TY - JOUR

T1 - Ex vivo effect of hemostatic therapy in subarachnoid and intracerebral hemorrhage

AU - Hvas, Christine Lodberg

AU - Lauridsen, Signe Voigt

AU - Pedersen, Emilie Sandgaard

AU - Gyldenholm, Tua

AU - Hvas, Anne Mette

N1 - Funding Information: We thank Mai Stenulm Veirup and Vivi Bo Mogensen for assistance in titration experiments and design of the ex vivo spiking experiments. We thank doctors, nurses and healthcare personnel at the Department of Neurology and the Department of Neurosurgery, Danish Stroke Centre at Aarhus University Hospital, Denmark, for their cooperation and assistance during enrolment procedures. We thank CLS Behring and Octapharma for financial research support and providing. Funding Information: The project was generously funded by Aarhus University , The Lippman Foundation , the Director Emil C. Hertz and Hustru Inger Hertz's Foundation, the Doctor Sofus Carl Emil Friis & Wife Olga Doris Friis Foundation , the Aase & Ejnar Danielsen's Foundation , the Director Werner Richter & Wife Foundation , the Danish Society of Anaesthesiology and Intensive Care Foundation (DASAIM), the Holger & Ruth Hesse's Memorial Foundation , the Lily Benthine Lund's Foundation of 1.6.1978, The Letterstedtske Foundation , King Christian the X's Foundation , CSL Behring and Octapharma . Publisher Copyright: © 2020 Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/5

Y1 - 2020/5

N2 - Background: Rebleeding 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. Aim: Firstly, 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. Methods: Blood 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. Results: Patients 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. Conclusion: Patients 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.

AB - Background: Rebleeding 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. Aim: Firstly, 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. Methods: Blood 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. Results: Patients 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. Conclusion: Patients 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.

KW - Blood coagulation

KW - Ex vivo

KW - Hemostatic agents

KW - Intracerebral hemorrhage

KW - Subarachnoid hemorrhage

UR - http://www.scopus.com/inward/record.url?scp=85080988828&partnerID=8YFLogxK

U2 - 10.1016/j.thromres.2020.02.012

DO - 10.1016/j.thromres.2020.02.012

M3 - Journal article

C2 - 32163792

AN - SCOPUS:85080988828

VL - 189

SP - 42

EP - 47

JO - Thrombosis Research. Supplement

JF - Thrombosis Research. Supplement

SN - 0896-0569

ER -