Abstract
Venous thromboembolism (VTE) is a common complication in newly diagnosed symptomatic multiple myeloma (NDMM) patients. We explored cellular and plasma hypercoagulability in NDMM patients to identify relevant biomarkers that can be used in combination with clinical factors in the development of a risk assessment model (RAM) for VTE. Untreated patients (n = 144) with NDMM were prospectively enrolled, baseline biomarkers prior to anti-myeloma treatment and thromboprophylaxis initiation were obtained. These were compared against values in a group of healthy individuals with similar age and sex distribution. The primary study end point was symptomatic VTE occurrence. At 12-month follow-up cumulative VTE rate was 10.4%. NDMM patients showed biological signs of cellular and plasma hypercoagulability and endothelial cell activation. Procoagulant phospholipid clotting time (Procoagulant-PPL) was shorter, P-selectin levels lower and thrombin generation attenuated overall compared to healthy subjects. Longer Procoag-PPL®, lower endogenous thrombin potential (ETP), and higher levels of tissue factor pathway inhibitor (TFPI) were associated with VTE occurrence. Multivariate analysis showed that Procoag-PPL® and ETP were independent risk factors for VTE. We conclude that Procoag-PPL® and ETP can be prospectively incorporated into a RAM for VTE in MM in combination with clinical and disease risk factors.
Highlights
Multiple myeloma (MM) is among malignancies that significantly increase the risk of venousFotiou et al Blood Cancer Journal (2018)8:102 thromboembolism (VTE)[1]
Proteasome inhibitor (PI) based therapy was given to 64% of patients, immunomodulatory drug (IMiD) based therapy in 32%, and 4% received other regimens
The analysis showed that patients with Procoag-PPL® ≥47 had a 3.49 times higher risk of Venous thromboembolism (VTE) compared to patients with Procoag-PPL®
Summary
Multiple myeloma (MM) is among malignancies that significantly increase the risk of venousFotiou et al Blood Cancer Journal (2018)8:102 thromboembolism (VTE)[1]. The choice of therapy has been shown to affect the risk of VTE to a large extent. The rate of VTE is about 1–2% in patients who receive conventional therapies, such as melphalan and prednisone. The effect on VTE rate is multiplied when IMiDs are combined with corticosteroids and chemotherapy and incidence can be as high as 26%3,7. The International Myeloma Working Group (IMWG) statement and the European Guidelines propose a VTE risk assessment method to guide pharmacological thromboprophylaxis application[8,9,10,11,12,13,14]. Despite administration of thromboprophylaxis as per guidelines, the risk of residual VTE remains as high as 10%, revealing that the available RAM is suboptimal[3,15]
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