Heparin binding to plasma proteins, an important mechanism for heparin resistance.
Heparin dosage requirements vary widely among patients with venous thromboembolism. In this study, we measured the proportion of anticoagulantly-active heparin which was reversibly bound and neutralized by plasma proteins (defined as reversible heparin neutralization) in the pre-treatment plasma (in vitro) and in the 6 h post-treatment plasma (ex vivo) of patients with venous thromboembolism treated with a fixed dose of heparin. Reversible heparin neutralization was assessed by comparing the heparin levels measured as anti-factor Xa activity before and after the addition of low affinity heparin which is essentially devoid of anti-factor Xa activity, in order to displace heparin bound to plasma proteins. The results indicate that reversible heparin neutralization due to binding to plasma proteins is a major determinant of the anticoagulant response to a fixed dose of standard heparin 6 h post-treatment and of the eventual heparin dose required to achieve a therapeutic anticoagulant effect on days 3-5 of heparin treatment.
Young
E
E
Department of Pathology, McMaster University, Hamilton, Canada.
Prins
M
M
Levine
M N
MN
Hirsh
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D004351:Drug Resistance / Q000502:physiology; D015951:Factor Xa / Q000276:immunology; D005260:Female; D006493:Heparin / Q000097:blood* / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011485:Protein Binding
D000906:Antibodies; D001798:Blood Proteins; D006493:Heparin; D015951:Factor Xa