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Dr. Pritam Madhukar Bawankar, B20198, Dr.Lahane Tatyarao
Pundlikrao, Dr.Preetam Samant

ABSTRACT PAGE

 OBJECTIVE: To study the relationship between platelet indices [mean platelet volume (MPV) & platelet count] and central retinal vein occlusion (CRVO) in hypertensive patients.

DESIGN: Hospital-based, retrospective, case control design.

PARTICIPANTS: Hundred patients with a known history of hypertension diagnosed with CRVO served as the sample group. 100 age and sex-matched patients with the sample group having sole history of hypertension without any other systemic diseases and the best corrected visual acuity of 20/20 in both the eyes served as the control group.

METHODS: Central retinal vein occlusion was diagnosed based on clinical examination. All cases and control subjects underwent complete ocular examination. MPV, platelet count, hemoglobin, white blood cell count and hematocrit parameters were recorded in both the groups. The data of patients with CRVO was compared with the control subjects. Confidence interval was set at 95% with a p-value of <0.05.

RESULTS: Mean platelet volume was significantly higher among hypertensive cases diagnosed with central retinal vein occlusion when compared with the hypertensive control group (8.059±.016 vs 7.442±0.15 fL, respectively; p < 0.001). The platelet count was lower in the control group but the difference did not reach a statistically significant level. The systolic blood pressure was significantly higher in the hypertensive cases group with central retinal vein occlusion.

CONCLUSIONS: Our results demonstrated that MPV values were significantly higher in patients with CRVO, suggesting that increased MPV may contribute to the development of CRVO.

TEXT

INTRODUCTION:

The retinal venous occlusive disease is a common sight-threatening retinal vascular disorder second only to diabetic retinopathy in incidence.1 The prevalence of retinal venous occlusion (RVO) was estimated globally and it was found that about 16.4 million adults were affected by RVO ( 2.5 million by central retinal venous occlusion, 13.9 million by branch retinal venous occlusion).2 Central retinal vein occlusion (CRVO) occurs most commonly in individuals over 50years of age,3,4 and can present as a non-ischaemic or an ischaemic variety based on the areas of capillary nonperfusion on fundus fluorescein angiography and the severity of clinical findings. Retinal and anterior segment neovascularization progressing to neovascular glaucoma are the potential complications.5,6 Pathogenesis of CRVO is multifactorial with both the local factors and systemic diseases playing a significant role in it.Systemic arterial hypertension, diabetes mellitus and atherosclerotic cardiovascular diseases are the most frequent systemic associations.7 Other systemic conditions include blood dyscrasias, vasculitis, autoimmune diseases resulting in hyperviscosity syndromes.4,8,9,10

Central retinal vein occlusion is a major cause of visual morbidity in hypertensive individuals. Platelet indices including platelet count and mean platelet volume (MPV) reflect platelet function which may be deranged in hypertensive patients contributing to retinal vein occlusion.11 Assessment of platelet indices may help in the determination of pathophysiologic relationship and prognosis of CRVO. Increased MPV is shown as a risk factor for stroke and myocardial infarction and also, in a recent study, significant correlation was found between the degree of diabetic retinopathy and MPV.12,13,14 Therefore the aim of this study was an attempt to understand and determine the role of mean platelet volume in patients with CRVO.

 METHODS:

The present study is a hospital-based retrospective, case-control design. The sample size was calculated using the Cochrane formula. 15 According to this formula, {n=z2pq/ ϵ 2}, where n was sample size, z was standard normal deviate corresponding to 5% significant level, p was prevalence, q = 1 – p and ϵ was precision set at 0.05. 100 was the sample size of a single group. For a 1:1 comparative study a control group was included having same sample size of 100. A total of 100 hypertensive patients with central retinal vein occlusion (60 males, 40 females with mean age of 64.47±3.97 years) inclusive of all age groups were studied at our institute during the period from August 2012 to July 2014. The patients presented with sudden painless loss of vision and diagnosed as CRVO on clinical examination at the time of presentation were included in the study. The control group consisted of 100 age and sex-matched hypertensive patients (61 males, 39 females with mean age of 64.43±5.79 years) who came to ophthalmology outpatient department of our hospital for refractive errors and who volunteered for the study after taking proper informed consent. All cases were subjected to a detailed ocular history with respect to onset, duration and progress of diminution of vision, history of any such episodes of diminution of vision in past, and any other significant past history or family history of ocular diseases. All the controls were also subjected to ocular history regarding ocular complaints, ocular surgery, and ocular medications. All subjects underwent detailed physical examination. Medical conditions like diabetes mellitus, systemic hypertension, cardiovascular diseases, renal diseases and blood dyscrasias were recorded. Only known hypertensive patients who were already on antihypertensive medications were selected as controls. A detailed antihypertensive drug history and compliance was noted. Blood pressure was recorded and the mean of two recordings taken at least 3 minutes apart was noted.The same air cuff sphygmomanometer was used for every measurement.

Exclusion criteria for the study included history of systemic diseases like diabetes, cardiovascular disease such as congestive heart failure, and heart valve disease treated with the anticoagulant, stroke, blood dyscrasias, renal failure, hepatic disorders, malignancy, vasculitis, and an antihypertensive drug which causes a decrease of MPV. The patients with ocular disorders of glaucoma and with known optic nerve disease were excluded. The patients with a history of drug use (statins, non-steroid anti-inflammatory drugs, anticoagulant medications and oral contraceptives etc.) and dense cataract obscuring the fundus view were also excluded from the study.

All the subjects underwent complete ophthalmic evaluation of both the eyes, including the best corrected visual acuity (BCVA), slit lamp examination, applanation tonometry and fundus biomicroscopy. Written informed consent was taken from each participant before inclusion. The patients having CRVO usually presented with unilateral moderate to severe visual impairment depending upon the type of venous occlusion (ischemic or non-ischemic). The fundus findings included dilated and tortuous veins, dot blot or flame-shaped retinal hemorrhages and cotton wool spots in all four retinal quadrants. The current study was approved by the institutional ethics committee and was conducted in full accord with the tenets of the Declaration of Helsinki.

Blood samples from the cases were collected at the time of diagnosis of central retinal vein occlusion and from the controls when matching with the cases was established. Complete blood count samples which were drawn into dipotassium ethylenediaminetetraacetic (EDTA) tubes were analyzed within 30 minutes after sampling with a commercially available analyzer (CELL-DYN 3700, Abbott Diagnostics, Abbott Park, IL, USA) in collaboration with the pathology department of our tertiary care center. Peripheral smear analyses were done along with complete blood count in all the cases and controls at our institute. Those patients showing platelet clumping were excluded from the study. MPV, platelet count, hemoglobin, white blood cell count and hematocrit parameters were recorded. The expected value for MPV in our laboratory ranged from 6.8 to 13.2 fL.

Statistical analysis

Data was analyzed with the Statistical Analysis System (SAS) software version 9.3 (SAS Institute Inc., Cary, North Carolina, USA) for Windows. Continuous variables from the study groups were reported as mean ± SD and categorical variables as percentages. To compare the continuous variables student’s t-test was used and categorical variables were compared using Chi-square test. Statistical significance was defined as the P value of less than 0.05.

RESULTS:

Hundred patients (40 female, 60 male) of CRVO with a mean age of 64.47±3.97 were included in this study. Control group had 100 (39 female, 61 male) subjects with a mean age of 64.43±5.79.There was no statistical difference in age and sex between the groups (p=0.95 and p=0.88, respectively) (Table 1). There was no statistically significant difference between the two groups with respect to diastolic blood pressures, smoking history, levels of fasting and postprandial glucose, creatinine, total cholesterol, hemoglobin and platelet count.

The mean platelet volume was significantly higher among the hypertensive cases with central retinal vein occlusion when compared with the hypertensive control group (8.059±.016 vs 7.442±0.15 fL, respectively; p < 0.001). The platelet count was lower in the control group but the difference did not reach a statistically significant level (Table 2). The systolic blood pressure was significantly higher in the hypertensive cases group with central retinal vein occlusion. White blood cell count was significantly higher in the hypertensive control group.

 DISCUSSION:

The retinal vein occlusion is a common cause of visual morbidity in older population; however, the exact pathogenic mechanism underlying the thrombotic tendency in this disorder is still not fully established. The proposed pathophysiology till date has been explained on the basis of thrombus formation in the central retinal vein at the level of or just posterior to the lamina cribrosa.16 The Virchow’s triad proposes that the vascular thromboembolism occurs as a result of stasis of blood flow, vascular endothelial abnormality and inherited or acquired hypercoagulable state.17 Hypertension and atherosclerosis are the major risk factors for CRVO and plays a significant role in its pathophysiology.18 They lead to thickening of the arteriolar wall and the thickened artery compresses the vein within a common adventitial sheath inducing turbulence, endothelial damage and thrombosis of the retinal venous tree.19,20,21 Platelet aggregation is an important sequel to thrombotic vascular occlusion. Platelet indices including platelet count and mean platelet volume reflect platelet function which may be deranged in hypertensive patients contributing to central retinal vein occlusion.

Platelets are the circulating cells that may differ in size and hemostatic potential. Their main role is to maintain the integrity of blood vessels through adequate hemostasis.22 Platelets are also involved in many pathophysiological processes like thrombosis, thrombus retraction, vessel constriction and repair and promotion of atherosclerosis. 23 Allen et al. 24 reported that platelets normally circulate in a quiescent disc-shaped form and when activated they undergo a disc-to-sphere transformation with the development of pseudopodia, causing a subsequent increase in size. Bath and Butterworth reported that platelet hyperactivity results in an increase in MPV.25 Larger platelets contain greater amounts of vasoactive and prothrombotic factors,  express greater number of adhesion molecules and aggregate more rapidly which leads to greater hemostatic efficiency and shortened bleeding times.26 Larger platelets contain more dense granules, increased thromboxane A2 synthesis, increased release of β-thromboglobulin and are enzymatically more active with respect to the prothrombotic activity as compared to the smaller ones.27,25

Mean platelet volume (MPV) is a machine-calculated measurement of the average size of platelets found in blood and is typically included in blood tests as part of the complete blood count. Mean platelet volume is considered as a marker of platelet function since larger platelets are hemostatically more reactive as compared to platelets with normal size.23 It is well documented that platelet activation plays an important role in atherothrombosis. Increase in MPV has a central role in the pathophysiology of atherothrombotic cardiovascular diseases and was seen in patients having known coronary artery disease risk factors like smoking, diabetes mellitus, hypertension and hypercholesterolemia.28,29,30  Moreover, increased mean platelet volume also has a prognostic role in cardiovascular diseases and it is associated with higher mortality in patients of myocardial infarction.31,32 These findings certainly raise the hypothesis of the potential importance of larger platelets in pathophysiology of the atherothrombotic cardiovascular diseases. The relationship between increased MPV and the severity of diabetic retinopathy 14, deep venous thrombosis 33 and acute ischemic cerebrovascular events 34 was also reported in the literature. In the present study, we examined MPV, an indicator of platelet activation in patients with newly diagnosed central retinal vein occlusion. We mainly showed that MPV was significantly higher in hypertensive patients with central retinal vein occlusion as compared to hypertensive controls.

The role of increased platelet size in retinal venous occlusive disease was also studied in the literature. Leonciniet al. 19 reported that platelet activation inducing thrombus formation might be an important factor in the onset and/or development of retinal venous occlusive diseases. Onder et al. 35 also reported the significant relation between increased MPV and branch retinal vein occlusion. Sahin et al. 36 reported significantly higher MPV in patients with retinal vein occlusion. However, the study conducted by Ornek N et al. 37 did not find a significant association between increased MPV and the occurrence of RVO, where they suggested that the crucial factor in the development of RVO seems to be the change in the adjacent arteries, and not systemic hematologic abnormalities. The present study is conducted on relatively large sample size where our team reported an increase MPV in patients with central retinal vein occlusion. In current study, we also found a statistically significant difference in WBC count between the 2 groups, however, cell counts were in normal physiological limits in both the groups.

In conclusion, we have shown that MPV is significantly higher among the hypertensive cases with CRVO in comparison to the hypertensive control subjects. The present study showed that platelet activation has a crucial role in the development of central retinal vein occlusion in hypertensive cases. However, further prospective studies are mandatory regarding its potential use as a prognostic biomarker in patients with CRVO and to establish the pathophysiology and clinical significance of increased MPV in these patients.

The limitations of our study are lack of body mass index and the retrospective nature of the study. We included the patients with newly diagnosed acute central retinal vein occlusion; therefore, the results merely demonstrate the hematologic status at the acute stage of the disease. Therefore, these results may not reflect the status of these patients over long periods.

REFERENCES

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TABLES:

TABLE 1: Descriptive Statistics (mean values for all the 100 cases and 100 controls)

Descriptive Statistics (mean values for all the 100 cases and 100 controls)
VARIABLE CASES N=100 CONTROLS N=100 t TEST p VALUE
AGE (YEARS) 64.47±3.97 64.43±5.79 0.06 0.9547
SEX Male/Female 60/40 61/39 0.88
SBP (mm of Hg) 155.18±4.63 153.2±3.79 3.30 0.001
DBP (mm of Hg) 95.16±4.85 95.76±4.51 1.90 0.36
SMOKING HISTORY PRESENT 28 30 0.7553
FBS (mg/dL ) 96.17±8.08 96.39±5.99 0.22 0.83
PPBS (mg/dL ) 113.84±7.30 115.64±6.86 1.79 0.07
BLOOD UREA (mg/dL) 26.38±4.33 28.0±5.04 2.44 0.0156
BLOOD CREATININE (mg/dL ) 92±.0426 0.923±.0446 0.49 0.6274
TOTAL BLOOD CHOLESTEROL (mg/dL ) 204.4±6.83 202.5±7.241 1.92 0.0565
HAEMOGLOBIN (g/dL) 12.94±0.56 12.93±0.44 0.14 0.88
WBC COUNT x103/microliter 6.52±0.98 7.03±1.03 3.58 <0.0001

 

 

SBP: Systolic blood pressure DBP: Diastolic blood pressure FBS: Fasting blood sugar

PPBS: Post prandil blood sugar

 

TABLE 2: Comparison of the platelets indices of the patients with CRVO and control participants

VARIABLE CASES N=100 CONTROLS N=100  t TEST  P -VALUE
PC x109/microliter 255.7±47.03 245.8±30.00 1.77 0.078
MPV fL 8.059±0.16 7.442±0.15 25.71 <.0001

 

MPV: Mean platelet volume PV: Platelet Count

 

 

 

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