Postthrombotic vein wall remodeling: preliminary observations.
BACKGROUND
Postthrombotic syndrome is characterized by a fibrotic vein injury following deep vein thrombosis (DVT). We sought to quantify the change in vein wall thickness in patients who fail to resolve DVT by 6 months and whether there were differences in blood or plasma levels of inflammatory proteins associated with venous remodeling.


METHODS
Patients presenting with confirmed lower extremity DVT were prospectively recruited for this study. Duplex imaging of the lower extremity venous system was performed, and blood was collected at entrance and repeat evaluation with blood draw and ultrasound imaging at 1 and 6 months. DVT resolution and thickness of the vein wall was quantified by ultrasound imaging in each segment affected by thrombus, and a contralateral, unaffected vein wall served as a control. Gene and protein expression of inflammatory markers were examined from leukocytes and serum, respectively. Analysis of variance or Student t-tests were used, and a P < .05 was significant. N = 10 to 12 for all analyses.


RESULTS
Thirty-two patients (12 patients with DVT resolution at 6 months, 10 patients with persistent thrombus at 6 months, and 10 healthy controls) were compared. Both resolving and nonresolving DVT were associated with a 1.5- to 1.8-fold increased vein wall thickness at 6 months (P = .008) as compared with nonaffected vein wall segments. However, the thickness of the affected segments was 1.4-fold greater in patients who had total resolution of the DVT by 6 months than in patients who had persistent chronic thrombus 6 months after presentation (P = .01). There was a four- to five-fold increased level of matrix metalloproteinase-9 (MMP-9) antigen in thrombosed patients compared with nonthrombosed patient controls (P < .05), while Toll-like receptor-9 (TLR-9) gene expression was three-fold less than controls (P < .05) at enrollment. D-dimer and P-selectin were higher in thrombosed as compared to controls at diagnosis but not at 6 months. Both TLR-4 (marker of inflammation) and P-selectin gene expression were higher in leukocytes from patients with chronic DVT compared with those who resolved at 1 month after diagnosis (P < .05).


CONCLUSIONS
This preliminary study suggests ongoing vein wall remodeling after DVT, measurable by ultrasound and associated with certain biomarkers. At 6 months, the vein wall is markedly thickened and directly correlates with resolution. This suggests that the vein wall response is initiated early following thrombus formation and persists even in the presence of total resolution.
Deatrick
Kristopher B
KB
Section of Vascular Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor, MI, USA.
Elfline
Megan
M
Baker
Nichole
N
Luke
Catherine E
CE
Blackburn
Susan
S
Stabler
Catherine
C
Wakefield
Thomas W
TW
Henke
Peter K
PK
D015415:Biomarkers / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D054070:Postthrombotic Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology*; D011446:Prospective Studies; D051193:Toll-Like Receptors / Q000097:blood; D018616:Ultrasonography, Doppler, Duplex; D014680:Veins / Q000000981:diagnostic imaging / Q000473:pathology*
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D019007:P-Selectin; D051193:Toll-Like Receptors; C036309:fibrin fragment D; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9