Abstract
Background and Objectives:
Parkinson’s disease (PD) is a neurodegenerative disorder involving depletion of dopaminergic neurons. Pathogenetic mechanisms leading to striatonigral degeneration are debatable. Chronic inflammation is proposed as one of the mechanisms. In any disease with underlying inflammation, immune system mediators called cytokines are released, leading to a procoagulant state. Our aim was to study the coagulation parameters in patients with PD and find their correlation with disease duration and antiparkinsonian drugs.
Methods:
This cross-sectional study was conducted between January 2021 and December 2021 in a tertiary care center. Sixty-eight patients with PD were subcategorized based on disease duration (<5 and ≥5 years), number of antiparkinsonian drugs (one drug and ≥2 drugs), and levodopa equivalent daily dose (LEDD; <350 and ≥350 mg). Hemoglobin (Hb), prothrombin time (PT), fibrinogen, bleeding time, and platelet aggregation study with adenosine diphosphate and collagen were assessed.
Results:
In our cohort of 68 patients, 53 were men and 15 were women. Mean disease duration was 5.97 ± 4.37 years. Hb was negatively associated with LEDD (P = 0.012) and duration of the disease (P = 0.02). Similarly, PT was negatively associated with disease duration (P = 0.041) and number of antiparkinsonian drugs (P = 0.03). LEDD showed a positive association with collagen-induced platelet aggregation (P = 0.03).
Conclusions:
In our study, patients using multiple antiparkinsonian drugs and higher LEDD were observed to have a prothrombotic state. Further studies are needed to confirm these findings.
Keywords: Parkinson’s disease, coagulation parameters, antiparkinsonian drugs, prothrombotic state, hemostatic system
Introduction
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, next to Alzheimer’s disease.[1] It is characterized by nigrostriatal dopaminergic denervation leading to a wide variety of motor and nonmotor symptoms, which can be disabling to the patient. Although a variety of mechanisms have been proposed over the years, the pathogenesis of PD is still largely uncertain. Some of the proposed theories are excessive release of oxygen free radicals during enzymatic dopamine breakdown, impairment of mitochondrial function, loss of trophic support, abnormal kinase activity, disruption of calcium homeostasis, dysfunction of protein degradation, and neuroinflammation.[2,3,4] However, emerging evidence indicates that sustained inflammatory responses like T-cell infiltration and glial cell activation are the common features of both human PD patients and animal models of PD and these play a vital role in the degeneration of dopaminergic neurons.[5,6] Any disease with underlying inflammation is likely to have an impact on coagulation responses and hemostasis. Literature regarding the impact of PD on coagulation responses is scarce. Our study might pave the way for finding out if patients with PD have a tendency to form clots or bleed. This might help in formulating preventive measures in patients with PD.
Methods
This was a cross-sectional, single-center, observational study conducted between January 2021 and December 2021 in a tertiary care institute in the southern part of India. The study protocol was approved by the local Institutional Ethics Committee. Written informed consent was obtained from the patients or their legally acceptable representatives before entry into the study. A total of 69 patients, who were diagnosed to have clinically established or clinically probable PD based on the 2015 Movement Disorder Society (MDS) clinical diagnostic criteria[7] and were using antiparkinsonian medication (levodopa with carbidopa combination, ropinirole, pramipexole, amantadine, safinamide, entacapone) were enrolled in our study. One patient was excluded from this cohort as he had an abnormally prolonged prothrombin time (PT) of 19 s. Data from the other 68 patients was analyzed using appropriate statistical methods. Exclusion criteria taken into consideration were recent febrile illness (in the last 3 months before enrollment), past history of peripheral vascular or cardiovascular or cerebrovascular disease, bleeding disorders (inherited or acquired), and use of medications like antiplatelets or anticoagulants, as these are likely to affect the coagulation parameters.
Clinical data
All demographic details including age of onset of symptoms, duration of symptoms, and medications being used and their dosage were taken. Motor impairment was assessed using the motor component of the Unified PD rating scale (UPDRS) Part-III[8] in “off” (without antiparkinsonian drugs for at least 8 h) and “on” (at least 1 h after a minimum of 200 mg of levodopa and 50 mg of carbidopa when there was good improvement) states. Cognition was assessed using the Montreal cognitive assessment (MoCA) scale.[9] As our patients were on different drug combinations, we used levodopa equivalent daily dose (LEDD) to standardize the dopamine dosage they were receiving per day and then compared the coagulation parameters. LEDD was calculated using the method reported by Tomlinson et al.[10] LEDD for safinamide was calculated using the conversion factor proposed by Schade et al.[11]
Laboratory workup
Under aseptic precautions, blood samples were collected from all patients for analyzing coagulation parameters. The parameters assessed were platelet count, PT, activated partial thromboplastin time (aPTT), bleeding time (BT), fibrinogen levels, thrombin time (TT), and platelet aggregation studies with adenosine diphosphate (ADP) and collagen.
Complete blood picture
Blood specimen was collected in a tube with ethylenediaminetetraacetic acid as the anticoagulant. Cell counting (red blood cells, white blood cells, and platelet count) was done using an automated hematology analyzer, which works with the Coulter principle of electrical impedance. Normal range of platelet count is 1.5–4 lakhs/mm3.
Prothrombin time
PT measures the activity of coagulation factors involved in extrinsic and common pathways (I, II, V, VII, X). Blood specimen was collected in a tube with 3.2% trisodium citrate as the anticoagulant. Plasma was separated, to which reagent (thromboplastin) was added. Thromboplastin (tissue factor) binds to factor VII and initiates coagulation. It was followed by addition of calcium. Time taken from the addition of calcium to form a fibrin clot was taken as PT. Normal range of PT is 12–16 s.
Activated partial thromboplastin time
aPTT measures the activity of coagulation factors involved in intrinsic and common pathways (XII, XI, IX, VIII, X, V, II, I). Blood specimen was collected in a tube with 3.2% trisodium citrate as the anticoagulant. Plasma was separated, to which reagent (cephalin phospholipid + silica activator) was added. This reagent activates factor XI and initiates coagulation. It was followed by addition of calcium. Time taken from the addition of calcium to form a fibrin clot was taken as aPTT. Normal range of aPTT is 25–40 s.
Fibrinogen
Blood specimen was collected in a tube with 3.2% trisodium citrate as the anticoagulant. Plasma was separated and diluted. Fibrinogen was measured by Simultaneous thermal analyzers (STA) based on Clauss clotting method combined with mechanical clot detection system. The Clauss method depends on the principle that in the presence of excess of thrombin, the clotting time of a diluted plasma has a direct bearing on the level of fibrinogen. Normal level of serum fibrinogen is 200–400 mg/dl.
Thrombin time
TT reflects the conversion of fibrinogen to fibrin. Blood specimen was collected in a tube with 3.2% trisodium citrate as the anticoagulant. Plasma was separated, to which reagent containing human thrombin was added. Time taken to form thrombin clot was taken as TT. Normal range of TT is 13–22 s.
Platelet aggregation tests
These assays depend on platelet function, calcium, fibrinogen, and the type of aggregating agent being used. Optical aggregation tests were used in our study. Blood specimen was collected in a tube with 3.2% trisodium citrate as the anticoagulant. Platelet-rich plasma (PRP) was collected. To this, an aggregating agent was added (ADP or collagen). As platelets start aggregating, PRP begins to clear, allowing more light to pass through. Increase in light transmittance was proportional to the amount of aggregation. Normal value of platelet aggregation (ADP or collagen) is 60%–90%.
All these hematologic parameters were compared between the study participants on single antiparkinsonian drug and those on multiple (two or more) antiparkinsonian drugs. Based on disease duration cut-off of 5 years, the coagulation parameters were assessed among those with early and advanced disease (<5 and ≥5 years of disease duration, respectively). Similarly, LEDD cut-off of 350 mg/day was used to compare the parameters between those on low dose and high dose of antiparkinsonian drugs (<350 and ≥350 mg/day of LEDD, respectively).
Statistical methods
Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) 14.0 Windows software (SPSS Inc.). Continuous variables were presented in terms of mean ± standard deviation. Categorical variables were expressed as proportions. The Student’s “t”-test was used to test the differences in continuous variables, and χ2 test was used to study the association in proportions. Pearson’s correlation coefficient was used to assess the correlation between various parameters. All tests were two sided, and a P value ≤ 0.05 was considered statistically significant.
Results
Demographic analysis
Demographic analysis of the study population is presented in Table 1.
Table 1.
Demographic analysis of the study population (n=68)
| Minimum–maximum | Mean±standard deviation | |
|---|---|---|
| Age | 25–80 years | 55.06±11.45 years |
| Disease duration | 0.5–24 years | 5.97±4.37 years |
| UPDRS Part-III off score | 20–79 | 50.75±10.98 |
| UPDRS Part-III on score | 6–40 | 21.95±7.96 |
| MoCA score | 18–30 | 27.94±2.15 |
| LEDD (mg/day) | 200–887.50 | 408.35±132.94 |
A total of 68 patients were included in our study, of whom 53 were male (77.9%) and 15 were female (22.1%). Mean age of the study participants was 55.06 ± 11.45 years. Mean disease duration was 5.97 ± 4.37 years. UPDRS Part-III mean “off” score was 50.75 ± 10.98 and mean “on” score was 21.95 ± 7.96. The mean LEDD was 408.35 ± 132.94. The MoCA score of the study population ranged between 18 and 30 with a mean value of 27.94 ± 2.15.
In our study group, patients were using different combinations of antiparkinsonian medications, which included levodopa with carbidopa, ropinirole, pramipexole, amantadine, safinamide, and entacapone. Twenty-three patients were using single antiparkinsonian drug, whereas 45 patients were using two or more antiparkinsonian medications. Out of 68 participants, 28 were considered as having an early disease (i.e., less than 5 years of disease duration), whereas 40 were considered to have an advanced disease (i.e., five or more years of disease duration). In our cohort, 23 patients were on low dose (i.e., LEDD of <350 mg/day), whereas 45 patients were on high dose (i.e., ≥350 mg/day of LEDD).
Hematologic parameters
The hematologic parameters of the patients are presented in Table 2. The hemoglobin (Hb) level in our study group was between 9.6 and 16.4 g/dl, and the platelet count was between 1.5 and 6.36 lakhs/mm3. Mean Hb and platelet counts were 13.28 ± 1.36 g/dl and 2.68 ± 0.84 lakhs/mm3, respectively.
Table 2.
Hematologic parameters (n=68)
| Parameter | Minimum–maximum | Mean±standard deviation |
|---|---|---|
| Hemoglobin (g/dl) | 9.6–16.4 | 13.28±1.36 |
| Platelet count (lakhs/mm3) | 1.5–6.36 | 2.68±0.84 |
| Prothrombin time (s) | 10.5–16 | 14.37±1.64 |
| Activated partial thromboplastin time (s) | 25–37.8 | 30.29±2.32 |
| Thrombin time (s) | 15–18 | 16.37±0.91 |
| Fibrinogen (mg/dl) | 209–540 | 340.75±64.71 |
| Platelet aggregation with ADP (%) | 2–99 | 62.11±17.25 |
| Platelet aggregation with collagen (%) | 1–99 | 62.13±16.93 |
ADP: adenosine diphosphate
PT of our study population ranged from 10.5 to 16 s, whereas aPTT ranged from 25 to 37.8 s. TT of the study participants was between 15 and 18 s. Mean values of PT, aPTT, and TT were 14.37 ± 1.64, 30.29 ± 2.32, and 16.37 ± 0.91 s, respectively.
Highest serum fibrinogen level was 540 mg/dl, whereas the lowest level was 209 mg/dl, with the mean serum fibrinogen level being 340.75 ± 64.71 mg/dl.
Platelet aggregation with ADP as the aggregating agent was between 2% and 99%, and platelet aggregation with collagen as the aggregating agent was between 1% and 99%. The mean values of platelet aggregation with ADP and collagen as aggregating agents were 62.11% ± 17.25% and 62.13% ± 16.93%, respectively.
Association between coagulation parameters and duration of the disease
The association between coagulation parameters and duration of the disease is shown in Table 3. In our study group, 28 were considered as having an early disease (i.e., less than 5 years of disease duration), whereas 40 were considered to have an advanced disease (i.e., five or more years of disease duration).
Table 3.
Association between coagulation parameters and duration of the disease
| Parameter | Disease duration (years) | Number of patients | Mean±Standard deviation | P |
|---|---|---|---|---|
| Hemoglobin (g/dl) | ≥5 | 40 | 12.97±1.40 | 0.022 |
| <5 | 28 | 13.72±1.19 | ||
| Platelet count (lakhs/mm3) | ≥5 | 40 | 2.54±0.78 | 0.127 |
| <5 | 28 | 2.86±0.92 | ||
| Prothrombin time (s) | ≥5 | 40 | 14.03±1.86 | 0.041 |
| <5 | 28 | 14.85±1.15 | ||
| Activated partial thromboplastin time (s) | ≥5 | 40 | 30.65±2.42 | 0.129 |
| <5 | 28 | 29.78±2.11 | ||
| Thrombin time (s) | ≥5 | 40 | 16.58±0.93 | 0.024 |
| <5 | 28 | 16.07±0.81 | ||
| Fibrinogen (mg/dl) | ≥5 | 40 | 324.20±64.72 | 0.011 |
| <5 | 28 | 364.39±57.94 | ||
| Platelet aggregation with ADP (%) | ≥5 | 40 | 59.05±19.94 | 0.080 |
| <5 | 28 | 66.50±11.44 | ||
| Platelet aggregation with collagen (%) | ≥5 | 40 | 58.73±20.59 | 0.047 |
| <5 | 28 | 67±7.57 | ||
| Bleeding time (s) | ≥5 | 40 | 117.88±29.59 | 0.562 |
| <5 | 28 | 113.21±36.14 |
ADP: adenosine diphosphate
Mean Hb value in patients with early disease (disease duration <5 years) was 12.97 g/dl and in those with advanced disease (disease duration ≥5 years) was 13.72 g/dl. This difference of 0.75 g/dl was statistically significant with a P value of 0.02.
Similarly, mean PT value was 14.85 s in those with early disease and 14.03 s in the patients with advanced disease. Difference in mean PT values (0.82 s) was statistically significant (P = 0.04).
Mean TT, platelet aggregation with collagen, and serum fibrinogen levels were 16.07 s, 67%, and 364.39 mg/dl, respectively, in patients with early disease. These values in patients with advanced disease were 16.58 s, 58.73%, and 324.20 mg/dl, respectively. Differences in mean TT (0.51 s), mean platelet aggregation with collagen (8.23%), and mean fibrinogen levels (40.2 mg/dl) were statistically significant with P values of 0.02, 0.04, and 0.01, respectively.
Association of coagulation parameters with LEDD
The association between coagulation parameters and LEDD is shown in Table 4. Out of 68 participants, 23 were on low dose (i.e., LEDD of <350 mg/day) and 45 were on high dose (i.e., ≥350 mg/day of LEDD).
Table 4.
Association between coagulation parameters and LEDD in milligrams per day
| Parameter | LEDD (mg/day) | Number of patients | Mean±Standard deviation | P |
|---|---|---|---|---|
| Hemoglobin (g/dl) | ≥350 | 45 | 12.99±1.21 | 0.012 |
| <350 | 23 | 13.85±1.48 | ||
| Platelet count (lakhs/mm3) | ≥350 | 45 | 2.72±0.91 | 0.541 |
| <350 | 23 | 2.59±0.72 | ||
| Prothrombin time (s) | ≥350 | 45 | 14.14±1.89 | 0.105 |
| <350 | 23 | 14.82±0.89 | ||
| Activated partial thromboplastin time (s) | ≥350 | 45 | 30.67±2.19 | 0.062 |
| <350 | 23 | 29.56±2.45 | ||
| Thrombin time (s) | ≥350 | 45 | 16.24±0.91 | 0.120 |
| <350 | 23 | 16.61±0.89 | ||
| Fibrinogen (mg/dl) | ≥350 | 45 | 342.35±65 | 0.777 |
| <350 | 23 | 337.60±65.49 | ||
| Platelet aggregation with ADP (%) | ≥350 | 45 | 63.82±14.53 | 0.258 |
| <350 | 23 | 58.78±21.62 | ||
| Platelet aggregation with collagen (%) | ≥350 | 45 | 65.29±12.75 | 0.030 |
| <350 | 23 | 55.96±22.09 | ||
| Bleeding time (s) | ≥350 | 45 | 110.78±28.38 | 0.064 |
| <350 | 23 | 126.09±37.39 |
ADP: adenosine diphosphate, LEDD: levodopa equivalent daily dose
Mean Hb value in patients on low dose (LEDD <350 mg/day) was 12.99 g/dl and in those on high dose (LEDD ≥350 mg/day) was 13.85 g/dl. This difference of 0.86 g/dl was statistically significant with a P value of 0.01.
Similarly, mean value of platelet aggregation with collagen was 65.29% in patients on high dose and 55.96% in those on low dose. Difference in mean values (9.33%) was statistically significant (P = 0.03).
LEDD showed a positive correlation with aPTT (r = 0.279, P = 0.02) and a negative correlation with Hb (r = -0.30, P = 0.013) and PT (r = -0.257, P = 0.035).
Association of coagulation parameters with the number of antiparkinsonian drugs
A total of 23 participants were using single antiparkinsonian drug, whereas 45 patients were using two or more antiparkinsonian medications.
More number of patients on two or more antiparkinsonian drugs (20%) had fibrinogen levels above the upper limit of 400 mg/dl, compared to those on single antiparkinsonian medication (4.3% of patients), but this did not reach statistical significance (P = 0.08). Shortened PT, that is, <12 s, was observed more frequently in patients using two or more antiparkinsonian drugs and this was statistically significant (P = 0.034). Similarly, shortened BT was more often seen in patients on multiple antiparkinsonian medications (73.3%) than in those on single medication (69.6%) (P = 0.74). Patients using multiple antiparkinsonian medications had an increased incidence of high platelet count (>4 lakhs/mm3) (P = 0.77) and increase in platelet aggregation with ADP (>90%) (P = 0.23).
Discussion
A total of 68 participants aged between 25 and 80 years were included in our study. Mean age of the participants was 55.06 ± 11.45 years. Patients included in our study were of lower age compared to the values reported in previous studies by Sato et al.,[12] in which the mean age of the study population was 59.7 years, Adams et al.,[13] and Sharma et al.,[14] where it was 66 and 69 years, respectively. This represents the possible increase in younger PD patients visiting movement disorders clinic.[15]
The mean UPDRS Part-III score of our study population was 50.75 ± 10.98 in the “off” state and 21.95 ± 7.96 in the “on” state. This suggests good response to levodopa in our patients with PD. The mean MoCA score of our study population was 27.94 ± 2.15. Most of the patients had normal cognition or mild cognitive impairment. Only one patient had severe cognitive impairment with a MoCA score of 18. The mean disease duration in our study population was 5.97 ± 4.37 years. This was longer compared to that reported in the study by Sato et al.,[12] in which the mean disease duration was 4.8 years.
Out of 68 participants, 23 were on low dose (i.e., LEDD of <350 mg/day) and 45 were on high dose (i.e., ≥350 mg/day of LEDD). Hb concentration was negatively associated with duration of the disease and LEDD. Chronic inflammation is described as one of the pathophysiologic mechanisms in PD.[16] This could be one of the reasons for low Hb in patients with long-standing disease. Added effect from reduced nutritional intake and lesser absorption due to poor gut motility might be responsible for reduction in Hb as the disease progresses. The mean Hb was 0.86 g/dl lesser in patients who were on LEDD of 350 mg or more per day [Table 4]. Hb and LEDD were negatively correlated (r = -0.3, P = 0.013) in our study. Henry et al.,[17] in their study on 80 PD patients using levodopa, showed that five patients developed anti-erythrocyte antibodies within the first year of levodopa therapy and one of them had anemia. One patient with anti-erythrocyte antibodies had resolution of these antibodies 2 months after stopping levodopa. Vitamin B12 and folic acid deficiencies[18] have also been described previously with long-standing PD and increased LEDD. Although the assessment of anti-erythrocyte antibodies, vitamin B12, and folic acid levels was not done in our study, these factors might have contributed to anemia.
In our study, PT was negatively associated with LEDD and duration of the disease. The mean PT was 14.85 s in patients with PD for less than 5 years, whereas it was 14.03 s in patients with disease duration of 5 years or more [Table 3]. Similarly, increased LEDD, which was associated with longer disease duration, was negatively correlated with PT (r = -0.25). This suggests that longer disease duration and higher LEDD might lower PT.
In our study, aPTT and LEDD were positively correlated (r = 0.27). This suggests an increased activation of the extrinsic pathway and a reduced activation of the intrinsic pathway. LEDD showed a positive association with collagen-induced platelet aggregation. The mean value of collagen-induced platelet aggregation was 9.33% higher in patients taking 350 mg or more of LEDD compared to patients who were taking less than 350 mg of LEDD. This suggests a positive influence by antiparkinsonian medication on platelet aggregation (P = 0.03). We also observed that the mean value of platelet aggregation with ADP was higher in patients taking LEDD of 350 mg or more compared to those using LEDD of less than 350 mg (P = 0.25). In our study, LEDD showed a positive association with platelet count and fibrinogen levels and a negative association with TT and BT, but these were statistically not significant. All these findings suggest an increased tendency for thrombosis in patients using higher doses of antiparkinsonian medications.
In our study, 36.76% patients were on single antiparkinsonian medication and the rest were on two or more antiparkinsonian drugs. PT was low in patients on multiple drugs compared to those on single antiparkinsonian medication (P = 0.034). Fibrinogen levels were higher in patients on multiple drug therapy compared to those on single drug therapy. Fibrinogen levels were raised above normal limits (>400 mg/dl) in 20% of patients on two or more drugs and 4.3% of patients on a single drug (P = 0.08). We noticed that higher proportion of patients on multiple drugs had shortened BT (<2 min) (P = 0.74). Higher platelet count was more frequently observed in patients on multiple drugs (4.4%) compared to those on a single drug (4.3%). But this was not significant statistically (P = 0.77). These results indicate that using multiple antiparkinsonian drugs might have a prothrombotic effect in patients with PD.
Our study is one of the first to suggest these alterations. Sato et al.[12] showed an increase in plasmin–antiplasmin complexes and D-dimers in PD patients on antiparkinsonian medication compared to those not on medication. Mean values of plasmin–antiplasmin complexes and D-dimers were higher in patients on levodopa and pramipexole combination compared to patients on either drug alone. Sharma et al.[14] also showed increased plasmin–antiplasmin complexes in patients with PD, suggesting increased activity of fibrinolytic system.
In our cohort, 28 were considered as having an early disease (i.e., less than 5 years of disease duration), whereas 40 were considered to have an advanced disease (i.e. five or more years of disease duration). Hb and PT were negatively associated with duration of disease, with P values of 0.02 and 0.04, respectively. We observed an increase in TT, decrease in fibrinogen, and reduced platelet aggregation with collagen with increase in disease duration. These observations were statistically significant with P values of 0.02, 0.01, and 0.04, respectively. These results suggest that duration of the disease had varied effects on coagulation parameters.
In our study, we excluded patients with history of cerebrovascular or cardiovascular or peripheral vascular diseases. However, 15 patients (22.05%) had hypertension and 12 patients (17.65%) had both hypertension and diabetes mellitus. Though we did not assess the lipid profile in our patients, none of them had history of dyslipidemia as per their old medical records or was on any medication for managing dyslipidemia. Eighteen (26.47%) of our patients were former smokers and the rest of them never smoked in their lifetime. Thirty (44.12%) of our patients gave history of occasional and infrequent consumption of alcohol; however, none of them had any alcohol use disorder in the past. These are some of the widely prevalent lifestyle diseases that might have an influence on coagulation parameters.
Neuroinflammation is considered as one of the crucial factors involved in the pathogenesis of other degenerative diseases like Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease.[19] Gupta et al.[20] studied the coagulation and inflammatory markers in patients with Alzheimer’s and vascular dementia. They found significantly elevated factor VII, prothrombin factors 1 and 2, and fibrin degradation products in patients with Alzheimer’s and vascular dementia, suggesting ongoing systemic inflammation and a hypercoagulable state.
There were some limitations in our study because of its small sample size and cross-sectional nature. This study was conducted during the coronavirus epidemic. Moreover, stringent exclusion criteria made our sample size small. Statistically significant changes in PT and aPTT were observed, but these changes were within the normal range most of the time. Individual variations can exist and these could not be addressed. Multivariate analysis could not be done due to the small sample size. Larger sample size and long-term follow-up might help in overcoming these limitations.
Conclusions
Literature regarding coagulation parameters in PD is very scarce. To the best of our knowledge, this study is the first of its kind analyzing all these hematologic parameters in patients with PD. The effect of PD and antiparkinsonian drugs on hemostatic system seems to be complex, affecting platelet aggregation, intrinsic pathway, and extrinsic pathway. More number of studies are required to confirm these findings.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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