A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms

Abstract

Background Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN are asymptomatic at diagnosis although some of them suffer from constitutional symptoms. Thrombosis and bleeding can also be one of the initial manifestations although the reported prevalence varied considerably across the studies. This systematic review and meta-analysis was conducted with the aims to better understand the prevalence and characteristics of thrombosis and bleeding among patients with newly-diagnosed MPN. Methods Using a search strategy that included the terms for myeloproliferative neoplasms, thrombosis, and bleeding, two investigators independently searched for published articles indexed in the MEDLINE and EMBASE databases from inception to August 2018. The pooled prevalence was calculated using the DerSimonian–Laird random-effects model with a double arcsine transformation. Results A total of 29 cohort studies (8 prospective and 21 retrospective) with 13,436 patients with MPN were included into this meta-analysis. At diagnosis, the pooled prevalence of overall thrombosis among patients with MPN was 20.0% (95% CI, 16.6–23.8%; I 2 96%), with the pooled prevalence of arterial thrombosis of 16.2% (95% CI, 13.0–20.0%; I 2 95%) and the pooled prevalence of venous thrombosis of 6.2% (95% CI, 4.9–7.8%; I 2 89%). Common thrombotic events included cerebrovascular disease/transient ischemic attack, coronary heart disease, and deep venous thrombosis. The pooled prevalence of hemorrhagic complications among patients who were newly diagnosed with MPN patients was 6.2% (95% CI, 5.0–7.8%; I 2 85%). Common sites of bleeding included gastrointestinal, mucosal, and cutaneous bleeding. Conclusions Thrombosis and bleeding are common initial manifestations of MPN. Investigations for MPN should be considered for patients who present with unexplained thrombosis or abnormal bleeding. Electronic supplementary material The online version of this article (10.1186/s12885-019-5387-9) contains supplementary material, which is available to authorized users.

Hemorrhage in Essential Thrombocythemia or Polycythemia Vera: Epidemiology, Location, Risk Factors, and Lessons Learned from the Literature

“…The most recent reviews on bleeding of MPN patients present a prevalence at diagnosis and an incidence during follow-up of 7.3 and 9% in ET and 6.9 and 8% in PV, respectively. 9,57,58 Thrombotic complications remain more frequent in this population (up to 39% of patients 16 Currently, management of PV and ET patients is based on European Leukemia Network (ELN) criteria for thrombotic risk evaluation (age over 60 years and/or history of thrombosis). Interestingly, patients with platelet counts over 1,500 G/L are also considered high-risk patients, because of increased bleeding risk.…”

Emerging Factors Implicated in Fibrotic Organ–Associated Thrombosis: The Case of Two Organs

“…5 6 A very recent meta-analysis estimated that the overall prevalence of thrombosis in patients with myeloproliferative neoplasms (MPNs) is 20% with the prevalence of arterial thrombosis (cerebrovascular disease, transient ischemic attack, coronary artery disease, and peripheral artery disease) being 16.2% and VTE being 6.2%. 7 Another meta-analysis led to the conclusion that JAK2V617F mutation in PMF patients is associated with an increased risk of thrombosis (odds ratio: 1.76, 95% confidence interval [CI]: 0.91–3.41). 4…”

Impact of platelets on major thrombosis in patients with a normal white blood cell count in essential thrombocythemia

“…Thromboembolic complications are prevalent in essential thrombocythemia (ET). A recent meta‐analysis including 13 436 patients with classical MPNs revealed a pooled prevalence of overall thrombosis in 20.7% of newly diagnosed patients with ET 1 . Moreover, a population‐based cohort study including 9429 patients with MPNs and 35 820 control participants confirmed highest rates of thromboembolic complications shortly after diagnosis, but thrombosis hazard ratios were also markedly increased at later time points compared to the control group 2 .…”