Incidence and clinical risk factors for bleeding and thrombotic complications in myeloproliferative disorders

Summary

Bleeding and thrombosis are frequent complications in myeloproliferative disorders (MPD) and are associated with severe organ damage and a high mortality. Elevated platelet count, elevated hematocrit, and patient age are regarded as risk factors for bleeding and thromboembolic events in MPD, although the significance of these parameters was not confirmed by clinical studies. We retrospectively analyzed vascular complications in 260 patients with MPD and tried to identify parameters predictive for bleeding and thromboembolic events. Our cohort consisted of 115 patients with chronic myeloid leukemia (CML), 84 patients with polycythemia vera (PV), 26 with essential thrombocythemia (ET), 25 with osteomyelofibrosis (OMF), and 10 patients with unclassifiable MPD. During a median follow-up period of 31 months, 126 patients with chronic MPD suffered bleeding or thrombotic events. Bleeding was observed in 57% of patients with OMF, 23% with PV, 20% with chronic phase CML, and 16% with ET. Thrombotic events were most common in patients with PV (36% of patients), followed by ET, OMF, and chronic phase CML (20%, 17%, and 6% of patients, respectively). Recurrent thrombotic episodes frequently occurred in patients with PV and ET, whereas patients with OMF often had more than one bleeding event. Thirty patients died of thrombohemorrhagic complications during follow-up. Multivariate analysis, including all patients with chronic MPD, revealed that elevated red blood cell count, higher hemoglobin level, and increased percentage of segmented neutrophils at the time of diagnosis were associated with thrombosis, whereas patients with bleeding complications were characterized by low red cell count, lower hemoglobin, and a lower percentage of segmented neutrophils. However, when analyzed by MPD subgroup, none of these parameters retained a predictive value for bleeding or thrombotic events. Moreover, elevated platelet count and patient age were not risk factors for bleeding complications. Thrombotic events were less frequent in patients below the age of 40, and were increased in patients aged 70 and above. However, this was primarily due to the high percentage of elderly patients in subgroups mainly affected by thrombosis (PV and ET). In most MPD subgroups, the rate of bleeding and thrombosis was highest just before and during the first months after diagnosis, and declined thereafter. Thrombohemorrhagic complications were less frequent after phlebotomy in PV and after therapy with alkylating agents in CML. The institution of cytoreductive therapy soon after the diagnosis was made may explain the reduced incidence of complications later in the disease. We conclude that morbidity and mortality from thrombohemorrhagic complications are high in myeloproliferative disorders. Subgroup and stage of the disease and previous complications are helpful in estimating the risk of a bleeding or thrombotic event. Conventional cytoreductive therapy may result in a reduction of these complications.