Potential mechanisms of resistance to current anti-thrombotic strategies in Multiple Myeloma.pdf (667.33 kB)
Potential mechanisms of resistance to current anti-thrombotic strategies in multiple myeloma
journal contributionposted on 2022-07-21, 06:56 authored by Claire ComerfordClaire Comerford, Siobhan GlaveySiobhan Glavey, Jamie O'SullivanJamie O'Sullivan, John QuinnJohn Quinn
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.
CommentsThe original article is available at https://cdrjournal.com/
Published CitationComerford C, Glavey S, O'Sullivan JM, Quinn J. Potential mechanisms of resistance to current anti-thrombotic strategies in multiple myeloma. Cancer Drug Resist. 2022;5(1):214-228.
Publication Date7 March 2022
- Beaumont Hospital
- Irish Centre for Vascular Biology
- School of Pharmacy and Biomolecular Sciences
- School of Medicine
- Immunity, Infection and Inflammation
- Vascular Biology
- Health Professions Education
PublisherOAE Publishing Inc.
- Published Version (Version of Record)