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Hemostatic abnormalities and increased vascular endothelial cell markers in patients with red cell fragmentation
1Second Department of Internal Medicine, Mile University School of Medicine, Japan.
Abstract:
We examined red cell fragmentation syndrome (RCFS) induced by mitomycin C (MMC) (13 patients), by thrombotic thrombocytopenic purpura (TTP) (17 patients), and by disseminated intravascular coagulation (DIC) (15 patients). Plasma cytokine levels were increased in the TTP and DIC patients, but not in those whose RCFS was induced by MMC, suggesting that the activation of the immune system plays an important role in the pathogenesis of RCFS due to TTP and DIC but did not in RCFS due to MMC. Plasma thrombomodulin, tissue type plasminogen activator, and plasminogen activator inhibitor-I levels were increased in all RCFS patients, suggesting that RCFS, whether MMC induced, or due to TTP or DIC, might be associated with vascular endothelial cell injury. In TTP, von Willebrand factor (vWF) antigen and high molecular weight vWF multimer levels were reduced, possibly as a result of microthrombus consumption. The hemostatic data in this study showed that the TTP patients were in a hypercoagulable state without hyperfibrinolysis, and that DIC patients were in both a hypercoagulable and a hyperfibrinolytic state, whereas hemostatic abnormalities were slight in patients with MMC induced RCFS. These findings suggest that vascular endothelial cell injuries might be associated with RCFS, and that those injuries in MMC-induced RCFS might not be related to microthrombi or an activated immune system.
Insights
Red cell fragmentation syndrome (RCFS) involves vascular endothelial cell injury. Unlike TTP and DIC, MMC-induced RCFS does not involve immune system activation or microthrombi.
Area of Science:
- Hematology
- Pathophysiology
- Oncology
Background:
- Red cell fragmentation syndrome (RCFS) is a serious condition.
- Causes of RCFS include thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), and mitomycin C (MMC) chemotherapy.
- Understanding the distinct mechanisms of RCFS is crucial for effective treatment.
Purpose of the Study:
- To investigate the underlying mechanisms of RCFS induced by MMC, TTP, and DIC.
- To compare plasma cytokine and hemostatic profiles in different RCFS etiologies.
- To elucidate the role of immune activation and endothelial cell injury in RCFS pathogenesis.
Main Methods:
- Patient cohort analysis: 13 MMC-induced RCFS, 17 TTP, 15 DIC.
- Plasma analysis: cytokine levels, thrombomodulin, tissue plasminogen activator, plasminogen activator inhibitor-I.
- Hemostatic evaluation: von Willebrand factor (vWF) antigen and multimer levels, coagulation and fibrinolysis markers.
Main Results:
- Elevated plasma cytokines observed in TTP and DIC, but not MMC-induced RCFS, indicating a role for immune activation in TTP/DIC.
- Increased thrombomodulin, t-PA, and PAI-I in all RCFS groups suggest common vascular endothelial cell injury.
- TTP showed reduced vWF and hypercoagulability without hyperfibrinolysis; DIC showed hypercoagulability and hyperfibrinolysis; MMC-RCFS had minimal hemostatic abnormalities.
Conclusions:
- Vascular endothelial cell injury is a common feature of RCFS across different causes.
- MMC-induced RCFS pathogenesis differs significantly, lacking immune system activation and microthrombi involvement.
- Distinct hemostatic profiles in TTP and DIC highlight their unique pathophysiological pathways in RCFS.