Risk of Thrombosis with Angiotensin II Use
Based on current evidence, angiotensin II (Ang 2) does not appear to significantly increase thrombotic risk compared to conventional vasopressors in critically ill patients with distributive shock, though vigilance remains warranted given limited long-term safety data.
Evidence from Clinical Studies
Thromboembolism Incidence
In the ARAMIS pilot study comparing Ang 2 as primary vasopressor versus conventional agents, the incidence of thromboembolic complications was similar between groups, suggesting no excess thrombotic risk with Ang 2 use 1.
The available literature on Ang 2 in septic shock has not demonstrated a clear signal for increased venous thromboembolism, though this remains an area requiring further investigation with longer follow-up periods 2.
Comparative Safety Profile
When used as primary vasopressor in 40 critically ill adults with vasodilatory hypotension, Ang 2 demonstrated lower ICU mortality (10% vs 26%, P = 0.04) compared to conventional vasopressors, without increased thrombotic complications 1.
Ang 2 patients had less frequent serum troponin elevations (8% vs 22%, P = 0.04), suggesting potential cardiovascular protective effects rather than increased thrombotic risk 1.
Clinical Context and Monitoring
Baseline Thrombotic Risk in Sepsis
Patients with severe sepsis and septic shock inherently carry high thrombotic risk due to endothelial activation, coagulopathy, and inflammatory responses 3.
The Surviving Sepsis Campaign guidelines recommend against antithrombin administration due to increased bleeding risk when combined with heparin, without mortality benefit 4, 5.
Standard VTE Prophylaxis Applies
All critically ill patients with septic shock should receive standard thromboprophylaxis with LMWH or unfractionated heparin unless contraindicated 4.
For COVID-19 patients (as a model for severe inflammatory states), LMWH is preferred over UFH for VTE prophylaxis in critically ill patients 4.
Practical Recommendations
When Using Ang 2
Continue standard VTE prophylaxis protocols as you would with any vasopressor - there is no evidence requiring modification of thromboprophylaxis specifically for Ang 2 use 1.
Monitor for signs of thromboembolism using the same clinical vigilance applied to patients on catecholamine vasopressors 2.
Consider that Ang 2 may be particularly useful in patients with prior renin-angiotensin-aldosterone system inhibitor exposure, who showed better renal outcomes in observational data 1.
Unanswered Questions
Larger randomized trials with extended follow-up are needed to definitively establish the long-term thrombotic safety profile of Ang 2, particularly regarding effects on microcirculation and venous thromboembolism risk 2, 6.
Current evidence suggests Ang 2 should be reserved for salvage therapy in refractory septic shock until more robust comparative safety data become available 7.
Key Caveat
The distinction between Ang 2 (angiotensin II vasopressor) and angiopoietin 2 (Ang-2, an endothelial activation marker) is critical - the latter is a biomarker associated with coagulopathy severity in sepsis 3, while the former is the therapeutic vasopressor agent with no demonstrated increase in thrombotic complications 1.