VTE event risk up in PD patients

Researchers from Singapore found an elevated risk of venous thromboembolism (VTE) events in individuals with Parkinson’s disease (PD) in a systematic review and meta-analysis of 13 studies.

The pooled relative risk (RR) for VTE was significantly higher in PD patients than controls (1.97; p<0.01), as was for deep venous thrombosis (DVT) events (RR, 2.20; p<0.01), but for pulmonary embolism (PE) events, it failed to reach statistical significance (RR, 1.88; p=0.33).

Furthermore, the risks of VTE, DVT, and PE events were consistently elevated in surgical settings (RRs, 1.74, 1.86, and 1.88). [Eur J Neurol 2025;doi:10.1111/ene.70047]

According to the investigators, these effects may have been driven by immobility, autonomic dysfunction, inflammatory changes, endothelial dysfunction, medication side effects, genetic predisposition, dehydration, and impaired respiratory function.

“PD patients are likely to have reduced mobility as they experience relative impairments in posture, balance, and gait, leading to a greater risk of falls … With reduced mobility, PD patients are likely to have greater venous stasis … thus leading to greater [VTE] events,” they said.

Pro-coagulation states may be triggered by inflammation and certain genes implicated in PD. [Front Pediatr 2018;6:142; J Clin Med 2022;11:6920] Anticholinergics, which are commonly prescribed in PD, may contribute to dehydration, which, in turn, may increase blood viscosity and promote clot formation. [J Clin Med 2019;8:1923]

Subgroup analyses

On subgroup analyses based on study designs, VTE risk was highest in cross-sectional than cohort and case-control studies (RRs, 5.31 vs 1.51 and 1.59), as was DVT risk (RRs, 6.54 vs 1.45 and 1.42). For PE, case-control and cross-sectional studies had similar outcomes (RRs, 1.74 and 1.71).

However, the elevated risk observed in cross-sectional studies may have been an overestimation due to the studies’ limitations. [Indian J Dermatol 2016;61:261-264] The similar risk estimates between cohort and case-control studies may signal a more reliable assessment of the true thromboembolic risk in PD patients. “The lack of a significant difference between these two study designs suggests that either design may [effectively] estimate thromboembolic risk in PD,” said the researchers.

In the analyses based on surgical settings, compared with PD patients who had non-neurological surgeries (eg, total knee arthroplasty), those who underwent neurological surgeries (eg, deep brain stimulation, spinal surgeries) had numerically higher risks of VTE (RRs, 1.99 vs 1.42) and DVT (RRs, 2.34 vs 1.18). However, the comparisons did not achieve statistical significance (p=0.35 and p=0.08, respectively).

“These results underscore the heightened vulnerability of PD patients to thromboembolic complications after surgical procedures, likely due to a combination of factors co-shared between PD and surgery, such as reduced mobility and autonomic dysfunction,” the researchers noted. The elevated VTE risk following neurological surgeries may also be due to longer durations and delayed ambulation post-surgery. [Malays J Med Sci 2019;26:139-147]

Heightened vigilance for VTE events in PD

The 13 studies included in the analysis comprised 775,144 participants. Seven were cohort studies, two were cross-sectional, and four were case-control studies.

“[This analysis implies that] incorporating PD as a potential risk factor in clinical tools like the modified Well’s score could improve identification of at-risk patients and guide implementation of targeted prophylactic measures, especially in current clinical practice where it is not considered,” the investigators said. “Moreover, clinicians should have heightened vigilance for VTE events while treating PD patients.”

It would be imperative to identify key factors contributing to thromboembolic risk in PD patients in future studies, they added. “Developing and validating tailored strategies for VTE prevention and management in both surgical and nonsurgical settings would be useful. It would also be useful to evaluate the long-term effects of VTE events in PD patients and potential effects on cognition and other neuropsychiatric complications in longitudinal studies.”