Endothelial damage after treatment with low-molecular weight heparins--a morphological study.
OBJECTIVE
Recent studies failed to show long-term benefit with low-molecular weight heparins (LMWH) in unstable coronary heart disease. A previous study of vascular effects of the cytostatic agent 5-fluorouracil (5-FU) showed that dalteparin prevented thrombosis induced by 5-FU but endothelial damage was not ameliorated and was present also in animals treated with dalteparin only. This study investigates the influence of LMWH currently in clinical use on arterial endothelium in vivo.


METHODS
Eighty rabbits in four groups were treated with dalteparin, enoxaparin, tinzaparin and saline, respectively. Arterial endothelium was examined after 3, 14, 30 and 60 days with scanning electron microscopy.


RESULTS
All three groups treated with LMWH showed moderate damage to the endothelium, with contracted vessel wall and endothelial cells, cell membrane damage, denudation of subendothelium and adhering platelets. Contrarily, the control group exhibited a normal endothelium.


CONCLUSIONS
Morphologic examination of arterial endothelium shows that all investigated LMWH exert a moderate toxic effect on endothelial cells. The clinical impact of these observations, e.g. concerning effect of long-term LMWH treatment, needs to be further elucidated.
Department of Oncology, University Hospital, Lund University, SE-221 85 Lund, Sweden. sara.kinhult@onk.lu.se
Sara
S
Kinhult
Jan
J
Eskilsson
Maria
M
Albertsson
Magdalena
M
Cwikiel
D000818:Animals; D000925:Anticoagulants / Q000633:toxicity*; D001158:Arteries / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D017985:Dalteparin / Q000633:toxicity; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D017984:Enoxaparin / Q000633:toxicity; D006495:Heparin, Low-Molecular-Weight / Q000633:toxicity*; D008297:Male; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D013997:Time Factors; D000078222:Tinzaparin
D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin; D017985:Dalteparin