Comment

Fibrinolytic trials report a 1% to 6% incidence of major bleeding and a 10% incidence of moderate bleeding during the first 30 days. The most common sources of major bleeding are the gastrointestinal tract and procedure-related bleeding. The principles of management of major bleeding in STEMI patients treated with fibrinolytic therapy are summarized in Table 65-2. Steps include (1) stop antithrombotic therapies; (2) use local measures when possible to control bleeding; (3) draw blood to measure fibrinogen, prothrombin time (PT), aPTT, and possibly anti-Xa levels (to measure the anticoagulant effect of low-molecular-weight heparin) and to crossmatch blood; and (4) administer therapies to mitigate or reverse the effects of fibrinolytic, antiplatelet, and anticoagulant drugs.

The extent and duration of the lytic effects of fibrinolytic drugs is determined by their fibrin specificity. Whereas streptokinase produces profound and sustained depletion of fibrinogen (<100 mg/dL) that lasts for up to 24 to 48 hours, alteplase and other more fibrin-specific agents exert a less pronounced and more short-lived effect on fibrinogen levels. The aPTT and PT can be markedly prolonged in patients with hypofibrinogenemia. Normal coagulation can be restored by elevating fibrinogen level to at least 100 mg/dL. This can be readily achieved by infusing cryoprecipitate (recommended dose, 10 units). Fresh-frozen plasma also contains fibrinogen but requires administration of much larger volumes.

Platelet dysfunction caused by aspirin, clopidogrel, and fibrinolytic therapy cannot be specifically reversed, but infusion of donor platelets can help to restore platelet function. Platelet transfusion is generally reserved for patients with life-threatening bleeding because of concerns about the risk of recurrent MI. A single unit of single donor platelets can be expected to increase the platelet count by 50 to 60 × 10⁹/L. Even a small number (e.g., 10%-20%) of functional (nonaspirinated) platelets are sufficient to generate sufficient thromboxane to sustain normal platelet aggregation, but a much larger number of transfused platelets are need to overcome the antiplatelet effects of clopidogrel. In this case, bleeding was controlled with cryoprecipitate, and local measures and platelet infusions were not required.

Table 65-2 Management of Major Bleeding in Patients With ST-Segment Elevation Myocardial Infarction Treated With Fibrinolytic Therapy

aPTT, Activated partial thromboplastin time; FFP, fresh-frozen plasma; GI, gastrointestinal; INR, international normalized ratio; LMWH, low-molecular-weight heparin; PT, prothrombin time

* Also requires restoration of adequate hemostasis.

Table 65-3 Pharmacologic Characteristics of Oral Antiplatelet Drugs Commonly Used in the Management of Acute Coronary Syndromes

ADP, Adenosine diphosphate; bid, twice daily; COX, cyclooxygenase.

* After loading dose.

† Increased antithrombotic benefit was seen after the first hour in patients enrolled in the COMMIT trial who did not receive a loading dose, but maximum effect is not seen until after 4 to 6 hours.

Table 65-4 Pharmacologic Characteristics of Intravenous Glycoprotein IIb/IIIa Inhibitors Used in the Management of Acute Coronary Syndrome