Evaluating Role of Leukocytosis and High Sedimentation Rate as Prognostic Factors in Acute Ischemic Cerebral Strokes
Daioush Savadi Oskouii
Leukocytosis and increased Erythrocyte Sedimentation Rate
(ESR) during the early phases of acute ischemic stroke has been proposed to
be related with poor prognosis. The aim of this study was to evaluate these
two parameters in patients with ischemic stroke. In this descriptive analytical
study, 150 patients with confirmed ischemic stroke were taken under study for
a period of 13 month. The White Blood Cell (WBC) count and ESR were determined
on admitting and after 3 days. Any history of Diabetes Mellitus (DM), Hypertension
(HTN), Heart Disease (HD), Hyperlipidemia (HLP), smoking, CT scan findings,
level of consciousness and the condition of patient on admission and discharge
(according to Rankin's scale) were assessed. In this study, 150 patients were
enrolled, in which 75 were males and 75 were females, with the mean age of 67.3±8.2
years. Leukocytosis on day one was significantly more prevalent in patients
passed away during hospitalization or discharged in not-so-well condition. High
WBC and ESR levels, altered consciousness, diffused lesions in CT scan and imperfect
neurological condition on day one, as well as positive history of DM and HTN
were significantly related with higher in-hospital death rate and/or poor condition
at discharge. Raised WBC count and ESR just after an ischemic stroke attack
might be related with a poor prognosis and necessitate immediate and meticulous
monitoring and therapies.
to cite this article:
Masoud Nikanfar, Sheyda Shaafi, Maziyar Hashemilar, Daioush Savadi Oskouii and Mohamad Goldust, 2012. Evaluating Role of Leukocytosis and High Sedimentation Rate as Prognostic Factors in Acute Ischemic Cerebral Strokes. Pakistan Journal of Biological Sciences, 15: 386-390.
Received: January 22, 2012;
Accepted: July 19, 2012;
Published: September 03, 2012
Considering that cerebral arteries incidences are the third mortality factor
in the world, patients, their relatives and physicians should always know prognosis
of cerebral strokes (Nayak et al., 2011). On
the other hand, neurologists are looking for ways to identify factors to determine
incidence of prognosis cerebral strokes from early hours. These factors should
be highly available, inexpensive and accessible without wasting time (Selvarajah
et al., 2011). For this purpose, blood markers including leukocytes
(WBC), Erythrocytes Sedimentation Rate (ESR), Hematocrit (HCT), blood glucose,
blood platelets count and other cases have recently been evaluated. The results
of these studies are controversial (Homburg et al.,
2011; Lakshmi et al., 2011). Exact mechanism
of ESR acute increase in patients suffering from ischemic cerebral stroke is
unknown (Brouns et al., 2010). Some hypotheses
have been suggested in this regard: (1) Undiagnosed infections one month before
acute attack of cerebral stroke leads to this increase, (2) High ESR is regarded
as indirect sign of thrombosis development and (3) there is a direct relationship
between ESR and levels of inflammatory factors and proteins involved in occlusion
(Bernard et al., 2010; Lidove
et al., 2009; Molnar et al., 2010).
Increase of WBC during acute cerebral stroke may originate from developing of
inflammatory response to brain parenchyma ischemic injury (De
Silva et al., 2008). Increase of cytokines is seen immediately after
ischemic cerebral stroke (before increase of WBC). Additionally, there is a
direct relationship between levels of inflammatory factors, proteins involved
in occlusion and ESR (De et al., 2008). Laboratory
samples show that increase of circulatory WBCs leads to decrease of cerebral
blood flow at penumbral less injured zones (De Silva et
al., 2009). We decided to conduct a study through evaluating two factors
of WBC count and ESR (which can be easily be easily evaluated during first day
of cerebral strokes incidence and compared with the third day) and its relationship
with ischemic stroke prognosis.
MATERIALS AND METHODS
One hundred and fifty patients having 75 males and 75 females were considered
under analytical study which were hospitalized with diagnosis of ischemic cerebral
stroke. The patients necessarily excluded from the study, if they received intervenient
drugs before hospitalization or if there is a disturbing factor in their medical
history. The patients of in-hospital mortality and in-hospital survived groups
as well as two groups of desired and undesired results while releasing from
hospital (in those patients who were survived) were compared. Desired and undesired
results of Rankins scale at the time of releasing from hospital were respectively
regarded as 0-2 and 3-5. Rankins scale was considered as follow:
||Symptomatic but performs routine activities well
||Trivial disability but performs daily activities without asking others
||Average disability, looking for others help to do activities but
walk by him/herself
||Need others help to walk but fulfils personal needs and requirements
||Severe disability, he/she cannot walk, suffers from feces incontinency
and needs a nurse
||Mortality has been considered. WBC higher than 10,000 mm-3
is regarded as leukocytosis
ESR was measured using Western green method in a single laboratory and considering
normal amounts for the desired age range. The obtained data was stated as Mean±standard
deviation (μ±SD), frequency and percentage and SPSS-16 is the used
statistical software. Quantitative variables were compared using student t-test
(independent samples) or paired samples t-test. Contingency tables using chi-square
test or Fischers exact test (considering conditions) were used to compare
categorical variables. Pearsons correlation coefficient was used to evaluate
correlation. Logistic regression test was used to conduct a multivariable study.
In all understudy cases, the results were known as statistically meaningful,
The understudy patients were consisted of 75 females and 75 males with mean
age of 67.33±8.17 (48-88) years and the patients mean Rankin scale
was 4±0.57 (1-5) while admission. Mean WBC was 10972.00±3617.47
(5600-24000) and 10319.33±2693.96 (5000-18600) per mm3 while
admission and after three days, i.e., mean WBC during the third day is meaningfully
less than that of the first day (p = 0.004). In-admission leukocytosis was observed
in 70 patients (46.7%). Mean ESR was 28.69±6.73 (16-45) and 24.8±10.1
(8.48) mL h-1 while admission and after three days, i.e., mean ESR
during the third day is meaningfully less than that of the first day (p<0.001).
Mean Rankin scale of release (or mortality) time was 3.92±1.53 (0-6).
Table 1 demonstrates comparison of the studied variables in
two groups with desired and undesired results at the time of release. According
to Table 1, mean WBC level of serum and ESR in the first day
of admission in the group with undesired results was meaningfully higher than
that of the group with desired results while releasing from hospital. Additionally,
frequency of cases with in-admission leukocytosis, records of diabetes and hypertension
and lowering of consciousness level in the group with undesired results was
higher than that of the group with desired results while releasing from hospital.
In order to find independent risk factor, the above-mentioned cases entered
a multivariable study and following results were obtained: Lowering of consciousness
level (p<0.674) and increasing in-admission ESR level (p = 0.123) were not
independent risk factors for undesired results while releasing from hospital
in patients suffering from cerebral ischemic stroke. Hypertension (p = 0.013),
increasing in-admission blood WBC level (p = 0.014) and in-admission Rankin
scale (p = 0.028) were regarded as independent risk factors for undesired results
while releasing from hospital in patients suffering from cerebral ischemic stroke.
In-admission WBC serum and ESR level as well as Rankin scale in predicting of
obtaining weak results while releasing from the hospital were respectively 0.719,
0.677 and 0.679 meaning that all three parameters are appropriate to predict
weak results while releasing from the hospital (p<0.05). Distributed cerebral
lesions observed in CT-scan (p<0.001), increasing in-admission blood WBC
level (p = 0.037), increasing in-admission ESR level (p = 0.006) and increasing
in-admission Rankin scale (p = 0.004) were regarded as independent risk factors
for in-hospital mortality of patients suffering from cerebral ischemic stroke.
Increasing in-admission serum WBC level has increased weak results at the time
of releasing from hospital as well as in-hospital mortality. Increasing in-admission
ESR level has led to increase of weak results at the time of releasing from
hospital as well as in-hospital mortality. In-admission Rankin scale is significantly
higher in the dead group. In-admission WBC serum and ESR level as well as Rankin
Scale in predicting of in-hospital mortality were respectively 0.739, 0.816
and 0.771 meaning that all three parameters are appropriate to predict in-hospital
|| Comparing the evaluated parameters in patients with desired
and undesired results while releasing from hospital
|*Values are as Mean±SD, Values in brackets are percentages
There is weak and significant correlation between in-admission serum WBC level
and in-admission Rankin scale (p = 0.001, r = 0.271), fair and meaningful correlation
between in-admission serum WBC level and Rankin Scale while releasing from hospital
(p = 0.001, r = 0.399) and between in-admission serum ESR level and in-admission
Rankin scale (p<0.001, r = 0.446) and strong and meaningful correlation between
in-admission serum ESR level and Rankin scale while releasing from hospital
(p<0.001, r = 0.508) and between in-admission Rankin scale and Rankin scale
while releasing from hospital (or in-hospital mortality) (p<0.001, r = 0.628).
As observed, increasing in-admission serum WBC level increases weak results
while releasing from hospital and in-hospital mortality.
This simple and practical system can quickly and accurately evaluate patients
condition without need to any special facilities. This is one of the most important
advantages of the present study. Efficiency of the system in evaluating these
patients has previously confirmed by Balestrino et al.
(1998). Use of multivariable studies to identify independent factors involved
in prognosis of patients with ischemic stroke is another advantage of our study.
These studies concluded that in-admission higher WBC and Rankin scale as well
as records of hypertension are of independent predictors of weak results while
releasing from hospital (Dulli et al., 1999).
They introduced in-admission higher WBC, ESR and Rankin scale as well as distributed
or wide lesions observed through initial CT-scan as independent predictors of
in-hospital mortality (Suwanwela et al., 2006).
Several studies have evaluated the relation between leukocytosis and prognosis
of patients suffering from cerebral stroke (especially ischemic stroke) while
there are few studies considering ESR (Swartz et al.,
2005). In a previous research, 400 patients are found with acute cerebral
stroke in Poland. In this study, the patients prognosis was evaluated
based on modified Rankin Scale. Accordingly, increasing in-admission WBC independently
was accompanied by worse prognosis and higher mortality rate. The main difference
of the study with our study is related to considering hemorrhagic cerebral stroke
along with its ischemic type (Kazmierski et al.,
2004). They evaluated 13555 African-American and whites suffering from acute
ischemic cerebral stroke. In this study, meaningful relationship was observed
between in-admission higher levels of blood WBC and patients weak prognosis
(Lee et al., 2001). Zaremba
et al. (2004) studied the relation between in-admission leukocytosis
and undesired prognosis of ischemic cerebral stroke in patients with coronary
heart disease and reported a meaningful result. Different studies have emphasized
the relation between increasing of in-admission WBCs and serious prognosis of
those patients with ischemic cerebral stroke (Vila et
al., 2000; Zeltser et al., 2001). In
the previous researches, it is demonstrated that increasing of ESR in patients
suffering from cerebral stroke at carotid artery area at 6 first h may be accompanied
by a serious prognosis (Elneihoum et al., 1996;
Zeltser et al., 2001). In another study, Suzuki
et al. (1995) indicated the relationship found between increased
ESR level during initial stages of cerebral stroke and the patients worse
prognosis. In another study on 208 patients with ischemic cerebral stroke, Chamorro
et al. (1995) suggested that increasing in-admission ESR is independently
accompanied by a worse prognosis in these patients.
Higher in-admission WBC and ESR is accompanied by weak results at the time
of release from hospital. Also, higher WBC is known as independent predictor
of weak results while releasing from the hospital. Higher in-admission WBC and
ESR and CT-scan findings indicating wide or distributed lesion are accompanied
by in-hospital mortality. Higher WBC and ESR and wide or distributed lesion
observed through CT-scan are known as independent predictors of in-hospital
Nayak, A.R., R.S. Kashyap, D. Kabra, P. Deoras, H.J. Purohit, G.M. Taori and H.F. Daginawala, 2011.
Evaluation of routinely performed hematological and biochemical parameters for the prognosis of acute ischemic stroke patients. Neurol. Sci., 32 : 855-860.PubMed | Direct Link |
Selvarajah, J.R., C.J. Smith, S. Hulme, R. Georgiou and C. Sherrington et al
Does inflammation predispose to recurrent vascular events after recent transient ischaemic attack and minor stroke? The North West of England transient ischaemic attack and minor stroke (NORTHSTAR) study. Int. J. Stroke., 6: 187-194.PubMed | Direct Link |
Homburg, P.J., Plas G.J., S. Rozie, A. van der Lugt and D.W. Dippel, 2011.
Prevalence and calcification of intracranial arterial stenotic lesions as assessed with multidetector computed tomography angiography. Stroke, 42: 1244-1250.PubMed | Direct Link |
Lakshmi, A.B., P. Uma, C. Venkatachalam and R.G.S. Nageswar, 2011.
A simple slide test to assess erythrocyte aggregation in acute ST-elevated myocardial infarction and acute ischemic stroke: Its prognostic significance. Indian J. Pathol. Microbiol., 54: 63-69.PubMed | Direct Link |
Brouns, R., R. Verkerk, T. Aerts, D. de Surgeloose, A. Wauters, S. Scharpe and P.P. de Deyn, 2010.
The role of tryptophan catabolism along the kynurenine pathway in acute ischemic stroke. Neurochem. Res., 35: 1315-1322.PubMed | Direct Link |
Molnar, T., V. Papp, M. Banati, L. Szereday and G. Pusch et al
Relationship between C-reactive protein and early activation of leukocytes indicated by Leukocyte Antisedimentation Rate (LAR) in patients with acute cerebrovascular events. Clin. Hemorheol. Microcirc., 44: 183-192.PubMed | Direct Link |
Bernard, T.J., L.Z. Fenton, S.D. Apkon, R. Boada and G.N. Wilkening et al
Biomarkers of hypercoagulability and inflammation in childhood-onset arterial ischemic stroke. J. Pediatrics, 156: 651-656.CrossRef |
Lidove, O., M.P. Chauveheid, C. Caillaud, R. Froissart and L. Benoist et al
Aseptic meningitis and ischaemic stroke in Fabry disease. Int. J. Clin. Pract., 63: 1663-1667.PubMed | Direct Link |
De Silva, D.A., F.P. Woon, H.Y. Gan, C. Chen and H.M. Chang et al
Arterial stiffness is associated with raised levels of the inflammatory marker erythrocyte sedimentation rate among ischaemic stroke patients. Intern Med J., 38: 918-920.Direct Link |
De, G.L., N.D. Brunetti, A. Cuculo, P.L. Pellegrino and M. di Biase, 2008.
Systemic inflammation in nonischemic dilated cardiomyopathy. Heart Vessels., 23: 445-450.Direct Link |
De Silva, D.A., F.P. Woon, C. Chen, H.M. Chang and M.C. Wong, 2009.
Serum erythrocyte sedimentation rate is higher among ethnic South Asian compared to ethnic Chinese ischemic stroke patients. Is this attributable to metabolic syndrome or central obesity?. J. Neurol. Sci., 276: 126-129.PubMed | Direct Link |
Balestrino, M., D. Partinico, C. Finocchi and C. Gandolfo, 1998.
White blood cell count and erythrocyte sedimentation rate correlate with outcome in patients with acute ischemic stroke. J. Stroke Cerebrovasc Dis., 7: 139-144.PubMed | Direct Link |
Dulli, D.A., H.S. Schutta, R.L. Levine and P.S. Rahko, 1999.
Ischemic stroke associated with activated protein C resistance and aortic valvular papillary fibroelastoma. J. Stroke Cerebrovasc Dis., 8: 45-48.PubMed | Direct Link |
Suwanwela, N.C., A. Chutinet and K. Phanthumchinda, 2006.
Inflammatory markers and conventional atherosclerotic risk factors in acute ischemic stroke: Comparative study between vascular disease subtypes. J. Med. Assoc. Thai., 89: 2021-2027.Direct Link |
Swartz, J.E., B.F. Jacobson, M.D. Connor, P.L. Bernstein and V.U. Fritz, 2005.
Erythrocyte sedimentation rate as a marker of inflammation and ongoing coagulation in stroke and transient ischaemic attack. S. Afr. Med. J., 95: 607-612.PubMed | Direct Link |
Kazmierski, R., P. Guzik, W. Ambrosius, A. Ciesielska, J. Moskal and W. Kozubski, 2004.
Predictive value of white blood cell count on admission for in-hospital mortality in acute stroke patients. Clin. Neurol. Neurosurg., 107: 38-43.CrossRef | Direct Link |
Lee, C.D., A.R. Folsom, F.J. Nieto, L.E. Chambless, E. Shahar and D.A.Wolfe, 2001.
White blood cell count and incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in African-American and White men and women: Atherosclerosis risk in communities study. Am. J. Epidemiol., 154: 758-764.Direct Link |
Zaremba, J., P. Skrobanski and J. Losy, 2004.
Acute ischaemic stroke increases the erythrocyte sedimentation rate, which correlates with early brain damage. Folia Morphol., 63: 373-376.PubMed |
Zeltser, D., N.M. Bornstein, R. Rotstein, V. Prochorov and I. Shapira et al
The erythrocyte adhesiveness/aggregation test in the peripheral blood of patients with ischemic brain events. Acta Neurol. Scand., 103: 316-319.Direct Link |
Vila, N., J.C. Reverter, J. Yague and A. Chamorro, 2000.
Interaction between interleukin-6 and the natural anticoagulant system in acute stroke. J. Interferon Cytokine Res., 20: 325-329.CrossRef | Direct Link |
Elneihoum, A.M., P. Falke, L. Axelsson, E. Lundberg, F. Lindgarde and K. Ohlsson, 1996.
Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. Stroke, 27: 1734-1738.Direct Link |
Suzuki, S., R.E. Kelley, Y. Reyes-Iglesias, V.M. Alfonso and W.D. Dietrich, 1995.
Cerebrospinal fluid and peripheral white blood cell response to acute cerebral ischemia. South. Med. J., 88: 819-824.PubMed |
Chamorro, A., N. Vila, C. Ascaso, A. Saiz, J. Montalvo, P. Alonso and E. Tolosa, 1995.
Early prediction of stroke severity: Role of the erythrocyte sedimentation rate. Stroke, 26: 573-576.Direct Link |