PMID- 10520784
OWN - NLM
STAT- MEDLINE
DCOM- 19991027
LR  - 20190708
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 34
IP  - 4
DP  - 1999 Oct
TI  - Thrombin generation after the abrupt cessation of intravenous unfractionated 
      heparin among patients with acute coronary syndromes: potential mechanisms for 
      heightened prothrombotic potential.
PG  - 1020-7
AB  - OBJECTIVES: The purpose of this study was to determine the mechanistic basis for 
      thrombin generation and increased prothrombotic potential after the abrupt 
      cessation of intravenous (i.v.) unfractionated heparin among patients with acute 
      coronary syndromes. BACKGROUND: A "rebound" increase in prothrombotic potential 
      has been observed biochemically and clinically after the abrupt cessation of 
      unfractionated heparin (UFH) among patients with acute coronary syndromes. 
      Although the mechanism is unknown, tissue factor and the extrinsic coagulation 
      cascade, both operative in atherosclerotic vascular disease and arterial 
      thrombosis, are thought to be centrally involved. METHODS: In a single-center, 
      pilot study, 30 patients with either unstable angina or non-ST segment elevation 
      myocardial infarction who had received a continuous i.v. infusion of UFH for 48 h 
      were randomly assigned to: 1) abrupt cessation, 2) i.v. weaning over 12 h or 3) 
      subcutaneous weaning over 12 h. RESULTS: Thrombin generation (prothrombin 
      fragment 1.2) was evident within 1 h of UFH cessation, increased progressively 
      (by nearly two-fold) at 24 h (p = 0.002) and correlated inversely with tissue 
      factor pathway inhibitor concentration (r = -0.61). Thrombin generation was 
      greatest among patients randomized to abrupt cessation (1.6-fold increase at 24 
      h) and least in those with i.v. weaning. CONCLUSIONS: Thrombin generation after 
      the abrupt cessation of UFH may represent a drug-induced impairment of 
      physiologic vascular thromboresistance in response to locally generated tissue 
      factor. A dosing strategy of abbreviated i.v. weaning attenuates but does not 
      prevent heparin rebound among patients with acute coronary syndromes.
FAU - Becker, R C
AU  - Becker RC
AD  - Cardiovascular Thrombosis Research Center, Laboratory for Vascular Biology 
      Research, University of Massachusetts Medical School, Worcester 01655, USA. 
      richard.becker@banyan.ummed.edu
FAU - Spencer, F A
AU  - Spencer FA
FAU - Li, Y
AU  - Li Y
FAU - Ball, S P
AU  - Ball SP
FAU - Ma, Y
AU  - Ma Y
FAU - Hurley, T
AU  - Hurley T
FAU - Hebert, J
AU  - Hebert J
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Anticoagulants)
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Lipoproteins)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
CIN - J Am Coll Cardiol. 2001 Jun 1;37(7):2007-8. PMID: 11401148
MH  - Adult
MH  - Aged
MH  - Angina, Unstable/blood/drug therapy
MH  - Anticoagulants/administration & dosage/*adverse effects/blood
MH  - Blood Coagulation Factors/metabolism
MH  - Coronary Disease/blood/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Heparin/administration & dosage/*adverse effects/blood
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Subcutaneous
MH  - Lipoproteins/blood
MH  - Male
MH  - Middle Aged
MH  - Myocardial Infarction/blood/*drug therapy
MH  - Partial Thromboplastin Time
MH  - Pilot Projects
MH  - Substance Withdrawal Syndrome/*blood
MH  - Thrombin/*metabolism
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - S0735-1097(99)00322-8 [pii]
AID - 10.1016/s0735-1097(99)00322-8 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 1999 Oct;34(4):1020-7. doi: 10.1016/s0735-1097(99)00322-8.