A glycosaminoglycan inhibitor of thrombin: A new mechanism for abnormal hemostatic assays in cancer

Authors

  • Howard A. Liebman MD,

    Corresponding author
    1. William B. Castle Hematology Research Laboratory, Division of Hematology-Oncology, Department of Medicine, Boston City Hospital and Boston University School of Medicine, Boston
    • Division of Hematology-Oncology, FGH-I Building, Boston City Hospital, 818 Harrison Avenue, Boston, MA 02118
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  • Raymond Comenzo,

    1. William B. Castle Hematology Research Laboratory, Division of Hematology-Oncology, Department of Medicine, Boston City Hospital and Boston University School of Medicine, Boston
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  • Suzanne T. Allen,

    1. William B. Castle Hematology Research Laboratory, Division of Hematology-Oncology, Department of Medicine, Boston City Hospital and Boston University School of Medicine, Boston
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  • Jere M. Dilorio

    1. William B. Castle Hematology Research Laboratory, Division of Hematology-Oncology, Department of Medicine, Boston City Hospital and Boston University School of Medicine, Boston
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Abstract

The isolation and partial characterization of a novel anticoagulant from the plasma of a patient with metastatic prostate cancer is described. The patient had a prolonged activated partial thromboplastic time, prothrombin time and thrombin time which did not correct by mixing with normal plasma. The reptilase time was normal and the prolonged thrombin time was corrected with protamine sulfate suggesting a heparin-like anticoagulant. A glycosaminoglycan anticoagulant (GAC) was isolated from the patient's plasma. The inhibitory activity of the GAC was destroyed by treatment with chondroitinase ABC. The GAC migrated on agarose gel electrophoresis between keratin sulfate and heparan sulfate. Purified GAC possessed only 2% (W/W) of the antithrombin III cofactor activity of porcine heparin. In assays using purified fibrinogen, the GAC was shown to directly inhibit fibrinogen proteolysis by thrombin. It is concluded that this glycosaminoglycan anticoagulant directly inhibits thrombin clotting of fibrinogen and is a new mechanism for abnormal hemostatic assays in cancer.

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