Low-dose low-molecular-weight heparin is anti-inflammatory during venous thrombosis.
OBJECTIVE
Venous thrombosis results in a vein wall inflammatory response initiated by thrombus. Although anticoagulation with standard heparin (SH) and low-molecular-weight heparin (LMWH) is known to limit further thrombosis, their anti-inflammatory properties are poorly defined. The anti-inflammatory properties of these heparins were studied.


METHODS
Sprague-Dawley rats were divided into groups and underwent inferior vena caval (IVC) ligation just below the renal level producing IVC thrombosis. One hour before ligation, animals received subcutaneous SH or LMWH at either high or low dose; normal saline (NS) was used as control. Six hours after ligation, animals were killed, and the IVCs were analyzed for clot presence, vein wall morphometrics, and vein wall permeability (VP) to define injury.


RESULTS
Animals in both low-dose groups had no measurable anticoagulation, whereas those in both high-dose groups were adequately anticoagulated. There were statistically less IVC neutrophils for all groups compared with the control group, with low-dose LMWH showing the least cells (low-dose LMWH, 16 +/- 3; high-dose LMWH, 37 +/- 10; low-dose SH, 37 +/- 6; high-dose SH, 32 +/- 9; NS control, 63 +/- 2). Similar results were noted for total inflammatory cells. The lowest VP was noted for low-dose LMWH.


CONCLUSIONS
Although both SH and LMWH inhibited vein wall neutrophils and total inflammatory cells, low-dose LMWH was most effective limiting neutrophil extravasation and was the only intervention to decrease VP below control levels. This occurred without preventing thrombus formation or causing a state of anticoagulation. Low-dose LMWH possesses anti-inflammatory properties distinct from its anticoagulant properties.
Downing
L J
LJ
Section of Vascular Surgery and Jobst Vascular Research Laboratory, Department of Surgery, and the Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA.
Strieter
R M
RM
Kadell
A M
AM
Wilke
C A
CA
Greenfield
L J
LJ
Wakefield
T W
TW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D007249:Inflammation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014680:Veins / Q000473:pathology; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000473:pathology
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight