Differential effects of in vitro norepinephrine on platelets isolated from severely traumatic brain injured patients

Introduction

Norepinephrine used in clinical routine to increase cerebral perfusion following severe traumatic brain injury (TBI) may activate α₂-adrenergic receptors on platelets, thereby possibly promoting formation of microthrombosis and inducing additional brain injury.

Methods

Arterial and jugular venous platelets isolated from norepinephrine-receiving TBI patients (n = 11) and healthy volunteers (n = 36) (cubital vein) were stimulated in vitro with increasing norepinephrine concentrations (10 nM to 100 μM); thrombin receptor activator peptide (TRAP) served as positive control. P-selectin expression was determined by flow cytometry (FACS).

Results

Following TBI, the number of unstimulated P-selectin-positive platelets was significantly decreased in the second week by 60%. During the first week, the in vitro stimulatory effect was significantly reduced; in the second week, however, norepinephrine-mediated effects exceeded changes in controls and the first week without a difference between arterial and jugular venous platelets (Figure 1).

Figure 1

Changes in P-selectin expression in isolated platelets stimulated in vitro with norepinephrine or TRAP. +P < 0.001 vs low-dose norepinephrine; *P < 0.001 vs controls; #P < 0.001 vs first week.

Conclusion

Clinically relevant norepinephrine concentrations are <25 nM. The present in vitro effects occurred at concentrations >500 nM. Thus, a clinically relevant impact appears doubtful.