Abstract
Multiple Myeloma (MM) is a common haematological malignancy that is associated with a high rate of venous thromboembolism (VTE) with almost 10% of patients suffering thrombosis during their disease course. Recent studies have shown that, despite current thromboprophylaxis strategies, VTE rates in MM remain disappointingly high. The pathophysiology behind this consistently high rate of VTE is likely multifactorial. A number of factors such as anti-thrombin deficiency or raised coagulation Factor VIII levels may confer resistance to heparin in these patients, however, the optimal method of clinically evaluating this is unclear at present, though some groups have attempted its characterisation with thrombin generation testing (TGT). In addition to testing for heparin resistance, TGT in patients with MM has shown markedly varied abnormalities in both endogenous thrombin potential and serum thrombomodulin levels. Apart from these thrombin-mediated processes, other mechanisms potentially contributing to thromboprophylaxis failure include activated protein C resistance, endothelial toxicity secondary to chemotherapy agents, tissue factor abnormalities and the effect of immunoglobulins/“M-proteins” on both the endothelium and on fibrin fibre polymerisation. It thus appears clear that there are a multitude of factors contributing to the prothrombotic milieu seen in MM and further work is necessitated to elucidate which factors may directly affect and inhibit response to anticoagulation and which factors are contributing in a broader fashion to the hypercoagulability phenotype observed in these patients so that effective thromboprophylaxis strategies can be employed.
Highlights
BackgroundMultiple Myeloma (MM) is a common haematological malignancy that remains a significant therapeutic challenge despite major advances in both treatments and biological understanding of the disease
Carfilzomib is a second generation proteasome inhibitor with reported venous thromboembolism (VTE) rates of 5%-14% in clinical trials and thromboprophylaxis is recommended for MM patients receiving carfilzomib-containing regimens, the most effective thromboprophylaxis strategy remains to be determined, nor has the mechanism underlying carfilzomibassociated thrombosis been adequately studied[26-29]
No evidence for an in vitro LMWH resistance in those with MM compared to patients without MM Possible “heparin resistance” with no heparin effect seen in 22% of patients and hypercoagulability seen in certain patients Patients who had a thrombotic event exhibited significantly higher endogenous thrombin potential (ETP) and peak height values than those who did not have a thrombotic event Lower ETP values were associated with VTE occurrence
Summary
BackgroundMultiple Myeloma (MM) is a common haematological malignancy that remains a significant therapeutic challenge despite major advances in both treatments and biological understanding of the disease. Carfilzomib is a second generation proteasome inhibitor with reported VTE rates of 5%-14% in clinical trials and thromboprophylaxis is recommended for MM patients receiving carfilzomib-containing regimens, the most effective thromboprophylaxis strategy remains to be determined, nor has the mechanism underlying carfilzomibassociated thrombosis been adequately studied[26-29].
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.