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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Inhibitory effects of bortezomib on platelet aggregation in patients with multiple myeloma
Joanna Rupa-Matysek1, Lidia Gil1, Ewelina Wojtasińska1
1Department of Haematology, Poznan University of Medical Sciences, Poznań, Poland.
Introduction:
Multiple myeloma (MM) therapy affects prothrombotic and anticoagulant processes. Patients receiving thalidomide, especially in combination with steroids, are at increased risk of venous thromboembolism (VTE), while the incidence of VTE on bortezomib is low. In vitro studies indicate that bortezomib causes a reduction in ADP-induced platelet aggregation.
Objectives:
To analyse the influence of bortezomib on platelet aggregation induced by various agonists in patients with MM.
Patients And Methods:
A total of 30 patients (median age 57.5years) with relapsed/refractory MM receiving bortezomib-based regimens were analysed. Optical platelet aggregometry was performed with the agonists collagen, ADP and ristocetin and measured over two 21-day cycles. The results from two groups: those treated with bortezomib and thalidomide (BT group, n=11) and those without thalidomide (B group, n=19) were analysed.
Results:
During the second cycle, significantly decreased platelet aggregation was observed in the B group: 5μM ADP (p=0.0285, day 1 versus 8); 3.5μM ADP (p=0.0005, day 1 versus 8 and day 1 versus 11), collagen (p=0.0014, day 4 versus 8, day 4 versus 11), 1.25mg/ml ristocetin (p=0.0017, day 1 versus 8 and day 1 versus 11). Agonist-induced platelet aggregation tended to be reduced over time during the 1st cycle in group B. In the thalidomide group, significant platelet aggregation inhibition by collagen only was found. Transient reduction in platelet count was observed in all patients, but more prominently in group B.
Conclusion:
The inhibitory effects of prolonged exposure of bortezomib on platelet aggregation were demonstrated in relapsed/refractory MM patients, but antithrombotic activity of bortezomib should be clarified in further prospective studies.
Insights
Bortezomib therapy in multiple myeloma patients significantly reduced platelet aggregation, suggesting potential antithrombotic effects. Further studies are needed to confirm bortezomib's antithrombotic activity.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Multiple myeloma (MM) therapies influence blood clotting processes.
- Thalidomide increases venous thromboembolism (VTE) risk in MM patients, while bortezomib has a low VTE incidence.
- In vitro studies suggest bortezomib reduces platelet aggregation.
Purpose of the Study:
- To investigate the impact of bortezomib on platelet aggregation in multiple myeloma patients.
- To compare the effects of bortezomib-based regimens with and without thalidomide on platelet function.
Main Methods:
- Analyzed 30 relapsed/refractory MM patients on bortezomib-based regimens.
- Used optical platelet aggregometry with collagen, ADP, and ristocetin over two cycles.
- Compared patients treated with bortezomib and thalidomide (BT group) versus bortezomib alone (B group).
Main Results:
- Bortezomib monotherapy (B group) significantly reduced platelet aggregation induced by ADP, collagen, and ristocetin during the second cycle.
- Platelet aggregation tended to decrease over the first cycle in the B group.
- Thalidomide combination (BT group) showed significant inhibition only with collagen; transient thrombocytopenia occurred in all patients, more in the B group.
Conclusions:
- Prolonged bortezomib exposure inhibits platelet aggregation in MM patients.
- Bortezomib demonstrates potential antithrombotic activity, warranting further investigation.
- Prospective studies are required to fully elucidate bortezomib's antithrombotic role.
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