Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures

Authors

  • Barbara A. Konkle,

    1. From the Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;
    2. Hematology/Oncology, the Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts;
    3. Hematology and Transfusion Medicine, St. Elizabeth's Medical Center, Boston, Masachusetts;
    4. Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana;
    5. Baylor University Medical Center, Dallas, Texas;
    6. GTC Biotherapeutics, Inc., Framingham, Massachusetts.
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  • Kenneth A. Bauer,

    1. From the Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;
    2. Hematology/Oncology, the Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts;
    3. Hematology and Transfusion Medicine, St. Elizabeth's Medical Center, Boston, Masachusetts;
    4. Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana;
    5. Baylor University Medical Center, Dallas, Texas;
    6. GTC Biotherapeutics, Inc., Framingham, Massachusetts.
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  • Robert Weinstein,

    1. From the Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;
    2. Hematology/Oncology, the Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts;
    3. Hematology and Transfusion Medicine, St. Elizabeth's Medical Center, Boston, Masachusetts;
    4. Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana;
    5. Baylor University Medical Center, Dallas, Texas;
    6. GTC Biotherapeutics, Inc., Framingham, Massachusetts.
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  • Anne Greist,

    1. From the Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;
    2. Hematology/Oncology, the Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts;
    3. Hematology and Transfusion Medicine, St. Elizabeth's Medical Center, Boston, Masachusetts;
    4. Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana;
    5. Baylor University Medical Center, Dallas, Texas;
    6. GTC Biotherapeutics, Inc., Framingham, Massachusetts.
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  • Houston E. Holmes,

    1. From the Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;
    2. Hematology/Oncology, the Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts;
    3. Hematology and Transfusion Medicine, St. Elizabeth's Medical Center, Boston, Masachusetts;
    4. Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana;
    5. Baylor University Medical Center, Dallas, Texas;
    6. GTC Biotherapeutics, Inc., Framingham, Massachusetts.
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  • Judith Bonfiglio

    1. From the Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;
    2. Hematology/Oncology, the Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts;
    3. Hematology and Transfusion Medicine, St. Elizabeth's Medical Center, Boston, Masachusetts;
    4. Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana;
    5. Baylor University Medical Center, Dallas, Texas;
    6. GTC Biotherapeutics, Inc., Framingham, Massachusetts.
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  • ABBREVIATIONS:

    AT = antithrombin; DVT = deep venous thrombosis; PBPC = peripheral blood progenitor cell; pdAT = plasma-derived antithrombin; PE = pulmonary embolism; rhAT = human antithrombin.

  • KAB was an employee of the US government when the study was performed. JB is an employee of GTC Biotherapeutics. Recombinant human AT was provided by GTC Biotherapeutics.

Address reprint requests to: Barbara A. Konkle, MD, Hematology/Oncology, PMC, MAB 103, 39th and Market St., Philadelphia, PA 19014; e-mail: konkleb@mail.med.upenn.edu .

Abstract

BACKGROUND : Hereditary antithrombin (AT) deficiency is associated with a significant risk of venous thromboembolism. Patients with this disorder frequently require long-term anticoagulation. Discontinuation of anticoagulation for childbirth or surgery may carry a substantial thrombotic risk. For this reason, replacement with AT concentrate has been used when anticoagulation is interrupted. A new recombinant human AT concentrate, produced using transgenic technology, has recently been developed.

STUDY DESIGN AND METHODS : Human recombinant AT (rhAT) was provided by GTC Biotherapeutics, Inc. on a compassionate-use basis for five patients with hereditary AT deficiency who underwent six surgical procedures. Patients were treated perioperatively. Dosing was determined individually by the investigators with a goal of maintaining an AT activity of 80 to 150 percent.

RESULTS : There was no clinical evidence of thrombosis or bleeding. Four of the five patients had postoperative duplex ultrasound studies of the lower extremities, which showed no evidence of acute thrombosis. Four patients were tested for antirecombinant rhAT antibodies postoperatively and were negative.

CONCLUSION : These case reports indicate that rhAT can provide effective support for AT-deficient patients who undergo surgery. Further study of this product is needed to define optimal dosing and further assess clinical response.

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