Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis

2006 ◽  
Vol 77 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Paul J. Thurmes ◽  
David P. Steensma
Keyword(s):  
Polycythemia Vera ◽  
Mutation Analysis ◽  
Elevated Serum ◽  
Clinical Implications ◽  
Budd Chiari Syndrome ◽  
Jak2 Mutation ◽  
Chiari Syndrome ◽  
Serum Erythropoietin

Myeloproliferative Disease in the Pathogenesis and Survival of Budd-Chiari Syndrome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1480-1480
Author(s):  
Jasper H. Smalberg ◽  
Sarwa D. Murad ◽  
Eric Braakman ◽  
Peter Valk ◽  
Mies C. Kappers-Klunne ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Survival Rates ◽  
Vena Cava ◽  
Aetiological Factor ◽  
Budd Chiari Syndrome ◽  
Jak2 Mutation ◽  
Who Criteria ◽  
Significant Difference ◽  
Chiari Syndrome

Abstract Budd-Chiari syndrome (BCS) is a rare disorder caused by obstruction of the hepatic veins or the suprahepatic inferior vena cava. Myeloproliferative diseases (MPD) are the most important aetiological factor in BCS. The aim of this study was to evaluate multifactorial aetiology in BCS patients with MPD, to assess potential added value of the recently discovered JAK2 mutation in the diagnostics of MPD in BCS, and to determine the survival of MPD patients in BCS. All patients referred to our university hospital with primary, non-malignant BCS between January 1980 and January 2006 were included in this study (n=40). Median age was 28.4 years (18.4–53.3), 26 patients (65%) were female and in nine patients (23%) additional portal vein thrombosis (PVT) was present. Overall mean follow-up was 7.1 ± 6.9 years. Only two patients were lost to follow-up, of which one MPD patient. In addition to standard MPD work-up according to WHO criteria, JAK2 mutation analysis was performed in 17 patients. MPD was present in 33% of the patients: Polycythemia Vera (n=6), Essential Thrombocythemia (ET) (n=6) and unclassifiable MPD (n=1). JAK2 mutation was identified in seven out of the 17 tested BCS patients (41%). In two patients suspect for ET, but who failed to meet WHO criteria, JAK2 mutation analysis led to the diagnosis of MPD. In 38% of patients with MPD additional pro-thrombotic factors were present. Survival rates in patients with MPD at 1, 5, and 10 years remained constant at 92% (95% CI, 78%–100%). Survival rates in patients without MPD at 1, 5, and 10 years were 89% (95% CI, 77%–100%), 64% (95% CI, 44%–85%) and 53% (95% CI, 28%–79%), respectively. There was no significant difference in survival between the two (P=0.18). Additional PVT was only present in patients without MPD in our population, which may account for the slightly lowered survival of these patients, since more extensive thrombosis in the splanchnic area is associated with poorer survival. In addition, three patients with and one patients without MPD underwent liver transplantation, which may have affected survival rate in favour of MPD patients. In conclusion, we report MPD in 33% of our BCS patients. In 38% of the patients with MPD, additional pro-thrombotic factors were present. These results enforce the necessity of extensive screening for additional pro-thrombotic conditions. Our study clearly confirms the importance of JAK2 mutation analysis in patients with BCS. Long term follow-up did not show a significant difference in survival between patients with and without MPD.

scholarly journals Elevated serum erythropoietin in a patient with polycythaemia vera presenting with Budd-Chiari syndrome

2014 ◽  
Vol 2014 (dec01 1) ◽  
pp. bcr2014205663-bcr2014205663 ◽  
Author(s):  
C. Jones ◽  
Y. Levy ◽  
A. W. Tong
Keyword(s):  
Elevated Serum ◽  
Polycythaemia Vera ◽  
Budd Chiari Syndrome ◽  
Chiari Syndrome ◽  
Serum Erythropoietin

Role of radiological imaging and interventions in management of Budd–Chiari syndrome

2018 ◽  
Vol 73 (7) ◽  
pp. 610-624 ◽  
Author(s):  
C.J. Das ◽  
M. Soneja ◽  
S. Tayal ◽  
A. Chahal ◽  
S. Srivastava ◽  
...  
Keyword(s):  
Radiological Imaging ◽  
Budd Chiari Syndrome ◽  
Chiari Syndrome

Role of JAK 2 Mutation Detection in Budd-Chiari Syndrome (BCS) and Portal Vein Thrombosis (PVT) Associated to MPD.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 377-377 ◽  
Author(s):  
Jean-Jacques Kiladjian ◽  
Francisco Cervantes ◽  
Frank W.G. Leebeek ◽  
Sylvie Chevret ◽  
Dominique Cazals-Hatem ◽  
...  
Keyword(s):  
Cell Mass ◽  
Prognostic Scores ◽  
Medium Term ◽  
Lower Serum ◽  
Jak2 Mutation ◽  
Term Outcome ◽  
Vein Thrombosis ◽  
Chiari Syndrome ◽  
Diagnostic And Prognostic Value

Abstract Background: MPD is found in up to 50% of BCS and 30% of PVT, but its diagnosis is often difficult, bone marrow biopsy (BMB) and endogenous erythroid colony (EEC) formation being the most reliable tests in our experience (Br J Haematol, 2005;129:553) and that of others. We assessed the diagnostic and prognostic value of V617F JAK2 detection in this situation. Methods: Underlying prothrombotic factors were studied in 241 pts (104 BCS, 137 PVT) from 3 centers (Paris, Barcelona, Rotterdam). Based on BMB results (blindly reviewed), 31% of patients had MPD, 67% no-MPD, and 2% were uncertain. Based on combined BMB+EEC results, 29% had MPD, 41% no-MPD and 31% had discordant features. V617F JAK2 mutation was studied in all patients by quantitative RT-PCR. Results: V617FJAK2 was detected in 45% of BCS and 34% of PVT (p=.08). Mean % circulating V617F allele was 37% and 28% in BCS and PVT pts, respectively (p<.04). In pts diagnosed with MPD using conventional criteria, V617F mutation was found in 84% pts with positive BMB, and in 97% pts with concordant BMB+EEC results (table). In pts previously diagnosed as no-MPD, V617F was present in 19% pts with negative BMB and in 7% pts with both negative BMB and EEC. This discrepancy was greater in BCS patients, where V617F was found in 25% pts previously not diagnosed with MPD. V617F was also found in 58% of pts with discordant BMB and EEC results, allowing to increase the rate of definite MPD diagnosis. On the other hand, 16% pts with wild type JAK2 had MPD features on BMB and 20% had positive EEC. Taking into account V617F JAK2 in addition to BMB and EEC, definite MPD incidence increased from 30 to 49% overall; from 32% to 60% in BCS patients; and from 29% to 49% in PVT patients. V617F JAK2 was significantly associated with higher Hb, WBC, and platelet counts, larger spleen size, lower serum EPO, and higher red cell mass. Other prothrombotic states were found in 19/92 V617F patients and 29/144 wtJAK2 patients (NS). Baseline BCS prognostic scores (Child Pugh, Clichy and Rotterdam scores) did not significantly differ between V617F and wtJAK2 patients. BCS and PVT survival was not affected by the presence of V617F JAK2. Conclusion: Detection of V617FJAK2 (1) is almost as common in PVT as in BCS but the % of mutant allele is higher in BCS; (2) is not fully redundant with EEC or BMB findings and increases the diagnosis of underlying MPD by 28% in BCS and by 20% in PVT; (3) has no discernible impact on medium term outcome of BCS or PVT. (Supported by EU: QLG1-CT-2002-01686). % of V617F JAK2 positive All patients BCS PVT BMB / EEC + / + 97 100 94 − / − 7 25 0 Discordant 58 53 62 BMB + 84 75 92 − 19 27 12 EEC + 77 84 72 − 25 38 18 inconclusive 33 36 30

scholarly journals Conditional expression of heterozygous or homozygous Jak2V617F from its endogenous promoter induces a polycythemia vera–like disease

Blood ◽  
2010 ◽  
Vol 115 (17) ◽  
pp. 3589-3597 ◽  
Author(s):  
Hajime Akada ◽  
Dongqing Yan ◽  
Haiying Zou ◽  
Steven Fiering ◽  
Robert E. Hutchison ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Gene Dosage ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Erythroid Progenitors ◽  
Conditional Expression ◽  
Biochemical Analyses ◽  
Genetic Events ◽  
Serum Erythropoietin

Abstract A somatic point mutation (V617F) in the JAK2 tyrosine kinase was found in a majority of patients with polycythemia vera (PV), essential thrombocythemia, and primary myelofibrosis. However, contribution of the JAK2V617F mutation in these 3 clinically distinct myeloproliferative neoplasms (MPNs) remained unclear. To investigate the role of JAK2V617F in the pathogenesis of these MPNs, we generated an inducible Jak2V617F knock-in mouse, in which the expression of Jak2V617F is under control of the endogenous Jak2 promoter. Expression of heterozygous mouse Jak2V617F evoked all major features of human polycythemia vera (PV), which included marked increase in hemoglobin and hematocrit, increased red blood cells, leukocytosis, thrombocytosis, splenomegaly, reduced serum erythropoietin (Epo) levels and Epo-independent erythroid colonies. Homozygous Jak2V617F expression also resulted in a PV-like disease associated with significantly greater reticulocytosis, leukocytosis, neutrophilia and thrombocytosis, marked expansion of erythroid progenitors and Epo-independent erythroid colonies, larger spleen size, and accelerated bone marrow fibrosis compared with heterozygous Jak2V617F expression. Biochemical analyses revealed Jak2V617F gene dosage-dependent activation of Stat5, Akt, and Erk signaling pathways. Our conditional Jak2V617F knock-in mice provide an excellent model that can be used to further understand the molecular pathogenesis of MPNs and to identify additional genetic events that cooperate with Jak2V617F in different MPNs.

scholarly journals Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Peijin Zhang ◽  
Yanyan Zhang ◽  
Jing Zhang ◽  
Hui Wang ◽  
He Ma ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Recessive Model ◽  
Elevated Risk ◽  
Budd Chiari Syndrome ◽  
Candidate Locus ◽  
Susceptibility Factor ◽  
Chiari Syndrome

Myeloproliferative neoplasms (MPNs) are the leading cause of Budd-Chiari syndrome (BCS), and the C allele of JAK2 rs4495487 was reported to be an additional candidate locus that contributed to MPNs. In the present study, we examined the role of JAK2 rs4495487 in the etiology and clinical presentation of Chinese BCS patients. 300 primary BCS patients and 311 healthy controls were enrolled to evaluate the association between JAK2 rs4495487 polymorphism and risk of BCS. All subjects were detected for JAK2 rs4495487 by real-time PCR.Results. The JAK2 rs4495487 polymorphism was associated with JAK2 V617F-positive BCS patients compared with controls (P<0.01). The CC genotype increased the risk of BCS in patients with JAK2 V617F mutation compared with individuals presenting TT genotype (OR = 13.60, 95% CI = 2.04–90.79) and non-CC genotype (OR = 12.00, 95% CI = 2.07–69.52). We also observed a significantly elevated risk of combined-type BCS associated with CC genotype in the recessive model (OR = 4.44, 95% CI = 1.31–15.12). This study provides statistical evidence that the JAK2 rs4495487 polymorphism is susceptibility factor JAK2 V617F positive BCS and combined BCS in China. Further larger studies are required to confirm these findings.

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