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2312 Part XII: Hemostasis and Thrombosis Chapter 135: Fibrinolysis and Thrombolysis 2313

PRINCIPLES OF THERAPY prolonged depending on the intensity of the lytic state. Tests reflecting
The basic principle of all fibrinolytic therapy is administration of suf- Plg activation, such as the euglobulin clot lysis time, will be abnormal.
ficient Plg activator to achieve a high local concentration at the site of Platelet membrane proteins may also be degraded, resulting in abnor-
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the thrombus, thereby accelerating conversion of Plg to plasmin, and mal platelet function. Overall, these effects contribute to a hypoco-
increasing the rate of fibrin dissolution. However, if large amounts of agulable lytic state that may be beneficial for vessel patency, but may
Plg activator overwhelm the natural regulatory systems, plasmin may also exacerbate a bleeding complication. High doses of a nonspecific
be formed in the blood, resulting in degradation of susceptible proteins, activator, such as streptokinase, will cause a more marked lytic state,
the “lytic state.” In addition, if high concentrations of activator reach compared to that seen with a fibrin-specific agent such as reteplase.
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fibrin deposits at sites of injury, bleeding, often exacerbated by plasmic Patient selection for fibrinolytic therapy depends on careful con-
proteolysis of other proteins in the blood may ensue. sideration of risks and benefits (Table 135–4). For patients with acute
Several therapeutic agents, from both recombinant and natural myocardial infarction or stroke there is a higher tolerance of bleeding
sources, are available and approved for thrombolytic use (Table 135–3). complications, because lytic therapy can be lifesaving and limit disabil-
The degree of “fibrin specificity,” is critical in determining the intensity ity. Timing of treatment is also critical, with greater benefit achieved with
of action at the site of a thrombus. The plasma half-life of most agents earlier administration. Whereas fibrinolytic therapy for acute pulmonary
is short, ranging, for example, from 5 to 70 minutes for t-PA and anis- embolism may be lifesaving, the potential benefits for venous disease are
treplase, respectively. Decisions to administer by bolus versus contin- less clear and more likely to be associated with bleeding problems.
uous infusion, as well as the duration of therapy, are determined by
the agent’s half-life and the condition being treated. Regarding site of THROMBOLYTIC THERAPY FOR STROKE
delivery, systemic therapy via peripheral vein is simpler and does not Stroke is the third leading cause of death, and the leading cause of seri-
require specialized facilities, but results in greater systemic complica- ous disability in the United States. Its incidence has been declining in
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tions. Regional delivery with a catheter placed close to the proximal end
of the thrombus can provide a high local concentration with a smaller
total dose, thereby increasing the local effect and limiting systemic TABLE 135–4. Selection of Patients for Thrombolytic
exposure. Fibrinolytic therapy is often administered in combination Therapy
with an anticoagulant to block fibrin formation and with an antiplatelet Treat those most likely to respond and benefit
agent to limit continued platelet deposition. Anticoagulant therapy is
routinely continued after completion of fibrinolytic therapy to prevent Acute MI: Within 12 hours of onset; consider percutaneous
reocclusion. In addition, mechanical approaches such as percutaneous intervention
coronary intervention often play a vital role in removing the underlying Stroke: Ischemic stroke within 4.5 hours of symptom onset
cause of thrombosis. Peripheral arterial obstruction
The activation of plasmin has effects beyond the thrombus, Acute occlusions
including a reduction in fibrinogen, increase in fibrinogen degrada- Distal obstruction not correctable by surgery
tion products, and depletion of Plg and α -plasmin inhibitor. Screening Deep vein thrombosis
2
coagulation tests, including the activated partial thromboplastin time
(aPTT), prothrombin time (PT), and thrombin clotting time, will be Large proximal thrombi with symptoms for less than 7 days
(Chap. 134)
Pulmonary embolism
TABLE 135–3. Comparison of Plasminogen Activators Massive or submassive embolism, especially with hemody-
namic compromise
Agent Half-Life
(Regimen) Source (Approved) Antigenic (min) Avoid bleeding complications
Major contraindications
Streptokinase Streptococcus (Y) Yes 20
(infusion) Risk of intracranial bleeding
Urokinase Cell culture; No 15 Recent head trauma or central nervous system surgery
(infusion) recombinant (Y) History of stroke or subarachnoid bleed
Alteplase (t-PA) Recombinant (Y) No 5 Intracranial metastatic disease
(infusion) Risk of major bleeding
Anistreplase Streptococcus + No 70 Active gastrointestinal or genitourinary bleeding
(bolus) plasma product (Y) Major surgery or trauma within 7 days
Reteplase Recombinant (Y) No 15 Dissecting aneurysm
(double bolus) Relative contraindications
Saruplase Recombinant (N) No 5 Remote history of gastrointestinal bleeding
(scu-PA) Remote history of genitourinary bleeding
(infusion)
Remote history of peptic ulcer
Staphylokinase Recombinant (N) Yes Other lesion with potential for bleeding
(infusion)
Recent minor surgery or trauma
Tenecteplase Recombinant (Y) No 15
(bolus) Severe, uncontrolled hypertension
Coexisting hemostatic abnormalities
N, no; scu-PA, single chain urokinase-type plasminogen activator; Pregnancy
t-PA, tissue-type plasminogen activator; Y, yes.

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