirin did not alter the pharmacokinetics or pharmacodynamic effects of ai atroban. Neither abciximab nor eptifibatide appeared to alter ai atroban pharmacokinetics. There is no pharmacodynamic interaction between bivalirudin and aspirin, ticlopidine, ciopidogrei, abciximab, eptifibatide or tirofiban. Nevertheless, the manufacturers warn of the increased bleeding risks if argatroban, bivalirudin or lepirudin are used with antiplatelet drugs or thrombolytics. 

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