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2004 | 51 | 1 | 73-80
Article title

The effect of some ε-aminocaproic acid derivatives on platelet responses.

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ε-Aminocaproic acid (EACA) is a synthetic low molecular drug with antifibrinolytic activity. However, treatment with this drug can be incidentally associated with an increased thrombotic tendency. The aim of the present work was to test synthetic EACA derivatives for their antiplatelet activities. We investigated the effect of three EACA derivatives with antifibrinolytic activity: I. ε-aminocaproyl-L-leucine hydrochloride (HClH-EACA-L-Leu-OH), II. ε-aminocaproyl-L-(S-benzyl)-cysteine hydrochloride (HClH-EACA-L-Cys(S-Bzl)-OH) and III. ε-aminocaproyl-L-norleucine (H-EACA-L-Nle-OH) on platelet responses (aggregation and adhesion) and on their integrity. It was found that: 1. as judged by LDH release test, none of the tested compounds, up to 20 mM, was toxic to platelets, 2. in comparison with EACA, all the synthetic derivatives inhibited much stronger the ADP- and collagen-induced aggregation of platelets suspended in plasma (platelet rich plasma) and aggregation of these cells in whole blood, 3. EACA and its derivatives exerted a similar inhibitory effect on the thrombin-induced adhesion of platelets to fibrinogen-coated surfaces. Since platelet activation and blood coagulation are tightly associated processes, the antiplatelet properties of EACA derivatives are expected to indicate reduced thrombotic properties of these derivatives compared to EACA.
Physical description
  • Department of Organic Chemistry, Medical University of Bialystok, Bialystok, Poland
  • Department of Physical Chemistry, Medical University of Bialystok, Bialystok, Poland
  • Department of Physical Chemistry, Medical University of Bialystok, Bialystok, Poland
  • Department of Organic Chemistry, Medical University of Bialystok, Bialystok, Poland
  • Barrons RW, Jahr JS. (1996) A review of post-cardiopulmonary bypass bleeding, aminocaproic acid, tranexamic acid, and aprotinin. Am J Ther.; 3: 821-38.
  • Bellavite P, Andrioli G, Guzzo P, Chirumbolo S, Manzato F, Santonastaso C. (1994) A colorimetric method for the measurement of platelet adhesion in microtiter plates. Anal Biochem.; 216: 444-50.
  • Bergmeyer HU, Bernt E, Hess B. (1965) Lactate dehydrogenase. In Methods of Enzymatic Analysis. Bergmeyer HU, ed, p 736. Academic Press Inc., New York.
  • Born GVR. (1963) Quantitative investigation into aggregation of blood platelets. J Physiol.; 168: 178-95.
  • Cardinal DC, Fower RJ. (1980) The electronic aggregometer: a novel device for assessing platelet behavior in blood. J Farmacol Methods.; 3: 135-43.
  • Chrono-Log Corp. (1987) Manual for Testing with the Whole-blood Aggregometer Model 550. Havertown, PA.
  • DelRossi AJ, Cernainau AC, Botros S, Lemole GM, Moore R. (1989) Prophylactic treatment of postperfusion bleeding using EACA. Chest.; 96: 27-30.
  • Dunn CJ, Goa KL. (1999) Tranexamic acid. A review of its use in surgery and other indications. Drugs.; 57: 1005-32.
  • Green D, Ts'ao CH, Cerullo L, Cohen I, Ruo TI, Atkinson AJ. (1985) Clinical and laboratory investigation of the effects of epsilon-aminocaproic acid on hemostasis. J Lab Clin Med.; 105: 321-7.
  • Hardy J. (1992) Natural and synthetic antifibrinolytics in cardiac surgery. Can J Anaesth.; 39: 353-65.
  • Heemskerk J, Bevers E, Lindhout T. (2002) Platelet activation and blood coagulation. Thromb Haemost.; 88: 186-93.
  • Maciejewska D, Midura-Nowaczek K, Wawer I. (2002) Conformational analysis of ε-aminocaproyl-α-aminoacids in solution and solid state by 1H, 13C NMR spectroscopy and molecular modeling. J Mol Struct.; 604: 269-78.
  • Mannucci PM. (1998) Hemostatic drugs. N Engl J Med.; 339: 245-53.
  • Markwardt F. (1978) Fibrinolytics and antifibrinolytics. In Handbook of Experimental Pharmacology, vol 46. Springer, Berlin, Heidelberg, New York.
  • Midura-Nowaczek K, Bruzgo I, Dubis E, Roszkowska-Jakimiec W, Worowski K. (1996) Antifibrinolytic activity of ε-aminocaproyl derivatives of amino acids. Pharmazie.; 51: 775-7.
  • Midura-Nowaczek K, Bruzgo I, Popławski J, Roszkowska-Jakimiec W, Worowski K. (1998) Effects of ε-aminocaproylaminoacids on fibrynolytic and caseinolytic activity of euglobulin fraction. Acta Pol Pharm.; 55: 159-61.
  • Monroe DM, Hoffman M, Roberts HR. (2002) Platelets and thrombin generation. Arterioscler Thromb Vasc Biol.; 22: 1381-9.
  • Munoz JJ, Birkmeyer NJO, Birkmeyer JD, O'Connor GTO, Dacey LJ. (1999) Is ε-aminocaproic acid as effective as aprotinin in reducing bleeding with cardiac surgery? A meta-analysis. Circulation.; 99: 81-9.
  • Peters DC, Noble S. (1999) Aprotinin. An update of its pharmacology and therapeutic use in open heart surgery and coronary bypass surgery. Drugs.; 57: 233-60.
  • Porte RJ, Leebeek FWG. (2002) Pharmacological strategies to decrease transfusion requirements in patients undergoing surgery. Drugs.; 62: 2193-211.
  • Verstraete M. (1985) Clinical application of inhibitors of fibrinolysis. Drugs.; 29: 236-61.
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