The Use of Epsilon-Aminocaproic Acid in the Management of Dental Extractions in the Hemophiliac

Reid, William O.; Lucas, O.; Francisco, José; Geisler, Philip H.; Erslev, Allan J.

doi:10.1097/00000441-196408000-00007

Cited by 56 publications

(14 citation statements)

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“…Another indication of disturbed down-regulation of fibrinolysis in hemophilia is the efficacy of antifibrinolytic drugs such as tranexamic acid and ⑀-aminocaproic acid in controlling bleedings in regions of the body with high fibrinolytic activity (eg, the oral cavity). 18,19 Alternative mechanisms for the therapeutic effects of rFVIIa have been proposed. A potential mechanism, hypothesized in the literature, 20 involves enhancement of activation of TAFI.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A

Lisman

Mosnier

Lambert

et al. 2002

Blood

147

114

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Recombinant factor VIIa (rFVIIa) is a novel prohemostatic drug for patients with hemophilia who have developed inhibitory antibodies. The postulation has been made that hemophilia is not only a disorder of coagulation, but that hyperfibrinolysis due to a defective activation of thrombin activatable fibrinolysis inhibitor (TAFI) might also play a role. In this in vitro study, the potential of rFVIIa to downregulate fibrinolysis via activation of TAFI was investigated. rFVIIa was able to prolong clot lysis time in plasmas from 17 patients with severe hemophilia A. The prolongation of clot lysis time by rFVIIa was completely abolished by addition of an inhibitor of activated TAFI. The concentration of rFVIIa required for half maximal prolongation of clot lysis time (C lys½ -VIIa) varied widely between patients (median, 73.0 U/mL; range, 10.8-250 U/mL). The concentration of rFVIIa required for half maximal reduction of clotting time (C clot½ -VIIa) was approximately 10-fold lower than the C lys½ -VIIa value (median, 8.4 U/mL; range, 1.7-22.5 U/mL). Inhibition of TFPI with a polyclonal antibody significantly decreased C lys½ -VIIa values (median, 2.6 U/mL; range, 0-86.9 U/mL), whereas C clot½ -VIIa values did not change (median, 7.2 U/mL; range, 2.2-22.5 U/mL). On addition of 100 ng/mL recombinant full-length TFPI, a nonsignificant increase of C lys½ -VIIa values was observed (median, 119.2 U/mL; range, 12.3-375.0 U/mL), whereas C clot½ -VIIa values did not change (median, 8.8 U/mL; range, 2.6-34.6 U/mL). In conclusion, this study shows that rFVIIa both accelerates clot formation and inhibits fibrinolysis by activation of TAFI in factor VIII-deficient plasma. However, a large variability in antifibrinolytic potential of rFVIIa exists between patients. IntroductionTreatment of patients suffering from hemophilia is often complicated by the development of inhibitory antibodies. In approximately 25% to 30% of patients with hemophilia A 1 and in approximately 1% to 3% of the patients with hemophilia B, 2 inhibitors develop during their lifetime. A novel way to treat hemophilia patients with inhibitors is the administration of recombinant factor VIIa (rFVIIa, NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). 3 rFVIIa has been shown to be a safe and effective prohemostatic drug during bleeding episodes or surgery. 4,5 Advantages over traditional treatment (ie, factor concentrates) are the lack of antigenicity and viral safety of rFVIIa. 6,7 rFVIIa exerts its prohemostatic effect via enhancement of the extrinsic coagulation pathway in a tissue factor-dependent manner. 8 On binding of factor VIIa to tissue factor, factor VIIa is able to activate both factors IX and X, thereby leading to a primary generation of thrombin. At high concentrations of tissue factor, factor X is the preferred substrate for the tissue factor-VIIa complex, whereas at low tissue factor concentrations factor IX is preferably activated (for a review, see Rapaport and Rao 9 ). The ability of high-dose rFVIIa to overcome the inhibitory effect of plasma factor...

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Section: Introductionmentioning

confidence: 99%

Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A

Lisman

Mosnier

Lambert

et al. 2002

Blood

147

114

View full text Add to dashboard Cite

show abstract

“…Despite these considerations, currently available information may justify the use of antifibrinolytic therapy [22,25,27, rather than factor replacement. For example, despite high doses and routine postoperative use of factor VIII or factor IX by Biggs et al [I] and Walsh et a1 [45], the frequency of postoperative bleeding was greater than when lower doses were used in conjunction with EACA.…”

Section: Discussionmentioning

confidence: 99%

“…Reid employed EACA alone in I 1 patients who had 31 teeth extracted during 19 procedures [22]. These patients required no replacement therapy and bleeding was controlled with local packing and topical thrombin.…”

Section: Antifibrinolytic Therapymentioning

confidence: 99%

“…Most authors have recommended a fixed schedule of specific factor replacement (Table I), although there are reports of tooth extractions without abnormal bleeding, using only EACA [15,16,22,34] or hypnosis [29]. We have reviewed our experience with dental extractions in patients with hemophilia A or B and have concluded that extractions can be performed safely with fewer units of specific factor replacement than current recommendations suggest.…”

Section: Introductionmentioning

confidence: 99%

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Evidence that less replacement therapy is required for dental extractions in hemophiliacs

1984

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The requirements for factor VIII (AHF) or factor IX (PTC) of hemophilic patients undergoing dental extractions were evaluated to determine the minimum effective regimen. Sixteen patients underwent 19 operative procedures. The mean total dose of factor VIII or IX was 45.8 U/kg for 11 procedures with preoperative replacement therapy and 34.5 U/kg for the 8 without. Four patients received no replacement therapy at all. Our results compared favorably to published studies employing factor replacement alone or in combination with antifibrinolytic agents such as epsilon-amino-caproic acid (EACA), with respect to blood products utilized and duration of hospitalization. However, our patients received less factor replacement than usually suggested. General anesthesia with intubation, a common recommendation, was not required in any patients. Dental extractions can be carried out in hemophiliacs using less replacement therapy than currently recommended. In some circumstances, no replacement therapy may be necessary. The reported efficacy of antifibrinolytic agents in reducing the requirement for replacement therapy is difficult to assess because of the relatively large amount of prophylactic factor replacement used in conjunction with these agents.

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“…For extractions EACA has proved very useful when associated with other topical therapy [1,6,9,15,16]. It has recently been pointed out that by administering EACA in doses of 0.4 g/kg/day for 6-8 days after dental extraction it is possible to avoid substitutive therapy with fresh frozen plasma or with cryoprecipitates [1].…”

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confidence: 99%

Epsilon-Aminocaproic Acid for Synovectomy in Haemophilic Patients

et al. 1972

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The study of coagulation and fibrinolysis in synovectomised haemophilic patients, treated by a new haemostatic combined therapy, is reported. This treatment is based on a combination of replacement therapy (fresh frozen plasma and/or cryoprecipitates) and ε-aminocaproic acid; the replacement therapy is continued for only 6 days, beginning on the day of operation. Our combined therapy scheme promotes a more efficient haemostasis than substitutive therapy alone and allows a considerable saving in plasma or plasma fractions.

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The Use of Epsilon-Aminocaproic Acid in the Management of Dental Extractions in the Hemophiliac

Cited by 56 publications

References 0 publications

Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A

Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A

Evidence that less replacement therapy is required for dental extractions in hemophiliacs

Epsilon-Aminocaproic Acid for Synovectomy in Haemophilic Patients

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