Highly variable anticoagulant response after subcutaneous administration of high-dose (12,500 IU) heparin in patients with myocardial infarction and healthy volunteers.
BACKGROUND
In this study, the anticoagulant response of 12,500 IU heparin s.c. was investigated in patients with myocardial infarction and healthy volunteers to determine variabilities in response and modifying factors.


RESULTS
On the fourth day after thrombolytic therapy, blood samples were taken before and at frequent intervals until 10 hours after the injection of 12,500 IU heparin s.c. Plasma anti-Xa activity, anti-IIa activity, and the activated partial thromboplastin time (APTT) were measured in addition to body weight and thickness of the abdominal subcutaneous fat layer. Contrary to expectations, the increase of anti-Xa activity, anti-IIa activity, and APTT compared with baseline (predrug) levels was very small, with an average maximal APTT of 42.6 seconds (SD, 12.4 seconds; range, 30.4-70.7 seconds). Subsequently, the influence of the length of the injection needle on the anticoagulant effect of 12,500 IU heparin s.c. was studied in 10 healthy volunteers to find a factor that could be responsible for the poor response in the patients. The length of the injection needle did not influence the anticoagulant effect of heparin. Large interindividual and intraindividual variabilities were seen in the volunteers. The majority of volunteers had minimal prolongation of the APTT, but very strong prolongation was also seen (maximal APTT, 163 seconds). There was no correlation between the abdominal skinfold thickness and anti-Xa activity, anti-IIa activity, or APTT (p > 0.05), but in the patient study, there was a correlation between weight and anti-Xa activity and anti-IIa activity (p < 0.05), and in the volunteer study, there was a correlation between weight and anti-Xa activity and APTT (p < 0.05).


CONCLUSIONS
Subcutaneous administration of heparin in a fixed dose for prophylactic and therapeutic purposes may be inadequate because of the large interindividual and intraindividual variations in anticoagulant effect.
Kroon
C
C
Centre for Human Drug Research, University Hospital, Leiden, The Netherlands.
ten Hove
W R
WR
de Boer
A
A
Kroon
J M
JM
van der Pol
J M
JM
Harthoorn-Lasthuizen
E J
EJ
Schoemaker
H C
HC
van der Meer
F J
FJ
Cohen
A F
AF
D000328:Adult; D001835:Body Weight / Q000502:physiology; D015951:Factor Xa / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy*; D009339:Needles; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000187:drug effects; D015912:Thrombolytic Therapy
D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa