Systemic fibrinolytics (Table 7)
These work by activating plasminogen to plasmin, and reducing or saturating anti-plasmin (t1/2 = 2.5 days). Streptokinase has a variable plasma half-life depending on anti-streptokinase antibody levels. Recombinant tissue plasminogen activator (Alteplase) has a plasma half-life of four to five minutes only, but there is a smaller tissue pool with a half-life of about 40 minutes. Anti-plasmin levels and plasminogen levels will increase after cessation of treatment. Fibrinogen levels may decrease markedly, particularly after streptokinase.
Management: Active treatment of haemorrhage, or preparation for emergency surgery, may include anti-fibrinolytic agents (e.g. aprotinin or tranexamic acid) and cryoprecipitate/FFP to restore reduced fibrinogen levels. The fibrinolytic activity of these drugs should be minimal a couple of hours after cessation of treatment, but reduced levels of plasmin, anti-plasmin and fibrinogen may persist for longer.
Aspirin or clopidogrel
Platelet inhibition by either one of these drugs alone will produce a small increase in clinical bleeding time.
Management: No specific action is needed but in a patient on either of these drugs who is bleeding, platelet transfusion may be considered even with a normal or moderately reduced platelet count.
Aspirin and clopidogrel
Used together, these drugs result in a much more clinically significant platelet defect. Both agents block platelet receptors permanently (platelet lifespan = 10 days). Even if the last dose was given as long as five days ago, these drugs should still be considered as a cause of bleeding tendency.
Management: Platelet transfusion should be considered early in bleeding patients who have been on this combination of drugs.
Inhibitors of platelet surface receptors GPIIb/IIIa
High-avidity agents such as Abciximab
These bind strongly to platelet receptors and inhibit platelet function for 12−24 hours, but little active drug remains in the plasma at two hours after administration.
Management: The drug effect can be partially reversed by platelet transfusion.
Low-molecular-weight agents (e.g. Eptifibatide, Tirofibam)
These bind reversibly to platelet receptors and will also bind donor platelet receptors. The half-life of these agents is short (1.5−2.5 hours) and the effect on the patient’s own platelets should reverse over a few hours.
Management: Platelet transfusion will be of little benefit in the absence of thrombocytopenia.