Page 2344 - Williams Hematology ( PDFDrive )

2318 Part XII: Hemostasis and Thrombosis Chapter 135: Fibrinolysis and Thrombolysis 2319

60 minutes followed by a continuous infusion of up to 1 g/h, or the accelerated fibrinolysis often contributes to bleeding, particularly dur-
dose can be divided for intermittent administration. For oral treatment, ing the anhepatic phase. Treatment with antifibrinolytic agents can
the same loading dose can be administered followed by a maximum improve bleeding complications and decrease blood loss. 444–447
dose of 24 g/day in divided doses given every 1 to 6 hours as indicated. Primary fibrinolysis with bleeding may rarely occur with some
The use of tranexamic acid follows similar principles. The intravenous malignant tumors including prostatic carcinoma, 444–453 and also with
dose is 10 mg/kg followed by 10 mg/kg every 2 to 6 hours as needed. It heat stroke. Fibrinolytic activation routinely occurs as a compensa-
454
can also be administered orally in a dose of 25 mg/kg given three or four tory mechanism in consumption coagulopathy. If fibrinolytic activation
times daily. Both ε-aminocaproic acid and tranexamic acid are generally is prominent in DIC and other measures do not control bleeding, use of
well tolerated, but patients must be observed for possible thrombotic antifibrinolytic therapy can be helpful, but must be used with caution, to
complications. Additionally, thrombotic ureteral obstruction can occur avoid exacerbation of underlying thrombotic events.
in patients with upper urinary tract bleeding, and such patients should The contact system is activated during cardiopulmonary bypass,
be treated only after careful consideration. The risks of ureteral obstruc- resulting in alterations in the coagulation, fibrinolytic and complement
tion can be decreased by insuring high urine flow. Thrombotic compli- systems 455,456 and both postoperative bleeding and the need for large
cations can occur in patients with hypercoagulability, and thrombotic transfusion volumes can be a major problems. Several trials of antifi-
events can be precipitated or worsened in patients with disseminated brinolytic therapy have established that total blood loss and transfusion
intravascular coagulation (DIC). Myonecrosis is a rare complication. requirements can be reduced, with aminocaproic acid and tranexamic
Minor complications, including rash, abdominal discomfort, nausea, acid often used for this purpose. 450,451,457–460 Antifibrinolytic therapy can
and vomiting, are reported. also be useful in treating bleeding associated with some snakebites and
Aprotinin is a naturally occurring, broad-spectrum, proteinase following administration of fibrinolytic therapy.
inhibitor derived from bovine lung. 425–427 It has both antiinflamma- In hemophilia or von Willebrand disease, bleeding associated with a
tory and antifibrinolytic properties. Until recently, aprotinin was used local lesion such as dental extraction may also respond to antifibrinolytic
in the United States for reducing perioperative blood loss and blood therapy. Both the oral and urinary mucosas are rich in fibrinolytic activ-
transfusions in patients undergoing cardiopulmonary bypass. How- ity, and inhibition of normal fibrinolysis can prevent local bleeding, such
ever, its use is associated with an increased risk of postoperative renal as after prostatectomy. 461–463 Similarly, endometrial fibrinolysis contrib-
dysfunction, cardiac and cerebral events, 428,429 and of increased short- utes to menstrual bleeding, and antifibrinolytic therapy can be useful in
and long-term mortality in patients who received aprotinin compared treating menorrhagia. 464,465 Antifibrinolytic therapy may also be useful in
to ε-aminocaproic acid, tranexamic acid, or placebo. In a retrospective rare cases of Kasabach-Merritt syndrome in which a giant hemangioma
analysis of electronic records from 33,517 aprotinin recipients and is associated with consumption coagulopathy. 466,467 Antifibrinolytic ther-
44,682 ε-aminocaproic acid recipients, the unadjusted risk of death apy has been used in treating gastrointestinal or genitourinary bleeding
within the first 7 days after coronary artery bypass graft was 4.5 percent in patients with severe thrombocytopenia, ulcerative colitis, hereditary
for aprotinin recipients compared to 2.5 percent for ε-aminocaproic hemorrhagic telangiectasia, traumatic hyphema, following tonsillectomy,
acid recipients. The relative risk of death was significantly increased in and with subarachnoid hemorrhage. However, caution is advised in the
430
the aprotinin group (relative risk: 1.64; 95 percent CI 1.50 to 1.78). latter condition, as rebleeding may be decreased with antifibrinolytic
Another retrospective study found that use of aprotinin was associated therapy, but vasospasm and distal ischemia may worsen. 467
with both a significantly increased mortality risk at 1 year, and a larger
431
risk-adjusted increase in serum creatinine (p <0.001). The prospec-
tive Blood Conservation Using Antifibrinolytics in a Randomized Con- REFERENCES
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