Pediatric Clinics of North America - CIPERJ

366 RODRIGUEZ & HOOTS
Antifibrinolytic agents, epsilon-aminocaproic acid and tranexamic acid,
both lysine derivatives, also are useful adjuvant therapy for patients who
have mild to severe hemophilia. They exert their effect by inhibiting the proteolytic
activity of plasmin and, therefore, inhibiting fibrinolysis. The use of
antifibrinolytic agents is indicated in the presence of mucosal bleeding, primarily
oral, nasal, and menstrual blood loss. Its use is contraindicated in presence
of hematuria because of increased risk for intrarenal or ureteral
thrombosis, in the presence of disseminated intravascular coagulation, or
thromboembolic disease. Both drugs are available for use in the United States
in an intravenous form (epsilon-aminocaproic acid at 100 mg/kg/dose every
6 hours; tranexamic acid at 10 mg/kg/dose every 6–8 hours). Currently,
only epsilon-aminocaproic acid is available for use in the United States
in an oral form.
Topical agents, such as fibrin sealant, which is prepared by mixing two
plasma-derived protein fractions (fibrinogen-rich concentrate and thrombin
concentrate), are used for local bleeding control in hemophilia. There are
concerns, however, regarding the use of bovine thrombin in this setting.
First, there seems to be a high rate (approximately 20% or higher) of antibody
formation [19] against thrombin and factor V, which may inactivate an
individual’s own endogenous factor V or thrombin production, thereby creating
a new bleeding diathesis. Another legitimate concern is the potential
risk for transmitting blood-borne pathogens, such as variant Creutzfeldt-
Jakob virus [20]. When available commercially, the use of recombinant
human thrombin will likely minimize these risks.
A phase 3, prospective, randomized, double-blind, comparative study
evaluating the safety and efficacy of topical recombinant human thrombin
and bovine thrombin in surgical hemostasis has been published [21]. The
primary objective of this study was to evaluate the efficacy of both products
whereas the secondary objective was to evaluate safety and antigenicity.
This multicenter study enrolled more than 400 patients, who were randomized
in a 1:1 ratio. The study showed that both topical agents had a comparable
efficacy of 95% with similar adverse events rates. A statistically
significant lower incidence of antibodies, however, was identified against recombinant
human thrombin (1.5%) compared with antibovine thrombin
(21.5%). Based on the results of this study, recombinant human thrombin
seems the preferred option to achieve topical hemostasis.
Recombinant factor VIIa is a Food and Drug Administration–approved
product used to promote hemostasis in patients who have hemophilia A or
B with inhibitors. Its mechanism of action includes binding of activated
factor VII to tissue factor, which activates factor X and leads to thrombin
generation. Recombinant factor VIIa also binds the surface of activated
platelets independent of tissue factor, activating factor X and leading to
thrombin generation. The standard dose in hemophilia with inhibitors is
90 to 120 mg/kg every 2 to 3 hours until hemostasis is achieved. Subsequent
dosing and interval is based on clinical judgment. At the present time, there