Can Pembrolizumab Cause Vein Injury?
Yes, pembrolizumab can cause vascular injury, including acute thrombosis and vasculitis, though these are rare immune-related adverse events occurring in less than 1% of patients. 1, 2
Documented Vascular Complications
Acute Thrombosis
- Pembrolizumab-induced acute thrombosis has been documented in NSCLC patients, presenting as an immune-related adverse event (irAE) requiring immediate anticoagulation with continuous heparin infusion 1
- The mechanism involves reinvigoration of exhausted T cells by pembrolizumab, inducing systemic inflammation that can result in thrombosis development 1
- Patients successfully continued pembrolizumab treatment with direct oral anticoagulants (DOACs) after initial heparin therapy, achieving tumor shrinkage 1
Vasculitis
- Pembrolizumab-induced acral vasculitis is an extremely rare but potentially fatal complication, occurring in less than 1% of cases 2
- Two documented cases presented 4-7 months after pembrolizumab initiation, both resulting in dry gangrene and poor outcomes 2
- One case was associated with positive antinuclear antibody (ANA) testing 2
- Early diagnosis and discontinuation of pembrolizumab are critical for improving clinical outcomes in vasculitis cases 2
Pulmonary Vascular Injury
- Pembrolizumab can cause pulmonary hypertension as a rare cardiopulmonary immune-related adverse event, which carries high mortality rates 3
Clinical Context from Guidelines
General Adverse Event Profile
- The most common adverse events with pembrolizumab include fatigue, pruritus, diarrhea, rash, and fever—not typically vascular complications 4
- Immune-mediated adverse events more commonly involve colitis, hepatitis, endocrinopathies, pneumonitis, or nephritis 4
Contraindications Related to Vascular Involvement
- Pembrolizumab has not been studied in patients with main portal vein invasion or inferior vena cava involvement and should be avoided in these populations 5
- Patients with cardiac involvement of HCC were excluded from major trials 5
Monitoring and Management Algorithm
When to Suspect Vascular Injury
- Monitor for signs of thrombosis: leg swelling, pain, dyspnea, or chest pain during pembrolizumab treatment 1
- Watch for acral vasculitis: digital ischemia, purpura, or skin necrosis on extremities 2
- Consider serum D-dimer testing and venous ultrasonography if thrombosis is suspected 1
- Enhanced CT imaging may be necessary for comprehensive vascular assessment 1
Immediate Management
- For acute thrombosis: initiate continuous heparin infusion immediately, transition to DOACs for long-term management, and pembrolizumab may be continued with anticoagulation 1
- For vasculitis: discontinue pembrolizumab immediately, as continuation can lead to gangrene and fatal outcomes 2
Risk Context
- Fatal adverse events with pembrolizumab occur in 1.2% of patients overall, with infectious complications (26.5%), cardiac toxicity (14.7%), and pneumonitis (13.2%) being more common than vascular events 6
- The risk of fatal adverse events increases to 7.0% when pembrolizumab is combined with chemotherapy versus 0.7% with pembrolizumab alone 6