Correlation between Serum Fibrinogen Level and Acute Ischemic Stroke Severity

ABSTRACT

BACKGROUND: Indonesia still has a high burden for stroke, and stroke became the number one cause of mortality, in which the condition caused 328,5 thousand deaths (21,2% of death from all cause) in 2012 according to WHO. Until now, there are multiple parameters that can be used to determine the severity of an acute ischemic stroke event, one of the laboratory parameters being serum fibrinogen level.

AIM: To find the relationship between serum fibrinogen level and the severity of acute ischemic stroke.

METHODS: The study used a cross-sectional design from acute ischemic stroke patients in the inpatient wards of H. Adam Malik Medan Hospital and network hospital. We used contingency coefficient correlation analysis test to determine the relationship between serum fibrinogen level and the severity of acute ischemic stroke. This study involved 40 acute ischemic stroke patients.

RESULTS: The results of statistical analysis found a significant positive correlation between serum fibrinogen level and acute ischemic stroke severity with weak correlation strength (p=0.028; r= 0.328) with the median NIHSS score of the subject 6,5 and median serum fibrinogen level being 320,9mg/dL (87 – 881mg/dL).

CONCLUSION: There was a significant relation between serum fibrinogen level and acute ischemic stroke severity. The result of this study proved that a higher serum fibrinogen level is associated with increased stroke severity.

Keywords: Acute ischemic stroke, fibrinogen, severity

* Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara / Haji Adam Malik Central General Hospital Medan. Correspondence: aviehann@gmail.com

INTRODUCTION

From all neurological diseases arising in the adulthood, stroke comes first in the level of frequency. Ischemic stroke itself is defined as an episode of neurological dysfunction caused by cerebral focal infarction, spinal cord, or retinal caused by an ischemia, which is based on pathological imaging or other objective evidence of a cerebral focal ischemic disorder, spinal cord, or retinal at a particular location of vascular distribution; or the presence of clinical evidence of a cerebral focal ischemic, spinal cord, or retinal disorder based on symptoms 2 that persist for more than 24 hours or cause death, and other etiologies have been excluded.¹ Many scales are available to measure stroke severity, including the National Institutes of Health Stroke Scale (NIHSS). The NIHSS is the most widely used deficit assessment scale in modern neurology.² Fibrinogen is a coagulation factor, the main determinant of plasma viscosity and a key factor for platelet activation. In patients with acute ischemic stroke, higher plasma fibrinogen levels are associated with an increased risk of unfavorable functional outcomes and death.³

METHOD

This research is descriptive-analytic with cross-sectional data collection. The study was conducted in an integrated inpatient room, Stroke Corner, and Intensive Care Unit of H. Adam Malik Medan Hospital and network hospital. The inclusion criteria for this study included patients with acute ischemic stroke who were established based on history, physical examination, neurological examination and head CT scan, patients aged ≥18 years and gave consent to participate in the study, by signing informed consent. A total of 40 patients have been selected using the nonrandom sampling method consecutively. The severity of stroke was determined using a NIHSS score with a total score of 42. The severity is divided into 2, the moderate-severe stroke is defined with a score of >4 and mild with a score of ≤3. Serum fibrinogen is divided into 2 groups, namely the group with increased fibrinogen levels > 360 mg/dL and normal. To determine the relationship between laboratory parameters and the severity of acute ischemic stroke, a contingency coefficient correlation analysis test was carried out to assess the strength of the relationship and the direction of the relationship.

RESULT

Based on the characteristics of 40 research subjects, it was found that the age of all research subjects had an average of 56.6 ±15.1 years with the most age group aged 51-60 years (32.5%). The gender of the study subjects was mostly male (60%). Based on educational background, the most are high school education (40%) with self-employment as the most jobs (30%). (Table 1)

Table 1. Description of demographic characteristics of the subject of study

Demographic Characteristics	n=40
Age, year Average (SD)	55.6 (±15.1)
Age, n (%)
21-30 31-40 41-50 51-60 61-70 71-80 >80	4 (10,0) 2 (5,0) 6 (15,0) 13 (32,5) 8 (20,0) 5 (12,5) 2 (5,0)
Gender, n (%)
Man Woman	24 (60,0) 16 (40,0)
Education, n (%)
No School SD JUNIOR SMA College	1 (2,5) 3 (7,5) 6 (15,0) 16 (40,0) 14 (35,0)
Occupation, n (%)
IRT Farmer Civil Servants Self employed Private Employees Not Working	10 (25,0) 9 (22,5) 6(15,0) 12 (30,0) 1 (2,5) 2 (5,0)

The severity of stroke at admission was divided into mild (NIHSS score 1 – 3) and moderate-severe (NIHSS score 4 – 42), this study found most of the subjects had moderate-severe stroke (55%), with a median NIHSS score of 6.5. Serum fibrinogen levels were divided into normal (fibrinogen levels 150 – 360 mg / dL) and elevated (fibrinogen levels > 360 mg / dL), and in this study found normal serum fibrinogen levels (65%) with a median value of 320.9mg / dL. (Table 2)

Table 2. Characteristics of severity and serum fibrinogen of the study subject

Characteristics of severity and serum fibrinogen
Severity of acute ischemic stroke Median (Min – Max) Severity of Acute Ischemic Stroke, n (%)	6,5 (1 – 29)
Mild Moderate-Severe	18 (45,0) 22 (55,0)
Serum Fibrinogen Levels, mg/dL Median (Min – Max) Serum Fibrinogen Levels, n (%)	320,9 (87 – 881)
Normal Elevated	26 (65,0) 14 (35,0)

The relationship between serum fibrinogen levels and the severity of acute phase ischemic stroke is shown in table 3. Based on the continental coefficient test, it is known that there is a relationship between serum fibrinogen levels and the level of acute phase ischemic stroke with a significance value of p = 0.028 and correlation r = 0.328 So it can be said that there is an influence of serum fibrinogen levels on the severity of acute phase ischemic stroke with a weak correlation level.

Table 3. Relationship between serum fibrinogen levels and severity of acute phase ischemic stroke

Severity of acute ischemic stroke	Fibrinogen		Total (%)	p	r
	Normal	Elevated
Mild	15	3	18(45%)	0,028*	0,328*
Moderate-Severe	11	11	22(55%)

*Contingency coefficient correlation test

DISCUSSION

This study was done with 40 research subjects who had met the criteria for inclusion and exclusion, the largest age group of research subjects was in the age range of 51-60 years, followed by the 61-70 years group, with a median value of 56.5 years, the youngest age was 21 years and the oldest age was 83 years. This result is in line with research by Torana, et al (2020) which states that there is an increase in the incidence of stroke at the age of ≥55 years.⁴ The results of RISKESDAS 2018 also show an increase in the incidence of stroke with increasing the age of a person.⁵ Research by Metipranolol, et al (2019) shows that the highest prevalence risk of stroke cases is 62 in the age range of 50-59 years.⁶ In this study, the most subjects were men (60%) compared to women (40%), RISKESDAS 2018 explained that the prevalence of stroke occurred in 11% of the male population and 10.9% female population.⁵

In the population of subjects studied, the highest level of education was found to be high school (40%) with the most jobs in the form of self-employed (30%). RISKESDAS in 2018, found the highest level of education in stroke patients, namely in patients who never attended school as much as 21.2%.⁵ The differences in education level distribution results seen in this study may be influenced by education level and its relationship to medical literacy, where previous studies have been shows that low health literacy leads to delays in diagnosis. Other research suggests that high health literacy can promote health-seeking behavior.^7,8

This study found a significant association between serum fibrinogen levels and the severity of acute ischemic stroke. This is in line with previous research which said that as an acute phase reactant, increased fibrinogen levels can be associated with the severity of an ischemic event. The study found that patients with fibrinogen levels of >360 mg/dL had worse outcomes based on NIHSS scores. They speculate that this may be due to more stable fibrin clots formed under conditions of higher serum fibrinogen levels.⁹

The effect of fibrinogen on blood viscosity has been widely studied before, the relationship between fibrinogen and blood viscosity has been found significantly. Increased blood viscosity in acute stroke is responsible for low cerebral blood flow and impaired perfusion, which can lead to ischemia and infarction. This process affects the severity of neurological disorders which can be observed through NIHSS scores.¹⁰

Elevated fibrinogen levels result in changes in the rheological properties of the blood that exacerbate complications in peripheral blood circulation during stroke.¹¹ The difference in yield at higher fibrinogen levels may be related to clot structure. Clumps formed in the presence of high concentrations of fibrinogen can be made of thinner, denser fibers that are more resistant to fibrinolysis than clots formed at lower concentrations. The structure of the clot also depends on the conditions during the polymerization of fibrinogen.⁹ Fibrinogen levels after acute ischemic stroke are associated with poorer neurological outcomes and efficacy for thrombolysis because they independently and directly shorten the time for occlusion and increases thrombus resistance to thrombolysis.¹²

This study concluded that there was a significant association between serum fibrinogen levels and the severity of acute phase ischemic stroke based on NIHSS scores. This relationship may be explained by changes in clot structure arising in high levels of fibrinogen.

ACKNOWLEDGEMENT

The researchers would like to thank the Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Haji Adam Malik Central General Hospital Medan that have facilitated this research.

REFERENCE

1. Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, et al. An updated definition of stroke for the 21st Century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. AHA Journals. 2013;44(7):2064–89.
2. Lyden P. Using the National Institutes of Health Stroke Scale. Stroke. 2017;48(2):513-19.
3. Li D, Xing C, Li Y, Zhu X. Elevated plasma fibrinogen indicates shortterm poor outcome in patients with acute ischemic stroke after intravenous thrombolysis. Journal of Stroke and Cerebrovascular Diseases. 2020;29(8):104991.
4. Riyadina, W., Pradono, J. and Turana, Y. “Stroke in Indonesia: Risk Factors and Predispositions in Young Adults,” J. Cardiovasc Disease Res, 2020;11(2), pp. 178–83. Available at: https://doi.org/10.31838/ jcdr.2020.11.02.30.
5. Kementrian Kesehatan Republik Indonesia. Riset Kesehatan Dasar (Riskesdas) [Internet]. Jakarta: Lembaga Penerbit Badan Penelitian dan Pengembangan Kesehatan; 2018. Available from: https://www.litbang.kemkes.go.id/laporan-riset-kesehatan-dasarriskesdas/
6. Setyopranoto I, Bayuangga H, Panggabean A, Alifaningdyah S, Lazuardi L, Dewi F et al. Prevalence of Stroke and Associated Risk Factors in Sleman District of Yogyakarta Special Region, Indonesia. Stroke Research and Treatment. 2019;2019:1-8.
7. Andiwijaya, F.R., Kadriyan, H., Syamsun, A. Education level as a predictor for health literacy levels in a rural community health centre, Advances in Health Sciences Research [Preprint]. 2021; Available at: https://doi.org/10.2991/ahsr.k.220206.051.
8. Li, X. et al. Effect of health education on healthcare-seeking behavior of migrant workers in China, International Journal of Environmental Research and Public Health, 2020; 17(7), p. 2344. Available at: https://doi.org/10.3390/ijerph17072344.
9. del Zoppo G, Levy D, Wasiewski W, Pancioli A, Demchuk A, Trammel J et al. Hyperfibrinogenemia and Functional Outcome From Acute Ischemic Stroke. Stroke. 2009;40(5):1687-1691.
10. Rasyid, A. Harris S, Kurniawan M, Mesiano T, Hidayat R. Fibrinogen and LDL influence on blood viscosity and outcome of acute ischemic stroke patients in Indonesia, Annals of Neurosciences, 2019; 26(3-4), pp. 30–4. Available at: https://doi.org/10.1177/0972753119900630.
11. Helmy M, Khodair R, El-Azab M, Butros M. Serum Level of Ferritin and Fibrinogen as Prognostic Indicator for Acute Ischemic Stroke. Benha Medical Journal. 2021;0(0):0-0.
12. Chalos V, van der Ende N, Lingsma H, Mulder M, Venema E, Dijkland S et al. National Institutes of Health Stroke Scale. Stroke. 2020;51(1):282-90.