Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis

Abstract

Thrombotic events are the most frequent manifestations of essential thrombocythemia (ET). The objective of this study is to determine the incidence of thrombosis at different sites on follow-up in patients with ET. We searched PubMed, Web of Science, and The Cochrane Library databases and calculated the incidence of thrombosis by pooling and analyzing the extracted data using a random-effects model. A total of 70 studies (N = 25,805) were included in the analysis. The total and annual incidences of arterial thrombosis on follow-up were 13.4% and 2.0%, respectively. The total and annual incidences of the different manifestations of arterial thrombosis were as follows: stroke (5.3% and 0.8%), transient ischemic attack (5.1% and 1.2%), myocardial infarction (2.4% and 0.5%), unstable angina (0.9% and 0.2%), and peripheral arterial thrombosis (2.0% and 0.2%), respectively. In contrast, the total and annual incidences of arterial thrombosis in JAK2-positive patients were 18.4% and 2.7%, respectively. The total and annual incidences of arterial thrombosis in JAK2-negative patients were 5.9% and 0.8%, respectively. The total and annual incidences of venous thrombosis were 5.5% and 0.7%, respectively, and the incidences of the different manifestations of venous thrombosis at different sites were as follows: peripheral venous thrombosis (2.9% and 0.5%), superficial venous thrombosis (1.8% and 0.7%), deep venous thrombosis (1.6% and 0.3%), abdominal venous thrombosis (0.8% and 0.1%), pulmonary embolism (0.3% and 0.1%), and cerebral venous thrombosis (0.2% and 0%), respectively. The total and annual incidences of venous thrombosis in JAK2-positive patients were 7.4% and 1.2%, respectively. The total and annual incidences of venous thrombosis in JAK2-negative patients were 1.6% and 0.4%, respectively. The incidence of arterial thrombosis was higher than that of venous thrombosis in patients with ET. Arterial thrombosis manifested with cerebral arterial thrombosis, followed by cardiac thrombosis. Venous thrombosis events were mainly peripheral and superficial venous thrombosis. JAK2-positive patients have a higher incidence of arterial and venous thromboses than JAK2-negative patients, the sequence of thrombsis sites was similar to that of the overall patients.

Keywords

essential thrombocythemia arterial thrombosis venous thrombosis cerebral thrombosis cardiac thrombosis

Introduction

Essential thrombocythemia (ET) is the most frequent type of chronic myeloproliferative disorder¹ and is characterized by a marked increase in platelet count, elevated risk of thrombosis, and increased risk of conversion to leukemia and fibrosis. The primary objective of treatment is to reduce the peripheral platelet count and risk of thrombosis. The occurrence of thrombotic events has the most serious effect on the quality of life and survival of patients. Therefore, to predict the risk of thrombosis in patients with ET, the World Health Organization has constructed the IPSET-thrombosis model for individualized prediction of thrombotic risk to facilitate precise clinical stratification of treatment.

With the inclusion of indicators, including JAK2 mutation, the prediction of thrombotic risk has entered the molecular era; however, no specific studies have determined the incidence of thrombosis at different sites in patients with ET. Nevertheless, determining the incidence of thrombosis at different sites is important for the accurate prediction and diagnosis of thrombotic events. Therefore, a systematic review and meta-analysis were performed to summarize the available evidence and to analyze the occurrence of thrombotic events at different sites in patients with ET and JAK2 mutations, providing possible research directions for accurate thrombosis prediction in patients with ET.

Methods

Search Strategy

This systematic review protocol was registered on the PROSPERO registry (CRD42022350747). We searched the PubMed (1966 to 2021), Web of Science (1963 to 2021), and The Cochrane Library (1946 to 2021) databases to retrieve studies that include the incidence of thrombosis in ET. The search strategy included the following search algorithm: ([essential thrombocythemia] OR [thrombocythemia] OR [primary thrombocythemias] OR [idiopathic thrombocythemia]) AND ([thrombosis] OR [thromboses] OR [blood clot]). Subsequently, we manually searched the databases to avoid omissions in search algorithms.

Data Collection

The data collected from the studies included: authors’ names, year of study, country or region, type of study, single-arm or not, study period, follow-up time, diagnostic criteria, participant characteristics, therapeutic drugs, incidence of bleeding, mortality, incidence of metastatic leukemia and myelodysplastic syndrome, incidence of metastatic fibrosis, and incidence of polycythemia vera, and the number of patients with ET and thrombosis. Data collection was conducted by four of the authors and verified by the others (Supplemental Data 1).

Annual Incidence of Thrombosis

Annual incidence of thrombosis $= ((n / T) / N)$ × 100%, where n = total number of thrombosis, T = follow-up time, N = total study population.

Study Quality Assessment

Two authors used the Quality Assessment Tool for Case Series Studies developed by the U.S. National Heart, Lung, and Blood Institute (NHLBI)² to assess the single-arm studies, whereas the Newcastle–Ottawa Scale (NOS)³ was used to evaluate other prospective or retrospective cohort studies (Supplemental Data 1).

Statistical Analysis

R 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria; www.r-project.org) was used to analyze the results, and a random-effects model was used to calculate the incidence and its 95% confidence interval (CI). For different data, we applied the log, logit, arcsine, and double arcsine transformations to obtain normally distributed rates (choosing the best-fit transformations). Then, we used a random-effects model to calculate the incidence of thrombosis.

Results

Results of Study Search

The selection process is shown in the flow chart in Figure 1. The search on PubMed, Web of Science, and The Cochrane Library retrieved 2739 articles. Our manual search of multiple databases found 78 studies that met the search criteria but were not retrieved through the keywords search. After eliminating duplicate titles and abstracts that did not relate to our study, 640 articles remained. Then, we carefully reviewed the full text and excluded 570 articles that did not meet the inclusion criteria (Figure 1). A final total of 70 studies with 25,805 ET patients were included, the results of this group are only presented in Supplemental Data 1.

Figure 1.

Study flow diagram.

Incidence of Arterial Thrombosis at Different Sites in ET Patients

The incidence of overall arterial thrombosis in ET patients was 13.4% (95% CI: 12.0-14.8%, I₂ = 93%), with annual incidence was 2.0% (95% CI: 1.70-2.3%, I₂ = 63%). We analyzed the incidence of arterial thrombosis at different sites, the total incidence of stroke was 5.3% (95% CI: 4.0-6.7%, I₂ = 79%), and annual incidence was 0.8% (95% CI: 0.6-1.1%, I2 = 0%). A total incidence of transient ischemic attack was 5.1% (95% CI: 3.3-7.8%, I₂ = 90%), with annual incidence was 1.2% (95% CI: 0.8-1.9%, I₂ = 0%). The total incidence of myocardial infarction was 2.4% (95% CI: 1.9-3.0%, I₂ = 59%), and annual incidence was 0.5% (95% CI: 0.4-0.7%, I₂ = 0%). The total incidence of unstable angina was 0.9% (95% CI: 0.5-1.2%, I₂ = 0%), with annual incidence was 0.2% (95% CI: 0-0.4%, I₂ = 0%). The total incidence of peripheral arterial thrombosis was 2.0% (95% CI: 1.4-2.5%, I₂ = 80%), with annual incidence was 0.2% (95% CI: 0.1-0.3%, I₂ = 0%). (Figure 2, the details are shown in Supplemental Data 2.)

Figure 2.

Forest plot of pooled prevalence and 95% confidence interval of arterial thrombosis complications in patients with ET.

To further assess the impact of JAK2 mutations on different thrombotic events in ET patients, we further analyzed the incidence of thrombosis at different sites in patients with or without JAK2 mutation. The overall incidence of arterial thrombosis in JAK2-positive patients was 18.4% (95% CI: 13.9-22.9%, I₂ = 94%), with annual incidence was 2.7% (95% CI: 1.9-3.5%, I₂ = 49%). The overall incidence of arterial thrombosis in JAK2-negative patients was 5.9% (95% CI: 3.2-8.6%, I₂ = 80%), with annual incidence was 0.8% (95% CI: 0.3-1.3%, I₂ = 0%). The total incidence of transient ischemic attack in JAK2-positive patients was 9.1% (95% CI: 0.2-18.0%, I₂ = 0%), with annual incidence was 2.0% (95% CI: 0-4.0%, I₂ = 0%). The total incidence of transient ischemic attack in JAK2-negative patients was 1.7% (95% CI: 0.8-2.7%, I₂ = 58%), with annual incidence was 0.7% (95% CI: 0-1.3%, I₂ = 0%). The overall incidence of stroke in JAK2-positive patients was 1.8% (95% CI: 0.7-3.0%, I₂ = 0), with annual incidence was 0.5% (95% CI: 0-1.1%, I₂ = 0). The overall incidence of stroke in JAK2-negative patients was 0.6% (95% CI: 0-1.8%, I₂ = 59), with annual incidence was 0.1% (95% CI: 0-0.4%, I₂ = 0). The total incidence of myocardial infarction in JAK2-positive patients was 4.6% (95% CI: 1.1-9.9%, I₂ = 87%), with annual incidence was 1.6% (95% CI: 0-3.3%, I₂ = 75%). The total incidence of myocardial infarction in JAK2-negative patients was 2.5% (95% CI: 1.4-3.5%, I₂ = 0%), with annual incidence was 0.7% (95% CI: 0.1-1.3%, I₂ = 0%). The total incidence of unstable angina in JAK2-positive patients was 2.9% (95% CI: 0-8.3%, I₂ = 55%), with annual incidence was 0.4% (95% CI: 0-0.9%, I₂ = 0%). The total incidence of unstable angina in JAK2-negative patients was 0.1% (95% CI: 0-0.4%, I₂ = 0%), with annual incidence was 0% (95% CI: 0-0.3%, I₂ = 0%). The total incidence of peripheral arterial thrombotic events in JAK2-positive patients was 2.2% (95% CI: 0.6-3.8%, I₂ = 55%), with annual incidence was 0.7% (95% CI : 0-1.7%, I₂ = 58%). The total incidence of peripheral arterial thrombotic events in JAK2-negative patients was 0.4% (95% CI: 0-0.9%, I₂ = 0%), with annual incidence was 0.1% (95% CI : 0-0.5%, I₂ = 0%). (Figure 3, the details are shown in Supplemental Data 3.)

Figure 3.

Forest plot of pooled prevalence and 95% confidence interval of arterial thrombosis complications in patients with JAK2 positive/negative ET.

Incidence of Venous Thrombotic Events at Different Sites in ET Patients

The overall incidence of venous thrombotic events in ET patients was 5.5% (95% CI: 4.7-6.2%, I₂ = 88%) and the annual incidence of thrombosis was 0.7% (95% CI: 0.6-0.9%, I₂ = 26%). The total incidence of peripheral vein thrombosis (thrombotic events occurring in the extremities and the neck) was 2.9% (95% CI: 2.3-3.6%, I₂ = 0%), with annual incidence was 0.5% (95% CI: 0.3-0.9%, I₂ = 0%). The total incidence of superficial vein thrombosis was 1.8% (95% CI: 0.3-9.8%, I₂ = 85%), with annual incidence was 0.7% (95% CI: 0.2 −2.4%, I₂ = 47%). Total incidence of deep vein thrombosis was 1.6% (95% CI: 1.1-2.1%, I₂ = 57%), with annual incidence was 0.3% (95% CI: 0.1-0.4%, I₂ = 0%). The total incidence of abdominal vein thrombosis was 0.8% (95% CI: 0.4-1.2%, I₂ = 62%), with annual incidence was 0.1% (95% CI: 0-0.2%, I₂ = 0%). Total incidence of pulmonary embolism was 0.3% (95% CI: 0.1-0.4%, I₂ = 0%), with annual incidence was 0.1% (95% CI: 0.1-0.4%, I₂ = 0%). Total incidence of cerebral vein thrombosis was 0.2% (95% CI: 0-0.6%, I₂ = 13%), the annual incidence was 0% (95% CI: 0-0.1%, I₂ = 0%). (Figure 4, the details are shown in Supplemental Data 4.)

Figure 4.

Forest plot of pooled prevalence and 95% confidence interval of overall venous thrombosis complications in patients with ET.

To further analyze the incidence of venous thrombosis at different sites in JAK2-mutation patients, we further analyzed the incidence of thrombosis at different sites in patients with or without JAK2 mutation. The overall incidence of venous thrombotic events in JAK2-positive patients was 7.4% (95% CI: 5.6-9.1%, I₂ = 79%), with annual incidence was 1.2% (95% CI: 0.8-1.6%, I₂ = 29%). The overall incidence of venous thrombotic events in JAK2-negative patients was 1.6% (95% CI: 1-2.3%, I₂ = 22%), with annual incidence was 0.4% (95% CI: 0.1-0.8%, I₂ = 0%). The total incidence of deep vein thrombosis in JAK2-positive patients was 1.6% (95% CI: 0.4-2.7%, I₂ = 1%), with annual incidence was 0.1% (95% CI: 0-0.3%, I₂ = 0%). The total incidence of deep vein thrombosis in JAK2-negative patients was 1.1% (95% CI: 0-2.1%, I₂ = 0%), with annual incidence was 0.2% (95% CI: 0-0.9%, I₂ = 0%). The total incidence of abdominal vein thrombosis in JAK2-positive patients was 1.3% (95% CI: 0.3-2.4%, I₂ = 0%), with annual incidence was 0.2% (95% CI: 0-0.7%, I2 = 0%). The total pulmonary embolism in JAK2-positive patients was 0.8% (95% CI: 0-1.6%, I₂ = 38%), the annual incidence was 0.1% (95% CI: 0.1-0.3%, I₂ = 0%). The total incidence of superficial vein thrombosis in JAK2-positive patients was 0.5% (95% CI: 0-1.2%, I₂ = 0%), the annual incidence was 0.1% (95% CI: 0-1.2%, I₂ = 0%). The total incidence of superficial vein thrombosis in JAK2-negative patients was 0% (95% CI: 0-0.4%, I₂ = 0%), the annual incidence was 0% (95% CI: 0-0.4%, I₂ = 0%). (Figure 5, the details are shown in Supplemental Data 5.)

Figure 5.

Forest plot of pooled prevalence and 95% confidence interval of overall venous thrombosis complications in patients with JAK2 positive/negative ET.

Meanwhile, to further analyze the incidence of bleeding at different sites, survival, transfer to AML/MDS, transfer to PV, and transfer to fibrosis in ET patients, we further collected and analyzed relevant data from the included literature, and the specific results are shown in Supplemental Data 6.

Summary of Study Results

To better understand the results of our study, we present the above results in Figure 6. At the same time, in order to analyze whether there was publication bias in the included studies, we selected the events of overall arterial thrombosis and vein thrombosis, respectively, and carried out funnel plot and Egger's regression analysis. The funnel plot of overall arterial thrombosis is shown in Figure 7A and Egger's regression analysis shows that P < .01, and the result is shown in Figure 7B. Then, the funnel plot of overall venous thrombosis is shown in Figure 7C and Egger's regression analysis shows that P < .01, and the result is shown in Figure 7D. It is suggested that the included studies may have publication bias.

Figure 6.

Bar chart of thrombosis incidence in ET patients. (A) Overall incidence of arterial thrombosis in ET patients and JAK2 positive/negative patients. (B) Annual incidence of arterial thrombosis in ET patients and JAK2 positive/negative patients. (C) Overall incidence of venous thrombosis in ET patients and JAK2 positive/negative patients. (D) Annual incidence of venous thrombosis in ET patients and JAK2 positive/negative patients.

Figure 7.

Funnel plot. (A) The funnel plot of overall arterial thrombosis. (B) Egger's regression analysis of overall arterial thrombosis. (C) The funnel plot of overall venous thrombosis. (D) Egger's regression analysis of overall venous thrombosis.

Discussion

This study is the first systematic review and meta-analysis to evaluate the incidence of thrombosis at different sites during the follow-up period in patients with ET. Thrombosis is the most important cause of death in patients with ET,⁴ studies have shown that the incidence of arterial thrombosis is two to three times higher than that of venous thrombosis in patients with ET, similar to the results of this study (2% vs 0.7%).

The most common arterial thrombotic events are cardiothrombotic events, accounting for approximately 80% of the total arterial thrombotic events. In our study, cerebrovascular thrombotic events had the highest incidence, which is consistent with the results of other studies.^5–8 Cerebral thrombotic events in patients with ET account for two-thirds of the total thrombotic events, with an annual incidence of approximately 7.3 to 8.3 per 1000 person-years.⁹ In contrast, the incidence of cerebral thrombotic events in the healthy population is about 3 to 4 per 1 million person-years.¹⁰ Cardiovascular events are the second most prevalent atherothrombotic event in patients with ET, accounting for approximately a quarter of the total arterial event rate. Cardiovascular risk factors play an important role in the occurrence of cardiovascular events, and their prevalence is significantly higher in patients with ET. A study showed that in 233 patients with ET, the prevalence of hypertension, dyslipidemia, diabetes, smoking, and obesity was 63.5%, 24%, 14.2%, 13.3%, and 9%,¹¹ respectively, which were higher than those in the normal population (7%-18%).¹² A multicenter study covering 52 countries showed that patients with cardiovascular risk factors comprised more than 90% of patients with myocardial infarction and stroke¹³; patients with nine cardiovascular risk factors had an odds ratio of 333.7 (99% confidence interval: 230.2-483.9) for myocardial infarction compared with patients without any cardiovascular risk factors.¹⁴ In a study that included 244 patients with ET, high-risk (3 points) patients with >1 cardiovascular risk factors (HR = 8.3; 2 points) and previous thrombosis (HR = 2.0; 1 point) had thrombosis rates in the 60% range, which was greater than the 3.8% and 16.7% in the low- and intermediate-risk groups, respectively, demonstrating the impact of cardiovascular risk (CVR) factors on thrombosis.¹⁵ Some investigators believe that treatment regimens for high-risk individuals should be adjusted, such as increasing the dose of aspirin, by separately assessing the risk of cerebral thromboses.¹⁶

The incidence of venous thrombosis in patients with ET was lower than that of arterial thrombosis. Additionally, previous studies suggested that venous thrombotic events in patients with ET tend to occur in unusual sites and were highly associated with death, such as visceral veins, cerebral veins, and the vena cava.¹⁷ However, our study showed that venous thrombosis in patients with ET occurred mainly in the peripheral and superficial veins, whereas pulmonary vein embolism, cerebral vein thrombosis, and abdominal vein thrombosis were uncommon. However, among JAK2-positive patients, the incidence of visceral venous thrombosis was significantly higher than those at other sites. This may be attributed to the differences in JAK2V617F expression in different endothelial cells (EC), which influenced the incidence of thrombosis at different sites, and that higher JAK2V617F expression resulted in a higher rate of venous thrombosis.¹⁸ Injury or activation of EC translates their properties into a prothrombotic phenotype, and in vivo EC activation in patients with ET is reflected by elevated biomarkers.¹⁹ To transform into this phenotype, the number of EC cells distributed in each organ and tissue varies. Interestingly, JAK2V617F promotes thrombosis by increasing levels of von Willebrand factor and soluble thrombomodulin in mouse EC cells, whereas JAK2V617F-carrying EC cells were found in patients with ET.²⁰ There is considerable heterogeneity in the morphology, structure, gene expression, function, and responsiveness of ECs in different regions of the circulation. Thus, EC cells carrying ET-driven mutations may be restricted to certain vascular regions. JAK2 mutations conferring a thrombogenic phenotype in such EC cells could explain the propensity for visceral venous thrombosis in ET patients.²¹

For treatment, most of the treatment regimens included in this study were low-dose aspirin (75-100 mg/d), but most of them were not clearly described for the choice of specific treatment regimens for patients in different strata, which also indicates that there is no unified view on thromboprophylaxis treatment regimens. The current therapeutic regimen is not effective in preventing thrombosis in patients with ET. Some basic and clinical studies have found that once-daily low-dose aspirin does not inhibit platelet function well in patients with myeloproliferative neoplasms (MPN), and platelet TxA2 does not remain inhibited for 24 h,^22,23 so some opinions recommend the use of twice-daily doses of aspirin.²⁴ Manoharan et al²⁵ followed 115 MPN patients using whole blood platelet aggregation studies for risk assessment and tailoring the aspirin (ASP) dose in individual patients. With this approach, they found that no thrombosis occurred in patients who regularly used ASP (100 mg/2-3/week, 100 mg/day, 200 mg/day, 300 mg/day, and 400 mg/day) during the follow-up period of 1-23 years. In contrast, two patients who discontinued antiplatelet therapy during treatment had multiple thrombotic events. This study explored the long-term thromboprophylaxis effects of different doses of ASP in the treatment of MPN, and also provided research ideas for further development of individualized long-term thromboprophylaxis programs to a certain extent.

However, the results of our study found that the incidence of bleeding events in patients during the follow-up period was about 7.2%, which shows that the occurrence of bleeding events in patients is also a problem that cannot be ignored. Considering that aspirin may increase the occurrence of bleeding events, stratified treatment regimens are mostly advocated for patients with ET. For example, low-dose aspirin is currently used mainly for patients at risk of thrombosis (JAK2 mutation, concomitant cardiovascular risk factors or microvascular symptoms, age ≥ 60 years, history of thrombosis, PLT ≥ 1500 × 10⁹/L).²⁶ For other low-risk patients, the decision to use aspirin is based on clinical experience, with about 50-90% of patients treated with aspirin in actual clinical care. Studies have begun to recommend a twice-daily dose of aspirin in the clinic for patients with a history of arterial thrombosis,²⁶ while the standard once-daily dose continues to be used for patients at risk for arterial thrombosis, while also highlighting the benefits of aspirin for the prevention of venous thrombotic events.^27,²⁸

Anticoagulation was rarely mentioned in most of the included studies and was recommended only in selected high-risk patients with a history of venous thrombosis. However, the results of one study showed that 4 of 11 patients with MPN treated with DOACs had a bleeding event within 180 days of follow-up.²⁹ In another study that included 133 patients with MPN treated with DOACs, at a median follow-up of 37 months, 16 had a thrombotic event while 29 had a bleeding event, including 6 major bleeds and 4 deaths due to major bleeds, which still warrants consideration of the benefit-risk ratio for anticoagulation.³⁰

This study is the first to analyze the incidence of thrombosis at different sites in patients with ET and JAK2 mutations. Additionally, it is an attempt to further stratify the prediction of thrombotic risk. However, as most of the reports included in this study were retrospective studies, the diagnostic criteria for ET between studies at different times varied, so heterogeneity of the results of the studies was unavoidable. Meanwhile, since most studies did not use the standard annual 100-person-years thrombosis rate, the average follow-up time of the study instead of the individual follow-up time in this study can only replace the annual 100-person-years thrombosis rate to some extent. It is also difficult to compare the incidence of thrombosis under different treatment regimens (including different antiplatelet and anticoagulation treatments) to provide better insight into treatment options because the included study regimens were not standardized and stratified. The scarcity of laboratory studies makes it difficult to assess the thrombosis risk in individual patients and use of tailored aspirin dose for longterm thromboprophylaxis. Further high-quality studies should explore our results.

Supplemental Material

sj-doc-1-cat-10.1177_10760296231181117 - Supplemental material for Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis

Supplemental material, sj-doc-1-cat-10.1177_10760296231181117 for Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis by Dehao Wang, Xinyue Yu, Yan Sun, Yan Lv, Yumeng Li, Pei Zhao, Jicong Niu, Yanyu Zhang, Yi Chen, Ke Chen, Zhuo Chen, Weiyi Liu, Mingjing Wang and Xiaomei Hu in Clinical and Applied Thrombosis/Hemostasis

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Supplemental material, sj-doc-2-cat-10.1177_10760296231181117 for Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis by Dehao Wang, Xinyue Yu, Yan Sun, Yan Lv, Yumeng Li, Pei Zhao, Jicong Niu, Yanyu Zhang, Yi Chen, Ke Chen, Zhuo Chen, Weiyi Liu, Mingjing Wang and Xiaomei Hu in Clinical and Applied Thrombosis/Hemostasis

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Supplemental material, sj-doc-3-cat-10.1177_10760296231181117 for Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis by Dehao Wang, Xinyue Yu, Yan Sun, Yan Lv, Yumeng Li, Pei Zhao, Jicong Niu, Yanyu Zhang, Yi Chen, Ke Chen, Zhuo Chen, Weiyi Liu, Mingjing Wang and Xiaomei Hu in Clinical and Applied Thrombosis/Hemostasis

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Supplemental material, sj-doc-4-cat-10.1177_10760296231181117 for Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis by Dehao Wang, Xinyue Yu, Yan Sun, Yan Lv, Yumeng Li, Pei Zhao, Jicong Niu, Yanyu Zhang, Yi Chen, Ke Chen, Zhuo Chen, Weiyi Liu, Mingjing Wang and Xiaomei Hu in Clinical and Applied Thrombosis/Hemostasis

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Supplemental material, sj-doc-5-cat-10.1177_10760296231181117 for Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis by Dehao Wang, Xinyue Yu, Yan Sun, Yan Lv, Yumeng Li, Pei Zhao, Jicong Niu, Yanyu Zhang, Yi Chen, Ke Chen, Zhuo Chen, Weiyi Liu, Mingjing Wang and Xiaomei Hu in Clinical and Applied Thrombosis/Hemostasis

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sj-doc-6-cat-10.1177_10760296231181117 - Supplemental material for Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis

Supplemental material, sj-doc-6-cat-10.1177_10760296231181117 for Incidence of Thrombosis at Different Sites During the Follow-Up Period in Essential Thrombocythemia: A Systematic Review and Meta-Analysis by Dehao Wang, Xinyue Yu, Yan Sun, Yan Lv, Yumeng Li, Pei Zhao, Jicong Niu, Yanyu Zhang, Yi Chen, Ke Chen, Zhuo Chen, Weiyi Liu, Mingjing Wang and Xiaomei Hu in Clinical and Applied Thrombosis/Hemostasis

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Scientific and technological innovation project of China Academy of Chinese Medical Sciences, National Natural Science Foundation of China, (grant number CI2021A01702, No. 82174360).

Supplemental Material

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ORCID iDs

Dehao Wang

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