Potential mechanisms of resistance to current antithrombotic strategies in Multiple Myeloma  

作　　者：Claire Comerford Siobhan Glavey Jamie M.O’Sullivan John Quinn 

机构地区：[1]Irish Centre for Vascular Biology,School of Pharmacy and Biomolecular Sciences,Royal College of Surgeons in Ireland,Dublin D02YNVV,Ireland [2]Department of Haematology,Beaumont Hospital,Dublin D09V2N0,Ireland [3]Hermitage Medical Clinic,Old Lucan Road,Dublin D20W722,Ireland [4]Department of Pathology,Royal College of Surgeons in Ireland,Dublin D02YNVV,Ireland [5]School of Medicine,Royal College of Surgeons in Ireland,Dublin D02YNVV,Ireland

出　　处：《Cancer Drug Resistance》2022年第1期214-228,共15页癌症耐药（英文）

摘　　要：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.

关 键 词：Multiple myeloma heparin resistance THROMBOPROPHYLAXIS venous thromboembolism thrombin generation testing ENDOTHELIUM IMMUNOGLOBULIN 

分 类 号：R73[医药卫生—肿瘤]