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Low hematocrit levels decreased risk of thrombosis among patients with polycythemia vera
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ATLANTA — The standard approach of maintaining hematocrit levels less than 45% in patients with polycythemia vera was associated with a lower risk of thrombosis than the less aggressive strategy of maintaining levels between 45% and 50%, according to data presented at the 2012 ASH Annual Meeting and Exposition.
“[Maintenance of hematocrit levels in] the 45% to 50% range was associated with a fourfold higher rate of cardiovascular events and major thrombosis,” Tiziano Barbui, MD, of Ospedali Riuniti di Bergamo in Italy, said during a presentation. “Therefore, hematocrit less than 45% should be the target therapy for patients with [polycythemia vera].”
Tiziano Barbui
Polycythemia vera (PV) is a rare blood disorder that causes bone marrow to produce too many red blood cells. This can dramatically increase the risk of deep vein thrombosis or pulmonary embolism, as well as cardiovascular events such as stroke or heart attack. Thrombosis is the most common cause of death in patients with PV, so efforts to reduce blood thickness in those patients are crucial, researchers said.
Patients with PV typically have hematocrit levels that range from 50% to 70%, while levels in the general population typically are less than 50%.
Current treatment recommendations call for maintaining hematocrit levels at less than45% among patients with PV.
Previous post-hoc analysis of two clinical trials have not demonstrated whether extensive efforts to maintain hematocrit levels less than 45% helps ot prevent or reduce blood clots in patients with PV.
Barbui and colleagues conducted a large-scale, randomized trial to examine the efficacy and safety of efforts to maintain hematocrit levels among patients with PV.
Twenty-six centers in Italy enrolled 365 patients from February 2008 to May 2012.
Barbui and colleagues assigned 182 patients to Arm A, which called for aggressive efforts to maintain hematocrit levels at less than 45%. They assigned 183 patients to Arm B, which called for maintenance of hematocrit levels between 45% and 50%.
Researchers observed no significant differences between the two arms with respect to patient age, sex, time from diagnosis, bleeding or cardiovascular risk factors.
Cardiovascular death and major thrombosis —including stroke, acute coronary syndrome, transient ischemic cerebral attack, peripheral arterial thrombosis, pulmonary embolism, abdominal thrombosis and deep vein thrombosis — served as a composite primary endpoint.
Median follow-up was 31 months. Median hematocrit levels were 44% among patients assigned to Arm A and 48% among patients assigned to Arm B.
Annual incidence of cardiovascular death and major thrombosis was lower among patients assigned to Arm A (1.1% vs. 4.4%; HR=3.90), the results showed.
Seven patients developed overt myelofibrosis, six in Arm A and one in Arm B (P=0.10). Three patients assigned to Arm A and one patient assigned to Arm B developed acute leukemias. The difference was not statistically significant, researchers said.
Leukocyte levels remained higher in patients assigned to Arm B, Barbui said.
The researchers reported no differences in safety profiles between the two arms.
“These data validate the notion that it is important to keep hematocrit levels below 45% for this population of patients who are at a high risk of developing clotting complications,” Barbui said. “The results from our study will be especially important in the development of new drugs for polycythemia vera as we look to maintain these levels more effectively and with minimal complications.”
For more information:
Barbui T. Abstract #4. Presented at: the 2012 ASH Annual Meeting and Exposition; Dec. 8-11, 2012; Atlanta.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopAgnes Y. Lee, MD
This was an extremely important study because it established the current recommended guidelines as the optimal hematocrit level we should aim for. This level was recommended but it was very difficult to enforce in daily practice because it is burdensome for patients to come in for repeated phlebotomies. With this evidence, it is very clear that you should aim for that low hematocrit level to prevent major cardiovascular and thrombotic deaths and complications. It really establishes a landmark in terms of all new trials and other potential therapies.
Perspective
Back to Top
Keith McCrae, MD
It has long been known that the major contributor to whole blood viscosity is the hematocrit. In polycythemia vera (PV), the elevated hematocrit — as well as several other factors — predispose patients to thrombotic events that lead to increased mortality. Many physicians use a hematocrit of 50% as a threshold for phlebotomy in PV patients. This study randomized patients with PV to be maintained at a hematocrit below 45% or between 45% and 50%.
The investigators observed a significant reduction in the composite endpoint of stroke, acute coronary syndrome, TIA, peripheral artery embolism, pulmonary embolism, abdominal thrombosis, deep vein thrombosis or cardiovascular death in patients whose hematocrit was maintained below 45%. These patients also had a lower white blood cell count, and while it is difficult to be certain that the reduced hematocrit was the only reason underlying the better outcome in this group, the results seem clear. It is likely that this study may change practice and lead physicians toward more aggressive treatment of the hematocrit in patients with PV.
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