On the basis of the new-onset BCS combined with the finding of the
JAK2 V617F mutation, our patient's condition was diagnosed as an underlying chronic MPN. Thromboses, including abdominal vein thromboses, constitute a major etiology of morbidity and mortality in MPN [
3]. MPN now constitutes the most common cause of abdominal venous thromboses, accounting for approximately 50% of BCS cases and 25% of portal vein thromboses [
4]. A recent study demonstrated MPN to be the most prevalent underlying condition (49%) in a series of 163 incident cases of BCS [
1]. In most of these patients, portal hypertension was a typical feature. This becomes important because it may help to explain the surprisingly low or normal blood counts observed in BCS
JAK2 V617F-positive patients; the subsequent hemodilution and hypersplenism resulting from the portal hypertension may decrease the actual hemoglobin and other blood cell counts, making the diagnosis of MPN quite challenging in many cases [
4]. Masking of the MPN by subsequent hemodilution from portal hypertension or even from hepatic dysfunction is evident in our patient, in whom the platelet count normalized from the previously mild elevation evident in the years before her BCS diagnosis (Table
1). Several groups have hypothesized that endothelial cell (EC) dysfunction may contribute to the prothrombotic state in MPN. In a seminal study, Sozer and colleagues [
5] demonstrated that the
JAK2 V617F mutation was present in the ECs from venules of liver biopsy specimens obtained from two patients with BCS and PV, suggesting that ECs in PV are involved in the malignant process and contribute to the prothrombotic state found in this disorder.
It has been suspected for decades that primary, occult MPN may play a role in the prevalence of BCS, especially in young women. One study demonstrated that erythroid colony formation in the absence of erythropoietin, a reliable indicator of MPN in the pre-
JAK2 V617F era, was present in 16 out of 20 patients with BCS, most of whom were young women (18 to 45 years old) [
6]. The authors concluded, some 20 years prior to the elucidation of the
JAK2 V617F mutation, that primary MPN is a major cause of BCS in young women. Many cases labeled as idiopathic BCS have been subsequently found to be secondary to underlying myeloproliferative disease upon
JAK2 V617F testing [
7]. In the literature reported to date, the largest series relating
JAK2 V617F mutation status to abdominal venous thrombosis showed that
JAK2 V617F-associated BCS was predominantly a disease of young women, that it was associated with relatively low
JAK2 V617F allele burdens, and that the majority of the patients did not have additional identified hypercoagulable risk factors, all features common to our patient [
4]. Also, the most common risks for thrombotic disease in MPN are older age (> 60 years), elevated white cell count, and prior thrombotic events [
8], none of which applies to either our patient or the MPN BCS patients at large [
4]. The discrepancy between the absence of traditional MPN thrombotic risk factors and the low
JAK2 V617F allele burdens in the patients with BCS indicates that other important risk factors for this devastating presentation, particularly relevant to young women with MPN, remain undefined [
9]. It is interesting to note that our patient's JAK2 V617 allele burden at diagnosis measured only 36%.
JAK2 V617F allele burdens are lower in women in comparison with men, suggesting that gender is an important modifier of disease phenotype and may in part account for differences in disease presentation and complications between men and women with
JAK2 V617F-positive MPNs [
3,
10].