|Year : 2015 | Volume
| Issue : 1 | Page : 24-29
Value of thrombopoietin level and platelet size in patients with ischemic stroke
Heba Allah A Sedky1, Yasmin N El-Sakhawy1, Hany A Hussein2, Mohamad A Tork3
1 Department of Clinical and Chemical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Internal Medicine and Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
3 Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||23-Nov-2014|
|Date of Acceptance||01-Dec-2014|
|Date of Web Publication||24-Apr-2015|
Yasmin N El-Sakhawy
Department of Clinical and Chemical Pathology, Faculty of Medicine, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Background Stroke is a disease that affects the blood vessels supplying the brain with interruption of blood flow and thus oxygen delivery to a certain area of the brain, with rapid loss of brain functions. It is the third most common cause of death worldwide, ranking behind heart diseases and all forms of cancers.
Aim The aim of this study was to evaluate the mean platelet volume (MPV) and thrombopoietin (TPO) hormone concentration in patients with acute ischemic stroke and compare this with healthy controls.
Patients and methods This study was carried out prospectively on 100 patients with acute ischemic stroke who fulfilled the inclusion criteria and compared with 50 control participants. All patients were recruited to the study within the first 24 h after stroke. MPV and TPO concentrations were measured on admission.
Results A high TPO concentration was found in two-third of the patients, whereas no participant in the control group had a high TPO concentration. In addition, high MPV was found in about half of the patients. There was a statistically significant difference in the levels of both MPV and TPO between the patient and the control group, which implies increased megakaryopoiesis and increased platelet activity in acute ischemic stroke.
Keywords: mean platelet volume, platelets, stroke, thrombopoietin
|How to cite this article:|
Sedky HA, El-Sakhawy YN, Hussein HA, Tork MA. Value of thrombopoietin level and platelet size in patients with ischemic stroke. Egypt J Haematol 2015;40:24-9
|How to cite this URL:|
Sedky HA, El-Sakhawy YN, Hussein HA, Tork MA. Value of thrombopoietin level and platelet size in patients with ischemic stroke. Egypt J Haematol [serial online] 2015 [cited 2020 Apr 4];40:24-9. Available from: http://www.ehj.eg.net/text.asp?2015/40/1/24/155790
| Introduction|| |
Ischemic stroke is a common cerebrovascular disorder associated with increased long-term mortality, residual physical, cognitive and behavioral impairments, recurrence, and increased risk of other types of vascular events  .
Several factors are known to increase the risk of stroke. The most important of these are hypertension, heart diseases such as atrial fibrillation, diabetes mellitus, cigarette smoking, and hyperlipidemia  .
Platelets play an essential role in the development of ischemic stroke as a result of intravascular thrombosis after the rupture of an atherosclerotic plaque  . Platelet size, detected by the mean platelet volume (MPV), is a marker and possible determinant of platelet function, large platelets being potentially more reactive. Although platelets are incapable of de-novo problem synthesis, they are very active metabolically and respond rapidly to vascular injury or trauma by undergoing a series of reactions (adhesion, release of granular contents, shape change, and aggregation) that ultimately result in the formation of a platelet-fibrin plug  . Platelet size is also found to be elevated in individuals with hypertension and diabetes mellitus  , both conditions that predispose toward the development of vascular disease  .
The process of proliferation and maturation of platelets, megakaryopoiesis, depends on early-acting and late-acting hematopoietic growth factors. Thrombopoietin (TPO), also known as megakaryocyte growth and development factor, is the most critical cytokine regulator of megakaryopoiesis  . It is a glycoprotein hormone produced mainly by the liver and the kidney. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets  .
Previous studies have shown higher MPV levels among patients with stroke, myocardial infarction, and accompanying diseases that lead to vascular risk factors such as diabetes mellitus, hypertension, and hyperlipidemia  ; however, some studies did not observe this effect  . There are few available data assessing the TPO level in patients with acute ischemic stroke  .
| Aim of this work|| |
The aim of this prospective study is to investigate the value of platelet activity determined by the MPV and TPO level in patients with acute cerebral ischemic stroke.
| Patients and methods|| |
During the period from February 2013 to February 2014, 100 patients with acute cerebral thrombotic stroke admitted at the Department of Neurology of Ain Shams University Hospitals were evaluated prospectively at the Department of Clinical Pathology.
Patients who fulfilled certain criteria were included in this study: patients older than 50 years of age with atherosclerotic cerebral stroke and those in whom no treatment protocol had been initiated. Echocardiography and ECG were performed to exclude cardiac lesions or arrhythmias, and thus an embolic cause of stroke. Also, a computed tomography or an MRI confirmation of the occlusive stroke (infarction) was performed.
A control group of 50 individuals who were subjected to the same laboratory tests was correlated statistically with the patient group to determine whether the results were statistically significant. Individuals in the control group were healthy, were in the same age range as the patients, and none of them had any previous neurological insults.
All patients in this study were subjected to a complete assessment of history and clinical examination; both a neurological and a systemic evaluation were performed. Neurological assessment included the site of vascular involvement, whether anterior or posterior cerebral circulation, and the size of the infarct brain, either small or less than one-third of the anteroposterior diameter of the hemisphere or large infarction of more than one-third of the anteroposterior diameter of the hemisphere; the severity of the neurological deficits of thrombotic stroke was assessed using the modified Rankin scale. Systemic evaluation was carried out to identify the risk factors of atherosclerosis, especially hypertension and diabetes mellitus, and to evaluate different body functions including cardiac status and peripheral vascular status.
For both patients and controls, complete blood picture was performed, with a special focus on platelets count and the MPV, which was measured using the electric impedance method (resistance-measuring principle). Cells pass one after the other through a capillary opening; the passing cell produces an electrical resistance and thus an electronic signal that is proportionate to its volume. Hence, the cells were identified on the basis of their size and were plotted in a volume distribution curve.
For both the patient and the control group, TPO serum level was measured using the human TPO ELISA kit, manufactured by Glory Science Co., USA.
The SPSS 10.0, USA for Windows was used for data management and analysis and the Microsoft power point for charts. Quantitative data were presented as mean ± SD. For comparison of the means of two groups, Student's t-test was used. Qualitative data were expressed as frequency and percentage. The association between qualitative data was determined using the χ2 -test. The receiver operating characteristic (ROC) curve was used to detect the best cutoff value. A P value was considered significant at 0.05.
| Results|| |
The age range of the patients was 50-85 years, mean age 60.8 years. The risk factors of atherosclerosis were present in 70% of patients; hypertension and diabetes mellitus were the most common risk factors, 70 and 56.7%, respectively ([Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]).
|Table 2 Laboratory investigations in patients with cerebral thrombotic stroke|
Click here to view
|Table 4 Mean platelet volume in patients with cerebral thrombotic stroke in correlation with the control group|
Click here to view
|Table 5 Thrombopoietin concentration in patients with cerebral thrombotic stroke in correlation with the control group|
Click here to view
|Table 6 Comparison between the thrombopoietin concentration and individual risk factors in patients with cerebral thrombotic stroke|
Click here to view
|Table 7 Comparison between mean platelet volume and individual atherosclerosis risk factors in patients with cerebral thrombotic stroke|
Click here to view
The platelet count was normal in 90% of patients in the range of 150-410 × 10 3 /Ul; only 10% of the patients had mild thrombocytopenia of lower than 150 × 10 3 /Ul.
The MPV range in the patient group was 8.0-12.4 versus 7.4-9.6 fl in the control group. The mean MPV in the patient group was higher, 10.1 versus 7.7 fl in the control group. This difference was highly significant (P ≤ 0.0001).
The TPO concentration range was 5-90 ng/ml in the patient group versus 1.5-5 ng/ml in the control group. The mean TPO concentration was much higher in the patient group, 45.4 ng/ml, versus 3.5 ng/ml in the control group, showing a highly statistically significant difference (P ≤ 0.0001).
The area under the ROC curve for MPV was 0.96 (95% confidence interval: 0.92-0.98, P = 0.0001). At the best cutoff value 10.4 fl, MPV had a sensitivity of 92%, a specificity of 86.2%, a positive predictive value of 93.2%, and a negative predictive value of 83.3%. The accuracy of the test was 88% for the detection of stroke ([Figure 1]).
|Figure 1 Receiver operating characteristic (ROC) curve of mean platelet volume (MPV).|
Click here to view
For TPO serum level, the area under the ROC curve was 0.94 (95% confidence interval: 0.89-97, P = 0.0001). At the best cutoff value of 22 ng/ml, TPO had a sensitivity of 88%, a specificity of 96%, a positive predictive value of 96.4%, and a negative predictive value of 80%. The accuracy of the test was 92% for the detection of stroke ([Figure 2]).
|Figure 2 Receiver operating characteristic (ROC) curve of thrombopoietin (TPO).|
Click here to view
Relations of mean platelet volume and thrombopoietin level with some variables
Patients' age and sex had no significant influence on the MPV level and TPO concentrations in patients with cerebral thrombotic stroke.
Diabetes mellitus as a risk factor for atherosclerosis was a significant factor in association with high MPV and a high TPO concentration in patients with cerebral thrombotic stroke. The mean value of MPV in patients with diabetes mellitus was 13.1 versus 7.1 in patients without diabetes (P = 0.041), and for TPO, the mean value was 39.8 versus 31.3 in patients without diabetes (P = 0.043).
Other atherosclerosis risk factors such as hypertension, hyperlipidemia, and smoking had no significant influence on the MPV value or the TPO concentration in patients with thrombotic stroke.
Neither the site and size of the cerebral infarction nor the severity of the neurological deficits had a statistically significant effect on MPV or TPO concentration. Two patients died because of the stroke and both had a very high mean TPO concentration of 56.3 ng/ml; however, no statistical analysis could be carried out.
| Discussion|| |
Platelets play an essential role in the development of ischemic stroke as a result of intravascular thrombosis after the rupture of an atherosclerotic plaque  . TPO is the most critical cytokine regulator of megakaryopoiesis  . Circulating platelets are heterogeneous with respect to their size, density of granules, and reactivity  .
MPV is increased in disorders affecting the platelet turnover or increased megakaryocytosis; thus, the MPV value indicates accelerated platelet production. Larger platelets contain more dense granules, have higher levels of prothrombotic substances, and decrease the effectiveness of prostaglandin in platelet aggregation  .
The aim of this study was to evaluate the MPV and TPO correlation in patients with acute ischemic stroke and compare this with healthy controls. If such an association exists, MPV and TPO might help to identify patients at an increased risk of a severe course of acute cerebrovascular disease.
Several large studies have emphasized the importance of higher MPV and TPO values in ischemic stroke  .
Our results were similar to those of other studies ,, that showed a significant relationship between MPV and TPO values and ischemic stroke. Balcik et al.  prospectively studied 50 patients with acute ischemic stroke and compared them with 37 control participants within 24 h of the stroke. Both MPV and TPO values were significantly higher in patients with stroke with a P value of 0.01, measured on admission.
In a series of 143 consecutive patients with acute ischemic stroke and 60 healthy controls, Dogan et al.  found that MPV results were significantly higher in patients with cortical infarction and transient ischemic attack compared with the control group (P = 0.001).
In contrast, a study carried out by Mc Cabe et al.  confirmed that MPV and TPO values showed no significant relationship with acute ischemic stroke. The other reports showed decreased MPV values in patients with acute ischemic stroke  .
In the current study, the best cutoff for MPV was 10.4 fl, with a sensitivity of 92% and a specificity of 86.2%. In a study carried out by Al-Obeid et al.  in 2013 on patients with acute coronary syndrome, the best cutoff for MPV was 9.15 fl with a sensitivity and a specificity of 100%. This difference could be attributed to the larger number of patients studied, together with more restricted inclusion and exclusion criteria in the current study.
Elevated MPV values in thrombotic diseases indicate macrothrombocytosis. It may contribute toward the disease process; this condition may result from previous activation of megakaryocytosis leading to release larger and more active platelets  . It is suggested that increased hemostatic activity of larger platelets is in part because of an increased number of glycoprotein IIb-IIIa receptors on each platelet in acute infarctions  .
As TPO is considered the primary physiological regulator of megakaryopoiesis, its level is very important for platelet production. An injection of recombinant TPO protein selectively induced thrombocytosis in vivo  .
Of the many risk factors of stroke, hypertension was the most prevalent in this study group, found in 70% of the cases, followed by diabetes mellitus, found in 56.7% of the cases. Christopher and Katleen also concluded that both hypertension and diabetes mellitus were the most common risk factors associated with higher MPV and TPO values , .
The correlation between individual risk factors for stroke and higher TPO and MPV values in the current study showed that diabetes mellitus was significantly associated with higher values compared with other stroke risk factors (P = 0.043 and 0.041), respectively, with an average TPO value of 42.9 ± 25.4 ng/ml and MPV of 13.1 ± 1.1 fl. A similar trend was reported in other studies carried out by Balcik et al.  , Cengiz  , and Ha et al.  .
Arévalo-Lorido et al.  reported an association between the degree of extracranial atherosclerotic carotid stenosis and MPV values in 215 patients with thromboembolic stroke and showed a positive significant relationship between MPV and degree of carotid atherosclerosis stenosis (P = 0.00007).
In this study, the clinical severity of stroke at presentation was determined using the modified Rankin's scale. Mild neurological deficits were noted in 26.7% of the patients and severe deficits were observed in 46.7% of the patients. The association of MPV and TPO with the severity of stroke was determined by comparing the modified Rankin's scale with the corresponding mean value of MPV and TPO, which showed no significant association as the mean value of TPO in patients with mild neurological deficits was 37.2 ± 21.4 versus 35.8 ± 24.7 ng/ml in patients with severe neurological deficits. The mean value of MPV in patients with mild deficits was 10.2 ± 0.8 versus 10.5 ± 0.6 fl in patients with severe deficits.
A similar trend was noted in many studies carried out by Balcik et al.  , Cengiz  , and Weber et al.  who found no significant relationship between the severity of stroke and MPV or TPO values.
In contrast, Ghaharemanfard et al.  divided 100 patients with first stroke into two groups on the basis of the Rankin scale 'group 1: score 0.2' and 'group 2: score 3 or more', and found that MPV and TPO values were higher and more significant in group 2 than group 1 (P < 0.001).
Also, Mayda-Domaç and colleagues studied MPV levels in 692 patients with ischemic stroke and compared these with 208 control participants; they found a significant association between severe neurological deficits in patients with stroke and the mean values of MPV (P = 0.012). They found that MPV was an independent risk factor for ischemic stroke (P = 0.007). Also, they noted that MPV may be an early and important predictor for the prognosis of ischemic stroke  .
The association of MPV and TPO with the size of the infarct brain area in the current study was determined by comparing the infarct size with the corresponding mean values of MPV and TPO, and showed no significant association as patients with small infarctions had a mean MPV of 9.7 ± 1.2 versus 10.5 ± 1.3 fl for large infarctions and a mean TPO value of 35.3 ± 22.4 ng/ml for small infarctions versus 36.9 ± 24.7 ng/ml for large infarctions. Similarly, Mayda-Domaç et al.  found that MPV was not statistically significantly related to the size of the infarct brain.
Two patients in this study, with mean TPO values of 56.3 ± 19 ng/ml and a mean MPV of 10.6 ± 1.1 fl, died, with no significant difference compared with other living patients with variable severity. This finding was also reported in other studies  .
Arévalo-Lorido et al., in their series of 379 patients with ischemic stroke, divided the MPV values into three categories and found that patients within the highest third had a significantly higher risk of deaths (P < 0.48), compared with patients within the lowest third  .
| Conclusion|| |
Acute ischemic stroke is associated with high MPV and TPO levels; this finding indicates increased megakaryopoiesis and increased platelet activity in patients with thrombotic stroke and point to large platelets and active megakaryopoiesis as risk factors for the development of thrombotic stroke. Prospective studies are needed to evaluate TPO and MPV to determine the prognosis of patients with acute ischemic stroke.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cordnnier C, Leys D. Stroke, the bare essentials. Neurol Pract
Victor M, Ropper AH, Adams RD. Edropper AH, Samuels MA. Cerebrovascular disease. Adam's and Victor's principles of neurology
. 9th ed. USA: McGraw Hill; 2009; 321-330.
Balcik OS, Bilen S, Ulusoy EK. Thrombopoietin and mean platelet volume in patients with ischemic stroke. Clin Appl Thromb Hemost
Renoy A. Association of mean platelet volume and ischemic stroke. Journal of Stroke and Cerebrovascular Diseases
Pathansali R, Smith NM, Bath O. Prothrombotic megakaryocyte and platelet changes in hypertension are reversed following treatment: a pilot study. Blood
Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med
Kurabayashi H, Tamura J, Naruse T, Kubota K. Possible existence of platelet activation before onset of cerebral infarction. Atherosclerosis
Tekbas E, Kara AF, Ariturk Z, Cil H. Mean platelet volume in predicting short- and long-term morbidity and mortality in patients with or without ST-segment elevation myocardial infarction. Scand J Clin Lab Invest
Ishiguro A, Nakahata T, Matsubara K, Hayashi Y, Kato T, Suzuki Y, Shimbo T. Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease. Thrombosis and Haemostasis,
Galan AM, Lozano M, Molina P, Navalon F, Marschner S, Goodrich R, et al.
Impact of pathogen reduction technology and storage in platelet additive solutions on platelet function. Transfusion
Kuter DJ, Gernsheimer TB. Thrombopoietin and Platelet Production in Chronic Immune Thrombocytopenia. Hematology/oncology clinics of North America
Cengiz B. Mean platelet volume is highly correlated to platelet count. Thromb Res
Katleen B, Hendrik B, Simon F, Karen V, Hans D. Platelets at work in primary hemostasis. Blood Rev
Christopher HR. Thrombopoietin: The comprehensive pharmacology reference.Pharmacology, 2007; 7:1-6.
Ha SI, Choi DH, et al.
Stroke prediction using mean platelet volume in patients with atrial fibrillation. Platelets
Arévalo-Lorido JC, Carretero-Gómez J, et al.
Mean platelet volume predicting carotid atherosclerosis in atherothrombotic ischemic stroke. Ir J Med Sci
Dogan, NO, Keles A et al.
Mean platelet volume as a risk stratification tool in the emergency department for evaluating patients with ischemic stroke and TIA. Platelets
Mc Cabe DJH, Harrison P, Sidhu PS, et al
. Circulating reticulated platelets in the early and late phases after ischemic stroke and transient ischemic stroke. Br J Haematol
Nadar SK,Gregory YH,Blann AD. Platelet morphology, soluble p selectin and platelet p-selectin in acute ischemic stroke. Thromb Haemost
Al-Obeid SRH, Ahmed SH, Obeid FA. Evaluation of platelet indices in patients with acute coronary syndrome. Mustansiriya Med J
Hakan O. Mean platelet volume in healthy subjects. Thromb Res
Geoffrey D. Thrombopoietin and platelet production in chronic immune thrombocytopenia. Hematol Oncol Clin North Am
Weber R, Diener HC, et al
. Why do acute ischemic stroke patients with a preceding transient ischemic attack present with less severe strokes? Insights from the German Stroke Study. Eur Neurol
Ghahremanfard F, Asghari N, Ghorbani R, Samaei A, Ghomi H, Tamadon M. The relationship between mean platelet volume and severity of acute ischemic brain stroke. Neurosciences (Riyadh)
Mayda-Domaç F, Misirli H, Yilmaz M. Prognostic role of mean platelet volume and platelet count in ischemic and hemorrhagic stroke. J Stroke Cerebrovasc Dis
Wolff V, Aleil B, Greisenegger S, Zehetmayer S. Clinical predictors of death in young and middle-aged patients with ischemic stroke or transient ischemic attack: long-term results of the Vienna Stroke Registry: clinical predictors of ischemic stroke mortality in patients. J Neurol
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]