Is Leukocytosis a Risk Factor for Thrombosis in Patients With Myeloproliferative Neoplasms?

Researchers recently conducted a systematic review and meta-analysis of articles published in the last 12 years to examine whether leukocytosis is a risk factor for thrombosis in patients with myeloproliferative neoplasms, predominantly in polycythemia vera (PV) and essential thrombocythemia (ET).

Previously, leukocytosis has not been formally included in risk models and prognostic scores. There are inconsistencies in the definition of leukocytosis, a lack of a clear cutoff value for white blood cell (WBC) counts, and heterogeneity in methods for its assessment, the researchers said.

In addition, past studies never specifically set out to assess the role of leukocytosis; as a result, the evidence that is available is inconclusive, since previous studies are highly heterogeneous in terms of size, statistical power, and duration of follow-up and exposure.

In this review, out of 515 articles screened, 41 were included in the analysis, comprising a pool of more than 30,000 patients. The primary outcome was a major thrombotic event, such as fatal or nonfatal myocardial infarction, stroke, transient ischemic attack, peripheral and visceral thromboembolism, or venous event (deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, splanchnic circulation thrombosis) associated with leukocyte count after the diagnosis of ET or PV.

Secondary outcomes were defined as major bleeding events, hematologic transformations and/or solid neoplasms, and overall mortality.

The relative risk (RR) of thrombosis in the presence of leukocytosis was 1.59 (95% CI, 1.40-1.80), mainly accounted for by ET (RR, 1.65; 95% CI, 1.43-1.91) and arterial thrombosis (RR, 1.45; 95% CI, 1.13-1.86) subgroups.

The primary results were confirmed by a sensitivity analyses considering recurrent events as well as white blood cell estimates adjusted or unadjusted for confounding factors. In addition, the pooled RR of studies that tested white blood cell counts in time-dependent models suggested a causative effect of leukocytes in the development of thrombosis.

The effect of leukocytosis on bleeding (RR, 1.87; 95% CI, 1.26-2.77) and death (RR, 1.89; 95% CI, 1.59-2.23) was confirmed.

However, conclusions on hematologic evolutions and solid tumors were uncertain, and the effect was not significant in venous thrombosis alone. The researchers said future studies should examine individual patient data in a large collective archive of homogeneous patients.

Reference

Carobbio A, Ferrari A, Masciulli A, Ghirardi A, Barosi G, Barbui T. Leukocytosis and thrombosis in essential thrombocythemia and polycythemia vera: a systematic review and meta-analysis. Blood Adv. 2019;3(11):1729-1737; doi:10.1182/bloodadvances.2019000211.