Thromb Haemost 1987; 57(03): 306-309
DOI: 10.1055/s-0038-1651122
Original Article
Schattauer GmbH Stuttgart

Excessive Deposition of Fibrin, Platelets and Platelet Thrombi on Vascular Subendothelium During Contraceptive Drug Treatment

W Inauen
The Department of Internal Medicine, University Hospital, Inselspital Bern, Switzerland
,
H R Baumgartner
*   The Department of Pharmaceutical Research, Hoffmann-La Roche & Co., Ltd., Basel, Switzerland
,
A Haeberli
The Department of Internal Medicine, University Hospital, Inselspital Bern, Switzerland
,
P W Straub
The Department of Internal Medicine, University Hospital, Inselspital Bern, Switzerland
› Author Affiliations
Further Information

Publication History

Received 05 November 1986

Accepted after revision 20 February 1987

Publication Date:
06 July 2018 (online)

Summary

We investigated the effect of oral contraceptives on thrombogenesis induced by subendothelium of rabbit aorta (SE), exposed to flowing non-anticoagulated blood in an annular flow chamber. Six healthy women on sequential contraceptive drugs (0.05 mg aethinylestradiol/day, 0.125 mg desogestrel/day) were compared with 6 women without hormonal contraception and 6 men. On contraceptive drug treatment, blood values were significantly increased for fibrinogen (2.6±0.2vsl.9±0.1 g/1) and fibrinopeptide A (3.9 ± 0.9 vs 0.9 ± 0.1 ng/ml), whereas antithrombin III was decreased (81 ± 4 vs 97 ± 6%). Fibrin deposition on vascular subendothelium was more than four-fold increased when measured morphologically (63.4 ± 2.5 vs 14.6 ± 6.8% coverage of SE surface with fibrin) as well as immunologically (29.3 ± 2.2 vs 4.5 ± 1.9 pg fibrin/cm2 of SE). Thrombus volumes were more than two-fold increased in women with contraceptives (9.0 ± 1.4 vs 3.7 ± 1.0 μm3/μm2).

Our study shows that during contraceptive drug treatment the exposure of flowing blood to vascular subendothelium leads to excessive deposition of fibrin and platelet thrombi. Measurement of blood interactions with subendothelium might be of predictive value in hypercoagulable states such as contraceptive treatment.

 
  • References

  • 1 Kaulla E v, Kaulla K Nv. Oral contraceptives and low antithrombin III activity. Lancet 1970; 1: 36
  • 2 Howie PW, Mallinson AC, Prentice C RM. Effect of combined oestrogenprogestogen oral contraceptives, oestrogen and progestogen on antiplasmin and antithrombin activity. Lancet 1970; 2: 1329-1332
  • 3 Alkjaersig N, Fletcher A, Burstein R. Association between oral contraceptive use and thromboembolism: A new approach to its investigation based on plasma fibrinogen chromatography. Am J Obstet Gynecol 1975; 122: 199-211
  • 4 Sagar S, Stamatakis JD, Thomas DP, Kakkar VV. Oral contraceptives, antithrombin-III activity, and postoperative deep-vein thrombosis. Lancet 1976; 1: 509-511
  • 5 Conard J, Cazenave B, Samama M, Hovellon MH, Zorn JR, Neau C. AT III content and antithrombin activity in oestrogen-progestogen and progestogenonly treated women. Thromb Res 1980; 18: 675-681
  • 6 McEntee MP, Jesty J, Hultin MB. Effect of oral contraceptives on antithrombin III. Thromb Res 1981; 24: 13-20
  • 7 Melis GB, Fruzzetti F, Paoletta AM, Carmassi F, Fioretti P. Fibrinopeptide A plasma levels during low-estrogen oral contraceptive treatment. Contraception 1984; 30: 575-583
  • 8 Notelovitz M, Levenson I, McKenzie L, Lane D, Kitchens CS. The effects of low-dose oral contraceptives on coagulation and fibrinolysis in two high-risk populations: Young female smokers and older premenopausal women. Am J Obstet Gynecol 1985; 152: 995-1000
  • 9 Mammen EF. Oral contraceptives and blood coagulation: A critical review. Am J Obst Gyn 1982; 142: 781-790
  • 10 Beller FK, Ebert C. Effects of oral contraceptives on blood coagulation. A review. Obstet Gyn 1985; 40: 425-426
  • 11 Baumgartner HR. Effects of anticoagulation on the interaction of human platelets with subendothelium in flowing blood. Schweiz Med Wschr 1976; 106: 1367-1368
  • 12 Weiss HJ, Turitto VT, Baumgartner HR. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear dependent decrease of adhesion in von Willebrand’s disease and the Bernard-Soulier syndrome. J Lab Clin Med 1978; 92: 750-764
  • 13 Baumgartner HR, Turitto VT, Weiss HJ. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. II. Relationship among platelet adhesion, thrombus dimensions and fibrin deposition. J Lab Clin Med 1980; 95: 203-221
  • 14 Weiss HJ, Turitto VT, Vicic WJ, Baumgartner HR. Fibrin formation, fibrinopeptide A release, and platelet thrombus dimension on subendothelium exposed to flowing native blood: Greater in factor XII and XI than in factor VIII and IX deficiency. Blood 1984; 63: 1004-1014
  • 15 Turitto VT, Weiss HJ, Baumgartner HR. Platelet interaction with rabbit subendothelium in von Willebrand’s disease: Altered thrombus formation distinct from defective platelet adhesion. J Clin Invest 1984; 74: 1730-1741
  • 16 Weiss HJ, Turitto VT, Baumgartner HR. Platelet adhesion and thrombus formation on subendothelium in platelets deficient in glycoproteins IIb-IIIa, Ib, and storage granules. Blood 1986; 67: 322-330
  • 17 Hoffmann V, Straub PW. A radioimmunoassay technique for the rapid measurement of human fibrinopeptide A. Thromb Res 1977; 11: 171-181
  • 18 Turitto VT. Blood viscosity, mass transport and thrombogenesis. Prog Hemostasis Thromb 1982; 6: 139-178
  • 19 Turitto VT, Baumgartner HR. Platelet-surface interactions. In: Hemostasis and Thrombosis, basic principles and clinical practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds.). JB Lippincott Company; Philadelphia: 1982. pp 364-379
  • 20 Aarts P AM M, van Broek J AT M, Kuiken G DC, Sixma JJ, Heethaar RM. Velocity profiles in annular perfusion chamber measured by laser-doppler velocimetry. J Biomechanics 1984; 17: 61-63
  • 21 Haeberli A, Straub PW. Quantitative determination of fibrin and fibrinogen in biological material. J Lab Clin Med 1980; 96: 258-266
  • 22 Asmussen I, Kjeldsen K. Intimal ultrastructure of human umbilical arteries. Observations on arteries from newborn children of smoking and non-smoking mothers. Circ Res 1975; 36: 579-589
  • 23 Mann JI, Vessey MP, Thorogood M, Doll R. Myocardial infarction in young women with special reference to oral contraceptive practice. Br Med J 1975; 2: 241-245
  • 24 Petitti DB, Wingerd J, Pellegrin F, Ramcharan S. Risk of vascular disease in women: smoking, oral contraceptives, noncontraceptive estrogens, and other factors. JAMA 1979; 242: 1150-1154