Post-TBI splenectomy may exacerbate coagulopathy and platelet activation in a murine model

Abstract

Introduction: Traumatic brain injury (TBI) induces acute hypocoagulability, subacute hypercoagulability, and persistently elevated risk for thromboembolic events. Splenectomy is associated with increased mortality in patients with moderate or severe TBI. We hypothesized that the adverse effects of splenectomy in TBI patients may be secondary to the exacerbation of pathologic coagulation and platelet activation changes.

Methods: An established murine weight-drop TBI model was utilized and a splenectomy was performed immediately following TBI. Sham as well as TBI and splenectomy alone mice were used as injury controls. Mice were sacrificed for blood draws at 1, 6, and 24 h, as well as 7 days post-TBI. Viscoelastic coagulation parameters were assessed by rotational thromboelastometry (ROTEM) and platelet activation was measured by expression of P-selectin via flow cytometry analysis of platelet rich plasma samples.

Results: At 6 h following injury, TBI/splenectomy demonstrated hypocoagulability with prolonged clot formation time (CFT) compared to TBI alone. By 24 h following injury, TBI/splenectomy and splenectomy mice were hypercoagulable with a shorter CFT, a higher alpha angle, and increased MCF, despite a lower percentage of platelet contribution to clot compared to TBI alone. However, only the TBI/splenectomy continued to display this hypercoagulable state at 7 days. While TBI/splenectomy had greater P-selectin expression at 1-h post-injury, TBI alone had significantly greater P-selectin expression at 24 h post-injury compared to TBI/splenectomy. Interestingly, P-selectin expression remained elevated only in TBI/splenectomy at 7 days post-injury.

Conclusion: Splenectomy following TBI exacerbates changes in the post-injury coagulation state. The combination of TBI and splenectomy induces an acute hypocoagulable state that could contribute to an increase in intracranial bleeding. Subacutely, the addition of splenectomy to TBI exacerbates post-injury hypercoagulability and induces persistent platelet activation. These polytrauma effects on coagulation may contribute to the increased mortality observed in patients with combined brain and splenic injuries.

Keywords: Coagulopathy; Platelets; Rotational thromboelastometry; Splenectomy; Traumatic brain injury.