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Increased Thrombosis Risk With Myeloproliferative Neoplasms


By Will Boggs MD

NEW YORK (Reuters Health) - Myeloproliferative neoplasms are associated with an increased risk for arterial and venous thrombosis, according to a population-based study of Swedish registries.

"One of the most interesting findings in this study is that the risk of thrombosis was highest shortly after diagnosis of the myeloproliferative neoplasm (MPN) and then decreased with follow-up time,” Dr. Malin Hultcrantz from Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden, and Memorial Sloan-Kettering Cancer Center, New York, told Reuters Health by email. “We also found an elevated risk of thrombosis in all age groups, not only those over the age of 60 years, which traditionally have been considered a high-risk group.”

MPNs have long been thought to increase the risk of thrombosis, but no previous population-based study has estimated this excess risk compared with matched control participants.

Dr. Hultcrantz and colleagues used data from five Swedish registries to assess the relative risk for thrombosis in 9,429 patients with MPNs and in 35,820 matched controls. The findings were reported online January 15 in Annals of Internal Medicine.

In analyses that excluded the first 30 days after diagnosis, MPN patients had a 4.0-fold increased risk for any thrombosis, a 3.0-fold increased risk for arterial thrombosis, and a 9.7-fold increased risk for venous thrombosis at 3 months after the diagnosis.

The increased risk for any thrombosis decreased with time, to 2.4-fold at 1 year and 1.8-fold at 5 years, as did the increased risks for arterial and venous thrombosis.

The elevated risks associated with MPN were found in men and women and across age groups.

Almost 10% of patients with MPNs had a thromboembolic event within 30 days before or after the diagnosis, with odds ratios of 15.6 for arterial thrombosis and 29.5 for venous thrombosis, compared with control participants.

“These findings underline the need for rapid disease control as soon as the MPN is diagnosed,” Dr. Hultcrantz said. “It is important to quickly initiate prophylaxis treatment for thrombosis as well as disease-targeted therapy where it is indicated.”

Among patients with MPNs, the risk of thrombosis was significantly higher for those age 60 or older (2.4-fold compared with <60), for those with a history of thrombosis (2.7-fold compared with no previous thrombosis), and for those with both risk factors (7.0-fold).

“It is important to follow treatment recommendations for MPNs as well as advocate for a healthy lifestyle in order to lower the risk of thrombosis in MPN patients of all age groups,” Dr. Hultcrantz concluded. “It is also likely that many MPN patients are diagnosed due to the occurrence of a blood clot, and patients with extensive or unusual clots and/or elevated blood values should be worked up for a possible MPN.”

“A personalized, precision medicine approach to primary and secondary thrombosis prevention for patients with MPNs should incorporate genomics, cardiovascular risk assessment, inflammatory biomarkers, and this new appreciation of the magnitude and cumulative nature of excess risk,” write Dr. Alison R. Moliterno and Dr. Elizabeth V. Ratchford from Johns Hopkins University School of Medicine, Baltimore, in a related editorial.

“Care of patients with MPNs should include aggressive treatment of traditional risk factors to reduce risk for arterial and venous thrombosis, regardless of age; adoption of dietary and lifestyle habits that reduce inflammation; and consideration of combined anticoagulant, antiplatelet, and anti-inflammatory treatment strategies,” they conclude.

Dr. Naseema Gangat from Mayo Clinic, Rochester, Minnesota, who has also evaluated the link between various MPNs and thrombosis, told Reuters Health by email, "All patients with MPN, both younger and older than 60 years, have an increased predisposition to both arterial and venous thrombosis compared to age-matched controls. Since the incidence of thrombosis is highest in the initial 5 years, these patients should be promptly referred by internists to a hematology center with expertise in MPN.”

“Arterial and venous thromboses are biologically distinct processes that require separate risk assessments, rather than using the conventional risk stratification, which lumps them together and utilizes age above 60 years and prior history of thrombosis,” she said.

“Since the risk of thrombosis was noted to be high even in younger patients, utilization of antithrombotic and cytoreductive strategies in young patients needs careful consideration,” she said, adding that the study’s results “do not account for hematocrit, leukocyte, and platelet count, cardiovascular risk factors, or genetic variables (driver mutational status JAK2/CALR/MPL or other recurrently mutated genes in myeloid malignancies), which play a key role in risk and incidence of thromboses in these patients.”


Ann Intern Med 2018.

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