Stratification of Vascular Profile in Multiple Myeloma Patients Using Thrombin Generation Test

Introduction: Multiple myeloma (MM) is an hematological disease linked to a high thrombotic risk, estimated at around 10%/year, irrespective to disease onset. An important proportion of MM patients presents at least one of the well-defined vascular risk factors, such as diabetes, cardiac disease, hypertension or hyperlipidemia, which contribute to thrombotic risk. Thrombin Generation Test (TGT) could be an useful biomarker reflecting the prothrombotic profile of MM patients.

Aim: To evaluate the potential correlation between vascular risk factors and TGT in MM patients.

Materials and methods: This is a monocentric, prospective, non-interventional study on a cohort of 82 MM patients referred to the Hemostasis Center at Tenon University Hospital. Patients receiving already anticoagulant treatment of any kind were excluded. Thrombin generation was performed at their first visit using the Calibrated Thrombogram Assay (CAT®,Stago, Genevilliers, France), according to manufacturer's instructions. We collected all TGT parameters: lag time (LT), Endogenous Thrombin Potential (ETP) and Mean Rate Index (MRI).We also measured factor VIII activity (FVIII). Results were statistically analyzed using a two-sample t-test.

Results: Among 82 patients with a male/female ratio of 44/35 and a median age at 65.2 years, 39 patients (48%) presented at least one cardiovascular risk factor (group A) and 42 had no vascular risk factors (group B) The LT value was reduced but not reaching a statistical difference between groups A and B (3 vs 3.95 sec, p= 0.8). MRI representing velocity was statistically shorter in group A (100 vs 118 nmol/min , p< 0.001). Surprisingly, ETP was significantly reduced in group A (1392 vs 1717 nmol/l x min, p < 0.001). FVIII levels were increased in group A (216% vs 192 %, p<0.05).

Conclusion: MM hypercoagulability can be easily identified with MRI, a chronometric TGT parameter. Increased FVIII levels observed in vascular patients are also facilitating an accelerated thrombin generation and are correlated with an endothelial activation. ETP decrease, reflecting the link between both content and container, must be seen as an adaptative response. Thus, endothelial activation could lead to TFPI release and this particular TGT profile in high vascular risk MM patients with a hypercoagulable state.