Phosphatidylserine-exposing cells contribute to the hypercoagulable state in patients with multiple myeloma

Area of Science:

• Hematology
• Oncology
• Vascular Biology

Background:

• Multiple myeloma (MM) patients exhibit a higher risk of thromboembolic events, especially when treated with immunomodulatory drugs (IMiDs) and dexamethasone.
• The precise mechanisms underlying the hypercoagulable state in MM and optimal prophylactic strategies remain under investigation.

Purpose of the Study:

• To investigate the role of phosphatidylserine (PS) in supporting procoagulant activity (PCA) in patients with multiple myeloma.
• To determine if PS exposure on blood cells and endothelial cells (ECs) contributes to the hypercoagulable state in MM.

Main Methods:

• Flow cytometry and confocal microscopy were used to analyze PS exposure on blood cells and ECs.
• Procoagulant activity was assessed through clotting time, coagulation complex assays, and fibrin production.
• In vitro studies involved incubating ECs with patient or healthy subject serum and evaluating PS exposure and PCA.

Main Results:

• Patients with MM showed significantly higher percentages of PS-positive blood cells compared to healthy subjects.
• MM patient serum induced greater PS exposure on ECs in vitro.
• PS-positive cells from MM patients and ECs treated with patient serum exhibited shortened coagulation times, increased factor Xa generation, and enhanced thrombin formation.
• Combined treatment with IMiDs and dexamethasone further increased PS exposure on erythrocytes, platelets, leukocytes, and ECs.

Conclusions:

• Elevated PS exposure on blood cells and ECs is implicated in the hypercoagulable state observed in multiple myeloma patients.
• Targeting PS may represent a novel therapeutic approach for preventing thrombosis in this patient population.