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2316 Part XII: Hemostasis and Thrombosis Chapter 135: Fibrinolysis and Thrombolysis 2317

Key points include early, accurate angiographic diagnosis, appropri- TABLE 135–8. Principal Uses of Antifibrinolytic Agents
ate intrathrombic catheter positioning, and, in some cases, definitive
endovascular or surgical procedures. 399–402 Evidence favors mechanical Condition Comment
thromboembolectomy as adjunctive therapy for acute limb ischemia SYSTEMIC FIBRINOLYSIS
resulting from peripheral arterial occlusion. 403
α -Plasmin inhibitor or Rare inherited disorders
2
plasminogen activating
OTHER INDICATIONS inhibitor (PAI)-1 deficiency
Thrombolytic therapy has been useful in treating acute venous and Acute promyelocytic Must distinguish fibrinolysis
arterial occlusions in a wide variety of sites. Reports document suc- leukemia from disseminated intravascu-
cessful treatment of intraabdominal thrombosis including Budd- lar coagulation (DIC)
Chiari Syndrome, portal vein thrombosis, 405–407 and mesenteric vein Cirrhosis and liver Occasional cases of cirrhosis;
404
thrombosis. 407–409 Thrombolytic agents are frequently used to open transplantation common in anhepatic phase of
thrombosed central venous catheters, 410–413 as well as access devices for liver transplantation
hemodialysis. 414–418 Malignancy Occasional cases of prostate
and other carcinomas
MANAGEMENT OF BLEEDING COMPLICATIONS DIC Must be used with caution;
thrombosis can result
Bleeding complications are more frequent with fibrinolytic than with Cardiopulmonary bypass Decreases blood loss and
anticoagulant therapy and require rapid diagnosis and management. transfusion needs
The most serious complication, intracranial hemorrhage, occurs in Fibrinolytic therapy Can be used in treating
approximately 1 percent of patients and is associated with a high mor- bleeding complications
tality and serious disability in survivors. Risk factors for intracranial Localized fibrinolysis
hemorrhage, including prior stroke, serious head trauma, intracranial Hemophilia and von Willebrand Decreases bleeding after dental
surgery, tumor or vascular disease such as aneurysms or arteriovenous disease extractions and possibly other
malformation and uncontrolled hypertension, are strong contraindica- procedures
tions to fibrinolytic therapy. Bleeding is most common at sites of inva- Prostatectomy Can decrease postoperative
419
sive vascular procedures or preexisting gastrointestinal or genitourinary bleeding
lesions, and should not interrupt therapy if it can be managed with local
pressure or other simple measures. Kasabach-Merritt syndrome May shrink hemangioma
Treatment of bleeding involves local measures as well as correc- Menorrhagia Often decreases bleeding
tion of the systemic hypocoagulable state resulting from proteolysis of
plasma proteins and platelets (Table 135–7). The fibrinolytic agent
420
should be discontinued, and most will be cleared rapidly, because of platelet dysfunction from proteolysis of surface proteins. Heparin can
the short half-life. For serious bleeding, an antifibrinolytic agent such be reversed by administration of protamine sulfate, and 1-deamino-8-
as epsilon aminocaproic acid can be administered, but will be effec- D-arginine vasopressin (DDAVP) may have some value in reversing
tive only if the fibrinolytic agent remains in the blood. Replacement of platelet dysfunction.
fibrinogen and other hemostatic proteins can be accomplished with cry-
oprecipitate and fresh frozen plasma, respectively; treatment should be
monitored with repeated coagulation tests. Administration of platelet ANTIFIBRINOLYTIC THERAPY
concentrates may also be useful because fibrinolytic therapy results in
Pharmacologic agents can be used to inhibit fibrinolytic bleeding, but
care must be exercised given the risk of thrombosis (Table 135–8). For
TABLE 135–7. Treatment of Fibrinolytic Bleeding example, in patients with consumption coagulopathies there may be
excessive activation of both the coagulation and fibrinolytic systems,
If intracranial bleeding is suspected, obtain imaging, consult
neurosurgery, and correct hemostasis as below. resulting in clinical manifestations of both bleeding and thrombosis. In
For major bleeding: this situation, inhibiting fibrinolysis to treat bleeding can precipitate or
worsen thrombosis.
Send diagnostic test: activated partial thromboplastin time
(aPTT), platelet count, and fibrinogen.
Attend to local hemostatic problems. Apply pressure if bleeding ANTIFIBRINOLYTIC AGENTS
related to arterial puncture. Proceed with general supportive Both ε-aminocaproic acid and tranexamic acid are synthetic lysine ana-
measures, including intravenous fluid hydration and transfu-
sion of packed red cells if indicated. Proceed with diagnostic logues. These agents inhibit fibrinolysis by competitively blocking bind-
evaluation for gastrointestinal or genitourinary tract bleeding. ing of Plg to lysine residues on fibrin. 421–424 Both can be administered
Correct abnormal hemostasis: orally or intravenously, have rapid absorption after oral administration
and are excreted primarily through the kidneys. Only ε-aminocaproic
Prevent further fibrinolysis: stop fibrinolytic therapy; consider acid is approved for use in the United States, with the exception that
ε-aminocaproic acid or tranexamic acid. tranexamic acid can be used for treatment of menorrhagia. Pharma-
Replacement therapy to repair hemostasis defect induced by cologically, tranexamic acid is approximately 10-fold more potent than
fibrinolytic therapy: give cryoprecipitate 5–10 U and 2 U fresh- ε-aminocaproic acid because of its higher binding affinity. Both drugs
frozen plasma; consider platelet transfusion. have a short half-life of 2 to 4 hours and must, therefore, be admin-
Correct other hemostatic defects: stop anticoagulant and anti- istered frequently. ε-Aminocaproic acid can be administered intra-
platelet agents; consider protamine to reverse heparin. venously with a loading dose of approximately 100 mg/kg over 30 to

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