title: The impact on coagulation of an intravenous loading dose in addition to a subcutaneous regimen of low-molecular-weight heparin in the initial treatment of acute coronary syndromes.
abstract: OBJECTIVE
  We sought to quantify the impact of adding an intravenous loading dose to a subcutaneous regimen of enoxaparin in patients with an acute coronary syndrome (ACS).
  
  
  BACKGROUND
  It is unclear whether an intravenous (i.v.) loading dose of enoxaparin should be added to a subcutaneous (s.c.) regimen in patients with ACS.
  
  
  METHODS
  Patients admitted with ACS were randomized to i.v.+s.c.(n = 14) or s.c. alone (n = 11) enoxaparin treatment. Coagulation markers were measured at nine time points during the first 24 h of treatment.
  
  
  RESULTS
  The i.v.+s.c. therapy immediately resulted in therapeutic anti-Xa levels, which remained significantly higher for 6 h compared with s.c. alone, without reaching excessively high levels. A rapid decrease of plasma prothrombin fragments 1+2 (F(1+2)) levels was observed as soon as 5 min after the i.v. injection (33% lower; p = 0.007), and these levels remained lower up to 2 h after the start of treatment compared with SQ alone. The ex vivo thrombin generation time was maximally prolonged at 5 min post-injection in the i.v.+s.c. group and remained significantly prolonged up to 6 h post-injection compared with s.c. alone. The tissue factor pathway inhibitor plasma activity was immediately increased by 194% with i.v.+s.c., whereas the maximum increase with s.c. alone was 47% at 3 h.
  
  
  CONCLUSIONS
  Therapeutic plasma levels of enoxaparin are achieved significantly earlier by an i.v.+s.c. regimen compared with s.c. alone, without leading to unacceptably high levels. As the risk of thrombotic complications is greatest early after admission, the observed differences in antithrombotic effects may translate into a clinical benefit. However, this remains to be established.
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands. n.r.bijsterveld@amc.uva.nl
authors.forename: Nick R
authors.initials: NR
authors.lastname: Bijsterveld
authors.forename: Arno H
authors.initials: AH
authors.lastname: Moons
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
authors.forename: Ron J G
authors.initials: RJ
authors.lastname: Peters
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy*; D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D017984:Enoxaparin / Q000008:administration & dosage*; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D011516:Prothrombin / Q000378:metabolism; D013925:Thromboplastin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D011516:Prothrombin; D013925:Thromboplastin; D015951:Factor Xa