From the Journals

Thrombosis risk is elevated with myeloproliferative neoplasms

Publish date: January 17, 2018
By
Andrew D. Bowser

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Thrombotic risk magnitude in the spotlight

The most notable contribution of the large cohort study by Hultcrantz and her colleagues is quantification of the magnitude of thrombotic risk that MPNs confer, according to Alison R. Moliterno, MD, and Elizabeth V. Ratchford, MD.

“Hultcrantz and colleagues have opened our eyes to the magnitude of thrombotic risk MPNs bring to affected patients,” Dr. Moliterno and Dr. Ratchford wrote in an editorial in Annals of Internal Medicine. “Their study shows us that the traditional approach to assessing thrombotic risk in patients with MPNs [who are age 60 years and older, have prior thrombotic event, and have traditional cardiovascular risk factors] lacks precision and personalization.”

Both arterial and venous thrombotic events were increased throughout patients’ lifetimes, though the highest risk was around the time of MPN diagnosis. According to study results, 10% of patients had a thrombotic event in the 30 days before or after 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,” Dr. Moliterno and Dr. Ratchford wrote.

Unfortunately, the study did not include data on genomics, they noted. The acquired JAK2 V617F mutation, which drives MPN phenotypes, is associated with elevated inflammatory cytokines, and inflammation is a recognized risk factor for thrombosis, according to the editorial authors.

Alison R. Moliterno, MD, and Elizabeth V. Ratchford, MD, are with Johns Hopkins University, Baltimore. These comments are adapted from an accompanying editorial (Ann Intern Med. 2018. doi: 10.7326/M17-3153). The authors reported having no relevant conflicts related to the study.


 

FROM ANNALS OF INTERNAL MEDICINE

Patients with myeloproliferative neoplasms (MPNs) have a higher rate of arterial and venous thrombosis than does the general population, with the greatest risk occurring around the time of diagnosis, according to results of a retrospective study.

Hazard ratios at 3 months after diagnosis were 3.0 (95% CI, 2.7-3.4) for arterial thrombosis and 9.7 (95% CI, 7.8-12.0) for venous thrombosis, compared with matched controls, Malin Hultcrantz, MD, PhD, of the Karolinska University Hospital, Stockholm, and her coauthors reported in the Annals of Internal Medicine.

Although previous studies have suggested patients with MPNs are at increased risk for thrombotic events, this large, population-based analysis is believed to be the first study to provide estimates of excess risk compared with matched control participants.

“These results are encouraging, and we believe that further refinement of risk scoring systems (such as by including time since MPN diagnosis and biomarkers); rethinking of recommendations for younger patients with MPNs; and emerging, more effective treatments will further improve outcomes for patients with MPNs,” the researchers wrote.

The retrospective, population-based cohort study included 9,429 Swedish patients diagnosed with MPNs between 1987 and 2009 and 35,820 matched control participants. Patient follow-up through 2010 was included in the analysis.

Thrombosis risk was highest near the time of diagnosis but decreased during the following year “likely because of effective thromboprophylactic and cytoreductive treatment of the MPN;”still, the risk remained elevated, the researchers wrote.

“This novel finding underlines the importance of initiating phlebotomy as well as thromboprophylactic and cytoreductive treatment, when indicated, as soon as the MPN is diagnosed,” they added.

Arterial thrombosis hazard ratios for MPN patients, compared with control participants, were 3.0 at 3 months after diagnosis, 2.0 at 1 year, and 1.5 at 5 years. Similarly, venous thrombosis hazard ratios were 9.7 at 3 months, 4.7 at 1 year, and 3.2 at 5 years.

Thrombosis risk was elevated in all age groups and all MPN subtypes, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Of note, the study confirmed prior thrombosis and older age (60 years or older) as risk factors. Among patients with both of those risk factors, risk of thrombosis was increased 7-fold, according to the researchers.

Hazard ratios for thrombosis decreased during more recent time periods, suggesting a “positive effect” of improved treatment strategies, including increased use of aspirin as primary prophylaxis, better cardiovascular risk management, and better adherence to recommendations for cytoreductive treatment and phlebotomy, the researchers noted. Additionally, treatment with interferon and Janus kinase 2 inhibitors, such as ruxolitinib, “may be effective in further reducing risk for thrombosis,” the researchers wrote.

The study was funded by the Cancer Research Foundations of Radiumhemmet, the Swedish Research Council, and Memorial Sloan Kettering Cancer Center, among other sources. The researchers reported having no financial disclosures relevant to the study.

SOURCE: Hultcrantz M et al. Ann Intern Med. 2018. doi: 10.7326/M17-0028.

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