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2144 Part XII Hemostasis and Thrombosis

TABLE Management of Major Bleeding in Patients With ST-Segment Elevation Myocardial Infarction Treated With Fibrinolytic
146.2 Therapy
Steps Approach Considerations
Stop treatment Stop fibrinolytic drug Recovery of fibrinogen levels can take 24–48 hours after stopping streptokinase
Stop antiplatelet drugs Antiplatelet effects of aspirin and clopidogrel last for life span of platelets (5–10 days)
Stop anticoagulant Heparin has a half-life of about 40 minutes; LMWH has a half-life of 3–6 hours
Local measures Local pressure Sustained local pressure (e.g., for 30 minutes) may be required
Endoscopy and local injection a Can be used for upper or distal lower GI bleeding
Embolization a Used in rare situations such as life-threatening pulmonary or intraabdominal bleeding
Laboratory evaluation Fibrinogen Levels may be undetectable (<100 mg/dL)
PT and aPTT Results are uninterpretable if fibrinogen levels are low (<100 mg/dL)
Anti-Xa level PT (INR) and aPTT are elevated with warfarin; aPTT is prolonged with therapeutic
Cross-match blood doses of heparin but not with LMWH or fondaparinux
Chromogenic antifactor Xa assay for LMWH and fondaparinux; this test is unaffected
by low fibrinogen levels
To restore blood volume and maintain hemoglobin
Reversal of fibrinolytic Cryoprecipitate Recommended initial dose is 10 U; monitor by repeating fibrinogen level
effect FFP The half-life of fibrinogen is about 4 days
Requires large volumes (e.g., 2 L) to restore fibrinogen levels
Reversal of antiplatelet Platelet transfusion Increases the number of functional platelets but does not reverse the antiplatelet
effect effects of aspirin and clopidogrel
Also see text under heading “Antiplatelet Therapy”
Reversal of Protamine Protamine reverses heparin and partially reverses LMWH; it has no effect on
anticoagulant effect fondaparinux (also see Table 146.6)
a Also requires restoration of adequate hemostasis.
aPTT, Activated partial thromboplastin time; FFP, fresh frozen plasma; GI, gastrointestinal; INR, international normalized ratio; LMWH, low-molecular-weight heparin;
PT, prothrombin time.

compared with alteplase (1% vs. 1%), but reduced the rate of major and tirofiban, are the foundation antiplatelet therapies for the man-
noncerebral bleeding (4.7% vs. 5.9%; p < .0002), possibly reflecting agement of ACS. Although the use of GP IIb/IIIa antagonists has
its enhanced fibrin specificity. decreased since the introduction of clopidogrel, they retain a role in
high-risk ACS patients, particularly STEMI patients undergoing
5,6,10
Adjunctive Antithrombotic Therapy in Patients primary PCI. In 2015, the US Food and Drug Administration
approved cangrelor, a short-acting parenteral ADP receptor antago-
Receiving Fibrinolytic Drugs nist, for ACS patients undergoing PCI who have not received an oral
ADP receptor antagonist and who are not given a GP IIb/IIIa inhibi-
A compelling rationale exists to administer adjunctive antithrombotic tor. The pharmacologic characteristics of antiplatelet drugs commonly
therapy to STEMI patients treated with fibrinolytic therapy. Platelet- used in the management of ACS are summarized in Tables 146.3
rich thrombi that form after plaque rupture are relatively resistant to (oral drugs) and 147.4 (IV drugs).
degradation, and the use of concomitant antiplatelet and anticoagu-
lant therapy may help to promote clot lysis. Fibrinolytic drugs have
an early activating effect on platelets, and the plaque rupture site Oral Antiplatelet Drugs
remains prothrombotic after successful reperfusion therapy. Evidence
in support of the efficacy of adjuvant antiplatelet and anticoagulant Aspirin
therapy in patients with STEMI is summarized in the sections on
antiplatelet and anticoagulant therapy, respectively. Aspirin inhibits platelets by irreversibly blocking the platelet enzyme
cyclooxygenase-1, thereby preventing the formation of thromboxane
A 2 , a potent platelet agonist and vasoconstrictor. Despite having a
Intracranial Bleeding half-life of only 20 minutes, the antiplatelet effect of aspirin lasts for
the lifetime of the platelet (5–10 days) because platelets are anucleate
The most important side effect of fibrinolytic therapy is intracranial and lack the machinery to synthesize new enzyme. 11
bleeding, which affects up to 1% of patients and, in the majority of Multiple randomized trials have demonstrated the efficacy of
8
cases, is either fatal or permanently disabling. Risk factors for intra- aspirin for the prevention of recurrent MI, stroke, or death in patients
12
cranial bleeding include increasing age (particularly patients older with ACS. The ISIS-2 investigators evaluated the efficacy and safety
than the age of 75 years), history of prior stroke, uncontrolled blood of aspirin in 17,187 STEMI patients who were also randomized to
pressure, female sex, and low body weight. Bolus dose fibrinolytic receive or not to receive fibrinolytic therapy. Aspirin (162 mg/day),
therapy may be associated with a higher risk of intracranial bleeding compared with no aspirin, significantly reduced 35-day mortality
than fibrinolytic therapy administered by continuous IV infusion (see (9.4% vs. 11.8%; p < .00001) as well as nonfatal reinfarction (1.0%
Table 146.2 and box on Case 1: Bleeding After Fibrinolytic Therapy). 9 vs. 2.0%) and stroke (0.3% vs. 0.6%) without increasing bleeding.
The Antithrombotic Trialists’ Collaboration (ATTC) pooled the data
from 15 randomized trials of antiplatelet therapy (predominantly
ANTIPLATELET THERAPY with aspirin) involving 19,302 acute MI patients who were also
treated with fibrinolytic therapy. Compared with placebo or no
Aspirin, oral adenosine diphosphate (ADP) receptor antagonists, antiplatelet therapy, antiplatelet therapy given for a mean duration of
such as clopidogrel, prasugrel, and ticagrelor, and glycoprotein (GP) 1 month significantly reduced the composite outcome of MI, stroke,
IIb/IIIa (GP IIb/IIIa) antagonists, such as abciximab, eptifibatide, or death (10.4% vs. 14.2%; p < .0001).