To our knowledge, this study is the first to count the incidence of VTE and risk factors in MDS patients in China. We will further expand the sample size for a joint multicenter study at a later stage.This study found the following main findings:1) The incidence of venous thrombosis in primary MDS in China is 5.26%. 2) SF3B1 mutations and PAI-1 gene 4G4G are associated with thrombotic events in Chinese MDS patients.
Although it is frequently reported that the occurrence of VTE in patients with solid tumors not only limits the use of therapeutic agents, but also seriously affects the quality of life, disability and even threatens the life of patients, requiring active intervention and standardized prevention and treatment of VTE. However, for hematologic malignancies, the data related to VTE are relatively poor. It may be related to factors such as hematologic malignancies with severe cytopenia (especially thrombocytopenia) and abnormal coagulation associated with the tumor[4]. These factors increase the risk of bleeding and then can also carry mortality risk. A large population-based study by Arafat et al. showed that VTE is common in patients with hematologic malignancies, with an 11% prevalence of MDS combined with VTE, and is associated with an increased risk of death in patients with MDS. According to Horváth-Puhó et al. [5], the incidence rates per 1,000 person-years for VTE, MI, and stroke were 10.8, 8.2, and 16. Alam et al.[6] studied adult VTE cases in Alberta, Canada, from 2003 to 2015 and found 1,647 (2.9%) patients had hematologic malignancies, of which 105 (6.4%) were patients with MDS. According to Younes et al.[7], patients with MDS have a higher rate of VTE (5.8%). The incidence of venous thrombosis in primary MDS in China was 5.26% in this study.
VTE risk factors in MDS patients have not yet been fully uncovered, to the best of our knowledge. Péan de Ponfilly-Sotier, M et al.[8] concluded from a retrospective multicenter case-control study that comorbid systemic inflammatory and autoimmune diseases and progression of the disease are independent risk factors for VTE. A two-center observational study by Martella, F et al.[9] revealed that previous VTE, platelet counts above 100*109/L, and active smoking were factors associated with an increased risk of thrombosis in patients with MDS. However, the possible of somatic cell mutations on the risk of VTE in MDS patients has not been confirmed. We analyzed the results of somatic mutations in MDS combined with thrombosis. Our results showed that SF3B1 was high-risk factor associated with VTE. There was no significant difference between VTE and gender ratio, age, white blood cell count, hemoglobin, platelets, or disease risk stratification. The sample size of our study is small and the findings need to be studied with a further expanded sample size.
To further investigate whether risk factors for hereditary thrombosis are associated with VTE in MDS patients, 7 MDS patients who developed VTE were tested for antithrombin III, protein C, protein S, antiphospholipid antibodies, and homocysteine. However, the findings did not show positive clinical significance, suggesting that the 7 patients with MDS combined with VTE were not involved in hereditary thrombosis.
Serine protease inhibitor 1 (PAI-1), a member of the serpin superfamily, is the main inhibitor of endogenous fibrinolysis[10]. As the main inhibitor of fibrinolysis, PAI-1 is associated with increased risk of future incident VTE[11–13]. Previous studies reported that high levels of PAI-1 gene 4G/4G in patients with malignant hematological diseases are strongly associated with associated thrombotic events[14–17]. There are no studies on what role PAI plays in MDS patients. Thrombotic events in Chinese MDS patients are associated with the PAI-1 gene 4G4G type, according to our results. In the 4G/4G genotype, plasma PAI-1 activity is high, which may lead to impaired fibrinolysis and increased thrombosis risk.
In conclusion, this study showed that the incidence of venous thrombosis in primary MDS in China is 5.26%. SF3B1 mutations and PAI-1 gene 4G4G are associated with thrombotic events in Chinese MDS patients. To improve management and regression of thrombotic events in MDS, there is a need to better understand the risk factors for thrombosis.
Due to the relatively small sample size and retrospective study design, this study has some limitations. Our center has not yet performed a cumulative frequency analysis of thrombotic events in Chinese MDS patients. Therefore, more research is needed .