title: Pharmacokinetics of low molecular weight heparin in patients with malignant tumors.
abstract: Cancer patients have an increased risk for venous thromboembolism (VTE). Low molecular weight heparin (LMWH) is the mainstay of VTE treatment in these patients. Heparanase, which degrades heparin and LMWH, is an enzyme secreted from a variety of malignant tumors. The objective of this study was to elucidate the pharmacokinetics of LMWH in patients with locally advanced or metastatic cancer. A total of 10 cancer patients with VTE treated with the LMWH enoxaparin at a standard dose of 1 mg/kg every 12 h were enrolled. Blood samples were obtained before the injection of LMWH and at 1, 2, 3, 4, 6, and 8 h after LMWH administration, and they were tested for anti-factor Xa activity and heparanase levels. Peak anti-Xa activity was achieved 2-8 h after subcutaneous administration of LMWH. Six patients did not reach a therapeutic anti-Xa activity target (0.6-1.2 IU/ml) at 4 h after LMWH administration. Four patients did not reach anti-factor Xa values of 0.6 IU/ml throughout the trial. The median anti-Xa activity before LMWH injection was 0.24 IU/ml (range 0.07-0.7 IU/ml), as opposed to 0.52 IU/ml in historical controls. The median anti-Xa activity 4 h after LMWH injection was 0.58 IU/ml (range 0.22-1.23 IU/ml), as opposed to 1.2 IU/ml in historical controls. The blood level of heparanase in patients with malignancy and VTE was 6.24 ± 4.3 ng/ml, compared with 2.67 ± 1.09 ng/ml in cancer-free, age-matched, normal controls. In this pilot study, a substantial proportion of cancer patients suffering from VTE and treated with LMWH had subtherapeutic anti-Xa activity.
authors.affiliation: aDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York bInstitute of Heart, Vascular, and Stroke Care, Massachusetts General Hospital, Boston, Massachusetts, USA cBlood Bank and Hematology Laboratory, Shaare Zedek Medical Center dDepartments of Oncology and Hematology, Shaare Zedek Medical Center eFaculty of Medicine, Hebrew University, Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Nasser
authors.forename: Mira
authors.initials: M
authors.lastname: Na'amad
authors.forename: Ido
authors.initials: I
authors.lastname: Weinberg
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Gabizon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017984:Enoxaparin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000150:complications* / Q000473:pathology; D010865:Pilot Projects; D054556:Venous Thromboembolism / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000099175:Heparanase
chemical_list: D017984:Enoxaparin; D015951:Factor Xa; D005966:Glucuronidase; D000099175:Heparanase