Elevated activated partial thromboplastin time during administration of first-generation adenoviral vectors for gene therapy for prostate cancer: identification of lupus anticoagulants.

OBJECTIVES: To evaluate the cause and significance of elevated activated partial thromboplastin time (aPTT) in a group of patients who received a first-generation adenoviral vector (Ad-OC-TK) delivering a toxic gene to prostate cancer cells as part of a Phase I clinical trial at the University of Virginia.
METHODS: Eleven subjects were injected intratumorally to metastatic lesions of prostate cancer in the prostatic fossa, retroperitoneal lymph nodes, or bone (iliac, ischium, or vertebrae). After the initial laboratory evaluation, patients with elevated aPTT underwent a series of additional tests, including mixing studies, coagulation factor, prekallikrein, and high-molecular-weight kininogen, and lupus anticoagulant studies (modified Russell viper venom time) with phospholipid correction, and a Staclot LA assay.
RESULTS: Of the 11 subjects who were enrolled in the trial, 6 had elevated aPTT values. Of the 6 patients, 3 had aPTT elevation of more than 10 seconds above normal. Two of the subjects with higher values demonstrated an inhibitory pattern with the factor VIII and XI assays, and the lupus anticoagulant studies were positive. No clinical sequelae to the elevated aPTT values were observed.
CONCLUSIONS: This is, to our knowledge, the first formal report of a first-generation adenoviral vector causing a slight transient elevation of the aPTT through the induction of an antiphospholipid antibody. No clinical sequelae related to elevated aPTT values were observed. The adenoviral protocol was safe; similar protocols should be aware of this phenomenon.