A study of the prognostic significance of platelet distribution width, mean platelet volume, and plateletcrit in cerebral venous sinus thrombosis

INTRODUCTION

Cerebral venous sinus thrombosis (CVST) can cause considerable cerebrovascular damage including hemorrhagic stroke.^[1] CVST affects approximately 3–4 individuals per million population in India annually. Furthermore, CVST is responsible for 10–20% of causes of cerebrovascular accidents among young people.^[2] CVST is 3 times more common in women than in men, and the risk is particularly higher during pregnancy and while using oral contraceptives.^[3] CVST has numerous risk factors, with each having a different odds ratio. Headache is the most common presentation of CVST.^[4-6] Magnetic resonance imaging (MRI) of the brain can accurately diagnose CVST.^[7]

Platelets, which are vital in the formation and propagation of thrombus, are involved in the etiopathogenesis of and morbidity in CVST.^[8] Platelet function can be examined using a total blood count analyzer, which provides the values of platelet indices, namely, platelet distribution width (PDW), mean platelet volume (MPV), and plateletcrit. MPV is a simple and accurate marker of the platelet activation and function.^[9] PDW indicates size variation range of platelets. It is thus a precise indicator of their activation.^[10] Plateletcrit refers to the total platelet mass and is beneficial for identifying platelet-related quantitative disorders.^[11]

Platelet indices may be predictive and prognostic in a wide range of conditions.^[12] PDW levels are higher in disease conditions such as myeloproliferative disorders, ischemic heart disease, and CVST.^[13-16] Myocardial infarction, venous thromboembolism, poor coronary collaterals, and pulmonary embolism have been linked to increased MPV.^[17-19] Plateletcrit has been examined in central retinal vein occlusion^[20] and venous thromboembolism.^[21] A higher plateletcrit value indicates a higher risk. Thus far, a Turkish study investigated the effects of platelet indices on CVST severity.^[19] There is not enough research on this subject. This study investigated the effects of platelet indices (PDW, MPV, and plateletcrit) on CVST severity and functional outcomes.

MATERIALS AND METHODS

RESULTS

Sixty-six patients (45 males and 21 females) recruited to this study. The mean age of the study participants was 35.2 ± 24.6 years. Alcohol use disorder (n = 32), hyperhomocysteinemia (n = 27), anemia (n = 15), polycythemia (n = 10), oral contraceptive pill use (n = 5), and puerperium (n = 4) were the main risk factors. All the patients with alcohol consumption disorder binge drank within 1–3 days of symptom onset. The most frequent risk factors among the men were hyperhomocysteinemia and after that alcohol use disorder. Hyperhomocysteinemia was significantly associated with alcohol use disorder in the men. Hence, hyperhomocysteinemia was not identified as a distinct risk factor. Polycythemia was the next frequent risk factor among the men. The most frequent risk factors among the women were iron deficiency anemia and after that oral contraceptive usage. All the participants had increased intracranial pressure. Seizures and focal neurological deficits were noted in 59% and 29% of the participants, respectively. Furthermore, 16 and 11 patients had high mRS scores (2–6) during admission and after 90 days, respectively. Two-thirds of the patients exhibited abnormal brain CT findings, and all of them had abnormal MRV brain findings. Superior sagittal sinus, sigmoid sinus, left transverse sinus, and right transverse were thrombosed in 76%, 38%, 26%, and 9% of study participants, respectively. In 47% of the participants, more than one sinus had been thrombosed [Figures 1 and 2].

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Figure 1:

(a) Magnetic resonance imaging brain T2 sequence showing hyperintensities in the superior sagittal sinus, (b) right transverse sinus, (c) and right sigmoid sinus. (d) In the MR venogram brain, superior sagittal sinus is not visible, transverse and the sigmoid sinuses are narrowed bilaterally with several collaterals.

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Figure 2:

(a) Computed tomography brain showing the right temporal lobe hypodensity. (b) Magnetic resonance imaging (MRI) brain T2 sequence showing the right temporal lobe hyperintensity. (c) MRI brain DWI sequence showing the right temporal lobe hyperintensity along with loss of flow void and thrombosis of the right sigmoid sinus. (d) In the MR venogram brain, right sigmoid, and the internal jugular veins are not visualized. DWI indicates diffusion-weighted imaging.

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We compared the patients’ platelet indices with their standard laboratory values [Table 1]. Their MPV values were within normal ranges. However, PDW and plateletcrit values were at the upper end of the normal limit.

Severe CVST and non-severe CVST were diagnosed in 33 patients in each group, respectively. The patients’ age and sex were similar in both the groups [Table 2]. The PDW is higher in severe CVST patients than in non-severe CVST patients, and this difference is statistically significant [P = 0.038; Table 2 and Figure 3]. Other variables, namely, old age (P < 0.05), high mRS scores at admission (P < 0.05), and high mRS scores at 90 days (P < 0.05), were significant. No correlation was noted between CVST severity and risk factors [Table 2].

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Figure 3:

Comparison of platelet distribution width values between “severe cerebral venous sinus thrombosis (CVST)” and “non-severe CVST” categories. PDW indicates platelet distribution width; CVST, cerebral venous sinus thrombosis.

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Multiple logistic regressions analyzed older age and larger PDW (P < 0.05) as the independent predictors of severe CVST [Table 3]. There was no significant difference in MPV or plateletcrit between the severe and non-severe CVST groups. A comparison of PDW with clinical and laboratory parameters indicated that increased PDW (>17) was associated with high mRS scores at admission (P < 0.05). High PDW values were significantly and inversely related to plateletcrit levels (P < 0.05; Table 4). Among the platelet indices, PDW exhibited a significant association with higher mRS scores at admission (P < 0.05). However, at 90 days, no effect of platelet indices on mRS scores was observed [Table 5]. In ROC analysis, a cutoff value of 16.5 for PDW could predict CVST severity with 45% sensitivity and 79% specificity (Area under ROC curve [AUC] = 0.649, 95% Confidence interval [CI] = 0.516–0.782, P = 0.037) [Figure 4].

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Figure 4:

A receiver operating characteristic curve showing platelet distribution width as a predictor of severity of cerebral venous sinus thrombosis.

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DISCUSSION

The average age of the study participants is in accordance to that reported in a comprehensive series published by Nizam institute’s cerebral venous stroke register located in Hyderabad, India.^[25] A previous study conducted in India reported that CVST was more frequently observed in women.^[26] This study’s male predominance is consistent with the findings of a recent Indian study.^[27] Improvements in women’s healthcare during the puerperium may be caused by this shift in sex predominance. Increasing alcohol abuse may be responsible for the increased frequency of CVST in men.

This study’s findings agree with those of a previous Turkish study on the effects of platelet indices (PDW and MPV) on CVST severity.^[18] PDW significantly differed between CVST cases and controls (P = 0.003). In addition, MPV did not differ significantly between the CVST case and control groups (P = 0.3). Alcohol use disorder did not affect mean MPV values in 40% of the patients. Moreover, age, sex, alcohol usage, smoking, and obesity did not affect MPV values.

The results of this study demonstrated no link between CVST severity and its risk factors; this finding is in accordance to that of another Indian study.^[28] No effect of risk factors on clinical parameters, imaging results, and outcomes was noted. Old age, mechanical ventilation requirement, and Glasgow Coma Scale scores were identified as the independent predictors of poor clinical outcomes.^[29]

Anemia (P < 0.05) and hyperhomocysteinemia (P < 0.05) risk factors demonstrated a statistically significant association with plateletcrit levels [Table 6 in supplementary material]. Furthermore, no association was observed between MPV and PDW levels and risk factors for CVST. This study recruited patients from only one academic institution. Hence, multicenter studies should be performed to validate our findings.

CONCLUSION

CVST is a serious neurological condition with a potential for delayed diagnosis because of its diverse presentation. Early intervention can significantly improve the outcome in affected individuals. Platelet distribution width is a platelet index that is associated with severe CVST. Large randomized control studies determining the relationship between platelet indices and CVST outcomes are warranted. The findings can facilitate the identification of patients who might benefit from endovascular therapy.