Smalberg, J.H.

Budd-Chiari Syndrome and Portal Vein Thrombosis: Etiology and Treatment (Doctoral Thesis)

2012-01-12T00:00:00Z

Venous thrombosis is a common disorder with an annual incidence of around 1-2 cases per 1.000 individuals and is the third leading cause of cardiovascular morbidity and mortality in developed countries.1-4 Thrombosis may arise in any section of the venous system, but it typically occurs in the deep veins of the lower extremities. The major concern in these patients is pulmonary embolism, which can be fatal. A more common, but often disabling, complication of deep vein thrombosis and its sequelae is the post-thrombotic syndrome.5 Rarely, thrombosis may involve other venous sites. One of these uncommon manifestations of thrombosis is located in the splanchnic veins, which is accompanied by a considerable morbidity and mortality.

Long-term follow-up of patients with portal vein thrombosis and myeloproliferative neoplasms (Article)

2011-11-01T00:00:00Z

Background:Myeloproliferative neoplasms (MPNs) are frequently identified as an underlying cause in patients with non-cirrhotic portal vein thrombosis (PVT). The aim of this study was to describe the long-term outcome of patients with PVT and MPN. Methods:A cohort study was performed including all adult patients referred to our hospital between 1980 and 2008 with non-cirrhotic, non-malignant PVT and confirmed MPN. Results:A total of 44 patients (70% female) were included, with a median age at PVT-diagnosis of 48years (range 18-79). In 31 patients (70%) PVT was the first manifestation of an MPN. Additional risk factors for thrombosis were present in 20 patients (45%). Median follow-up was 5.8years (range 0.4-21). Twenty-three patients (52%) were treated with oral anticoagulants after diagnosis of PVT, of whom 15 (34%) received long-term therapy. During follow-up, 17 patients (39%) experienced at least one episode of gastrointestinal bleeding. Additional thrombotic events occurred in 12 patients (27%). Twelve patients (27%) had progression of the underlying MPN. Seventeen patients (39%) died at a median age of 64years (range 30-88). Death was directly related to end-stage MPN in eight patients (47%) and to a new thrombotic event in three patients (18%). No patients died from gastrointestinal bleeding. Conclusions:PVT is often the presenting symptom of an underlying MPN, highlighting the need for thorough screening for this disease. Recurrent thrombosis is a common and severe complication in patients with PVT and MPN. Mortality is primarily related to the underlying MPN and not to complications of portal hypertension.

The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis (Article)

2011-04-14T00:00:00Z

The germline JAK2 46/1 haplotype has been associated with the development of JAK2V617F-positive as well as JAK2V617F-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 singlenucleotide polymorphism rs12343867, which tags 46/1, was genotyped in 199 SVT patients. The 46/1 haplotype was overrepresented in JAK2V617F-positive SVT patients compared with controls (P<.01). Prevalence of the 46/1 haplotype in JAK2V617F-negative SVT patients did not differ from prevalence in the controls. However, JAK2V617F-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 JAK2V617F-negative SVT patients. We conclude that the 46/1 haplotype is associated with the development of JAK2V617F-positive SVT. In addition, our findings in JAK2V617F-negative SVT patients indicate an important role for the 46/1 haplotype in the etiology and diagnosis of SVT-related MPNs, independent of JAK2V617F, that requires further exploration.

Hypercoagulability and hypofibrinolysis and risk of deep vein thrombosis and splanchnic vein thrombosis: Similarities and differences (Article)

2011-03-01T00:00:00Z

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. Copyright

Absence of the JAK2 V617F mutation in patients with arterial thrombosis without overt myeloproliferative disease (Article)

2008-08-26T00:00:00Z