Role of hemostatic risk factors for restenosis in peripheral arterial occlusive disease after transluminal angioplasty.
In a prospective study, the role of various hemostatic factors known to be associated with thrombotic risk was investigated in 71 patients with peripheral arterial occlusive disease (PAOD, stages II through IV, Fontaine; aged 68 +/- 13 years). Laboratory investigations were done before; 1, 24, and 48 hours after; and 3 and 6 months after percutaneous transluminal angioplasty (PTA). Thirty of 71 (42.3%) patients developed restenosis (> 50% reduction of the lumen diameter) at the site of PTA within 6 months, verified by color-coded duplex sonography. Significantly increased levels of thrombin-antithrombin III complexes (P < .01), prothrombin fragments 1 + 2 (P < .01), and D-dimers (P < .01) were found 1 hour, as well as 24 to 48 hours, after PTA. Fibrinogen (P < .01) and von Willebrand factor (P < .01) were significantly higher 48 hours after PTA. Restenotic patients as a whole had higher plasma fibrinogen (3.46 +/- 1.12 versus 2.95 +/- 0.62 g/L, P < .01) and C-reactive protein (25.4 +/- 46.7 versus 7.9 +/- 6.9 mg/L, P < .05) at baseline, as well as higher fibrinogen (P < .05) and prothrombin fragments 1 + 2 (P < .01) during months 3 to 6 after PTA. There was a nonsignificant tendency for higher values of von Willebrand factor (206 +/- 98% versus 184 +/- 100%, P = .2) at baseline in patients with restenosis, whereas tissue plasminogen activator, plasminogen activator inhibitor, coagulation screening tests, blood cell counts, and serum lipids showed no significant difference between the two groups. The relative risk for developing restenosis within 6 months while having high fibrinogen (> 2.8 g/L) or C-reactive protein at baseline was 2.80 (95% CI: 1.30-6.02, P < .01) and 1.96 (95% CI: 1.07-3.58, P < .05), respectively. Patients with critical limb ischemia (stage III/IV, Fontaine) had significantly higher fibrinogen and von Willebrand factor at repeated points of time, as well as significantly higher C-reactive protein and lower creatinine clearance at entry. In the logistic regression risk factor analysis, baseline plasma fibrinogen, C-reactive protein concentration, and the severity of the arterial disease were significantly predictive of restenosis. Our results indicate that high procoagulant factors and persistent thrombin generation of the hemostatic system might promote restenosis, particularly in patients with extended atherosclerosis. This finding suggests that new treatment strategies should be taken under consideration for patients with PAOD and PTA.
Tschopl
M
M
Department of Internal Medicine, University Hospital Basel, Switzerland.
Tsakiris
D A
DA
Marbet
G A
GA
Labs
K H
KH
Jäger
K
K
D000800:Angioplasty, Balloon; D000990:Antithrombin III / Q000032:analysis; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000628:therapy*; D015415:Biomarkers; D001780:Blood Coagulation Tests; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015897:Comorbidity; D003404:Creatinine / Q000378:metabolism; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011150:Popliteal Artery / Q000000981:diagnostic imaging; D011446:Prospective Studies; D011516:Prothrombin / Q000032:analysis; D012008:Recurrence; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013917:Thrombin / Q000096:biosynthesis*; D019851:Thrombophilia / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000032:analysis; D017211:Treatment Failure; D018615:Ultrasonography, Doppler, Color; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D008055:Lipids; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D014841:von Willebrand Factor; D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen; D002097:C-Reactive Protein; D003404:Creatinine; D010447:Peptide Hydrolases; D013917:Thrombin; D010959:Tissue Plasminogen Activator