Year: 2023
Type: article
Abstract: BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. The World Maternal Antifibrinolytic trial showed that antifibrinolytic tranexamic acid (TXA) reduces PPH deaths. Maternal anemia increases the risk of PPH. The World Maternal Antifibrinolytic-2 trial is now assessing whether TXA can prevent PPH in women with anemia. Low red blood cell (RBC) counts promote fibrinolysis by altering fibrin structure and plasminogen activation. OBJECTIVES: We explored interactions between RBCs and TXA in inhibiting fibrinolysis. METHODS: We used global fibrinolytic assays (ball sedimentation and viscoelasticity) to monitor the lysis of fibrin containing plasminogen and tissue-type plasminogen activator. We applied a fluorogenic kinetic assay to measure plasmin generation in fibrin clots and scanning electron microscopy to study fibrin structure. RESULTS: According to parallel-line bioassay analysis of the fibrin lysis-time data, the antifibrinolytic potency of 4-128 μM TXA was increased in the presence of 10% to 40% (v/v) RBCs. Global fibrinolysis assays showed that the joint effect of RBCs and TXA was about 15% larger than the sum of their individual effects in the inhibition of fibrinolysis. In plasminogen activation, TXA added the same increment of inhibition to the effect of RBCs at any cell count in the fibrin clot. Regarding fibrin structure, TXA thickened fibrin fibers, which impaired plasminogen activation, whereas RBCs promoted fine fibers that were more resistant to plasmin. CONCLUSIONS: The antifibrinolytic potency of TXA is enhanced in fibrin formed in the presence of RBCs through inhibition of plasminogen activation and fibrin lysis, which correlates with modifications of fibrin structures.
Institutions: Semmelweis University, National Institute for Biological Standards and Control, London School of Hygiene & Tropical Medicine, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, University of Tasmania, Australian Maritime College, Nikola Vaptsarov Naval Academy, Defence Science and Technology Group
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,750
Awards: CRASH-4 trial (Clinical Randomisation of an Anti-fibrinolytic in Symptomatic mild Head injury in older adults)
Intramuscular tranexamic acid for the treatment of symptomatic mild traumatic brain injury in older adults: a randomised, double-blind, placebo-controlled trial, G134384773, G1618036359, G2898078231, G3463726684, G3744551884, The CRASH-3 Trial: Tranexamic acid for the treatment of significant traumatic brain injury., G4706417285, G4862200628, CRASH2 Trial, a large randomised placebo controlled trial among trauma patients with significant haemorrhage of the effects of an antifibrinolytic treatment on death and transfusion requirement, G6686244781, NIHR Senior Investigator Award, The CRASH-3 Trial: Tranexamic acid for the treatment of significant traumatic brain injury, G7596933463, G7694217703, G8406587161
OpenAlex ID: W4389028219