Plasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis.
AuthorsMaher, Vincent M G
Davies, Graham J
Thompson, Gilbert R
AffiliationDepartment of Cardiology, Adelaide Meath Hospital, Dublin, Ireland. firstname.lastname@example.org
Blood Component Removal
Coronary Artery Disease
Hyperlipoproteinemia Type II
Plasminogen Activator Inhibitor 1
MetadataShow full item record
CitationPlasminogen activator inhibitor-1 removal using dextran sulphate columns. Evidence of PAI-1 homeostasis. 2009, 28 (2):166-72 J. Thromb. Thrombolysis
PublisherJournal of thrombosis and thrombolysis
JournalJournal of thrombosis and thrombolysis
AbstractPatients with high plasma plasminogen activator inhibitor-1 (PAI-1) antigen levels are prone to develop thrombosis. Lowering PAI-1 levels may offer a therapeutic option and help to better understand PAI-1 metabolism. We examined the effect on plasma PAI-1 levels of LDL-apheresis using dextran sulphate (DS) columns in 12 patients (9 male, 3 female, 49 +/- 10 years) with heterozygous familial hypercholesterolaemia and coronary artery disease. One plasma volume equivalent (2.3-4.0 l) was treated during each procedure (at flow rates of 23 +/- 2 ml/min). Lipids and PAI-1 antigen levels were measured in plasma before and immediately after 19 aphereses (once in 7 patients, twice in 3 patients and three times in 2 patients) and also at 3 and 7 days post apheresis in five of these patients and in the column eluates from 8 of these patients. DS-apheresis reduced plasma cholesterol (50 +/- 8%), triglyceride (45 +/- 27%), apolipoprotein B (59 +/- 10%) and PAI-1 antigen levels from 10.2 +/- 5.2 to 6.0 +/- 3.1 ng/ml (P = 0.005). The PAI-I changes were independent of circadian variation. PAI-I bound to the DS-columns (3.51 +/- 1.03 ng/ml filtered plasma) and the percent of filtered PAI-1 that was bound correlated inversely (r = -0.81, P < 0.02) with basal PAI-1 levels indicating a high affinity saturable binding process. In four patients, plasma PAI-1 levels post-apheresis were higher than expected based on the amount of PAI-removed by the DS columns. The difference between the expected and actual PAI-1 level post apheresis, reflecting PAI-1 secretion or extracellular redistribution, correlated inversely with basal PAI-1 levels (r = -0.83, P = 0.01). PAI-1 levels returned to baseline pre-apheresis values 7 days post apheresis. PAI-1 antigen may be removed from plasma without adverse effect, resulting temporarily in its extracellular redistribution and restoration to baseline levels over one week. PAI-1 redistribution particularly when baseline pre-apheresis values were low may reflect a homeostatic mechanism to maintain sufficient PAI-1 levels. Procedures that could selectively remove PAI-1 from plasma may offer a treatment option for those with very high plasma PAI-1 levels and thrombosis.
- Hemostatic variables in homozygous familial hypercholesterolemia. Effect of regular plasma cholesterol removal by low density lipoprotein apheresis.
- Authors: Di Minno G, Cerbone AM, Cirillo F, Postiglione A, Colucci M, Semeraro N, Scarpato N, Gnasso A, Margaglione M, Gallotta G
- Issue date: 1990 Nov-Dec
- Changes in lipoprotein(a), LDL-cholesterol and apolipoprotein B in homozygous familial hypercholesterolaemic patients treated with dextran sulfate LDL-apheresis.
- Authors: Lasunción MA, Teruel JL, Alvarez JJ, Carrero P, Ortuño J, Gómez-Coronado D
- Issue date: 1993 Dec
- Hematologic and hemostatic changes induced by different columns during LDL apheresis.
- Authors: Hovland A, Hardersen R, Nielsen EW, Mollnes TE, Lappegård KT
- Issue date: 2010
- Effective reduction of plasma LDL levels by LDL apheresis in familial defective apolipoprotein B-100.
- Authors: Maher VM, Kitano Y, Neuwirth C, Gallagher JJ, Thompson GR, Myant NB
- Issue date: 1992 Aug
- Extracorporeal treatment of hypercholesterolaemia.
- Authors: Olbricht CJ
- Issue date: 1993