It’s common knowledge among hematologists-oncologists that rates of arterial and venous thrombosis are increased in patients with myeloproliferative neoplasms (MPNs), such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
However, the first-ever population-based study now gives fresh and surprising insight into the magnitude of those rates, according to experts.
In the study, Swedish investigators assessed the risk for the two types of thrombosis among 9429 patients with MPNs and 35,820 matched control persons from Sweden from 1987 to 2009. Follow-up extended to 2010.
The researchers calculated hazard ratios (HRs) among MPN patients compared to control persons.
For arterial thrombosis, the HRs were 3.0 at 3 months, 2.0 at 1 year, and 1.5 at 5 years.
For venous thrombosis, the HRs were 9.7 at 3 months, 4.7 at 1 year, and 3.2 at 5 years.
“Patients with MPNs across all age groups have a significantly increased rate of arterial and venous thrombosis compared to matched controls,” conclude the authors, led by Malin Hultcrantz, MD, PhD, from the Karolinska Institute in Stockholm and the Memorial Sloan kettering Cancer Center in New York City.
The fact that the rates are highest “shortly after diagnosis” underlines the importance of “initiating phlebotomy as well as thromboprophylatic and cytoreductive treatment, when indicated, as soon as the MPN is diagnosed,” they say.
They also point out that nearly 10% of patients had a thromboembolic event within 30 days before or after their MPN diagnosis.
The team explains that the reason the HRs decreased during the first year after diagnosis is “likely because of effective thromboprophylatic and cytoreductive treatment of the MPN.”
The authors also point out that many studies have assessed the incidence of thrombosis in patients with MPNs, but most are “hampered” by a lack of a control population. Hence the importance of their current study, which features a large set of control persons.
The current study was published online 15 January in the Annals of Internal Medicine.
In an accompanying editorial, two experts from Johns Hopkins School of Medicine in Baltimore, Maryland, express some surprise at the results.
“Hultcrantz and colleagues have opened our eyes to the magnitude of thrombotic risk MPNs bring to affected patients,” write Allison Moliterno, MD, and Elizabeth Ratchford, MD, of the Division of Hematology in the School of Medicine.
Hultcrantz and colleagues have opened our eyes to the magnitude of thrombotic risk.
Quantifying that risk is “the most notable contribution” of the study, say the editorialists. They explain that the HRs for arterial events are “similar to those for cigarette smoking” and that the HRs for venous events are comparable to those for factor V Leiden heterozygosity.
The study authors report that the rate of thrombosis was significantly elevated across all age groups and was similar among MPN subtypes.
The investigators also calculated cumulative incidence. They report that during a 5-year period, there was “an initial rapid increase followed by gentler increases during follow-up.”
Still, the HRs remained “significantly elevated” throughout follow-up, the authors emphasize.
Takeaway Messages
The editorialists note a number of takeaway messages for clinicians from the new study.
First, they say the findings show that the “traditional approach” to assessing thrombotic risk in patients with MPNs “lacks precision and personalization.” Traditionally, clinicians have regarded that risk as hinging on three main factors: age 60 years or older, prior thrombotic event, and presence of traditional cardiovascular risk factors.
But the new study shows that younger patients bear significant risk. In fact, the highest HRs were observed in younger age groups (up to age 59). However, the study authors temper this finding by observing that there were a limited number of events in the youngest age group (age 18 to 49), so that finding requires some caution.
The editorialists also highlight the heightened risk for events in the 30-day period before and after a diagnosis. “Patients and clinicians should be keenly aware of this particularly risky period, during which risk for thrombosis is similar to that in the month after a transient ischemic attack,” write Dr Moliterno and Dr Ratchford.
Patients and clinicians should be keenly aware of this particularly risky period.
The pair say there is one disappointment with the new study: it did not include genomics data. The acquired mutation of the hematopoietic stem cell JAK2 V617F was discovered in 2005, and its presence “provides a proliferative advantage and drives MPN phenotypes.”
These mutations are detected in 0.1% to 0.2% of the general population. Even in the absence of MPN, rates of thrombotic events are higher in individuals who carry the mutations, say the editorialists. The mutations are rare in persons younger than 50 years but occur in as many as 6% of those older than 65 years.
A more precise and personalized assessment of the risk for thromboses should include genomics. Such an assessment would include evaluating the status of JAK2 V617F, because it increases risk for thrombosis, say the editorialists.
The study was supported by the Cancer Research Foundations of Radiumhemmet, the Swedish Research Council, and other organizations. The study authors have disclosed no relevant financial relationships. Dr Ratchford has financial ties to Novartis and MedImmune.
Ann Intern Med. Published online January 15, 2018.
Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick.
For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc.
Tidak ada komentar:
Posting Komentar