Fibrinolytic activity in multiple myeloma
Münci Yağci1, Gülsan Türköz Sucak, Rauf Haznedar
1Gazi Medical School Division of Hematology, Ankara, Turkey. ayagci@gazi.edu.tr
Abstract:
The incidence of thromboembolic events is high as a result of disease, disease-related complications, and therapy in multiple myeloma (MM). In patients with hematologic tumors, impaired fibrinolysis may be present and may contribute to the development of thrombotic complications. Therefore, we designed a study to investigate fibrinolytic activity in MM. We compared plasma levels of interleukin (IL)-6, C-reactive protein (CRP), IL-1beta, IL-11, tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor-1 (PAI-1) activity, and global fibrinolytic capacity (GFC) in patients with MM (n = 66) and in control subjects (n = 18). The prevalence of venous thromboembolism was 4.5%, with a median follow-up period of 7 months in our myeloma group. Results are given as mean (median, range). Plasma levels of IL-6 (8.27 +/- 0.74 [9.65, 0.90-13.32] pg/mL versus 2.64 +/- 0.66 [1.80, 0.10-11.86] pg/mL, P < 0.001), CRP (45.57 +/- 9.92 [21.00, 1.34-330.00] mg/L versus 1.96 +/- 0.50 [1.05, 0.19-8.03] mg/L, P < 0.001), PAI-1 (7.40 +/- 0.67 [5.57, 2.40-31.80] IU/mL versus 4.73 +/- 0.65 [3.60, 2.32-11.00] IU/mL, P < 0.01), GFC score (1.90 +/- 0.02 [2, 1-3] versus 2.50 +/- 0.14 [3, 1-3], P < 0.001) were increased compared with controls. In patients with MM, the level of IL-6 was positively correlated with CRP (r = 0.66, P < 0.001), IL-1beta (r = 0.29, P < 0.05), and PAI-1 (r = 0.35, P < 0.01) and negatively correlated with GFC (r = -0.37, P < 0.01). CRP level was positively correlated with plasma PAI-1 level (r = 0.40, P < 0.01) and negatively correlated with GFC (r = -0.44, P < 0.001). A significant negative correlation between PAI-1 level and GFC (r = -0.75, P < 0.001) was also detected. IL-1beta levels were negatively correlated with tPA level (r = -0.26, P < 0.05). These results suggest that patients with myeloma have a decreased fibrinolytic activity mainly because of increased PAI-1 activity. In MM, increased PAI-1 activity seems to be related with elevated IL-6 level. MM should be considered as a hypercoagulable state as a result of both increased procoagulant activity and decreased fibrinolytic activity. Achieving a plateau by means of conventional chemotherapies does not improve the decreased fibrinolytic activity.
Insights
Multiple myeloma (MM) patients exhibit reduced fibrinolytic activity, primarily due to elevated plasminogen activator inhibitor-1 (PAI-1). This impaired clotting regulation contributes to a hypercoagulable state in MM, unaffected by conventional therapies.
Area of Science:
- Hematology
- Oncology
- Thrombosis Research
Background:
- Multiple myeloma (MM) is associated with a high incidence of thromboembolic events.
- Impaired fibrinolysis in hematologic tumors may contribute to thrombotic complications.
Purpose of the Study:
- To investigate fibrinolytic activity in patients with multiple myeloma.
- To compare plasma levels of key inflammatory markers and fibrinolytic factors between MM patients and healthy controls.
Main Methods:
- Compared plasma levels of interleukin-6 (IL-6), C-reactive protein (CRP), IL-1beta, IL-11, tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor-1 (PAI-1) activity, and global fibrinolytic capacity (GFC).
- Included 66 patients with MM and 18 healthy control subjects.
- Analyzed correlations between inflammatory markers and fibrinolytic parameters.
Main Results:
- MM patients showed significantly increased levels of IL-6, CRP, and PAI-1 compared to controls.
- Global fibrinolytic capacity (GFC) was significantly decreased in MM patients.
- Elevated IL-6 and CRP levels correlated positively with PAI-1 and negatively with GFC.
- PAI-1 activity was strongly negatively correlated with GFC.
Conclusions:
- Multiple myeloma patients exhibit decreased fibrinolytic activity, primarily driven by increased PAI-1.
- Elevated PAI-1 activity in MM appears linked to higher IL-6 levels.
- MM should be recognized as a hypercoagulable state due to both procoagulant and hypofibrinolytic activities, which are not improved by standard chemotherapy.
