Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group [see comments]

Abstract

Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.

The plasma turnover of transfused antithrombin concentrate in patients with acquired antithrombin deficiency

“…This depends largely on the half-life and recovery of the transfused material. Recovery in the patients studied was similar to earlier reports (Menache et al, 1990) and was unaffected by the underlying disease process ( Table 1). The mean half-life of antithrombin concentrate in patients with a congenital deficiency of antithrombin has been reported to be of the order of 60 h (Collen et al, 1977).…”

“…Guidelines on treatment are further complicated by the fact that there are a number of different antithrombin preparations available, each prepared by a different technique (Hoffman, 1989). Antithrombin recovery and half-life data have been reported in patients with congenital antithrombin deficiency, but less data are available from patients with an acquired deficiency (Schwartz et al, 1989;Menache et al, 1990). We report here studies of the plasma recovery and turnover rate of one antithrombin preparation (Bio Products Laboratory).…”

Prophylaxis and Treatment of Venous Thromboembolism in Individuals with Inherited Thrombophilia

“…71 Infusion of AT concentrate has been reported in the peripartum period to normalize AT circulating levels and allow a reduction in the heparin dosage. [73][74][75] The main suggestions for prevention of VTE during pregnancy and puerperium are summarized in Table 2.…”

Antithrombin III: physiology, deficiency, and replacement therapy

“…The mean AT 111 half-life of radiolabeled AT IW2 or AT 111 concentrates, assessed after administration in normal subjects or in hereditarily AT III-deficient patients, ranges from 60 to 70 hours.13-15 "Pasteurization" of AT I11 concentrates does not alter the turnover of the protein.13-" The AT 111 half-life is not modified by the concomitant administration of coumarin derivatives. 15,16 Administration of heparin produces a decrease in the circulating level of AT IIP7 and a significant shortening of the half-life,12 whereas oral anticoagulants may result in an increase of the circulating level. '* The effect of estrogens on the AT 111 circulating level remains controversial, but oral contraceptives containing estrogens are known to increase the risk of thrombosis in women with hereditary AT 111 deficiency.…”