Prevalence of CALR mutations in splanchnic vein thrombosis: A systematic review and meta-analysis

Li, Miaomiao; Stefano, Valerio De; Song, Tingxue; Zhou, Xinmiao; Guo, Zeqi; Zhu, Jiang; Qi, Xingshun

doi:10.1016/j.thromres.2018.05.007

Cited by 24 publications

(19 citation statements)

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“…A recent systematic review and meta‐analysis of eleven publications (two from Asia) explored the significance of screening for CALR mutations in patients with SVT. The pooled prevalence of CALR mutation in all BCS patients was 1.41%; in patients with MPN it was 2.79%; in BCS with JAK2V617F negative MPN it was as high as 17.22% …”

Section: Aetiology and Pathogenesismentioning

confidence: 93%

Review article: a multidisciplinary approach to the diagnosis and management of Budd‐Chiari syndrome

Khan

Armstrong

Mehrzad

et al. 2019

Aliment Pharmacol Ther

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Background: Budd-Chiari syndrome (BCS) is a rare but fatal disease caused by obstruction in the hepatic venous outflow tract. Aim: To provide an update of the pathophysiology, aetiology, diagnosis, management and follow-up of BCS. Methods: Analysis of recent literature by using Medline, PubMed and EMBASE databases. Results: Primary BCS is usually caused by thrombosis and is further classified into "classical BCS" type where obstruction occurs within the hepatic vein and "hepatic vena cava BCS" which involves thrombosis of the intra/suprahepatic portion of the inferior vena cava (IVC). BCS patients often have a combination of prothrombotic risk factors. Aetiology and presentation differ between Western and certain Asian countries. Myeloproliferative neoplasms are present in 35%-50% of European patients and are usually associated with the JAK2-V617F mutation. Clinical presentation is diverse and BCS should be excluded in any patient with acute or chronic liver disease. Non-invasive imaging (Doppler ultrasound, computed tomography, or magnetic resonance imaging) usually provides the diagnosis. Liver biopsy should be obtained if small vessel BCS is suspected. Stepwise management strategy includes anticoagulation, treatment of identified prothrombotic risk factors, percutaneous revascularisation and transjugular intrahepatic portosystemic stent shunt to re-establish hepatic venous drainage, and liver transplantation in unresponsive patients. This strategy provides a 5-year survival rate of nearly 90%. Long-term outcome is influenced by any underlying haematological condition and development of hepatocellular carcinoma. Conclusions: With the advent of newer treatment strategies and improved understanding of BCS, outcomes in this rare disease have improved over the last three decades. An underlying haematological disorder can be the major determinant of outcome. Primary BCS is considered a multifactorial disease and multicentre data found a combination of several prothrombotic conditions in 25% to 46% of the patients with BCS, 11,19-21 several times greater than expected in the general population. The discovery of one causal factor should not discourage further investigation to identify other prothrombotic conditions. Multifactorial causes may explain the rarity of BCS. 2 The prothrombotic conditions found in BCS, in particular the classical type, include: Factor V Leiden mutation, prothrombin (PT) gene mutation, protein C deficiency, protein S deficiency, antithrombin deficiency, antiphospholipid syndrome, hyperhomocysteinemia and paroxysmal nocturnal haemoglobinuria. 22 BCS is also associated with systemic inflammatory diseases, such as Behçet's disease, sarcoidosis, vasculitis and other connective tissue diseases. 22 A detailed description of the frequency of inherited/acquired thrombophilias and risk factors found in patients with BCS compared to those with portal vein thrombosis is summarised by Poisson and colleagues. 23

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Section: Aetiology and Pathogenesismentioning

confidence: 93%

Review article: a multidisciplinary approach to the diagnosis and management of Budd‐Chiari syndrome

Khan

Armstrong

Mehrzad

et al. 2019

Aliment Pharmacol Ther

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“…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. JAK2V617F 6 and calreticulin (CALR) 7,8 mutations are found in 80% and 4% of MPN-SVT, respectively, [9][10][11] whereas JAK2 exon 12 or MPL gene mutations are very rarely identified. 9 Similarly to classical MPN patients, MPN-SVT patients may harbor additional nondriver mutations targeting genes involved in the regulation of various intracellular pathways like epigenetics, messenger RNA splicing, signalization, and transcription.…”

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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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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“…18 Although the presence of the calreticulin (CALR) mutation was not evaluated in the present study, it should be noted that results of a meta-analysis suggest that screening for CALR mutations may have a role in SVT patients with a high probability of MPN in whom the JAK2V617F mutation has been excluded. 20 Thus, we will have in mind the screening for CALR mutation in this specific group of patients in the future.…”

Section: Discussionmentioning

confidence: 99%

JAK2V617F mutation prevalence on Chilean adults suffering from primary mesenteric and portal venous thromboses

González-Montero

Valle-Batalla

Castillo-Astorga

et al. 2020

Int J Lab Hematology

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Introduction Mesenteric and portal venous thromboses are rare diseases with high mortality rates and are strongly associated with hepatic cirrhosis, and abdominal inflammatory or tumoral processes, but in some cases can be the first sign of myeloproliferative neoplasm (MPN) or hereditary thrombophilia. JAK2V617F mutation detection is an important diagnostic tool for MPN patients. The aim of this study was to describe the JAK2V617F mutation prevalence on Chilean patients suffering from a primary splanchnic venous thrombosis (SVT), in order to assess how it relates to primary MVT and PVT in our specific population. Methods A retrospective observational study was conducted in patients referred to the University of Chile Clinical Hospital with mesenteric and/or portal venous thrombosis diagnosis over a 7‐year period. Patients with primary thrombosis underwent hereditary thrombophilia study and JAK2V617F mutation screening. Results A total of 123 patients had splanchnic venous thrombosis (mesenteric and/or portal) as their main discharge diagnosis. Sixty patients (49%) had primary mesenteric or portal venous thrombosis (no attributable secondary cause). Hereditary thrombophilia and MPN were diagnosed in 21.6% and 43.3% of SVT patients, respectively. Twenty SVT patients remained without an etiologic diagnosis. In MPN patients, almost all had the JAK2V617F mutation (92.3%). About 16% of patients who had positive JAK2V617F mutation did not meet diagnostic criteria for MPN. Conclusions In this Chilean cohort, half of mesenteric or portal venous thrombosis showed no secondary cause. In this group, the main causes were MPN and hereditary thrombophilia. Nearly, all MPN patients had JAK2V617F mutation, but there was a group of patients having JAK2V617F mutation but did not meet MPN criteria.

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Prevalence of CALR mutations in splanchnic vein thrombosis: A systematic review and meta-analysis

Cited by 24 publications

References 46 publications

Review article: a multidisciplinary approach to the diagnosis and management of Budd‐Chiari syndrome

Review article: a multidisciplinary approach to the diagnosis and management of Budd‐Chiari syndrome

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

JAK2V617F mutation prevalence on Chilean adults suffering from primary mesenteric and portal venous thromboses

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