The hypercoagulable state in multiple myeloma: The contribution of thrombin generation test

Abstract

Background Multiple myeloma is a hematologic malignancy which confers a high venous thromboembolic risk. This risk is linked to patient‐related factors, disease‐specific mechanisms, and antimyeloma therapy, especially immunomodulatory drugs. Some studies have suggested that the thrombin generation assay may be a predictive marker of thrombosis. This study aimed to assess the hypercoagulable state in patients with multiple myeloma at diagnosis and after myeloma therapy. Methods Thirty‐one patients with multiple myeloma were included in a prospective study and were compared with 31 matched controls with age and gender. Thrombin generation assay was performed in patients at diagnosis prior to treatment initiation and at the end of myeloma therapy, and in controls. Parameters of lag time, peak thrombin concentration, time to peak, endogenous thrombin potential, and velocity index were analyzed. Results Median age of patients at diagnosis was 58 years (11 men and 20 women). Twenty‐three patients (74%) were classified as high vascular risk and received thromboprophylaxis. No thromboembolic events have been reported during follow‐up, except a symptomatic pulmonary embolism in one patient which occurred at diagnosis. At baseline, patients with myeloma had significantly elevated velocity index as compared to controls (178 vs 128 nmol/L/min; P = .013). High‐risk patients showed an elevation of plasma thrombin generation as compared to low‐risk patients (endogenous thrombin potential = 1244 vs 1052 nmol/L/min; P = .043). Myeloma therapy did not significantly change the thrombin generation parameters. Conclusion Thrombin generation appears to be higher in patients with myeloma compared with controls, especially in high‐risk patients, and does not change significantly after treatment completion.

Approach to Contemporary Risk Assessment, Prevention and Management of Thrombotic Complications in Multiple Myeloma

“…A recent study assessed thrombin generation, procoagulant phospholipids (PPL), neutrophil extracellular traps (NETs) and circulating microvesicle (MV)-associated TF in 38 patients and 19 MGUS patients, and compared them to healthy controls [ 14 ]. As confirmed by other studies [ 38 , 39 , 40 ], MM and MGUS patients have increased thrombin generation and PPL activity compared to healthy controls. Cell-free DNA (cfDNA) is not a specific marker of NETs and increased thrombotic risk in MM patients, but it may reflect NETs formation [ 41 , 42 , 43 ].…”

Patients With Multiple Myeloma Have a Disbalanced Whole Blood Thrombin Generation Profile

“…Several studies have tried to study coagulation in MM-patients with standard plasma thrombin generation profiles. The results of those studies were inconclusive: some studies observed an increased TG (ETP) in PPP ( 29 – 32 ), other studies, including ours, found no difference between MM patients and controls ( 33 , 34 ) while there are also studies that reported a reduced TG (ETP) in MM patients ( 35 , 36 ). One study observed no effect on the ETP and Peak, however, the TTP was reduced and the velocity index increased in MM patients compared to controls ( 37 ).…”

Analysis of Coagulation Abnormality in Patients with Multiple Myeloma and Its Clinical Significance

“…In addition, tumor cells metastasize and invade tissues and organs, resulting in tissue damage and endothelial cell damage. After endothelial cell injury, a large number of tissue factors can be released to activate the body's coagulation system, which then leads to coagulation-fibrinolysis dysfunction in patients [ 9 , 10 ]. D-dimer (D-D), fibrinogen (FIB), prothrombin time (PT), etc.…”