Predictive values of X-chromosome inactivation patterns and clinicohematologic parameters for vascular complications in female patients with essential thrombocythemia

Essential thrombocythemia (ET) is a heterogeneous disorder in which the clonality of hematopoiesis varies. The clinical significance of clonality status in ET remains to be determined. We used the human androgen receptor gene (HUMARA)-polymerase chain reaction assay to investigate X-chromosome inactivation patterns (XCIPs) and their value in predicting vascular complications in 89 female patients with ET. Fifty-four (68.4%) patients had a clonal pattern of XCIP, and 15 (19.0%) had a polyclonal pattern. The remaining 20 patients had either an ambiguous or a homozygous pattern of XCIP and were therefore excluded from further analysis. Patients with clonal XCIPs were older (P = .029) and were at greater risk for thrombosis (P = .007) than were those with polyclonal XCIPs. We did not find a correlation between the occurrence of hemorrhage and XCIP (P = .492). Advanced age was predictive of thrombosis and hemorrhage. Platelet count did not influence the risk for vascular complications. Hypertension was significantly correlated with thrombotic events (P = .002), whereas diabetes mellitus and hypercholesterolemia were of no predictive value. In a multivariate analysis, age was the significant predictor of thrombosis (P = .030); however, XCIPs (P = .083) and hypertension (P = .073) tended to predict thrombosis. Our results suggest that older patients who have clonal XCIPs or hypertension are at increased risk for thrombosis and should be monitored closely for this complication.