Ex vivo effect of hemostatic therapy in subarachnoid and intracerebral hemorrhage

Abstract

BackgroundRebleeding and hematoma growth are serious complications in subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). As treatment options are sparse, a mechanistic approach may reveal new therapeutic targets. AimFirstly, to evaluate hemostasis using a sensitive low tissue factor thromboelastometry (ROTEM®) assay in patients with SAH or ICH and compare them with healthy controls. Secondly, to investigate the ex vivo effect of hemostatic or antifibrinolytic medications in blood from patients with SAH or ICH. MethodsBlood was drawn on admission to hospital in patients with SAH (n = 39) or ICH (n = 35). We included 41 sex and age matched healthy controls for comparison. A low tissue factor (diluted 1:100,000) ROTEM® assay was run in patients and healthy controls. In parallel, coagulation factor XIII, fibrinogen concentrate, prothrombin complex concentrate, and recombinant soluble thrombomodulin were added in concentrations equivalent to doses used in clinical practice. ResultsPatients with SAH or ICH demonstrated a hypercoagulable profile indicated by significantly shorter clotting time, faster maximum velocity, shorter time to maximum velocity, and higher maximum clot firmness than healthy controls (all p-values <.0001). Ex vivo addition of coagulation factor XIII, fibrinogen concentrate, prothrombin complex concentrate, and recombinant soluble thrombomodulin, respectively, did not improve the hemostatic potential in patients with SAH or ICH. ConclusionPatients with SAH or ICH demonstrated a hypercoagulable state in the systemic circulation as evaluated by a sensitive low tissue factor assay. Ex vivo addition of hemostatic medication did not further improve coagulation.