Patients treated for acute VTE during periods of treatment-related thrombocytopenia have high rates of recurrent thrombosis and transfusion-related adverse outcomes.

Venous thromboembolism (VTE) is a common complication of hematologic malignancies. Prolonged periods of thrombocytopenia are experienced universally by patients undergoing treatment for these diseases, yet data to guide management of anticoagulation in this setting are lacking. To obtain data on the management and outcomes of VTE in patients with thrombocytopenia related to the treatment of hematologic malignancies. This was an observational cohort study of patients experiencing VTE during periods of treatment-related thrombocytopenia over a 5-year period at the Fred Hutchinson Cancer Research Center. Medical records were reviewed for diagnostic, treatment and outcomes data, including bleeding events (categorized by WHO criteria) and progression or recurrence of VTE. Eighty-two patients meeting inclusion criteria were identified. Forty-eight percent were male and the median age was 55. Sixty-seven patients received anticoagulation, 88% of these were managed with transfusion support for a platelet goal of 50 × 109/L. Thirty-one patients experienced bleeding events, 22 of which were grade 2 and nine of which were grade 3/4. The median platelet count at the time of bleeding event was 54 × 109/L. Seven patients experienced progression of thrombosis and/or recurrence. Eleven patients experienced transfusion reactions and 30 experienced volume overload requiring diuretics or dialysis. While bleeding events were not uncommon, the majority of events were non-major/non-clinically relevant. Most bleeding events occurred while the platelet count was within the 'goal' range of ≥50 × 109/L, and many patients experienced transfusion related adverse events. Prospective studies are urgently needed to identify the optimal transfusion strategy for these patients.

Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP).

BACKGROUND: Romiplostim is a peptibody protein that raises platelet counts during long-term treatment of patients with chronic immune thrombocytopenia (ITP). Clinical outcomes related to increased platelet counts include a reduced risk of bleeding and a potential risk of thrombosis. OBJECTIVE: To evaluate bleeding and thrombotic events occurring in chronic ITP patients during two phase 3, randomized, placebo-controlled, 24-week studies of romiplostim and during subsequent treatment in an open-label extension study. PATIENTS/METHODS: In the phase 3 trials, 125 patients were randomized to romiplostim or placebo; romiplostim dose was adjusted to maintain platelet counts of 50-200 x 10(9) L(-1). Patients who completed the phase 3 trials could enroll in the extension study in which all patients received romiplostim. RESULTS: In the phase 3 trials, a significantly greater percentage of patients treated with placebo (34%) had bleeding adverse events of moderate or greater severity than did patients treated with romiplostim (15%, P = 0.018). In the extension study, the incidence of bleeding adverse events of moderate or greater severity decreased from 23% of patients in the first 24 weeks to 12% after 24-48 weeks, remaining < or = 6% thereafter. The exposure-adjusted incidence of thrombotic events was 0.1 per 100 patient-weeks in the phase 3 studies, and 0.08 per 100 patient-weeks in the extension study where patients received romiplostim for up to 144 additional weeks. CONCLUSIONS: The incidence and severity of bleeding was decreased in chronic ITP patients treated with romiplostim compared with placebo, and the incidence of thrombotic events was not different between the two groups.