A 58-year-old man was diagnosed with a right parietal glioblastoma multiforme in June 2004. He underwent gross total resection, placement of Gliadel (BCNU, carmustine) wafers, and external beam radiation therapy (total 60 Gy) with daily concomitant temozolomide. This was followed by six cycles of monthly adjuvant temozolomide. During the first treatment cycle, he developed symptomatic, bilateral pulmonary emboli. He was anticoagulated with low molecular weight heparin (LMWH) followed by warfarin.
In April 2005, a routine follow-up magnetic resonance imaging scan demonstrated local tumor recurrence. In May 2005, he underwent a second resection and placement of GliaSite RTS. Approximately 6 weeks later, he was admitted to the inpatient oncology service for radioisotope loading, with a planned dose of 45 Gy to a depth of 0.5 cm. On hospital day 1, 15 ml of an aqueous solution of I-125 (Iotrex) was placed using a non-coring needle in the GliaSite subcutaneous port after a CT scan () confirmed proper GliaSite placement. At the time, the patient remained on his outpatient warfarin dose, though he had a subtherapeutic international normalized ratio of 1.4 (typical therapeutic range 2–3) ().
Figure 2 Non-contrast head CT scans performed during hospitalization. (a) The GliaSite planning CT (Hospital Day 1) shows no hemorrhage, (b) Approximately 8 hours after Iotrex removal from the GliaSite RTS (Hospital Day 5), there is a 4.7 × 3.2cm right (more ...)
Clinical events and laboratory data during hospitalization
The patient reported a mild headache over the next 3 days, but had no other neurologic symptoms. In response to subtherapeutic anticoagulation with warfarin, an infusion of intravenous unfractionated heparin was started without bolus on hospital day 2. The follow-up activated partial thromboplastin time (aPTT) was subtherapeutic, and a heparin bolus was administered and the infusion rate increased. This led to a transiently supratherapeutic aPTT ratio (). Later that day, owing to lack of intravenous access, the unfractionated heparin infusion was discontinued and weight-based LMWH (enoxaparin 90 mg subcutaneously twice daily) was started.
On hospital day 4, warfarin, which had been administered since admission, was discontinued. On hospital day 5, the patient received his morning enoxaparin dose. Approximately 4 hours later, the Iotrex aqueous I-125 solution was removed from the GliaSite RTS using a non-coring needle in the subcutaneous port. Shortly after this procedure, the patient reported worsening headaches. These persisted despite analgesics, and a non-contrast head computed tomography was performed (). This demonstrated a right parietal intraparenchymal hematoma. At the time, the patient’s international normalized ratio was 1.4, and the aPTT was normal (). The patient was transferred to the neurosurgical intensive care unit, where he received fresh frozen plasma.
On hospital day 6, the patient deteriorated clinically and was intubated. A repeat non-contrast head computed tomography (), performed approximately 5 hours after the previous scan, revealed dissection of the hematoma into the right ventricular system. The patient was taken to the operating room, where he underwent craniotomy, hematoma evacuation, removal of the GliaSite RTS, and intraventricular catheter placement. The platelet count, which had been normal throughout the hospitalization and was 149,000/ml at the time of hemorrhage, fell to 66,000/ml after surgery. Platelets were transfused. The patient did not recover and died on hospital day 14.