Hematology Referral, Stroke Recurrence and Mortality Among Patients with First Ischemic Stroke and Polycythemia or Thrombocytosis

Introduction: Stroke is the second leading cause of death and disability worldwide. In developing countries, the burden of stroke is expected to increase due to aging populations and poor management of risk factors. Essential thrombocytosis (ET), polycythemia vera (PV) and other myeloproliferative neoplasms (MPNs) are known risk factors for ischemic stroke (IS), yet the prognostic value of abnormal values of hemoglobin and platelet on admission for IS and the frequency of IS as a first manifestation of MPN are still uncertain.

Objective: To determine clinical outcomes of patients with a first IS or transient ischemic attack (TIA) with and without polycythemia or thrombocytosis.

Methods: We performed a retrospective analysis of all public-setting IS and TIA patients included in the Joinville Stroke Registry (JOINVASC) between January 2018 and December 2019. Data cutoff was December 2021. Patients with previous IS or TIA (n = 359), or without a complete blood count (CBC) on hospital admission were excluded (n = 13). Polycythemia was defined as hemoglobin ≥ 16 grams per deciliter in females and ≥ 16.5 in males, thrombocytosis as platelet count ≥ 450,000 platelets per microliter. Stroke recurrence was defined as a new IS or TIA after hospital discharge and event-free survival (EFS) was defined as the period over which the patient remained free from stroke recurrence or death. Study protocol was approved at the institutional review board.

Results: One thousand and eleven patients were included. Median age was 67 years (interquartile range, IQR: 59-76) and 54% were male (n =546). TIA was observed as a first event in 191 patients (19%), small vessel occlusion in 143 (14%), cardioembolism in 146 (14%) and undetermined cause in 394 (39%). Mean length of hospital stay (days ± standard deviation, SD) was 12 ± 13 and 90-day mean Rankin Score (± SD) was 2 ± 1.6. At hospital admission, polycythemia was observed in 76 patients (8%), with CBCs > 6 months before admission, at hospital discharge and on outpatient follow-up also showing polycythemia in 26 (34%), 31 (41%) and 13 patients (17%). Thrombocytosis was seen in 30 patients (3%), with CBCs > 6 months before admission, at hospital discharge and on outpatient follow-up also showing thrombocytosis in 12 (40%), 20 (67%) and 11 patients (37%). Among 104 patients with either polycythemia or thrombocytosis, hematology referral was seen in 10 patients (10%), with diagnosis of MPN in 5 (5%) and solid tumor in 3 patients (3%). First IS or TIA patients with polycythemia or thrombocytosis were younger (median age 64 versus 67 years, p= 0.04) and more frequently male (72% versus 52%, p <0.0001). No differences in the incidence of stroke subtypes, length of hospital stay or 90-day Rankin Scores were observed. Stroke recurrences were more frequent among patients with polycythemia or thrombocytosis (15% versus 9%, p = 0.04) with a trend of higher mortality (34% versus 23%, p = 0.07) and a statistically significant lower 2-year EFS probability (58% versus 74%, p = 0.02)

Conclusion: Polycythemia or thrombocytosis at hospital admission with first IS or TIA was associated with shorter EFS. Hematology referrals were alarmingly low, with one in every ten stroke patients with polycythemia or thrombocytosis being referred. Improving the awareness of hematological abnormalities in this patient population is key for better diagnoses of MPN or secondary polycythemia and thrombocytosis, which may result in better patient management and prevention of stroke recurrence.

No relevant conflicts of interest to declare.