PMID- 9462526
OWN - NLM
STAT- MEDLINE
DCOM- 19980223
LR  - 20201209
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 97
IP  - 3
DP  - 1998 Jan 27
TI  - Platelet activation with unfractionated heparin at therapeutic concentrations and 
      comparisons with a low-molecular-weight heparin and with a direct thrombin 
      inhibitor.
PG  - 251-6
AB  - BACKGROUND: The growing use of heparin in acute thrombotic disorders, coupled 
      with the availability of many new antithrombotic agents, emphasizes the need for 
      adequate characterization of the platelet effects of the various anticoagulants. 
      Controversial platelet effects have been reported with heparin (eg, enhanced 
      platelet activation in vitro with high doses and no such effect in vivo at 
      therapeutic doses). This study examined platelet receptor activation and platelet 
      aggregation at therapeutic concentrations of unfractionated heparin (UFH), of 
      enoxaparin, a low-molecular-weight heparin, and of argatroban, a direct thrombin 
      inhibitor. METHODS AND RESULTS: Platelet P-selectin (CD62) and activated GP 
      IIb/IIIa (PAC-1) expression on platelet membrane was quantified in whole blood as 
      well as platelet aggregation in platelet-rich plasma in 43 patients with unstable 
      angina before and during treatment with UFH or enoxaparin. Studies were also 
      carried out in blood of seven normal volunteers after addition ex vivo of UFH 
      (0.25 U/mL), enoxaparin (0.25 U/mL), argatroban (1 ng/mL), and normal saline. UFH 
      in patients with unstable angina increased the percentage of circulating 
      platelets positive to PAC-1 from 2.7+/-1.7% to 4.4+/-3.4% (P<.05) and to CD62 
      from 1.6+/-0.9% to 2.7+/-1.5% (P<.01). Platelets were also hyperresponsive to 
      stimulation with ADP and with the thrombin-receptor agonist peptide. Aggregation 
      to ADP increased from 6.8+/-4.6% to 11.2+/-7.0% and to TRAP from 5.2+/-3.5% to 
      11.1+/-6.0% (P<.001). The addition of UFH to blood of normal volunteers resulted 
      also in activation of GP IIb/IIIa receptors, expression of P-selectin, and 
      enhanced platelet aggregation. Enoxaparin had only minor effects on platelet 
      activation in vivo and ex vivo, and argatroban, evaluated ex vivo, had no 
      detectable effects. CONCLUSIONS: Therapeutic concentrations of UFH are associated 
      with platelet activation.
FAU - Xiao, Z
AU  - Xiao Z
AD  - Department of Medicine, Montreal Heart Institute and University of Montreal, 
      Quebec, Canada.
FAU - Theroux, P
AU  - Theroux P
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Controlled Clinical Trial
PT  - Journal Article
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Anticoagulants)
RN  - 0 (Antithrombins)
RN  - 0 (Enoxaparin)
RN  - 0 (P-Selectin)
RN  - 0 (Peptide Fragments)
RN  - 0 (Pipecolic Acids)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 0 (Sulfonamides)
RN  - 137339-65-2 (thrombin receptor peptide (42-55))
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 9005-49-6 (Heparin)
RN  - 94ZLA3W45F (Arginine)
RN  - IY90U61Z3S (argatroban)
SB  - IM
CIN - Circulation. 1999 Jun 29;99(25):3323. PMID: 10385510
CIN - Circulation. 1999 Dec 21;100(25):e155. PMID: 10604921
MH  - Adenosine Diphosphate/pharmacology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angina, Unstable/blood/drug therapy
MH  - Anticoagulants/administration & dosage/*therapeutic use
MH  - Antithrombins/administration & dosage/*therapeutic use
MH  - Arginine/analogs & derivatives
MH  - Dose-Response Relationship, Drug
MH  - Enoxaparin/administration & dosage/*therapeutic use
MH  - Female
MH  - Heparin/administration & dosage/*therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - P-Selectin/blood/drug effects
MH  - Partial Thromboplastin Time
MH  - Peptide Fragments/pharmacology
MH  - Pipecolic Acids/administration & dosage/*therapeutic use
MH  - Platelet Activation/*drug effects
MH  - Platelet Count
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/drug effects/metabolism
MH  - Sulfonamides
EDAT- 1998/02/14 05:48
MHDA- 2000/04/15 09:00
CRDT- 1998/02/14 05:48
PHST- 1998/02/14 05:48 [pubmed]
PHST- 2000/04/15 09:00 [medline]
PHST- 1998/02/14 05:48 [entrez]
AID - 10.1161/01.cir.97.3.251 [doi]
PST - ppublish
SO  - Circulation. 1998 Jan 27;97(3):251-6. doi: 10.1161/01.cir.97.3.251.