From Budd-Chiari syndrome to acquired von Willebrand syndrome: thrombosis and bleeding complications in the myeloproliferative neoplasms

Stein, Brady L.; Martin, Karlyn A.

doi:10.1182/blood.2019001318

Cited by 27 publications

(32 citation statements)

References 92 publications

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“…15 Median JAK2V617F allele burden was low in our study as expected in MPN-SVT patients. 4 However, patients with a high JAK2V617F allele burden had adverse hematologic outcomes (OR, 14.7), in agreement with previous studies in patients with homozygous JAK2 mutation. 15,19,20 We included in the high-risk molecular criteria the presence of TP53 *Missing data for 8 and 6 patients in initial and validation cohort, respectively.…”

Section: Discussionsupporting

confidence: 88%

“…Indeed, MPNs represent 30% to 40% of the etiologies of BCS and PVT. [2][3][4] However, the subgroup of MPN patients with SVT (MPN-SVT) has been shown to have peculiar clinical (young age, female predominance) 5 and molecular features (large predominance of Janus kinase 2 [JAK2] gene V617F mutation 6 ). During SVT, portal hypertension leads to hypersplenism and hemodilution, which may mask features of MPNs (high blood counts and splenomegaly) and blur the usual diagnostic criteria, the most reliable of which remains the presence of an MPN-related driver mutation.…”

Section: Introductionmentioning

confidence: 99%

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Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses

et al. 2020

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Myeloproliferative neoplasms (MPNs) are the most frequent underlying causes of splanchnic vein thromboses (SVTs). MPN patients with SVTs (MPN-SVT) often have a unique presentation including younger age, female predominance, and low Janus kinase 2 (JAK2) mutation allele burden. This study aimed at identifying risk factors for adverse hematologic outcomes in MPN-SVT patients. We performed a retrospective study of a fully characterized cohort of MPN-SVT patients. The primary outcome was the incidence of evolution to myelofibrosis, acute leukemia, or death. Eighty patients were included in the testing cohort. Median follow-up was 11 years. Most of the patients were women with a mean age of 42 years and a diagnosis of polycythemia vera. The primary outcome was met in 13% of the patients and was associated with a JAK2V617F allele burden ≥50% (odds ratio [OR], 14.7) and presence of additional mutations in genes affecting chromatin/spliceosome (OR, 9). We identified high-risk patients (29% of the cohort) as those harboring at least 1 molecular risk factor: JAK2-mutant allele burden ≥50%, presence of chromatin/spliceosome/TP53 mutation. High-risk patients had worse event-free survival (81% vs 100%; P = .001) and overall survival at 10 years (89% vs 100%; P = .01) than low-risk patients. These results were confirmed in an independent validation cohort of 30 MPN-SVT patients. In conclusion, molecular profiling identified MPN-SVT patients with dismal outcome. In this high-risk population, a disease-modifying therapy should be taken into consideration to minimize the probability of transformation.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses

et al. 2020

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…Proposed bleeding management strategies in MPNs have been recently published: (1) AWS testing prior to aspirin when platelet counts are >1,000 Â 10 9 /L and the consideration of testing even with modest thrombocytosis, (2) cytoreduction to a lower platelet count in the presence of AWS, (3) supportive measures such as desmopressin and von Willebrand factor concentrates in AWS, (4) empirical platelet transfusion if bleeding is suspected to be due to qualitative platelet dysfunction, and (5) collaboration with a hemophilia specialist if there are questions regarding AWS testing/management. 9 To conclude, bleeding risk of ET/PV patients should not be underestimated because of the high fatality rates, even compared with bleeding fatality rates in cancer patients with anticoagulant drugs.…”

Section: Thrombosis and Haemostasismentioning

confidence: 94%

“…A recent review on thrombosis and bleeding complications in MPNs underlined the lack of evidence-based data to support guidelines for the prevention and management of bleeding in MPN patients. 9 In this review, data from the literature concerning bleeding epidemiology, locations, and risk factors, particularly in ET and PV patients, are presented and discussed.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Hemorrhage is a well-known complication of essential thrombocythemia (ET) and polycythemia vera (PV), but evidence-based data on its management and prevention are lacking to help inform clinicians. In this review, appropriate published data from the past 15 years regarding bleeding epidemiology, classification, location, and risk factors are presented and discussed. Research was conducted using the Medline database. The bleeding classifications were heterogeneous among the collected studies. The median incidences of bleeding and major bleeding were 4.6 and 0.79% patients/year, in ET patients and 6.5 and 1.05% patients/year in PV patients, respectively. The most frequent location was the gastrointestinal tract. Bleeding accounted for up to 13.7% of deaths, and cerebral bleeding was the main cause of lethal hemorrhage. Thirty-nine potential risk factors were analyzed at least once, but the results were discrepant. Among them, age >60 years, bleeding history, splenomegaly, myeloproliferative neoplasm subtype, and platelet count should deserve more attention in future studies. Among the treatments, aspirin seemed to be problematic for young patients with ET (especially CALR-mutated ET patients) and anagrelide was also identified as a bleeding inducer, especially when associated with aspirin. Future studies should analyze bleeding risk factors in more homogeneous populations and with common bleeding classifications. More tools are needed to help clinicians manage the increased risk of potentially lethal bleeding events in these diseases.

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Myeloproliferative neoplasms and splanchnic vein thrombosis: Contemporary diagnostic and therapeutic strategies

Kiladjian

Cassinat

2023

American J Hematol

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Myeloproliferative neoplasms (MPNs) are the most common etiologies of primary splanchnic vein thrombosis, present in almost forty percent of patients with Budd‐Chiari syndrome or portal vein thrombosis. Diagnosis of MPNs can be difficult in these patients because key characteristics, such as elevated blood cell counts and splenomegaly, are confounded by portal hypertension or bleeding complications. In recent years, diagnostic tools have improved to provide more accurate diagnosis and classification of MPNs. Although bone marrow biopsy findings remain a major diagnostic criterion, molecular markers are playing an increasing role not only in diagnosis but also in better estimating prognosis. Therefore, though screening for JAK2V617F mutation should be the starting point of the diagnostic workup performed in all patients with splanchnic vein thrombosis, a multidisciplinary approach is needed to accurately diagnose the subtype of myeloproliferative neoplasm, recommend the useful additional tests (bone marrow biopsy, search for an additional mutation using targeted next‐generation sequencing), and suggest the best treatment strategy. Indeed, providing a specific expert care pathway for patients with splanchnic vein thrombosis and underlying myeloproliferative neoplasm is crucial to determine the optimal management to reduce the risk of both hematological and hepatic complications.

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From Budd-Chiari syndrome to acquired von Willebrand syndrome: thrombosis and bleeding complications in the myeloproliferative neoplasms

Abstract: Stein and Martin provide a review of the thrombotic and bleeding complications of myeloproliferative neoplasms and provide a roadmap for appropriate therapy.

Cited by 27 publications

References 92 publications

Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses

Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses

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

Myeloproliferative neoplasms and splanchnic vein thrombosis: Contemporary diagnostic and therapeutic strategies

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