Subject(s)
Fibrinogen/genetics , Fibrinogens, Abnormal/genetics , Portal Vein/pathology , Venous Thrombosis/genetics , Alleles , Case-Control Studies , Cohort Studies , Female , Fibrinogen/metabolism , Fibrinogens, Abnormal/metabolism , Genotype , Haplotypes , Humans , Liver Diseases/genetics , Male , Polymorphism, Single Nucleotide , Venous Thrombosis/etiologyABSTRACT
Myeloproliferative neoplasms (MPNs) are the most common cause of Budd-Chiari syndrome (BCS) and nonmalignant, noncirrhotic portal vein thrombosis (PVT). In this meta-analysis, we determined the prevalence of MPNs and their subtypes as well as JAK2V617F and its diagnostic role in these uncommon disorders. MEDLINE and EMBASE databases were searched. Prevalence of MPNs, JAK2V617F, and MPN subtypes were calculated using a random-effects model. A total of 1062 BCS and 855 PVT patients were included. In BCS, mean prevalence of MPNs and JAK2V617F was 40.9% (95% CI, 32.9%-49.5%) and 41.1% (95% CI, 32.3%-50.6%), respectively. In PVT, mean prevalence of MPNs and JAK2V617F was 31.5% (95% CI, 25.1%-38.8%) and 27.7% (95% CI, 20.8%-35.8%), respectively. JAK2V617F and MPNs were more frequent in BCS compared with PVT (P = .03 and P = .09, respectively). Polycythemia vera was more prevalent in BCS than in PVT (P = .001). JAK2V617F screening in splanchnic vein thrombosis (SVT) patients without typical hematologic MPN features identified MPN in 17.1% and 15.4% of screened BCS and PVT patients, respectively. These results demonstrate a high prevalence of MPNs and JAK2V617F in SVT patients and show differences in underlying etiology between these disorders. Furthermore, these results validate routine inclusion of JAK2V617F in the diagnostic workup of SVT patients.
Subject(s)
Budd-Chiari Syndrome/complications , Janus Kinase 2/genetics , Myeloproliferative Disorders/complications , Portal Vein/pathology , Venous Thrombosis/complications , Animals , Budd-Chiari Syndrome/diagnosis , Budd-Chiari Syndrome/genetics , Humans , Mutation , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , Portal Vein/metabolism , Venous Thrombosis/diagnosis , Venous Thrombosis/geneticsABSTRACT
The germline JAK2 46/1 haplotype has been associated with the development of JAK2(V617F)-positive as well as JAK2(V617F)-negative myeloproliferative neoplasms (MPNs). In this study we examined the role of the 46/1 haplotype in the etiology and clinical presentation of patients with splanchnic vein thrombosis (SVT), in which MPNs are the most prominent underlying etiological factor. The single-nucleotide polymorphism rs12343867, which tags 46/1, was genotyped in 199 SVT patients. The 46/1 haplotype was overrepresented in JAK2(V617F)-positive SVT patients compared with controls (P < .01). Prevalence of the 46/1 haplotype in JAK2(V617F)-negative SVT patients did not differ from prevalence in the controls. However, JAK2(V617F)-negative SVT patients with a proven MPN also exhibited an increased frequency of the 46/1 haplotype (P = .06). Interestingly, 46/1 was associated with increased erythropoiesis in JAK2(V617F)-negative SVT patients. We conclude that the 46/1 haplotype is associated with the development of JAK2(V617F)-positive SVT. In addition, our findings in JAK2(V617F)-negative SVT patients indicate an important role for the 46/1 haplotype in the etiology and diagnosis of SVT-related MPNs, independent of JAK2(V617F), that requires further exploration.
Subject(s)
Budd-Chiari Syndrome/genetics , Janus Kinase 2/genetics , Portal Vein , Splanchnic Circulation , Venous Thrombosis/genetics , Adult , Budd-Chiari Syndrome/epidemiology , Case-Control Studies , Factor V/genetics , Female , Genetic Predisposition to Disease/epidemiology , Haplotypes , Humans , Male , Middle Aged , Prothrombin/genetics , Risk Factors , Venous Thrombosis/epidemiologyABSTRACT
In this review, we provide an overview of the risk factors for venous thromboembolism, focusing on hypercoagulability and hypofibrinolysis. In the first part of this review, we discuss the risk factors for commonly occurring venous thrombosis, in particular deep vein thrombosis and pulmonary embolism. In the second part, we provide an overview of the risk factors for the Budd-Chiari syndrome and portal vein thrombosis. These are rare, life-threatening forms of venous thromboembolism located in the splanchnic veins. There are many similarities in the risk profiles of patients with common venous thrombosis and splanchnic vein thrombosis. Inherited thrombophilia and hypofibrinolysis increase the risk of both common venous thrombosis and splanchnic vein thrombosis. However, there are also apparent differences. Myeloproliferative neoplasms and paroxysmal nocturnal hemoglobinuria have a remarkably high frequency in patients with thrombosis at these unusual sites but are rarely seen in patients with common venous thrombosis. There are also clear differences in the underlying risk factors for Budd-Chiari syndrome and for portal vein thrombosis, suggesting site specificity of thrombosis even within the splanchnic venous system. These clear differences in underlying risk factors provide leads for further research on the site specificity of venous thrombosis and the development of thrombosis at these distinct sites.
Subject(s)
Budd-Chiari Syndrome/etiology , Fibrinolysis , Pulmonary Embolism/etiology , Thrombophilia/complications , Venous Thromboembolism/etiology , Budd-Chiari Syndrome/blood , Budd-Chiari Syndrome/genetics , Fibrinolysis/genetics , Genetic Predisposition to Disease , Hemoglobinuria, Paroxysmal/blood , Hemoglobinuria, Paroxysmal/complications , Humans , Myeloproliferative Disorders/blood , Myeloproliferative Disorders/complications , Pulmonary Embolism/blood , Pulmonary Embolism/genetics , Risk Assessment , Risk Factors , Thrombophilia/blood , Thrombophilia/genetics , Venous Thromboembolism/blood , Venous Thromboembolism/geneticsABSTRACT
In this article, the authors discuss three pathophysiologic mechanisms that influence the coagulation system in patients who have liver disease. First, bacterial infections may play an important role in the cause of variceal bleeding in patients who have liver cirrhosis, affecting coagulation through multiple pathways. One of the pathways through which this occurs is dependent on endogenous heparinoids, on which the authors focus in this article. Secondly, the authors discuss renal failure, a condition that is frequently encountered in patients who have liver cirrhosis. Finally, they review dysfunction of the endothelial system. The role of markers of endothelial function in cirrhotic patients, such as von Willebrand factor and endothelin-1, is discussed.
Subject(s)
Bacterial Infections/complications , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/physiopathology , Heparinoids/metabolism , Liver Cirrhosis/complications , Renal Insufficiency/etiology , Biomarkers/metabolism , Blood Coagulation , Endothelin-1/metabolism , Endothelium, Vascular/physiopathology , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/metabolism , Varicose Veins/pathology , von Willebrand Factor/metabolismABSTRACT
Transcatheter local thrombolytic therapy in patients with acute, extended splanchnic venous thrombosis is controversial. Here we present our single-center experience with transcatheter thrombolytic therapy in these patients. All consecutive patients (n = 12) with acute, extended splanchnic venous thrombosis who underwent transcatheter thrombolytic therapy in our hospital, were included in this study. Thrombolytic therapy was successful for three thrombotic events and partially successful for four thrombotic events. Two patients developed minor procedure-related bleeding (17%). Six patients (50%) developed major procedure-related bleeding, with a fatal outcome in two. Transcatheter thrombolytic therapy in patients with acute, extended splanchnic vein thrombosis is found to be associated with a high rate of procedure-related bleeding. Therefore, thrombolysis should be reserved for patients in whom the venous flow cannot be restored by using conventional anticoagulant therapy or stent placement across the thrombosed vessel segment.
Subject(s)
Budd-Chiari Syndrome/drug therapy , Fibrinolytic Agents/administration & dosage , Portal Vein , Splanchnic Circulation , Thrombolytic Therapy , Venous Thrombosis/drug therapy , Adult , Budd-Chiari Syndrome/etiology , Budd-Chiari Syndrome/physiopathology , Female , Fibrinogen/analysis , Fibrinolytic Agents/adverse effects , Hemorrhage/chemically induced , Hemorrhage/mortality , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Liver Cirrhosis/physiopathology , Liver Function Tests , Male , Middle Aged , Patient Selection , Portal Vein/physiopathology , Portasystemic Shunt, Transjugular Intrahepatic , Retrospective Studies , Risk Assessment , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Treatment Outcome , Vascular Patency , Venous Thrombosis/etiology , Venous Thrombosis/physiopathologyABSTRACT
We studied the etiology, diagnosis and natural course of myeloproliferative disease (MPD) in 40 consecutive patients with Budd-Chiari syndrome (BCS). In 38% of the BCS patients with MPD another etiological factor was found. JAK2 mutation was present in 41% of the tested BCS patients. Survival was not significantly affected by the presence of MPD.
