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Patients with multiple myeloma have an increased prevalence of acquired platelet secretion defects and a disbalanced whole blood thrombin generation profile

1Synapse Research Institute, Maastricht, the Netherlands, Maastricht, Limburg, Netherlands, 2Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, Chapel Hill, North Carolina, United States, 3Department of Platelet pathophysiology, Synapse Research Institute, Maastricht, the Netherlands, Maastricht, Limburg, Netherlands, 4Department of Clinical Chemistry. Meander Medical Center, Amersfoort, Amersfoort, Utrecht, Netherlands, 5Meander Medical Center, Amersfoort, The Netherlands, Amersfoort, Utrecht, Netherlands, 6Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands, Utrecht, Utrecht, Netherlands, 7 Synapse Research Institute, Maastricht, Limburg, Netherlands, 8Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands, Maastricht, Limburg, Netherlands, 9Synapse Research Institute, Maastricht, the Netherlands, MAASTRICHT, Limburg, Netherlands

Abstract Number: PB0780

Meeting: ISTH 2022 Congress

Theme: Hemostatic Systems in Cancer, Inflammation and Immunity » Proteases and Cancer

Background: Multiple myeloma (MM) is associated with a mild thrombocytopenia and/or anemia as well as an increased risk of thrombo-embolism.

Aims: To determine if the disbalanced platelets and erythrocyte state play a role in the high thrombosis risk in patients with MM.

Methods: To study platelet and erythrocyte dependent haemostasis in MM patients, we conducted a case-control study in 21 MM patients and 21 related controls and measured thrombin generation in whole blood (WB-TG) and platelet poor plasma (PPP-TG), and the platelet activation profiles and platelet vitality in WB. Mann-Whitney U test was used to compare the groups. The study was approved by the Medical Ethical Committee of Maastricht University Medical Center, and patients and volunteers gave full informed consent according to the Helsinki declaration.

Results: In WB-TG, we observed that the median time to the thrombin Peak was 52% longer in MM patients than in controls, while the median endogenous thrombin potential until the Peak (ETPp) was 39% higher in MM-patients than in controls (Fig. 1). In line with these findings, platelet response to agonists, agonist induced platelet granule release, as well as the whole blood cell counts (platelets, erythrocytes and white blood cells) were decreased in MM patients compared to controls. The plasma TG experiments showed no differences between MM-patients and controls.

Conclusion(s): Our results show that patients with MM have a disturbed blood cell count, a disturbed platelet phenotype and a disbalanced WB-TG profile. This disbalance may explain the paradoxical high prevalence of thrombosis in MM patients, despite low platelet counts and impaired function.

Figure 1

Whole blood thrombin generation -WB-TG- in multiple myeloma -MM- patients and controls. Thrombin generation was stimulated with 0 pM and 1 pM tissue factor in whole blood of MM patients and controls, and Lag time -panel A-, time to the thrombin Peak -TTP, panel B-, Peak thrombin -panel C-, and endogenous thrombin potential until the peak -ETPp, panel D- are presented. Median and IQR are presented as error bars. Patients and controls on anticoagulant medication are indicated in grey. Mann-Whitney U test was used to compare the groups. * P < 0.05, ** P < 0.01.

To cite this abstract in AMA style:

Roest M, Sang Y, Li L, Remijn J, Fijnheer R, Urbanus R, Huskens D, Wan J, de Laat B, Konings J. Patients with multiple myeloma have an increased prevalence of acquired platelet secretion defects and a disbalanced whole blood thrombin generation profile [abstract]. https://abstracts.isth.org/abstract/patients-with-multiple-myeloma-have-an-increased-prevalence-of-acquired-platelet-secretion-defects-and-a-disbalanced-whole-blood-thrombin-generation-profile/. Accessed June 6, 2023.

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