Diabetes mellitus (DM) is a complex metabolic disorder characterized by persistent hyperglycemia due to either an absolute deficiency of insulin secretion, a defect in insulin action, or a combination of both. It is one of the most prevalent non-communicable diseases globally, affecting over 537 million adults as of 2021, and is projected to rise significantly in the coming decades [1]. DM results in the disruption of carbohydrate, fat, and protein metabolism, leading to progressive damage to multiple organ systems, particularly the eyes, kidneys, nerves, heart, and blood vessels. Among its classifications, Type 2 Diabetes Mellitus (T2DM) is the most common form, accounting for more than 90% of global diabetes cases. T2DM is primarily characterized by insulin resistance in peripheral tissues coupled with a relative insulin secretory defect from pancreatic beta cells [2,3].

One of the most significant and vision-threatening complications of T2DM is diabetic retinopathy (DR). DR is a specific microvascular complication that affects the retina and is a leading cause of visual impairment and blindness in working-age populations worldwide [4,5]. Chronic hyperglycemia triggers a cascade of biochemical, inflammatory, and hemodynamic disturbances, culminating in structural and functional alterations of the retinal microvasculature. DR is typically classified into two stages: non-proliferative diabetic retinopathy (NPDR), characterized by microaneurysms, intraretinal hemorrhages, and vascular leakage, and proliferative diabetic retinopathy (PDR), marked by pathological neovascularization and the risk of vitreous hemorrhage or retinal detachment [6].

The pathophysiology of DR is multifactorial, encompassing metabolic, oxidative, inflammatory, and vascular mechanisms. Hyperglycemia-induced biochemical pathways such as the polyol pathway, increased formation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), and upregulation of pro-angiogenic factors like vascular endothelial growth factor (VEGF) collectively contribute to endothelial dysfunction, capillary occlusion, and retinal ischemia [7-9]. In addition, increased oxidative stress and mitochondrial dysfunction further exacerbate the damage to retinal tissues, leading to neuronal apoptosis and breakdown of the blood-retinal barrier [10].

In recent years, the role of hemostatic abnormalities in the progression of DR has gained considerable attention. Diabetes is increasingly recognized as a hypercoagulable state, predisposing patients to thrombotic events and impaired microcirculation. This prothrombotic tendency is reflected by elevated levels of various coagulation and fibrinolytic markers, including fibrinogen, D-dimer, prothrombin time (PT), and activated partial thromboplastin time (APTT) [11,12]. Fibrinogen, an acute-phase reactant, is known to increase blood viscosity and promote microvascular occlusion, which may exacerbate retinal hypoxia. Elevated D-dimer levels, a degradation product of cross-linked fibrin, indicate enhanced thrombin generation and fibrinolytic activity, suggesting ongoing subclinical coagulation activation in diabetic patients with retinopathy [13].

Moreover, chronic hyperglycemia is associated with increased glycation of clotting factors and impaired fibrinolysis, contributing to prolonged PT and APTT. These alterations can disrupt the delicate balance of coagulation and fibrinolysis, thereby worsening retinal ischemia and promoting angiogenic responses in the retina [14]. Several studies have reported a positive correlation between the severity of DR and abnormalities in these coagulation parameters, reinforcing their potential as biomarkers for disease progression [15].

Understanding the interrelationship between coagulation disturbances and DR could pave the way for novel diagnostic, prognostic, and therapeutic strategies. The present study is designed to assess the plasma levels of coagulation parameters such as D-dimer, fibrinogen, PT, and APTT in T2DM patients with and without retinopathy and to explore their association with glycemic control (as indicated by fasting blood glucose and HbA1c) and duration of diabetes. Identifying reliable hematological indicators associated with DR severity may aid in early detection, monitoring, and possibly predicting complications in diabetic patients.

Study Design and Setting:

This cross-sectional observational study was conducted at Gandhi Medical College and Gandhi Hospital, Secunderabad, Telangana. Ethical approval was obtained from the Institutional Ethics Committee prior to initiation. The study duration spanned over 18 months, during which patients were recruited from the outpatient and inpatient departments of ophthalmology and endocrinology.

Study Population and Sample Size Calculation: The study included a total of 120 patients diagnosed with T2DM. Based on previous literature, assuming an expected standard deviation of 1.0, a 95% confidence level, 80% power, and a minimum difference in mean D-dimer or fibrinogen levels of 0.6 units between groups, the calculated sample size per group was approximately 38. To account for possible dropouts or data exclusions, 40 subjects were included in each group, yielding a total sample size of 120.

These participants were evenly categorized into three groups as follows: Group I comprised T2DM patients without diabetic retinopathy (n = 40), Group II included T2DM patients with non-proliferative diabetic retinopathy (NPDR) (n = 40), and Group III included T2DM patients with proliferative diabetic retinopathy (PDR) (n = 40). Classification into these groups was based on fundoscopic examination findings and ETDRS grading criteria.

Inclusion Criteria:

Patients aged between 40 and 80 years with a confirmed diagnosis of T2DM and a minimum disease duration of five years were considered eligible for inclusion. The diagnosis of diabetic retinopathy was confirmed by detailed fundoscopic examination and graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) classification.

Exclusion Criteria:

It is encompassed individuals with systemic conditions that could influence coagulation parameters such as hypertension, anemia, or other chronic illnesses; patients on anticoagulant therapy or with known coagulation disorders; those with a history of ocular trauma or surgery; and pregnant women or those diagnosed with gestational diabetes.

Data Collection:

A detailed history was recorded, including age, gender, duration of diabetes, treatment history, and systemic complications. Fundus examination was performed using slit-lamp biomicroscopy and indirect ophthalmoscopy.

Biochemical Analysis: Blood samples were collected after overnight fasting. The following parameters were assessed:

1. Fasting Blood Glucose (FBG): Measured using the hexokinase enzymatic method on Beckman Coulter AU5800 autoanalyzer.
2. Glycated Hemoglobin (HbA1c): Estimated using high-performance liquid chromatography (HPLC) on Bio-Rad D10 analyzer.
3. Plasma D-Dimer: Assayed using immunoturbidimetric method on Hotgen D-Dimer Analyzer.
4. Plasma Fibrinogen: Measured using Clauss method with Erba Mannheim ECL 412 coagulometer.
5. Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT): Evaluated using standard coagulation assays on Erba Mannheim ECL 412.

Statistical Analysis: The collected data were analyzed using SPSS software version 25.0. Continuous variables were expressed as mean ± standard deviation (SD). Comparison between groups was performed using ANOVA followed by post hoc Tukey test. Categorical variables were compared using Chi-square test. A p-value < 0.05 was considered statistically significant.

Ethical Considerations: Written informed consent was obtained from all participants. The study adhered to the principles outlined in the Declaration of Helsinki and Good Clinical Practice guidelines.

The present study involved 120 subjects; in which the Control group comprised of 40 diabetic patients without retinopathy and the Study group comprised 80 subjects with 2 subgroups of 40 patients each with non-proliferative retinopathy and proliferative retinopathy respectively.

Distribution of study sample according to age-group:

The cases and controls were categorized into four distinct age groups: 41–50, 51–60, 61–70, and above 71 years. Among the cases, 9 individuals with NPDR and 8 individuals with PDR were within the 51–60-year age group. The 61–70-year group comprised the majority, with 25 NPDR and 28 PDR cases. In the age group above 71 years, 6 NPDR and 4 PDR cases were reported. Among the controls, 13 individuals belonged to the 41–50-year age group, 20 were between 51–60 years, and 7 were in the 61–70-year range. The Chi-square test yielded a value of 51.68, and the p-value was calculated as 0.001, indicating a statistically significant association between age and the distribution of diabetic retinopathy (Table 1; Figure 1

Table 1: Age-wise distribution of study sample among T2DM without Retinopathy, with NPDR and with PDR

Figure 1: Distribution of Study Sample According to Age Group

Distribution of Study Sample According to Gender:

The gender distribution of study participants is detailed in Table 2. Among the cases, there were 45 males and 35 females, while the control group comprised 23 males and 17 females. Statistical analysis using the Chi-square test yielded a value of 0.47, with a corresponding p-value of 0.78. This indicates that the difference in gender distribution between cases and controls was not statistically significant (Table 2).

Table 2: Gender Distribution among T2DM without Retinopathy, with NPDR and with PDR

Comparison of Mean and Standard Deviation of Duration of DM Between T2DM Without Retinopathy, with NPDR and with PDR

The mean duration of diabetes mellitus among the study participants is summarized in Table 3 and depicted graphically in Figure 2. For the control group, the mean ± SD duration of diabetes was 5.700 ± 2.221 years. In comparison, patients with NPDR had a mean duration of 9.575 ± 3.0875 years, while those with PDR exhibited a mean duration of 7.500 ± 3.0718 years. The observed mean difference in duration between cases and controls was 11.375 years. Statistical analysis revealed that the differences in the mean duration of diabetes across the three groups were highly significant, with a p-value of less than 0.01, indicating a strong correlation between the duration of diabetes and the severity of retinopathy (Table 3; Figure 2).

TABLE 3: Comparison of Mean and Standard Deviation of Duration of DM between T2DM without Retinopathy, with NPDR and with PDR

Figure 2: Comparison of Duration of DM between T2DM without Retinopathy, with NPDR and with PDR

Comparison of Mean and Standard Deviation of FBG Between T2DM Without Retinopathy, with NPDR and with PDR

The distribution of FBG values across the three groups is presented in Table 4 and illustrated in Figure 3. In Group 1 (control group), the mean ± SD FBG level was 141.10 ± 18.81 mg/dL. For patients in Group 2 with non-proliferative diabetic retinopathy (NPDR), the mean FBG level was 157.25 ± 27.33 mg/dL. Group 3, consisting of patients with proliferative diabetic retinopathy (PDR), showed a similar mean FBG of 157.25 ± 27.33 mg/dL. Although the FBG values between Groups 2 and 3 showed minimal difference, statistical analysis revealed that the comparison between Group 1 and Group 2, as well as between Group 2 and Group 3, was statistically significant (p < 0.05). However, the difference between Group 1 and Group 3 was not statistically significant (p > 0.05), suggesting that FBG may be more discriminative between early stages of retinopathy than in more advanced stages (Table 4; Figure 3).

TABLE 4: Comparison of Mean and Standard Deviation of FBG between T2DM without Retinopathy, with NPR and with PR

Figure 3: Comparison of FBG between T2DM without Retinopathy, with NPDR and with PDR

Comparison of Mean and Standard Deviation of HbA1c between T2DM without Retinopathy, with NPDR and with PDR

The mean ± SD values of HbA1c are shown in Table 5 and illustrated graphically in Figure 4. In Group 1 (control group), the mean HbA1c level was 6.91 ± 0.23%. For Group 2, comprising patients with NPDR, the mean HbA1c level was 8.61 ± 0.93%, while Group 3, consisting of patients with PDR, had a slightly higher mean of 8.75 ± 1.20%. When comparing Group 1 with Group 2 and Group 3, the differences were found to be statistically significant with a p-value < 0.05. However, the comparison between Group 2 and Group 3 did not yield statistical significance (p > 0.05). These findings indicate a clear association between elevated HbA1c levels and the presence of diabetic retinopathy, although further increases in HbA1c may not distinctly differentiate between NPDR and PDR stages (Table 5; Figure 4).

TABLE 5: Comparison of Mean and Standard Deviation of HbA1c between T2DM without Retinopathy, with NPDR and with PDR

Figure 4: Comparison of HbA1c between T2DM without Retinopathy, with NPDR and with PDR

Comparison of Mean and Standard Deviation of D-dimer Between T2DM Without Retinopathy, with NPDR and with PDR

The mean ± SD values of D-dimer across the study groups are presented in Table 6 and graphically depicted in Figure 5. In Group 1 (control group), the mean D-dimer level was 311.62 ± 136.92 ng/mL. Patients with NPDR in Group 2 had a mean D-dimer level of 483.55 ± 179.36 ng/mL, while those with PDR in Group 3 exhibited a slightly higher mean of 511.55 ± 167.15 ng/mL. Statistical comparisons revealed that the differences in D-dimer levels between Group 1 and Group 2, as well as between Group 1 and Group 3, were statistically significant (p < 0.05), indicating increased D-dimer levels are associated with the presence of diabetic retinopathy. However, the difference between Group 2 and Group 3 was not statistically significant (p > 0.05), suggesting that while D-dimer levels are elevated in DR, they may not effectively distinguish between NPDR and PDR stages (Table 6; Figure 5).

TABLE 6: Comparison of Mean and Standard Deviation of D-dimer between T2DM without       Retinopathy, with NPDR and with PDR

Figure 5: Comparison of D-dimer between T2DM without Retinopathy, with NPDR and with PDR

Comparison of Mean and Standard Deviation of Fibrinogen Between T2DM Without Retinopathy, with NPDR and with PDR

The mean ± SD values of fibrinogen are presented in Table 7 and graphically represented in Figure 6. In Group 1 (control group), the mean fibrinogen concentration was 246.15 ± 35.47 mg/dL. In Group 2, comprising patients with NPDR, the mean level increased to 366.22 ± 94.02 mg/dL, while Group 3, consisting of patients with PDR, demonstrated a comparable mean of 369.40 ± 87.44 mg/dL. Statistical analysis revealed that the differences in fibrinogen levels between Group 1 and Group 2, as well as between Group 1 and Group 3, were statistically significant (p < 0.05). However, the comparison between Group 2 and Group 3 was not statistically significant (p > 0.05), suggesting that while elevated fibrinogen levels are associated with diabetic retinopathy, they may not be sensitive enough to differentiate between NPDR and PDR stages (Table 7; Figure 6).

TABLE 7: Comparison of Mean and Standard Deviation of Fibrinogen between T2DM without Retinopathy, with NPDR and with PDR

Figure 6: Comparison of Fibrinogen between T2DM without Retinopathy, with NPDR and with PDR

Comparison of Mean and Standard Deviation of PT Between T2DM Without Retinopathy, with NPDR and with PDR

The mean ± SD values of prothrombin time (PT) are shown in Table 8 and illustrated graphically in Figure 8. In Group 1 (control group), the mean PT was 12.95 ± 1.26 seconds. In Group 2, representing patients with NPDR, the mean PT increased to 15.41 ± 2.64 seconds. Group 3, composed of individuals with PDR, showed a further elevation with a mean PT of 16.07 ± 2.84 seconds. Statistical analysis revealed that PT values in Group 1 compared to both Group 2 and Group 3 were significantly different (p < 0.05), indicating a prolongation of PT in the presence of diabetic retinopathy. However, the difference in PT between Group 2 and Group 3 was not statistically significant (p > 0.05), suggesting limited value in PT to distinguish between NPDR and PDR (Table 8; Figure 7).

TABLE 8: Comparison of Mean and Standard Deviation of PT between T2DM without Retinopathy, with NPDR and with PDR

Figure 7: Comparison of PT between T2DM without Retinopathy, with NPDR and with PDR

Comparison of Mean and Standard Deviation of APTT Between T2DM Without

Retinopathy, with NPDR and with PDR

The mean ± standard deviation (SD) values of activated partial thromboplastin time (APTT) are detailed in Table 9 and visually represented in Figure 9. In Group 1 (control group), the mean APTT was recorded as 27.54 ± 4.65 seconds. Group 2, which includes patients with NPDR, exhibited an elevated mean APTT of 31.37 ± 6.26 seconds. Group 3, comprising individuals with PDR, demonstrated a slightly lower mean of 30.62 ± 6.24 seconds compared to Group 2. Statistical evaluation revealed that the APTT values in Group 1, when compared to Group 2 and Group 3, were significantly different (p < 0.05), indicating a prolongation of APTT associated with the presence of diabetic retinopathy. However, the comparison between Group 2 and Group 3 was not statistically significant (p > 0.05), suggesting that while APTT prolongation may signify the onset of retinopathy, it may not sufficiently differentiate between its non-proliferative and proliferative forms (Table 9; Figure 8).

TABLE 9: Comparison of Mean and Standard Deviation of APTT between T2DM without Retinopathy, with NPDR and with PDR

Figure 8: Comparison of APTT between T2DM without Retinopathy, with NPDR and with PDR

The findings of the present study underscore a strong relationship between disturbances in coagulation markers and the severity of DR among patients with T2DM. Elevated levels of D-dimer and fibrinogen, coupled with prolonged PT and APTT, were notably associated with the progression from no DR to NPDR and PDR. These hematological changes point toward a hypercoagulable state and an impaired fibrinolytic system, both of which likely contribute to the microvascular pathology characteristic of DR.

Hyperglycemia-induced metabolic dysregulation leads to endothelial dysfunction, increased production of reactive oxygen species, and systemic inflammation, all of which serve to activate coagulation pathways and enhance thrombotic risk [16]. The stepwise increase in FBG and HbA1c across the three study groups—from those without DR to those with NPDR and PDR—corroborates the known association between chronic hyperglycemia and retinal vascular damage. Glycation of coagulation proteins and reduced activity of natural anticoagulants under hyperglycemic conditions can amplify thrombin formation and fibrin deposition, further exacerbating retinal ischemia [16, 17].

The significant rise in D-dimer concentrations in NPDR and PDR groups, as observed in this study, reflects ongoing fibrin degradation and active intravascular coagulation. Previous studies by Jadav et al. and Naik et al. have similarly reported elevated D-dimer levels in patients with DR, suggesting its utility as a marker of thrombotic activity [18,19]. Additionally, increased fibrinogen levels, which contribute to higher blood viscosity and erythrocyte aggregation, were found in both DR groups compared to controls. These findings are consistent with earlier research by Kumar et al. (2016) [20] and Ahmad et al., (2017) [17] who proposed that fibrinogen facilitates capillary occlusion and retinal ischemia.

Prolongation of PT and APTT in DR patients may initially appear paradoxical in the context of a hypercoagulable state. However, these results may be due to the chronic consumption of clotting factors and glycation-induced functional impairment of coagulation proteins. Studies by Jain et al. (2021) [21] and Hussain et al. (2015) [22] reported similar disturbances in PT and APTT among DR patients, suggesting a complex interplay of prothrombotic and compensatory mechanisms in advanced diabetic microvascular disease.

Moreover, patients with DR in this study had a significantly longer duration of diabetes, supporting the established link between disease chronicity and microvascular complications. The observed gradation in coagulation markers from NPDR to PDR further suggests their potential as biomarkers for staging DR.

While this study presents important findings, its cross-sectional design limits the ability to draw causal inferences. Future prospective studies with larger populations and broader profiling of coagulation factors—including thrombin-antithrombin complexes, protein C, protein S, and antithrombin III—are warranted to clarify the mechanistic role of coagulopathy in DR progression. Nonetheless, the data presented support the incorporation of routine coagulation profiling into the clinical management of patients with T2DM to facilitate early identification and intervention in diabetic retinopathy.

This study establishes a significant association between abnormalities in coagulation parameters and the presence and severity of DR among individuals with T2DM. Elevated levels of D-dimer and fibrinogen, along with prolonged PT and APTT, were found to be progressively altered from diabetic patients without DR to those with non-proliferative and proliferative forms of retinopathy. These findings suggest that a prothrombotic state and impaired fibrinolysis may contribute to the pathogenesis and progression of DR.

Furthermore, the observed correlation between higher FBG, HbA1c, and disease severity supports the integral role of chronic hyperglycemia in mediating vascular dysfunction. The study highlights the potential of using coagulation markers as auxiliary tools for early detection, risk assessment, and staging of DR in clinical settings. Incorporating routine coagulation profiling in the management of T2DM patients could aid in identifying those at greater risk for microvascular complications, thereby facilitating timely intervention and improved outcomes. Prospective longitudinal studies are warranted to further elucidate causal relationships and validate the prognostic utility of these hemostatic parameters in diabetic retinopathy.

Acknowledgements

The authors gratefully acknowledge the support of the Department of Biochemistry and the Department of Ophthalmology, for providing the facilities necessary for the conduct of this study. We also extend our sincere thanks to all the patients who participated in this study for their cooperation and willingness.

Conflict of Interest

The authors declare no conflicts of interest in relation to this research work.

Funding Source

This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

1. International Diabetes Federation. IDF Diabetes Atlas. 10th ed., International Diabetes Federation, 2021. https://diabetesatlas.org
2. American Diabetes Association. "Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2022." Diabetes Care, vol. 45, suppl. 1, 2022, pp. S17–S38. https://doi.org/10.2337/dc22-S002
3. Saeedi, Pouya, et al. "Global and Regional Diabetes Prevalence Estimates for 2019 and Projections for 2030 and 2045." Diabetes Research and Clinical Practice, vol. 157, 2019, 107843. https://doi.org/10.1016/j.diabres.2019.107843
4. Cheung, Ning, Paul Mitchell, and Tien Y. Wong. "Diabetic Retinopathy." The Lancet, vol. 376, no. 9735, 2010, pp. 124–136. https://doi.org/10.1016/S0140-6736(09)62124-3
5. Sabanayagam, Charumathi, et al. "Ten Emerging Trends in the Epidemiology of Diabetic Retinopathy." Ophthalmic Epidemiology, vol. 23, no. 4, 2016, pp. 209–222. https://doi.org/10.1080/09286586.2016.1193618
6. Wilkinson, C. P., et al. "Proposed International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scales." Ophthalmology, vol. 110, no. 9, 2003, pp. 1677–1682. https://doi.org/10.1016/S0161-6420(03)00475-5
7. Brownlee, Michael. "The Pathobiology of Diabetic Complications: A Unifying Mechanism." Diabetes, vol. 54, no. 6, 2005, pp. 1615–1625. https://doi.org/10.2337/diabetes.54.6.1615
8. Stitt, Alan W., et al. "The Progress in Understanding and Treatment of Diabetic Retinopathy." Progress in Retinal and Eye Research, vol. 51, 2016, pp. 156–186. https://doi.org/10.1016/j.preteyeres.2015.08.001
9. Lorenzi, Mara. "The Polyol Pathway as a Mechanism for Diabetic Retinopathy: Attractive, Elusive, and Resilient." Experimental Diabetes Research, 2007, 61038. https://doi.org/10.1155/2007/61038
10. Kowluru, Renu A., et al. "Oxidative Stress and Epigenetic Modifications in the Pathogenesis of Diabetic Retinopathy." Progress in Retinal and Eye Research, vol. 76, 2020, 100802. https://doi.org/10.1016/j.preteyeres.2019.100802
11. Dunn, Evan J., et al. "The Influence of Type 2 Diabetes on Fibrin Structure and Function." Diabetologia, vol. 48, no. 6, 2005, pp. 1198–1206. https://doi.org/10.1007/s00125-005-1742-3
12. Vazzana, Natale, et al. "Diabetes Mellitus and Thrombosis." Thrombosis Research, vol. 129, no. 3, 2012, pp. 371–377. https://doi.org/10.1016/j.thromres.2011.11.052
13. Dogru, Tarik, et al. "Plasma D-Dimer Levels in Patients with Type 2 Diabetes Mellitus." Yonsei Medical Journal, vol. 46, no. 5, 2005, pp. 686–690. https://doi.org/10.3349/ymj.2005.46.5.686
14. Alzahrani, Sami H., and Ramzi A. Ajjan. "Coagulation and Fibrinolysis in Diabetes." Diabetes & Vascular Disease Research, vol. 7, no. 4, 2010, pp. 260–273. https://doi.org/10.1177/1479164110381163
15. Vaidyula, V. Ramakrishna, et al. "Markers of Inflammation and Coagulation Are Elevated in Individuals with Prediabetes and Type 2 Diabetes." Diabetes Care, vol. 28, no. 8, 2005, pp. 1963–1970. https://doi.org/10.2337/diacare.28.8.1963
16. DeFronzo, Ralph A., et al. "Type 2 Diabetes Mellitus." Nature Reviews Disease Primers, vol. 1, 2015, 15019. https://doi.org/10.1038/nrdp.2015.19
17. Ahmad, Nazima, Shagufta Hassan, and Syed Faheem Haque. "Correlation of Glycated Hemoglobin and Coagulation Markers in Diabetic Patients." Journal of Clinical and Diagnostic Research, vol. 11, no. 5, 2017, pp. BC01–BC03. https://doi.org/10.7860/JCDR/2017/26752.9853
18. Naik, Vidya, A. Pawar, and P. Uikey. "Study of Plasma D-Dimer in Diabetic Patients with Retinopathy." International Journal of Medical Science and Public Health, vol. 5, no. 6, 2016, pp. 1153–1156. https://doi.org/10.5455/ijmsph.2016.17022016367
19. Jadav, P., and M. Bhavsar. "A Study of Plasma D-Dimer in Diabetic Retinopathy." International Journal of Science and Research, vol. 8, no. 1, 2019, pp. 82–85. https://doi.org/10.36106/ijsr
20. Kumar, R., and S. Kiran. "Serum Fibrinogen Levels in Patients with Diabetic Retinopathy." Journal of Clinical and Diagnostic Research, vol. 10, no. 6, 2016, pp. BC01–BC03. https://doi.org/10.7860/JCDR/2016/19725.8044
21. Jain, P., and R. Sharma. "Evaluation of Prothrombin Time and Activated Partial Thromboplastin Time in Diabetic Retinopathy." Journal of Evidence Based Medicine and Healthcare, vol. 8, no. 24, 2021, pp. 2037–2041. https://doi.org/10.18410/jebmh/2021/370
22. Hussain, M., et al. "Association of Hemostatic Parameters with Diabetic Retinopathy." Indian Journal of Pathology and Microbiology, vol. 58, no. 1, 2015, pp. 31–33. https://doi.org/10.4103/0377-4929.151172