title: Using antifibrinolytics in the peripartum period - concern for a hypercoagulable effect?
abstract: BACKGROUND
  Although antifibrinolytic agents are used to prevent and treat hemorrhage, there are concerns about a potential increased risk for peripartum venous thromboembolism. We sought to determine the impact of tranexamic acid and ɛ-aminocaproic acid on in vitro clotting properties in pregnancy.
  
  
  METHODS
  Blood samples were obtained from healthy pregnant, obese, and preeclamptic pregnant women (n = 10 in each group) prior to delivery as well as from healthy non-pregnant controls (n = 10). Maximum clot firmness (MCF) and clotting time (CT) were measured using rotation thromboelastometry in the presence of tranexamic acid (3, 30, or 300 μg/mL) or ɛ-aminocaproic acid (30, 300, or 3000 μg/mL). ANOVA and regression analyses were performed.
  
  
  RESULTS
  Mean whole blood MCF was significantly higher in healthy pregnant vs. non-pregnant women (66.5 vs. 57.5 mm, p < 0.001). Among healthy pregnant women, there was no significant difference between mean MCF (whole blood alone, and with increasing tranexamic acid doses = 66.5, 66.1, 66.4, 66.3 mm, respectively; p = 0.25) or mean CT (409, 412, 420, 424 sec; p = 0.30) after addition of tranexamic acid. Similar results were found using ɛ-aminocaproic acid. Preeclamptic women had a higher mean MCF after the addition of ɛ-aminocaproic acid and tranexamic acid (p = 0.05 and p = 0.04, respectively) compared to whole blood alone.
  
  
  CONCLUSIONS
  Pregnancy is a hypercoagulable state, as reflected by an increased MCF compared to non-pregnant women. Addition of antifibrinolytic therapy in vitro does not appear to increase MCF or CT for non-pregnant, pregnant, and obese women. Whether antifibrinolytics are safe in preeclampsia may require further study.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Duke University, Durham, NC, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Ahmadzia
authors.affiliation: Department of Pathology, Division of Pathology Clinical Services, Duke University, Durham, NC, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Lockhart
authors.affiliation: Department of Biostatistics, Duke University, Durham, NC, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Thomas
authors.affiliation: Department of Anesthesiology, Division of Cardiac Anesthesiology, Duke University, Durham, NC, USA.
authors.forename: I J
authors.initials: IJ
authors.lastname: Welsby
authors.affiliation: Department of Pathology, Division of General Pathology, Duke University Durham, NC, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Hoffman
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Duke University, Durham, NC, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: James
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Duke University, Durham, NC, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Murtha
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Duke University, Durham, NC, USA.
authors.forename: G K
authors.initials: GK
authors.lastname: Swamy
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Duke University, Durham, NC, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Grotegut
mesh_terms: D000328:Adult; D015119:Aminocaproic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D016022:Case-Control Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009765:Obesity / Q000097:blood; D058725:Peripartum Period; D006473:Postpartum Hemorrhage / Q000188:drug therapy / Q000517:prevention & control; D011225:Pre-Eclampsia / Q000097:blood; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood; D011263:Pregnancy Trimester, Third; D013916:Thrombelastography; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014148:Tranexamic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000933:Antifibrinolytic Agents; D005343:Fibrinolytic Agents; D014148:Tranexamic Acid; D010959:Tissue Plasminogen Activator; D015119:Aminocaproic Acid
keywords: Antifibrinolytic therapy; maximum clot firmness; postpartum haemorrhage; thromboelastometry; tranexamic acid