European Journal of Cardiovascular Medicine

Cerebrovascular accidents (CVAs), commonly known as strokes, represent a significant public health concern worldwide due to their high morbidity and mortality rates. [1] They result from the sudden interruption of blood flow to a part of the brain, leading to neurological deficits that can range from mild to severe. [2] Ischemic strokes, caused by the blockage of blood vessels supplying the brain, account for the majority of cases, while hemorrhagic strokes, caused by the rupture of blood vessels, constitute a smaller but equally critical subset. [3]

Among the various biomarkers studied in the context of strokes, plasma fibrinogen levels have garnered considerable attention. [4] Fibrinogen, a glycoprotein synthesized by the liver, plays a crucial role in the blood coagulation cascade. Elevated levels of fibrinogen are associated with increased thrombotic potential, potentially contributing to the pathophysiology of ischemic strokes. [5] Conversely, fibrinogen levels may also reflect underlying inflammatory processes, which are increasingly recognized as pivotal in the development and progression of atherosclerosis, a common underlying cause of ischemic stroke. [6]

Understanding the role of plasma fibrinogen levels in cerebrovascular accidents is essential for several reasons. [7] Firstly, it may provide insights into the mechanisms underlying stroke development, potentially offering avenues for targeted therapeutic interventions. Secondly, fibrinogen levels could serve as a biomarker for risk stratification, aiding in the identification of individuals at higher risk of stroke who may benefit from preventive measures. [8] Finally, elucidating the relationship between fibrinogen and stroke could contribute to the broader understanding of the interplay between hemostasis, inflammation, and vascular disease. [9]

Normal fibrinogen level is 200-350 mg/dl. Fibrinogen Levels higher than 350 mg/dl is a risk factor for coronary artery disease and stroke. Increased levels suggest that there is increased risk of further cardiovascular events and cerebrovascular events in stroke survivors. [10]

This study aims to explore the current literature on plasma fibrinogen levels in cerebrovascular accidents, encompassing both ischemic and hemorrhagic strokes. By synthesizing existing evidence, we seek to clarify the role of fibrinogen in stroke pathophysiology, its implications for clinical practice, and potential directions for future research.

This is a hospital based Prospective analytical study was conducted in Department of General Medicine at Sapthagiri Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka over a period of 1 year. Total 50 adult patients who are getting admitted in medical wards and acute medical care with first episode of stroke.

Inclusion Criteria

1. Patients age more than 14 years with first episode of stroke.
2. Patients with stroke confirmed by CT scan or MRI brain.

Exclusion Criteria:

1. Patients having evidence of renal disease, active hepatic disease, history of prior MI or surgery within preceding 3 months
2. Patients with history of any infection in prior 4 weeks.
3. Patients with Trauma, Subdural Haematoma, Tumours.
4. Patients who are not willing to participate in this study.

After completion of selection of patients, written consent is taken from the patients or their attender’s, detailed history was taken, Physical examination was done, subjects are investigated with routine blood tests like CBC, Blood Urea, Serum creatinine, Random blood sugar, CRP, urine Routine Microscopy, ECG, carotid doppler, Lipid profile, CT BRAIN. MRI BRAIN done in selected cases.

Plasma Fibrinogen level estimation will be carried between 24-72 hours after onset of Cerebro Vascular accidents.

Fibrinogen is a plasma protein, which is converted from a soluble protein to an insoluble polymer by action of thrombin resulting in the formation of fibrin clot. The thrombin clotting time of dilute plasma is inversely proportional to the fibrinogen concentration of the plasma.

Using this principle, Clauss developed a simple quantitative assay for fibrinogen by measuring the clotting time of dilute plasma when excess thrombin is added. The clotting time obtained is then compared with that of a standardized fibrinogen preparation.

Statistical Analysis:

Mean, Standard deviation and p value are calculated.

Ethical Clearance: Patients are informed prior to the study and written consent is taken from the patients or their attenders. No ethical issues are involved. The test is done along with the sample of blood taken for other routine investigations. No financial burden to the patient.

TABLE 1: Age distribution

In the present study, the most common age group affected is between50-69 years (46%), followed by 70-89 years (30%) and 30-49 years (24%). The least common age group observed in the present study is≥ 90 years (2%). The oldest subject is 90 years old and the youngest is 30 years.

TABLE 2. Sex distribution:

78 % of patients are male and 22% are female in the present study. Male preponderance is observed in the present study with a male to female ratio is 3.5:1.

TABLE 3. Risk Factors in Stroke:

Commonest risk factor observed in the present study is smoking which is seen in 64% of patients followed by hypertension and alcoholism seen in 62% and 54% respectively. Least common risk factor observed is cardiovascular diseases (10%). Other risk factors are Diabetes and Dyslipidemias, observed in 26% and 20% respectively.

TABLE 4. Type of stroke:

In the present study,Ischemic stroke is seen in 68% of patients and Hemorrhagic stroke in 32% of patients’ .It shows that ischemic stroke is more common than hemorrhagic stroke.

TABLE 5. Plasma Fibrinogen levels in Ischemic stroke:

Out of 34 patients of ischemic stroke,22(65%) showed their plasma fibrinogen levels ≥350 mg/dl4. Of them, 2 patients showed higher plasma fibrinogen levels between 450-549 mg/dl. Normal plasma fibrinogen levels are seen in 12 patients (35%).

TABLE 6. Plasma Fibrinogen levels in haemorrhagic stroke

Higher fibrinogen levels are seen in 9 out of 16 patients (56%) in haemorrhagic stroke group. 7 patients showed normal fibrinogen level.

TABLE 7. Type of stroke

In the present study, the most common type of stroke seen is ischemic stroke in 68% and haemorrhagic stroke in 32% . But the mean value of fibrinogen is almost similar to both ischemic and hemorrhagic strokes. It is not statistically significant ( P value is 0.84 ).

TABLE 8. Stroke outcome

Out of 50 patients, 7 patients expired and 43 patients survived. Among deceased 7 patients, 4 patients had ischemic stroke and 3 patients had hemorrhagic stroke.

TABLE 9. Fibrinogen levels and outcome:

All non survivors have higher fibrinogen level. Out of 50 patients 14% expired and 86% discharged.

The most common type of stroke is ischemic compared to hemorrhagic stroke. [11] The present study shows ischemic stroke in 68% of study subjects and hemorrhagic stroke in 32%. More or less similar results were reported by Narayanaswamy et al and Shretha et al. Higher incidence of ischemic stroke was observed by Ramanamurthy et al (90%) and Kamalchandra et al (88%). Lower incidence of ischemic stroke was observed by Ahmad et al (40%).[12-15]

Fibrinogen is emerging as an Independent and major risk factor for thrombo atherosclerotic diseases and peripheral vascular diseases. [16] Elevated plasma fibrinogen is an independent risk factor for stroke and cardiovascular events.

In the present study mean plasma fibrinogen levels are slightly higher in ischemic stroke than hemorrhagic stroke. Similar results were observed in the studies done by Kamalchandra et al, Narayanaswamy et al and Shrestha et al. But mean plasma fibrinogen levels are lower in ischemic stroke compared to hemorrhagic in a study done by Ahmad et al. [17,18]

Haritha et al and Venkateswarlu et al conducted studies only on ischemic stroke and their mean fibrinogen levels were 498.1 mg/dl and 523.1 mg/dl respectively. The values are higher compared to the present study. [19] Gregory et al in their study of ischemic stroke observed mean plasma fibrinogen levels of 376mg/dl which is similar to the present study. [20]

It has been observed in various epidemiological studies that plasma fibrinogen level increases with increasing age. [21] In this study, age wise comparison of plasma fibrinogen has shown that 4 out of 11 patients in the age group of 30-49 years, 15 out of 23 patients in the age group 50-69 years and 12 out of 15 patients in the age group 70-89yearshavehyperfibrinogenemia (> 350 mg/dl). But the single subject in the age group ≥90 years has normal fibrinogen level. Overall, there is increase in percentage of subjects with hyperfibrinogenemia with increasing age. [22]

Spada et al[23] have shown that patients with ischemic stroke have an earlier and more evident age related increase in fibrinogen values than controls, showing that fibrinogen is an important risk factor in elderly for stroke. Kamalchandra et al54also have shown that fibrinogen level increases with age. [24]

A.R.Kumar et al [25] in their study on plasma fibrinogen level in stroke showed elevated fibrinogen levels in 65% of their total subjects. And the elevated levels were seen in 80% of male subjects and 50% of female. Haritha et al [26] observed elevated plasma fibrinogen levels in 73% of males and 59% of females in their study. Kamalchandra et al have shown increased fibrinogen level in males (62%) compared to females (38%).

The present study shows higher mean fibrinogen levels in non-survival group compared to survival group. High mean fibrinogen levels are associated with poor outcome.

Swarowska M et al [27] showed that sustained increase of plasma fibrinogen during ischemic stroke predicts worse outcome independently of baseline fibrinogen level. Appuraj et al observed that outcome was poor in patients with higher fibrinogen levels at the onset of stroke. [28]

Conclusions

Stroke due to ischemia (68%) is more common than stroke due to haemorrhage (32%). Elevated fibrinogen level is one of the independent risk factors for stroke. Fibrinogen levels are slightly higher in ischemic stroke individuals compared to hemorrhagic stroke but not statistically significant. All non survivors have higher fibrinogen levels. It is evident from this study that there is increased mortality with increase in fibrinogen levels, higher the fibrinogen levels poorer the outcome.

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