Laboratory monitoring of the clinical effects of low molecular weight heparins.
Despite a clinical prophylactic efficacy of low molecular weight heparins (LMWHs) for 24 hrs after a single subcutaneous administration, the routine laboratory tests (anti-Xa, anti-IIa, Heptest, APTT which show a reliable in vitro dose-response) exhibit no ex vivo response after 6 hours. In addition, the values obtained in these assays do not correlate with clinical efficacy or bleeding side effects. With therapeutic doses of LMWHs, a proportionately higher effect was noted in these tests including, in addition, thrombin generation, Heptest-Hi, and thrombin time assays. However, the relevance of these assays to the clinical efficacy/toxicity of LMWHs remains unclear since they do not relate to the total pharmacodynamic effect. For example, protamine neutralization, adjunct drug treatment and a patient's own predisposing factors which contribute to the hemostatic balance may not be reflected in these assays. These observations point to the limitations of the available laboratory tests for monitoring LMWHs. In order to find a more sensitive means to detect the effects of LMWH, assays for specific molecular markers of coagulation and fibrinolysis activation were evaluated. Alterations in the levels of thrombin-antithrombin complex, t-PA, total degradation products and D-dimer assays were observed over a 7-10 day LMWH treatment period. Prothrombin fragment F1+2, modified antithrombin, PAI and fibrinogen degradation products were not significantly effected. The association of the changes observed in these markers to the mechanism of action of LMWH or to the efficacy of the treatment, however, remains to be determined.
Walenga
J M
JM
Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Illinois.
Hoppensteadt
D
D
Fareed
J
J
D000818:Animals; D001780:Blood Coagulation Tests; D004341:Drug Evaluation; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D011817:Rabbits; D013927:Thrombosis / Q000517:prevention & control
D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight