Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage

Abstract

Background and Purpose— Stroke-associated immunosuppression is an increasingly recognized factor triggering infections and thus potentially influencing outcome after stroke. Specifically, lymphocytopenia after intracerebral hemorrhage (ICH) has only been addressed in small-sized retrospective studies of mixed intracranial bleedings. This cohort study investigated the natural course of lymphocytopenia, parameters associated with lymphocytopenia on admission (LOA) and during stay, and evaluated the clinical impact of lymphocytopenia in solely ICH patients. Methods— This observational study included 855 consecutive patients with ICH. Patient demographics, clinical and neuroradiological data as well as laboratory and in-hospital measures were retrieved from institutional prospective databases. Functional 3-month outcome was assessed by mailed questionnaires. Lymphocytopenia was defined as <1.0 (10 9 /L) and was correlated with patient’s characteristics and outcome. Results— Prevalence of LOA was 27.3%. Patients with LOA showed significant associations with poorer neurological status (18 [10–32] versus 13 [5–24]; P <0.001), larger hematoma volume (18.5 [6.2–46.2] versus 12.8 [4.4–37.8]; P =0.006), and unfavorable outcome (74.7% versus 63.3%; P =0.0018). Natural course of lymphocyte count during hospital stay revealed a lymphocyte nadir of 1.1 (0.80–1.53 [10 9 /L]) at day 5. Focusing on patients with day-5-lymphocytopenia, compared with patients with LOA, revealed increased rates of infections (63 [71.6] versus 113 [48.5]; P <0.001) and poorer functional outcome at 3 months (76 [86.4] versus 175 [75.1); P =0.029). Adjusting for baseline confounders, multivariable logistic and receiver operating characteristics analyses documented independent associations of day-5-lymphocytopenia with unfavorable outcome (day-5-lymphocytopenia: odds ratio, 2.017 [95% confidence interval, 1.029–3.955], P =0.041; LOA: odds ratio, 1.391 [0.795–2.432], P =0.248; receiver operating characteristics: day-5-lymphocytopenia: area under the curve=0.673, P <0.0001, Youden’s index=0.290; LOA: area under the curve=0.513, P =0.676, Youden’s index=0.084), whereas receiver operating characteristics analyses revealed no association of age or hematoma volume with day-5-lymphocytopenia (age: area under the curve=0.540, P =0.198, Youden’s index=0.106; volume: area under the curve=0.550, P =0.0898, Youden’s index=0.1224). Conclusions— Lymphocytopenia is frequently present in patients with ICH and may represent an independent parameter associated with unfavorable functional outcome. Developing lymphocytopenia affected outcome even stronger than LOA, a finding that may open up new therapeutic avenues in specific subsets of patients with ICH.

Lymphopenia, Infectious Complications, and Outcome in Spontaneous Intracerebral Hemorrhage

“…Because previous reports have demonstrated that the relationship between total lymphocyte count and susceptibility to infections is not linear and that the odds of experiencing an IC increase only when the lymphocyte count drops below a critical threshold [7, 12], we analyzed admission lymphopenia (AL) defined as absolute lymphocyte count < 1000/µL [7, 13]. We also collected data on admission leukopenia (absolute leukocyte count < 4000/µL), admission neutropenia (absolute neutrophil count < 1500/µL), and admission monocytopenia (absolute monocyte count < 200/µL) [14, 15].…”

Letter by Guo et al Regarding Article, “Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage”

“…Many thanks, and here we express our best sincere respect to Giede-Jeppe et al 1 for their innovative and interesting study.…”

“…We would like to highlight 3 important issues raised in the study by Giede-Jeppe et al 1 First, why does the number of circulating lymphocytes decrease in patients with ICH? Two major reasons come to mind: one has to do with the severity and progression of ICH, and the second reason is related to some external environment factors, such as infections that can potentially change lymphocytes.…”

“…This immunosuppression syndrome is characterized by lymphocytopenia and reduced monocyte functions, which is closely related to the severity of ICH. 1,3 However, Giede-Jeppe et al 1 revealed no association of hematoma volume with day-5 lymphocytopenia. Therefore, we proposed that day-5 lymphocytopenia might be a concomitant phenomenon of infections, such as sepsis, which can significantly induce lymphocyte apoptotic cell death.…”

“…1 However, the study by Giede-Jeppe et al 1 does not provide related information on how many hours from the onset time to baseline blood samples obtained time (onset to blood samples time). We mean that the onset to blood samples time may be having an influence on lymphocytopenia on admission and may affect the association between lymphocytopenia and end points.…”