Covert Brain Infarcts in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders

Polina I Kuznetsova; Anton A Raskurazhev; Rodion N Konovalov; Marina V Krotenkova; Andrey O Chechetkin; Olga V Lagoda; Anait L Melikhyan; Marine M Tanashyan

doi:10.3390/jcm11010013

Covert Brain Infarcts in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders

J Clin Med. 2021 Dec 21;11(1):13. doi: 10.3390/jcm11010013.

Authors

Polina I Kuznetsova¹, Anton A Raskurazhev¹, Rodion N Konovalov², Marina V Krotenkova², Andrey O Chechetkin³, Olga V Lagoda¹, Anait L Melikhyan⁴, Marine M Tanashyan¹

Affiliations

¹ Department of Angioneurology, Research Center of Neurology, 125367 Moscow, Russia.
² Neuroimaging Department, Research Center of Neurology, 125367 Moscow, Russia.
³ Ultrasound Diagnostics Department, Research Center of Neurology, 125367 Moscow, Russia.
⁴ Department of Standardization and Treatment Methods, National Research Center for Hematology, 125167 Moscow, Russia.

Abstract

Backgrounds and purpose: Philadelphia chromosome-negative myeloproliferative disorders (Ph-negative MPD) are a rare group of hematological diseases, including three distinct pathologies: essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). They most often manifest with thrombotic complications, including cerebrovascular events. Covert brain infarcts (CBIs) are defin ed as predominantly small ischemic cerebral lesions that are detected using magnetic resonance imaging (MRI) in the absence of clinical stroke events. The relationship between MPD and CBIs remains unclear.

Methods: Included in the study were 103 patients with the diagnosis of Ph-MPD (according to WHO 2016 criteria) (median age-47 (35; 54) years; 67% female). In total, 38 patients had ET, 42 had PV, and 23 had PMF. They underwent clinical examination, routine laboratory analyses (complete blood count), brain MRI, ultrasound carotid artery, flow-mediated dilatation (as a measure of endothelial dysfunction-FMD).

Results: Overall, 23 patients experienced an ischemic stroke (as per MRI and/or clinical history), of which 16 (15.5%) could be classified as CBIs. The rate of CBIs per MPD subtype was statistically non-significant between groups (p = 0.35): ET-13.2%, PV-21.4%, and PMF-8.7%. The major vascular risk factors, including arterial hypertension, carotid atherosclerosis, and prior venous thrombosis, were not associated with CBIs (p > 0.05). Age was significantly higher in patients with CBIs compared to patients without MRI ischemic lesions: 50 (43; 57) years vs. 36 (29; 48) (p = 0.002). The frequency of headaches was comparable between the two groups. CBIs were associated with endothelial dysfunction (OR - 0.71 (95% CI: 0.49-0.90; p = 0.02)) and higher hemoglobin levels (OR-1.21 (95% CI: 1.06-1.55); p =0.03).

Conclusions: CBIs are common in patients with Ph-negative MPD. Arterial hypertension and carotid atherosclerosis were not associated with CBIs in this group of patients. The most significant factors in the development of CBIs were endothelial dysfunction (as measured by FMD) and high hemoglobin levels. Patients with Ph-negative MPD and CBIs were older and had more prevalent endothelial dysfunction.

Keywords: Philadelphia chromosome-negative myeloproliferative disorders; covert brain infarcts; endothelial dysfunction; hematology.