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DOI: 10.1055/s-0038-1649715
Effect of Isotretinoin on Endogenous Tissue-Type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor 1 (PAI-1) in Humans
Publication History
Received 28 April 1993
Accepted after revision 14 July 1993
Publication Date:
06 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199306/lookinside/thumbnails/10-1055-s-0038-1649715-1.jpg)
Summary
The effect of isotretinoin on fibrinolysis was investigated in 10 healthy, male volunteers in a randomized, double-blind, crossover-designed study. Isotretinoin (40 mg) was administered in the morning and in the evening for 5 days. t-PA, u-PA and PAI-1 antigen and activity in plasma were measured every morning at 9 a.m. on days 1 to 4 and every 3 hours over 24 hours on day 5. Isotretinoin treatment had no significant stimulatory effect on endogenous t-PA antigen and activity in morning plasma samples nor on their circadian variation. Also, u-PA antigen levels did not change after isotretinoin treatment. Mean PAI-1 antigen and PAI activity in 9 a.m. plasma samples were non-significantly higher during isotretinoin than during placebo treatment. After treatment with isotretinoin a significant rise of fasting triglyceride plasma levels was observed as compared to placebo. The study shows that isotretinoin has no clinically significant effect on endogenous fibrinolysis.
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References
- 1 Wiman B, Hamsten A. Impaired fibrinolysis and risk of thromboem bolism. Prog Cardiovasc Dis 1991; 34: 179-192
- 2 de BoerA, Kluft C, Kroon JM, Kasper FJ, Schoemaker HC, Pruis J, Breimer DD, Soons PA, Emeis JJ, Cohen AF. Liver blood flow as a major determinant of the clearance of recombinant human tissue-type plasminogen activator. Thromb Haemostas 1992; 67: 83-87
- 3 Brommer EJP, Barrett-Bergshoeff MM, Allen RA, Schicht I, Bertina RM, Schalekamp MADH. The use of desmopressin acetate (DDAVP) as a test of the fibrinolytic capacity of patients – Analysis of responders and non-responders. Thromb Haemostas 1982; 48: 156-161
- 4 Agnelli G, Borm J, Cosmi B, Levi M, ten Cate JW. Effects of standard heparin and low molecular weight heparin (Kabi 2165) on fibrinolysis. Thromb Haemostas 1988; 60: 311-313
- 5 Smith D, Gilbert M, Owen WG. Tissue plasminogen activator release in vivo in response to vasoactive agents. Blood 1985; 66: 835-839
- 6 Kooistra T, Opdenberg JP, Toet K, Hendriks HFJ, van den Hoogen RM, Emeis JJ. Stimulation of tissue-type plasminogen activator synthesis by retinoids in cultured human endothelial cells and rat issues in vivo. Thromb Haemostas 1991; 65: 565-572
- 7 Rollman O, Vahlquist A. Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin. J Invest Dermatol 1986; 86: 384-389
- 8 Meyskens FL, Goodman GE, Alberts DS. 13-cis retinoic acid: Pharmacology, toxicology and clinical applications for the prevention and treatment of human cancer. Crit Rev Oncology/Haematology 1985; 3 (01) 075-101
- 9 Andreotti F, Kluft C. Circadian variation of fibrinolytic activity in blood. Chronobiol Internat 1991; 8: 336-351
- 10 Angleton P, Chandler W, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation 1989; 79: 101-106
- 11 Bos R, Hoegee-de Nobel A, Laterveer R, Meijer P, Nieuwenhuizen W. A one step enzyme immunoassay for the determination of total tissue-type plasminogen activator (t-PA) antigen in plasma. Blood Coagulation and Fibrinolysis 1992; 3: 303-307
- 12 Wejkum L, Rosen S, Sörskog L, Brandt B, Chmieleska J. Blood sampling and determination of tissue plasminogen activator activity with COA-SET t-PA. Fibrinolysis 1990; 4 (Suppl. 02) 152-154
- 13 Meijer P, Boon R, Jie AFH, Rosen S, Kluft C. Bioimmunoassay for tissue-type plasminogen activator (t-PA) in human plasma: evaluation of blood sampling and handling procedures and comparison with other t-PA activity methods. Fibrinolysis 1992; 6 (Suppl. 03) 97-99
- 14 Verheijen JH, Chang GTG, Kluft C. Evidence for occurrence of a fast-acting inhibitor of tissue-type plasminogen activator in human plasma. Thromb Haemostas 1984; 51: 392-395
- 15 Binnema DJ, van Iersel JJL, Dooijewaard G. Quantitation of urokinase antigen in plasma and culture media by use of an ELISA. Thromb Res 1986; 43: 569-577
- 16 Dooijewaard G, van Iersel JJL, Brommer EJP. Quantitation of pro UK, UK and UK-inhibitor levels in plasma of patients and healthy man. Fibrinolysis 1986; 1 (suppl.): 142
- 17 Van Bennekum AM, Emeis JJ, Kooistra T, Hendriks HFJ. Modulation of tissue-type plasminogen activator by retinoids in rat plasma and tissue. Am J Physiol 1993; 264: 931-937
- 18 Petkovich M, Brand NJ, Krust A, Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature (London) 1987; 330: 444-450
- 19 Brand N, Petkovich M, Krust A, Chambon P, De Thé H, Marchio A, Tiollais P, Dejean A. Identification of a second human retinoic acid receptor. Nature (London) 1988; 332: 850-853
- 20 Duell EA, Astrom A, Griffiths CEM, Chambon P, Voorhees JJ. Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptors-mediated transcription in vitro. J Clin Invest 1992; 90: 1269-1274
- 21 Gustafson S, Vahlquist C, Sjöblom L, Eklund A, Vahlquist A. Metablism of very low density lipoproteins in rats with isoretinoin induced hyperlipidemia. J Lipid Res 1990; 31: 183-190
- 22 Mehta J, Mehta P, Lawson D, Saldeen T. Plasma tissue plasminogen inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations. J Am Coll Cardiol 1987; 9: 263-268
- 23 Low GDO, Wood DA, Douglas JT, Riersma RA, McIntyre CCA, Takase T, Tuddenham EGD, Forbes CD, Elton RA, Oliver MF. Relationship of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina. Thromb Haemost 1987; 57: 137-139