The α-globin chain of hemoglobin potentiates tissue plasminogen activator induced hyperfibrinolysis in vitro

BACKGROUND

Severe injury predisposes patients to trauma-induced coagulopathy, which may be subdivided by the state of fibrinolysis. Systemic hyperfibrinolysis (HF) occurs in approximately 25% of these patients with mortality as high as 70%. Severe injury also causes the release of numerous intracellular proteins, which may affect coagulation, one of which is hemoglobin, and hemoglobin substitutes induce HF in vitro. We hypothesize that the α-globin chain of hemoglobin potentiates HF in vitro by augmenting plasmin activity.

METHODS

Proteomic analysis was completed on a pilot study of 30 injured patients before blood component resuscitation, stratified by their state of fibrinolysis, plus 10 healthy controls. Different concentrations of intact hemoglobin A, the α- and β-globin chains, or normal saline (controls) were added to whole blood, and tissue plasminogen activator (tPA)–challenged thrombelastography was used to assess the degree of fibrinolysis. Interactions with plasminogen (PLG) were evaluated using surface plasmon resonance. Tissue plasminogen activator–induced plasmin activity was evaluated in the presence of the α-globin chain.

RESULTS

Only the α- and β-globin chains increased in HF patients (p

Source: The Journal of Trauma: Injury, Infection, and Critical Care - December 28, 2021 Category: Orthopaedics Tags: ORIGINAL RESEARCH: INDEPENDENT SUBMISSIONS Source Type: research